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Freund O, Hadad Y, Bergeron A, Fried S, Pomerantz G, Shaffer A, Paz D, Barel N, Perluk TM, Amit O, Ram R, Bar-Shai A. Bronchiectasis after allogeneic hematopoietic cell transplantation - an underdiagnosed complication. Respir Med 2025; 245:108208. [PMID: 40513968 DOI: 10.1016/j.rmed.2025.108208] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2025] [Revised: 05/17/2025] [Accepted: 06/11/2025] [Indexed: 06/16/2025]
Abstract
BACKGROUND Bronchiectasis (BE) following allogeneic hematopoietic cell transplantation (allo-HCT) are described in the context of bronchiolitis obliterans syndrome (BOS). However, data on its overall prevalence and characteristics in allo-HCT patients are scarce. OBJECTIVES To assess the prevalence, characteristics, and outcomes of symptomatic new-onset bronchiectasis after allo-HCT. METHODS A prospective database with all subjects that underwent allo-HCT between 2014 and 2022 in a tertiary center was utilized. Chest CT scans of subjects with respiratory symptoms were analyzed and compared to pre-HCT scans for BE. Changes in pulmonary function tests (PFTs) and mortality were compared between patients with and without BE. RESULTS Overall, 282 subjects underwent allo-HCT and 182 survived at 6 months. Thirty-six patients (20 %) were diagnosed with new-onset BE. Median (IQR) duration from HCT to BE diagnosis was 304 (202-547) days. Of those with BE and serial PFTs, 39 % met the criteria for BOS. Independent predictors for BE included chronic graft vs. host disease (adjusted OR 6.8, 95 % CI 1.34-34.6) and a lower baseline FEV1 % (aOR 0.95, 95 % CI 0.92-0.98). BE was associated with increased hazard of mortality (HR 1.91, 95 % CI 1.1-3.6), validated by an extended cox model and sub-group analyses. Patients meeting the criteria for BOS had lower follow-up PFTs and a higher rate of diffuse distribution of bronchiectasis (67 % vs. 32 %). Moreover, patients with BOS had increased mortality compared to BE not meeting these criteria (HR 3.40, 95 % CI 1.2-9.4). CONCLUSIONS Bronchiectasis is prevalent after allo-HCT with major impact, not solely explained by BOS.
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Affiliation(s)
- Ophir Freund
- The Institute of Pulmonary Medicine, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
| | - Yitzhac Hadad
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Department of Radiology, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel
| | - Anne Bergeron
- Service de pneumologie, hôpitaux universitaires de Genève, Genève, Switzerland
| | - Sabrina Fried
- The Institute of Pulmonary Medicine, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Gidon Pomerantz
- The Institute of Pulmonary Medicine, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Avshalom Shaffer
- The Institute of Pulmonary Medicine, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Dolev Paz
- The Institute of Pulmonary Medicine, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Nevo Barel
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Internal medicine B, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel
| | - Tal Moshe Perluk
- The Institute of Pulmonary Medicine, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Odelia Amit
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Bone Marrow Transplantation Unit, The Division of Hematology, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel
| | - Ron Ram
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Bone Marrow Transplantation Unit, The Division of Hematology, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel
| | - Amir Bar-Shai
- The Institute of Pulmonary Medicine, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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Amin R, Vaishali K, Maiya GA, Mohapatra AK, Acharya V, Dale MT, Alison JA. Relationships between disease severity and measures of health status in people with interstitial lung disease in India: an observational study. Sci Rep 2025; 15:16985. [PMID: 40374826 DOI: 10.1038/s41598-025-01877-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2024] [Accepted: 05/08/2025] [Indexed: 05/18/2025] Open
Abstract
The severity and progression of Interstitial Lung Disease (ILD) can vary due to environmental, cultural and genetic factors. The relationship between disease severity and factors that determine the health status of people with ILD living in lower middle-income countries like India has not been evaluated. This study aimed to determine whether there were relationships between disease severity with functional exercise capacity and Health Related Quality of Life (HRQoL) among people with ILD in India. This was a prospective, single center observational study. All participants performed Pulmonary Function Test (PFT) including Forced Vital Capacity (FVC) % predicted, Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) % predicted, 6 min Walk Distance (6MWD), St. George's Respiratory Questionnaire (SGRQ), modified Medical Research Council (mMRC) dyspnoea scale. Eighty participants with ILD were recruited from September 2020 and December 2022. There were strong correlations between 6MWD with DLCO % pred (Spearman rho 0.891) and between SGRQ Total score and DLCO % pred (Spearman rho 0.906). There were no correlations between 6MWD and FVC % pred (Spearman rho 0.206) or between SGRQ and FVC % pred (Spearman rho 0.113). This study demonstrated strong correlations between disease severity measured by DLCO % pred with both functional exercise capacity and HRQoL in people with ILD in India.
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Affiliation(s)
- Revati Amin
- Department of Physiotherapy, Kasturba Medical College Mangalore, Manipal Academy of Higher Education, Manipal, India
| | - K Vaishali
- Department of Physiotherapy, Manipal College of Health Professions, Manipal Academy of Higher Education, Manipal, India.
| | - G Arun Maiya
- Department of Physiotherapy, Manipal College of Health Professions, Manipal Academy of Higher Education, Manipal, India
| | - Aswini Kumar Mohapatra
- Department of Respiratory Medicine, Kasturba Medical College Manipal, Manipal Academy of Higher Education, Manipal, India
| | - Vishak Acharya
- Department of Pulmonary Medicine, Kasturba Medical College Mangalore, Manipal Academy of Higher Education, Manipal, India
| | - Marita T Dale
- Sydney School of Health Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia
| | - Jennifer A Alison
- Sydney School of Health Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia
- Allied Health, Sydney Local Health District, Sydney, Australia
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De Lorenzis E, Del Galdo F, Natalello G, Varone F, Di Donato S, Verardi L, Calandriello L, Kakkar V, Cerasuolo PG, Larici AR, D'Agostino MA, Bosello SL, Richeldi L. Concordance and Prognostic Relevance of Different Definitions of Systemic Sclerosis Interstitial Lung Disease Progression. Am J Respir Crit Care Med 2024; 210:1348-1357. [PMID: 39078207 DOI: 10.1164/rccm.202311-2153oc] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2023] [Accepted: 07/29/2024] [Indexed: 07/31/2024] Open
Abstract
Rationale: Interstitial lung disease (ILD) in systemic sclerosis (SSc) is a common complication that has a varied progression rate and prognosis. Different progression definitions are available, including minimal clinically important worsening of FVC, EUSTAR (European Scleroderma Trials and Research Group) progression, OMERACT (Outcome Measures in Rheumatology Clinical Trials) progression, and Erice ILD working group progression. Pulmonary function and symptom changes may act as specific confounding factors when applying these definitions in SSc. Objectives: To assess the concordance and prognostic value of four different definitions in patients with SSc-ILD overall and in specific clinical groups. Methods: Progression status in consecutive patients with SSc-ILD was assessed over 24 months, and 60-month disease-related mortality risk was compared between progressors and nonprogressors using four definitions. Measurements and Main Results: Among 245 patients, 26 SSc-related deaths were reported. Mortality was linked to progression for minimal clinically important worsening of FVC (hazard ratio [HR], 2.27; 95% confidence interval [CI], 1.03-4.97), OMERACT (HR, 2.90; 95% CI, 1.28-6.57), and Erice definitions (HR, 2.69; 95% CI, 1.23-5.89). The association between progression and mortality was poor in patients with disease duration ≥3 years, mild functional impairment, and pulmonary artery systolic pressure ≥40 mm Hg. Erice criteria appeared superior in patients with duration ≥3 years, limited cutaneous variant, and pulmonary artery systolic pressure <40 mm Hg. OMERACT criteria performed better in diffuse cutaneous variant patients with severe functional impairment. Conclusions: The four evaluated definitions of progression in SSc-ILD are not interchangeable, resulting in up to one-third of cases being classified differently on the basis of adopted criteria and presenting different prognostic values, particularly within specific clinical groups.
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Affiliation(s)
- Enrico De Lorenzis
- Division of Rheumatology, Department of Geriatrics, Orthopedics and Rheumatology
- Scleroderma Program, Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, United Kingdom
| | - Francesco Del Galdo
- Scleroderma Program, Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, United Kingdom
| | - Gerlando Natalello
- Division of Rheumatology, Department of Geriatrics, Orthopedics and Rheumatology
| | - Francesco Varone
- Division of Pulmonology, Department of Neurosciences, Sense organs and Thorax, and
| | - Stefano Di Donato
- Scleroderma Program, Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, United Kingdom
| | - Lucrezia Verardi
- Division of Rheumatology, Department of Geriatrics, Orthopedics and Rheumatology
| | - Lucio Calandriello
- Division of Thorax and Cardiovascular Radiology, Department of Diagnostic Imaging, Oncological Radiotherapy and Hematology, Catholic University of the Sacred Heart - Fondazione Policlinico Universitario A. Gemelli-IRCCS, Rome, Italy; and
| | - Vishal Kakkar
- Scleroderma Program, Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, United Kingdom
| | | | - Anna Rita Larici
- Division of Thorax and Cardiovascular Radiology, Department of Diagnostic Imaging, Oncological Radiotherapy and Hematology, Catholic University of the Sacred Heart - Fondazione Policlinico Universitario A. Gemelli-IRCCS, Rome, Italy; and
| | | | - Silvia Laura Bosello
- Division of Rheumatology, Department of Geriatrics, Orthopedics and Rheumatology
| | - Luca Richeldi
- Division of Pulmonology, Department of Neurosciences, Sense organs and Thorax, and
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Zhang H, Li X, Zhang X, Yuan Y, Zhao C, Zhang J. Quantitative CT analysis of idiopathic pulmonary fibrosis and correlation with lung function study. BMC Pulm Med 2024; 24:437. [PMID: 39238010 PMCID: PMC11378381 DOI: 10.1186/s12890-024-03254-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2024] [Accepted: 08/29/2024] [Indexed: 09/07/2024] Open
Abstract
BACKGROUND Idiopathic Pulmonary Fibrosis (IPF) is a progressive fibrotic lung disease. However, the field of quantitative CT scan analysis in conjunction with pulmonary function test for IPF patients remains relatively understudied. In this study, we evaluated the diagnostic value of features derived high-resolution computed tomography (HRCT) for patients with IPF and correlated them with pulmonary function tests. METHODS We retrospectively analyzed the chest HRCT images and pulmonary function test results of 52 patients with IPF during the same period (1 week) and selected 52 healthy individuals, matched for sex, age, and body mass index (BMI) and with normal chest HRCT as controls. HRCT scans were performed using a Philips 256-row Brilliance iCT scanner with standardized parameters. Lung function tests were performed using a Jaeger volumetric tracer for forced vital capacity (FVC), total lung capacity (TLC), forced expiratory volume in first second (FEV1), FEV1/FVC, carbon monoxide diffusing capacity (DLCO), and maximum ventilation volume (MVV) metrics. CT quantitative analysis, including tissue segmentation and threshold-based quantification of lung abnormalities, was performed using 3D-Slicer software to calculate the percentage of normal lung areas (NL%), percentage of ground-glass opacity areas (GGO%), percentage of fibrotic area (F%) and abnormal lesion area percentage (AA%). Semi-quantitative analyses were performed by two experienced radiologists to assess disease progression. The aortic-to-sternal distance (ASD) was measured on axial images as a standardized parameter. Spearman or Pearson correlation analysis and multivariate stepwise linear regression were used to analyze the relationship between the data in each group, and the ROC curve was used to determine the optimal quantitative CT metrics for identifying IPF and controls. RESULTS ROC curve analysis showed that F% distinguished the IPF patient group from the control group with the largest area under the curve (AUC) of 0.962 (95% confidence interval: 0.85-0.96). Additionally, with F% = 4.05% as the threshold, the Youden's J statistic was 0.827, with a sensitivity of 92.3% and a specificity of 90.4%. The ASD was significantly lower in the late stage of progression than in the early stage (t = 5.691, P < 0.001), with a mean reduction of 2.45% per month. Quantitative CT indices correlated with all pulmonary function parameters except FEV1/FVC, with the highest correlation coefficients observed for F% and TLC%, FEV1%, FVC%, MVV% (r = - 0.571, - 0.520, - 0.521, - 0.555, respectively, all P-values < 0.001), and GGO% was significantly correlated with DLCO% (r = - 0.600, P < 0.001). Multiple stepwise linear regression analysis showed that F% was the best predictor of TLC%, FEV1%, FVC%, and MVV% (R2 = 0.301, 0.301, 0.300, and 0.302, respectively, all P-values < 0.001), and GGO% was the best predictor of DLCO% (R2 = 0.360, P < 0.001). CONCLUSIONS Quantitative CT analysis can be used to diagnose IPF and assess lung function impairment. A decrease in the ASD may indicate disease progression.
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Affiliation(s)
- Hongmei Zhang
- Department of Radiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150000, China
| | - Xinyi Li
- Department of Radiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150000, China
| | - Xiaoyue Zhang
- Department of Radiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150000, China
| | - Yu Yuan
- Department of Radiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150000, China
| | - Chenglei Zhao
- Department of Radiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150000, China
| | - Jinling Zhang
- Department of Radiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150000, China.
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Chung E, Woo A, Yong SH, Park Y, Lee SH, Kim SY, Kim EY, Jung JY, Kang YA, Kim YS, Park MS. Malnutrition is associated with mortality in Sjögren's syndrome-associated interstitial lung disease. Sci Rep 2024; 14:17842. [PMID: 39090289 PMCID: PMC11294537 DOI: 10.1038/s41598-024-68754-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2023] [Accepted: 07/26/2024] [Indexed: 08/04/2024] Open
Abstract
The role of nutritional status as a prognostic factor in patients with Sjögren's syndrome-associated interstitial lung disease (SjS-ILD) is currently unclear. This study aimed to predict the prognosis of patients with SjS-ILD through their nutritional status assessment. In this retrospective observational study, nutritional status was evaluated at the time of diagnosis using body mass index (BMI) and nutritional markers such as controlling nutritional status (CONUT), the Glasgow prognostic score (GPS), and prognostic nutrition index (PNI) for all participants. Receiver operating characteristic (ROC) analyses were performed using BMI and each nutritional marker data to compare the area under the ROC curve (AUC) and find the cutoff value using the maximum Youden index. Kaplan-Meier analysis and Cox proportional hazards regression analysis were performed to predict the prognosis of SjS-ILD patients. A total of 112 SjS-ILD patients were enrolled in the study, and 8.9% died during the follow-up period. The median time from diagnosis to follow-up period was 4.2 years. The AUC for PNI was the highest among nutritional markers and BMI, and PNI cutoff value was used to distinguish between the PNI < 47.7 and PNI ≥ 47.7 groups. A statistical difference was observed in the Kaplan-Meier analysis and log-rank test (p = 0.005). In multivariable analyses, PNI < 47.7 (hazard ratio 9.40, 95% confidence interval 1.54-57.21) is associated with increased mortality, suggesting the importance of early nutritional intervention for malnutrition in SjS-ILD patients.
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Affiliation(s)
- Eunki Chung
- Division of Pulmonology, Department of Internal Medicine, National Health Insurance Service Ilsan Hospital, Goyang, Republic of Korea
- Yonsei University Graduate School of Medicine, Seoul, Republic of Korea
| | - Ala Woo
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
| | - Seung Hyun Yong
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
| | - Youngmok Park
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
| | - Sang Hoon Lee
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
| | - Song Yee Kim
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
| | - Eun Young Kim
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
| | - Ji Ye Jung
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
| | - Young Ae Kang
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
| | - Young Sam Kim
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
| | - Moo Suk Park
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
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Koh SY, Lee JH, Park H, Goo JM. Value of CT quantification in progressive fibrosing interstitial lung disease: a deep learning approach. Eur Radiol 2024; 34:4195-4205. [PMID: 38085286 DOI: 10.1007/s00330-023-10483-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Revised: 10/23/2023] [Accepted: 10/27/2023] [Indexed: 06/29/2024]
Abstract
OBJECTIVES To evaluate the relationship of changes in the deep learning-based CT quantification of interstitial lung disease (ILD) with changes in forced vital capacity (FVC) and visual assessments of ILD progression, and to investigate their prognostic implications. METHODS This study included ILD patients with CT scans at intervals of over 2 years between January 2015 and June 2021. Deep learning-based texture analysis software was used to segment ILD findings on CT images (fibrosis: reticular opacity + honeycombing cysts; total ILD extent: ground-glass opacity + fibrosis). Patients were grouped according to the absolute decline of predicted FVC (< 5%, 5-10%, and ≥ 10%) and ILD progression assessed by thoracic radiologists, and their quantification results were compared among these groups. The associations between quantification results and survival were evaluated using multivariable Cox regression analysis. RESULTS In total, 468 patients (239 men; 64 ± 9.5 years) were included. Fibrosis and total ILD extents more increased in patients with larger FVC decline (p < .001 in both). Patients with ILD progression had higher fibrosis and total ILD extent increases than those without ILD progression (p < .001 in both). Increases in fibrosis and total ILD extent were significant prognostic factors when adjusted for absolute FVC declines of ≥ 5% (hazard ratio [HR] 1.844, p = .01 for fibrosis; HR 2.484, p < .001 for total ILD extent) and ≥ 10% (HR 2.918, p < .001 for fibrosis; HR 3.125, p < .001 for total ILD extent). CONCLUSION Changes in ILD CT quantification correlated with changes in FVC and visual assessment of ILD progression, and they were independent prognostic factors in ILD patients. CLINICAL RELEVANCE STATEMENT Quantifying the CT features of interstitial lung disease using deep learning techniques could play a key role in defining and predicting the prognosis of progressive fibrosing interstitial lung disease. KEY POINTS • Radiologic findings on high-resolution CT are important in diagnosing progressive fibrosing interstitial lung disease. • Deep learning-based quantification results for fibrosis and total interstitial lung disease extents correlated with the decline in forced vital capacity and visual assessments of interstitial lung disease progression, and emerged as independent prognostic factors. • Deep learning-based interstitial lung disease CT quantification can play a key role in diagnosing and prognosticating progressive fibrosing interstitial lung disease.
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Affiliation(s)
- Seok Young Koh
- Department of Radiology, Seoul National University Hospital, 101, Daehak-ro, Jongno-gu, Seoul, 03080, South Korea
| | - Jong Hyuk Lee
- Department of Radiology, Seoul National University Hospital, 101, Daehak-ro, Jongno-gu, Seoul, 03080, South Korea
| | - Hyungin Park
- Department of Radiology, Seoul National University Hospital, 101, Daehak-ro, Jongno-gu, Seoul, 03080, South Korea
| | - Jin Mo Goo
- Department of Radiology, Seoul National University Hospital, 101, Daehak-ro, Jongno-gu, Seoul, 03080, South Korea.
- Department of Radiology, Seoul National University College of Medicine, 101, Daehak-ro, Jongno-gu, Seoul, 03080, South Korea.
- Institute of Radiation Medicine, Seoul National University Medical Research Center, 101, Daehak-ro, Jongno-gu, Seoul, 03080, South Korea.
- Cancer Research Institute, Seoul National University, 101, Daehak-ro, Jongno-gu, Seoul, 03080, South Korea.
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Zanini U, Luppi F, Kaur K, Anzani N, Franco G, Ferrara G, Kalluri M, Mura M. Use of 6-minute walk distance to predict lung transplant-free survival in fibrosing non-IPF interstitial lung diseases. Respirology 2024; 29:387-395. [PMID: 38320863 DOI: 10.1111/resp.14669] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2023] [Accepted: 01/23/2024] [Indexed: 02/08/2024]
Abstract
BACKGROUND AND OBJECTIVE The identification of progression in patients with fibrosing non-idiopathic pulmonary fibrosis (IPF) interstitial lung diseases (ILDs) represents an ongoing clinical challenge. Lung function decline alone may have significant limitations in the detection of clinically significant progression. We hypothesized that longitudinal changes of 6-min walk distance (6MWD) from baseline, simultaneously considered with measures of lung function, may independently predict survival and identifying clinically significant progression of disease. METHODS Forced vital capacity (FVC), diffusing lung capacity (DLCO) and 6MWD were considered both at baseline and at 1 year in a discovery cohort (n = 105) and in a validation cohort (n = 138) from different centres. The primary endpoint was lung transplant (LTx)-free survival. RESULTS Average follow-up was 3 years in both cohorts. Combined incidence of deaths and LTx was 29% and 21%, respectively. No collinearity and no strong correlations were observed among FVC, DLCO and 6MWD longitudinal changes. While age, gender and BMI were not significant, 6MWD decline ≥24 m predicted LTx-free-survival significantly and independently from FVC and DLCO declines, with high sensitivity and specificity, in both the discovery and the validation cohorts. Although FVC and DLCO declines remained significant predictors of LTx-free survival, 6MWD decline was more accurate than the proposed ATS/ERS/JRS/ALAT functional criteria. Results were confirmed after stratifying patients by baseline FVC. CONCLUSION Longitudinal declines of 6MWD are associated with poor survival in fibrosing ILDs across a wide range of baseline severity, with high accuracy. 6MWD longitudinal decline is largely independent from lung function decline and may be integrated into the routine assessment of progression.
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Affiliation(s)
- Umberto Zanini
- Department of Medicine and Surgery, University of Milan-Bicocca, SC Pneumologia, Fondazione IRCCS "San Gerardo dei Tintori", Monza, Italy
- Division of Pulmonary Medicine, University of Alberta, and Alberta Health Services, Edmonton, Alberta, Canada
| | - Fabrizio Luppi
- Department of Medicine and Surgery, University of Milan-Bicocca, SC Pneumologia, Fondazione IRCCS "San Gerardo dei Tintori", Monza, Italy
| | - Karina Kaur
- Division of Pulmonary Medicine, University of Alberta, and Alberta Health Services, Edmonton, Alberta, Canada
| | - Niccolò Anzani
- Department of Medicine and Surgery, University of Milan-Bicocca, SC Pneumologia, Fondazione IRCCS "San Gerardo dei Tintori", Monza, Italy
| | - Giovanni Franco
- Department of Medicine and Surgery, University of Milan-Bicocca, SC Pneumologia, Fondazione IRCCS "San Gerardo dei Tintori", Monza, Italy
| | - Giovanni Ferrara
- Division of Pulmonary Medicine, University of Alberta, and Alberta Health Services, Edmonton, Alberta, Canada
| | - Meena Kalluri
- Division of Pulmonary Medicine, University of Alberta, and Alberta Health Services, Edmonton, Alberta, Canada
| | - Marco Mura
- Division of Respirology, Western University, London, Ontario, Canada
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Yoon HY, Kim SY, Song JW. Effects of indoor air pollution on clinical outcomes in patients with interstitial lung disease: protocol of a multicentre prospective observational study. BMJ Open Respir Res 2024; 11:e002053. [PMID: 38262669 PMCID: PMC10806566 DOI: 10.1136/bmjresp-2023-002053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2023] [Accepted: 01/09/2024] [Indexed: 01/25/2024] Open
Abstract
BACKGROUND Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrosing interstitial lung disease with a poor prognosis. While there is evidence suggesting that outdoor air pollution affects the clinical course of IPF, the impact of indoor air pollution on patients with IPF has not been extensively studied. Therefore, this prospective multicentre observational study aims to investigate the association between indoor air pollution and clinical outcomes in patients with IPF. METHODS AND ANALYSIS This study enrolled 140 patients with IPF from 12 medical institutes in the Seoul and Metropolitan areas of the Republic of Korea. Over the course of 1 year, participants visited the institutes every 3 months, during which their clinical data and blood samples were collected. Additionally, indoor exposure to particulate matter ≤2.5 µm (PM2.5) was measured using MicroPEM (RTI International, Research Triangle Park, North Carolina, USA) in each participant's house for 5 days every 3 months. Lung function was assessed using both site spirometry at each institution and portable spirometry at each participant's house every 3 months. The study will analyse the impact of indoor PM2.5 on clinical outcomes, including mortality, acute exacerbation, changes in lung function and health-related quality of life, in the participants. This study represents the first attempt to evaluate the influence of indoor air pollution on the prognosis of patients with IPF. ETHICS AND DISSEMINATION This study has received approval from the institutional review board of all participating institutions, including Asan Medical Center, Seoul, Republic of Korea (2021-0072). TRIAL REGISTRATION NUMBER KCT0006217.
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Affiliation(s)
- Hee-Young Yoon
- Division of Allergy and Respiratory Diseases, Soonchunhyang University Seoul Hospital, Seoul, Korea (the Republic of)
| | - Sun-Young Kim
- Department of Cancer AI & Digital Health, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea (the Republic of)
| | - Jin Woo Song
- Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Songpa-gu, Korea (the Republic of)
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Yeo HJ, Ha M, Shin DH, Lee HR, Kim YH, Cho WH. Development of a Novel Biomarker for the Progression of Idiopathic Pulmonary Fibrosis. Int J Mol Sci 2024; 25:599. [PMID: 38203769 PMCID: PMC10779374 DOI: 10.3390/ijms25010599] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2023] [Revised: 12/22/2023] [Accepted: 01/01/2024] [Indexed: 01/12/2024] Open
Abstract
The progression of idiopathic pulmonary fibrosis (IPF) is diverse and unpredictable. We identified and validated a new biomarker for IPF progression. To identify a candidate gene to predict progression, we assessed differentially expressed genes in patients with advanced IPF compared with early IPF and controls in three lung sample cohorts. Candidate gene expression was confirmed using immunohistochemistry and Western blotting of lung tissue samples from an independent IPF clinical cohort. Biomarker potential was assessed using an enzyme-linked immunosorbent assay of serum samples from the retrospective validation cohort. We verified that the final candidate gene reflected the progression of IPF in a prospective validation cohort. In the RNA-seq comparative analysis of lung tissues, CD276, COL7A1, CTSB, GLI2, PIK3R2, PRAF2, IGF2BP3, and NUPR1 were up-regulated, and ADAMTS8 was down-regulated in the samples of advanced IPF. Only CTSB showed significant differences in expression based on Western blotting (n = 12; p < 0.001) and immunohistochemistry between the three groups of the independent IPF cohort. In the retrospective validation cohort (n = 78), serum CTSB levels were higher in the progressive group (n = 25) than in the control (n = 29, mean 7.37 ng/mL vs. 2.70 ng/mL, p < 0.001) and nonprogressive groups (n = 24, mean 7.37 ng/mL vs. 2.56 ng/mL, p < 0.001). In the prospective validation cohort (n = 129), serum CTSB levels were higher in the progressive group than in the nonprogressive group (mean 8.30 ng/mL vs. 3.00 ng/mL, p < 0.001). After adjusting for baseline FVC, we found that CTSB was independently associated with IPF progression (adjusted OR = 2.61, p < 0.001). Serum CTSB levels significantly predicted IPF progression (AUC = 0.944, p < 0.001). Serum CTSB level significantly distinguished the progression of IPF from the non-progression of IPF or healthy control.
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Affiliation(s)
- Hye Ju Yeo
- Department of Internal Medicine, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea;
- Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea
- Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea; (D.H.S.); (H.R.L.)
| | - Mihyang Ha
- Interdisciplinary Program of Genomic Data Science, Pusan National University, Busan 46241, Republic of Korea;
- Department of Nuclear Medicine, Pusan National University Medical Research Institute, Pusan National University Hospital, Busan 49241, Republic of Korea
| | - Dong Hoon Shin
- Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea; (D.H.S.); (H.R.L.)
- Department of Pathology, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea
| | - Hye Rin Lee
- Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea; (D.H.S.); (H.R.L.)
| | - Yun Hak Kim
- Department of Anatomy, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea
- Department of Biomedical Informatics, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea
| | - Woo Hyun Cho
- Department of Internal Medicine, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea;
- Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea
- Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea; (D.H.S.); (H.R.L.)
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Achaiah A, Fraser E, Saunders P, Hoyles RK, Benamore R, Ho LP. Neutrophil levels correlate with quantitative extent and progression of fibrosis in IPF: results of a single-centre cohort study. BMJ Open Respir Res 2023; 10:e001801. [PMID: 37816551 PMCID: PMC10565140 DOI: 10.1136/bmjresp-2023-001801] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2023] [Accepted: 09/15/2023] [Indexed: 10/12/2023] Open
Abstract
BACKGROUND Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease with poor prognosis. Clinical studies have demonstrated association between different blood leucocytes and mortality and forced vital capacity (FVC) decline. Here, we question which blood leucocyte levels are specifically associated with progression of fibrosis, measured by accumulation of fibrosis on CT scan using a standardised automated method. METHODS Using the Computer-Aided Lung Informatics for Pathology Evaluation and Rating CT algorithm, we determined the correlation between different blood leucocytes (<4 months from CT) and total lung fibrosis (TLF) scores, pulmonary vessel volume (PVV), FVC% and transfer factor of lung for carbon monoxide% at baseline (n=171) and with progression of fibrosis (n=71), the latter using multivariate Cox regression. RESULTS Neutrophils (but not monocyte or lymphocytes) correlated with extent of lung fibrosis (TLF/litre) (r=0.208, p=0.007), PVV (r=0.259, p=0.001), FVC% (r=-0.127, p=0.029) at baseline. For the 71 cases with repeat CT; median interval between CTs was 25.9 (16.8-39.9) months. Neutrophil but not monocyte levels are associated with increase in TLF/litre (HR 2.66, 95% CI 1.35 to 5.25, p=0.005). CONCLUSION Our study shows that neutrophil rather than monocyte levels correlated with quantifiable increase in fibrosis on imaging of the lungs in IPF, suggesting its relative greater contribution to progression of fibrosis in IPF.
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Affiliation(s)
- Andrew Achaiah
- Translational Immunology Discovery Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK
| | - Emily Fraser
- Oxford Interstitial Lung Disease Service, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - Peter Saunders
- Oxford Interstitial Lung Disease Service, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - Rachel K Hoyles
- Oxford Interstitial Lung Disease Service, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - Rachel Benamore
- Thoracic Radiology Department, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - Ling-Pei Ho
- Translational Immunology Discovery Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK
- Oxford Interstitial Lung Disease Service, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
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11
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Singer D, Chastek B, Sargent A, Johnson JC, Shetty S, Conoscenti C, Bernstein EJ. Impact of chronic fibrosing interstitial lung disease on healthcare use: association between fvc decline and inpatient hospitalization. BMC Pulm Med 2023; 23:337. [PMID: 37689630 PMCID: PMC10492374 DOI: 10.1186/s12890-023-02637-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Accepted: 09/06/2023] [Indexed: 09/11/2023] Open
Abstract
BACKGROUND Many types of interstitial lung diseases (ILDs) may transition to progressive chronic-fibrosing ILDs with rapid lung function decline and a negative survival prognosis. In real-world clinical settings, forced vital capacity (FVC) measures demonstrating progressive decline may be linked to negative outcomes, including increased risks of costly healthcare resource utilization (HRU). Thus, we assessed the relationship between rate of decline in lung function and an increase in HRU, specifically inpatient hospitalization, among patients with chronic fibrosing ILD. METHODS This study utilized electronic health records from 01-Oct-2015 to 31-Oct-2019. Eligible patients (≥ 18 years old) had ≥ 2 fibrosing ILD diagnosis codes, clinical activity for ≥ 15 months, and ≥ 2 FVC tests occurring 6 months apart. Patients with missing demographic data, IPF, or use of nintedanib or pirfenidone were excluded. Two groups were defined by relative change in percent of predicted FVC (FVC% pred) from baseline to 6 months: significant decline (≥ 10%) vs. marginal decline/stable FVC (decrease < 10% or increase). The primary outcome was defined as the occurrence of an inpatient hospitalization 6 months after the first FVC value. Descriptive and multivariable analysis was conducted to examine the impact of FVC decline on occurrence of inpatient hospitalization. RESULTS The sample included 566 patients: 13% (n = 75) with significant decline and 87% (n = 491) with marginal decline/stable FVC; their mean age (SD) was 65 (13.7) years and 56% were female. Autoimmune diagnoses were observed among 40% of patients with significant decline, and 27% with marginal decline/stable FVC. The significant decline group had better lung function at baseline than the marginal/stable group. For patients with FVC% <80% at baseline, reduction of FVC% ≥10% was associated with significantly increased odds of an inpatient hospitalization (odds ratio [OR] 2.85; confidence interval [CI] 1.17, 6.94 [p = 0.021]). CONCLUSION Decline in FVC% ≥10% was associated with increased odds of inpatient hospitalization among patients with reduced lung function at baseline. These findings support the importance of preserving lung function among patients with fibrosing ILD.
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Affiliation(s)
- David Singer
- Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT USA
| | - Benjamin Chastek
- Optum, Health Economics and Outcomes Research, Eden Prairie, MN USA
| | - Andrew Sargent
- Optum, Health Economics and Outcomes Research, Eden Prairie, MN USA
| | | | - Sharash Shetty
- Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT USA
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12
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Neely ML, Hellkamp AS, Bender S, Todd JL, Liesching T, Luckhardt TR, Oldham JM, Raj R, White ES, Palmer SM. Lung function trajectories in patients with idiopathic pulmonary fibrosis. Respir Res 2023; 24:209. [PMID: 37612608 PMCID: PMC10463468 DOI: 10.1186/s12931-023-02503-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Accepted: 08/01/2023] [Indexed: 08/25/2023] Open
Abstract
BACKGROUND Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease characterised by decline in lung function. We evaluated trajectories of forced vital capacity (FVC) and diffusing capacity (DLco) in a cohort of patients with IPF. METHODS Patients with IPF that was diagnosed or confirmed at the enrolling centre in the previous 6 months were enrolled into the IPF-PRO Registry between June 2014 and October 2018. Patients were followed prospectively, with lung function data collected as part of routine clinical care. Mean trajectories of FVC and DLco % predicted in all patients and in subgroups by characteristics assessed at enrolment were estimated using a joint model that accounted for factors such as disease severity and visit patterns. RESULTS Of 1002 patients in the registry, 941 had ≥ 1 FVC and/or DLco measurement after enrolment. The median (Q1, Q3) follow-up period was 35.1 (18.9, 47.2) months. Overall, mean estimated declines in FVC and DLco % predicted were 2.8% and 2.9% per year, respectively. There was no evidence that the mean trajectories of FVC or DLco had a non-linear relationship with time at the population level. Patients who were male, white, had a family history of ILD, were using oxygen, or had prior/current use of antifibrotic therapy at enrolment had greater rates of decline in FVC % predicted. Patients who were male or white had greater rates of decline in DLco % predicted. CONCLUSIONS Data from the IPF-PRO Registry suggest a constant rate of decline in lung function over a prolonged period, supporting the inexorably progressive nature of IPF. A graphical abstract summarising the data in this manuscript is available at: https://www.usscicomms.com/respiratory/IPF-PRORegistry_LungFunctionTrajectories . TRIAL REGISTRATION NCT01915511.
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Affiliation(s)
- Megan L Neely
- Duke Clinical Research Institute, Durham, NC, USA.
- Duke University Medical Center, Durham, NC, USA.
| | - Anne S Hellkamp
- Duke Clinical Research Institute, Durham, NC, USA
- Duke University Medical Center, Durham, NC, USA
| | - Shaun Bender
- Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, CT, USA
| | - Jamie L Todd
- Duke Clinical Research Institute, Durham, NC, USA
- Duke University Medical Center, Durham, NC, USA
| | | | - Tracy R Luckhardt
- Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Justin M Oldham
- Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI, USA
| | - Rishi Raj
- Stanford University School of Medicine, Stanford, CA, USA
| | - Eric S White
- Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, CT, USA
| | - Scott M Palmer
- Duke Clinical Research Institute, Durham, NC, USA
- Duke University Medical Center, Durham, NC, USA
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13
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Pereira CAC, Cordero S, Resende AC. Progressive fibrotic interstitial lung disease. J Bras Pneumol 2023; 49:e20230098. [PMID: 37610955 PMCID: PMC10578905 DOI: 10.36416/1806-3756/e20230098] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Accepted: 06/24/2023] [Indexed: 08/25/2023] Open
Abstract
Many interstitial lung diseases (ILDs) share mechanisms that result in a progressive fibrosing phenotype. In Brazil, the most common progressive fibrosing interstitial lung diseases (PF-ILDs) are chronic hypersensitivity pneumonitis, idiopathic pulmonary fibrosis, unclassified ILD, and connective tissue diseases. PF-ILD is seen in approximately 30% of patients with ILD. Because PF-ILD is characterized by disease progression after initiation of appropriate treatment, a diagnosis of the disease resulting in fibrosis is critical. Different criteria have been proposed to define progressive disease, including worsening respiratory symptoms, lung function decline, and radiological evidence of disease progression. Although the time elapsed between diagnosis and progression varies, progression can occur at any time after diagnosis. Several factors indicate an increased risk of progression and death. In the last few years, antifibrotic drugs used in patients with idiopathic pulmonary fibrosis have been tested in patients with PF-ILD. The effects of nintedanib and placebo have been compared in patients with PF-ILD, a mean difference of 107.0 mL/year being observed, favoring nintedanib. The U.S. Food and Drug Administration and the Brazilian Health Regulatory Agency have approved the use of nintedanib in such patients on the basis of this finding. Pirfenidone has been evaluated in patients with unclassified ILD and in patients with other ILDs, the results being similar to those for nintedanib. More studies are needed in order to identify markers of increased risk of progression in patients with ILD and determine the likelihood of response to treatment with standard or new drugs.
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Affiliation(s)
- Carlos A C Pereira
- . Programa de Assistência e Pesquisa em Doenças Pulmonares Intersticiais, Departamento de Clínica Médica, Serviço de Pneumologia, Universidade Federal de São Paulo, São Paulo (SP) Brasil
| | - Soraya Cordero
- . Programa de Pós-Graduação em Doenças Pulmonares Intersticiais, Departamento de Clínica Médica, Serviço de Pneumologia, Universidade Federal de São Paulo, São Paulo (SP) Brasil
| | - Ana Carolina Resende
- . Programa de Pós-Graduação em Doenças Pulmonares Intersticiais, Departamento de Clínica Médica, Serviço de Pneumologia, Universidade Federal de São Paulo, São Paulo (SP) Brasil
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14
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Amaral AF, Colares PDFB, Kairalla RA. Idiopathic pulmonary fibrosis: current diagnosis and treatment. J Bras Pneumol 2023; 49:e20230085. [PMID: 37556670 PMCID: PMC10578906 DOI: 10.36416/1806-3756/e20230085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Accepted: 04/20/2023] [Indexed: 08/11/2023] Open
Abstract
Idiopathic pulmonary fibrosis (IPF) is a devastating chronic lung disease without a clear recognizable cause. IPF has been at the forefront of new diagnostic algorithms and treatment developments that led to a shift in patients' care in the past decade, indeed influencing the management of fibrotic interstitial lung diseases other than IPF itself. Clinical presentation, pathophysiology, and diagnostic criteria are briefly addressed in this review article. Additionally, evidence regarding the use of antifibrotics beyond the settings of clinical trials, impact of comorbidities, and therapeutic approaches other than pharmacological treatments are discussed in further detail.
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Affiliation(s)
- Alexandre Franco Amaral
- . Divisão de Pneumologia, Instituto do Coração - InCor - Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo (SP) Brasil
| | - Philippe de Figueiredo Braga Colares
- . Divisão de Pneumologia, Instituto do Coração - InCor - Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo (SP) Brasil
| | - Ronaldo Adib Kairalla
- . Divisão de Pneumologia, Instituto do Coração - InCor - Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo (SP) Brasil
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15
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Alabed S, Garg P, Alandejani F, Dwivedi K, Maiter A, Karunasaagarar K, Rajaram S, Hill C, Thomas S, Gossling R, Sharkey MJ, Salehi M, Wild JM, Watson L, Hameed A, Charalampopoulos A, Lu H, Rothman AMK, Thompson AAR, Elliot CA, Hamilton N, Johns CS, Armstrong I, Condliffe R, van der Geest RJ, Swift AJ, Kiely DG. Establishing minimally important differences for cardiac MRI end-points in pulmonary arterial hypertension. Eur Respir J 2023; 62:2202225. [PMID: 37414419 PMCID: PMC10397469 DOI: 10.1183/13993003.02225-2022] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2022] [Accepted: 05/23/2023] [Indexed: 07/08/2023]
Abstract
BACKGROUND Cardiac magnetic resonance (CMR) is the gold standard technique to assess biventricular volumes and function, and is increasingly being considered as an end-point in clinical studies. Currently, with the exception of right ventricular (RV) stroke volume and RV end-diastolic volume, there is only limited data on minimally important differences (MIDs) reported for CMR metrics. Our study aimed to identify MIDs for CMR metrics based on US Food and Drug Administration recommendations for a clinical outcome measure that should reflect how a patient "feels, functions or survives". METHODS Consecutive treatment-naïve patients with pulmonary arterial hypertension (PAH) between 2010 and 2022 who had two CMR scans (at baseline prior to treatment and 12 months following treatment) were identified from the ASPIRE registry. All patients were followed up for 1 additional year after the second scan. For both scans, cardiac measurements were obtained from a validated fully automated segmentation tool. The MID in CMR metrics was determined using two distribution-based (0.5sd and minimal detectable change) and two anchor-based (change difference and generalised linear model regression) methods benchmarked to how a patient "feels" (emPHasis-10 quality of life questionnaire), "functions" (incremental shuttle walk test) or "survives" for 1-year mortality to changes in CMR measurements. RESULTS 254 patients with PAH were included (mean±sd age 53±16 years, 79% female and 66% categorised as intermediate risk based on the 2022 European Society of Cardiology/European Respiratory Society risk score). We identified a 5% absolute increase in RV ejection fraction and a 17 mL decrease in RV end-diastolic or end-systolic volumes as the MIDs for improvement. Conversely, a 5% decrease in RV ejection fraction and a 10 mL increase in RV volumes were associated with worsening. CONCLUSIONS This study establishes clinically relevant CMR MIDs for how a patient "feels, functions or survives" in response to PAH treatment. These findings provide further support for the use of CMR as a clinically relevant clinical outcome measure and will aid trial size calculations for studies using CMR.
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Affiliation(s)
- Samer Alabed
- Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
- Department of Clinical Radiology, Sheffield Teaching Hospitals, Sheffield, UK
- INSIGNEO, Institute for in silico Medicine, University of Sheffield, Sheffield, UK
| | - Pankaj Garg
- Norwich Medical School, University of East Anglia, Norwich, UK
| | - Faisal Alandejani
- Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
| | - Krit Dwivedi
- Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
- Department of Clinical Radiology, Sheffield Teaching Hospitals, Sheffield, UK
| | - Ahmed Maiter
- Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
- Department of Clinical Radiology, Sheffield Teaching Hospitals, Sheffield, UK
| | - Kavita Karunasaagarar
- Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
- Department of Clinical Radiology, Sheffield Teaching Hospitals, Sheffield, UK
| | - Smitha Rajaram
- Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
- Department of Clinical Radiology, Sheffield Teaching Hospitals, Sheffield, UK
| | - Catherine Hill
- Department of Clinical Radiology, Sheffield Teaching Hospitals, Sheffield, UK
| | - Steven Thomas
- Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
- Department of Clinical Radiology, Sheffield Teaching Hospitals, Sheffield, UK
| | - Rebecca Gossling
- Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
| | - Michael J Sharkey
- Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
| | - Mahan Salehi
- Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
| | - Jim M Wild
- Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
- INSIGNEO, Institute for in silico Medicine, University of Sheffield, Sheffield, UK
| | - Lisa Watson
- Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield, UK
| | - Abdul Hameed
- Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield, UK
| | | | - Haiping Lu
- INSIGNEO, Institute for in silico Medicine, University of Sheffield, Sheffield, UK
- Department of Computer Science, University of Sheffield, Sheffield, UK
| | - Alex M K Rothman
- Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
| | - A A Roger Thompson
- Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
- Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield, UK
| | - Charlie A Elliot
- Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
- Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield, UK
| | - Neil Hamilton
- Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
- Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield, UK
| | - Christopher S Johns
- Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
- Department of Clinical Radiology, Sheffield Teaching Hospitals, Sheffield, UK
| | - Iain Armstrong
- Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
- Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield, UK
| | - Robin Condliffe
- Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
- Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield, UK
| | | | - Andrew J Swift
- Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
- Department of Clinical Radiology, Sheffield Teaching Hospitals, Sheffield, UK
- INSIGNEO, Institute for in silico Medicine, University of Sheffield, Sheffield, UK
- National Institute for Health and Care Research, Sheffield Biomedical Research Centre, Sheffield, UK
- Joint senior authors
| | - David G Kiely
- Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
- INSIGNEO, Institute for in silico Medicine, University of Sheffield, Sheffield, UK
- Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield, UK
- National Institute for Health and Care Research, Sheffield Biomedical Research Centre, Sheffield, UK
- Joint senior authors
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16
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Jang Y, Yoon HY, Kim HS. The Efficacy and Safety of Rituximab in Patients with Idiopathic Inflammatory Myopathy-Associated Interstitial Lung Disease: Case Series. J Clin Med 2023; 12:jcm12103406. [PMID: 37240516 DOI: 10.3390/jcm12103406] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2023] [Revised: 04/30/2023] [Accepted: 05/10/2023] [Indexed: 05/28/2023] Open
Abstract
Idiopathic inflammatory myopathy (IIM)-associated interstitial lung disease (ILD) is often rapidly progressive with a poor prognosis; however, no standard therapeutic regimen has been identified. This study aimed to investigate the efficacy and safety of rituximab in IIM-ILD patients. Five patients who had been administered rituximab for IIM-ILD at least once between August 2016 and November 2021 were included. Lung function decline was compared one year before and after rituximab. Disease progression, defined as a greater than 10% relative decline in forced vital capacity (FVC) compared to the baseline, was also compared before and after treatment. Adverse events were recorded for safety analysis. Five IIM-ILD patients received eight cycles. FVC-predicted values significantly decreased from 6 months before rituximab administration to those at the baseline (54.1% predicted (pre-6 months) vs. 48.5% predicted (baseline), p = 0.043); however, the FVC decline stabilized after rituximab. The rate of disease progression before rituximab showed a tendency to decrease after rituximab (75% (before) vs. 12.5% (6 months after, p = 0.059) vs. 14.3% (12 months after, p = 0.102)). Three adverse events developed, but none resulted in death. Rituximab can stabilize lung function decline with tolerable safety in Korean IIM patients with refractory ILD.
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Affiliation(s)
- Youngeun Jang
- Division of Allergy and Respiratory Diseases, Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Seoul 04401, Republic of Korea
| | - Hee-Young Yoon
- Division of Allergy and Respiratory Diseases, Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Seoul 04401, Republic of Korea
| | - Hyun-Sook Kim
- Division of Rheumatology, Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Seoul 04401, Republic of Korea
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17
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Yoon HY, Kim SY, Kim OJ, Song JW. Nitrogen dioxide increases the risk of disease progression in idiopathic pulmonary fibrosis. Respirology 2023; 28:254-261. [PMID: 36123769 DOI: 10.1111/resp.14373] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2022] [Accepted: 09/05/2022] [Indexed: 11/29/2022]
Abstract
BACKGROUND AND OBJECTIVE Air pollution affects clinical course and prognosis of idiopathic pulmonary fibrosis (IPF). However, the effect of individual exposure to air pollutants on disease progression is unclear. We aimed to identify the effect of individual exposure to nitrogen dioxide (NO2 ) and particulate matter (aerodynamic diameter ≤ 10 μm [PM10 ]) on disease progression in patients with IPF. METHODS The serial lung function data of 946 IPF patients (mean age: 65.4 years, male: 80.9%) were analysed. Individual-level long-term exposures to NO2 and PM10 at the residential addresses of patients were estimated using a national-scale exposure prediction model, constructed based on air quality regulatory monitoring data. Progression was defined as a relative decline (≥10%) in forced vital capacity. Individual- and area-level covariates were adjusted in the primary analysis model. RESULTS Overall, 547 patients (57.8%) experienced progression during a median follow-up of 1.0 year (interquartile range: 0.4-2.6 years). In the primary model, a 10-ppb increase in NO2 concentration was associated with a 10.5% increase in the risk of progression (hazard ratio [HR] = 1.105; 95% CI = 1.000-1.219) in patients with IPF. There was also an increasing trend of progression in patients with IPF according to the second to fourth quartiles of NO2 (Q2 [HR = 1.299; 95% CI = 0.972-1.735], Q3 [1.409; 1.001-1.984], Q4 [1.598; 1.106-2.310]) compared to the first quartile. We found no association between PM10 and progression in IPF patients. CONCLUSION Our data suggest that increased individual exposure to NO2 can increase the risk of progression in patients with IPF.
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Affiliation(s)
- Hee-Young Yoon
- Division of Allergy and Respiratory Diseases, Soonchunhyang University Seoul Hospital, Seoul, Republic of Korea
| | - Sun-Young Kim
- Department of Cancer Control and Population Health, Graduate School of Cancer Science and Policy, National Cancer Center, Gyeonggi, Republic of Korea
| | - Ok-Jin Kim
- Department of Cancer Control and Population Health, Graduate School of Cancer Science and Policy, National Cancer Center, Gyeonggi, Republic of Korea.,Environmental Health Research Division, Environmental Health Research Department, National Institute of Environmental Research, Incheon, Republic of Korea
| | - Jin Woo Song
- Department of Pulmonary and Critical Care Medicine Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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18
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Valecchi D, Bargagli E, Pieroni MG, Refini MR, Sestini P, Rottoli P, Melani AS. Prognostic Significance of Obstructive Sleep Apnea in a Population of Subjects with Interstitial Lung Diseases. Pulm Ther 2023; 9:223-236. [PMID: 36790678 DOI: 10.1007/s41030-023-00215-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Accepted: 01/16/2023] [Indexed: 02/16/2023] Open
Abstract
INTRODUCTION Obstructive sleep apnea (OSA) is often observed in subjects with interstitial lung disease (ILD). It may have a negative impact on the course of ILD, but its prognostic significance in relation to other known indicators of poor outcome is unclear. METHODS After a detailed work-up, including overnight unattended type III polygraphy, all subjects newly diagnosed with ILDs referred to our clinics were followed-up for at least 1.5 years or until death or progression of disease [> 10% decline in forced vital capacity (FVC) below baseline]. We analyzed relationships between some prespecified variables of interest, including sleeping results, to establish parameters predictive of progressive course. RESULTS Our population consisted of 46 subjects (mean age 59.6 years; males 61%); 23.9% and 41% had idiopathic pulmonary fibrosis and ILD associated with systemic diseases, respectively. Mean baseline forced vital capacity and diffusion capacity of carbon monoxide were 83% and 57% of predicted, respectively. Mean (± SE) Apnea-Hypopnea Index (AHI) was 17 (± 3) events/h. AHI in the ranges 5-14.9, 15-29.9, and ≥ 30 was recorded in 14 (31%), 6 (13%), and 9 (20%) subjects, respectively. Mean distance covered in the 6-MWG walk test (6MWT) was 302 (± 19) m and 26 subjects (57%) showed exertional oxyhemoglobin desaturation. The median follow-up was about 18 months. Multivariate logistic regression analysis showed that exertional desaturation (HR 8.2; 1.8-36.5 95% CI; p = 0.006) and AHI ≥ 30, namely the threshold of severe OSA (HR 7.5; 1.8-30.6; p = 0.005), were the only independent variables related to progressive disease course. CONCLUSION We conclude that exertional desaturation and elevated AHI had independent negative prognostic significance in our ILD population.
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Affiliation(s)
- Debora Valecchi
- Department of Medical Science, Surgery and Neuroscience, Respiratory Diseases and Lung Transplant Unit, University of Siena, Siena, Italy
| | - Elena Bargagli
- Department of Medical Science, Surgery and Neuroscience, Respiratory Diseases and Lung Transplant Unit, University of Siena, Siena, Italy
| | - Maria Grazia Pieroni
- Department of Medical Science, Surgery and Neuroscience, Respiratory Diseases and Lung Transplant Unit, University of Siena, Siena, Italy
| | - Metella Rosa Refini
- Department of Medical Science, Surgery and Neuroscience, Respiratory Diseases and Lung Transplant Unit, University of Siena, Siena, Italy
| | - Piersante Sestini
- Department of Medical Science, Surgery and Neuroscience, Respiratory Diseases and Lung Transplant Unit, University of Siena, Siena, Italy
| | - Paola Rottoli
- Department of Medical Science, Surgery and Neuroscience, Respiratory Diseases and Lung Transplant Unit, University of Siena, Siena, Italy
| | - Andrea S Melani
- Dipartimento di Scienze Mediche, Laboratorio per lo Studio dei Disturbi Respiratori Sonno-Correlati, Respiratory Diseases and Lung Transplant Unit, Policlinico Le Scotte, CMR, Azienda Ospedaliera Universitaria Senese, Viale Bracci, 53100, Siena, Italy.
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19
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Vu Pugashetti J, Newton CA, Molyneaux PL, Oldham JM. Reply to Noboa-Sevilla et al.. Am J Respir Crit Care Med 2023; 207:369-370. [PMID: 36174209 PMCID: PMC9896651 DOI: 10.1164/rccm.202209-1807le] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023] Open
Affiliation(s)
| | - Chad A Newton
- University of Texas Southwestern Medical Center Dallas, Texas
| | - Philip L Molyneaux
- Imperial College London London, United Kingdom and.,Guy's and St Thomas' National Health Service Foundation Trust London, United Kingdom
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20
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Noboa-Sevilla M, Hernández-González F, Alsina-Restoy X, Pérez-Rodas N, Sellarés J. Functional Criteria to Define Progressive Pulmonary Fibrosis: Searching for the Holy Grail. Am J Respir Crit Care Med 2023; 207:368-369. [PMID: 36174219 PMCID: PMC9896650 DOI: 10.1164/rccm.202209-1772le] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023] Open
Affiliation(s)
| | | | | | | | - Jacobo Sellarés
- Respiratory Clinical InstituteBarcelona, Spain,Barcelona Research NetworkBarcelona, Spain,CIBER of Respiratory DiseasesBarcelona, Spain,Corresponding author (e-mail: )
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21
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Kim MJ, Lee D, Choe J, Song JW. Long-term clinical course and outcomes of patients with microscopic polyangiitis-associated interstitial lung disease. Front Pharmacol 2023; 14:1064307. [PMID: 36794274 PMCID: PMC9922778 DOI: 10.3389/fphar.2023.1064307] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2022] [Accepted: 01/18/2023] [Indexed: 01/31/2023] Open
Abstract
Background: Interstitial lung disease (ILD) is a significant complication associated with microscopic polyangiitis (MPA) that has a poor prognosis. However, the long-term clinical course, outcomes, and prognostic factors of MPA-ILD are not well defined. Hence, this study aimed to investigate the long-term clinical course, outcomes, and prognostic factors in patients with MPA-ILD. Methods: Clinical data of 39 patients with MPA-ILD (biopsy proven cases, n = 6) were retrospectively analyzed. High resolution computed tomography (HRCT) patterns were assessed based on the 2018 idiopathic pulmonary fibrosis diagnostic criteria. Acute exacerbation (AE) was defined as the worsening of dyspnea within 30 days, with new bilateral lung infiltration that is not fully explained by heart failure or fluid overload and that does not have identified extra-parenchymal causes (pneumothorax, pleural effusion, or pulmonary embolism). Results: The median follow-up period was 72.0 months (interquartile range: 44-117 months). The mean age of the patients was 62.7 years and 59.0% were male. Usual interstitial pneumonia (UIP) and probable usual interstitial pneumonia patterns on high resolution computed tomography were identified in 61.5 and 17.9% of the patients, respectively. During the follow-up, 51.3% of patients died, and the 5- and 10-year overall survival rates were 73.5% and 42.0%, respectively. Acute exacerbation occurred in 17.9% of the patients. The non-survivors had higher neutrophil counts in bronchoalveolar lavage (BAL) fluid and more frequent acute exacerbation than the survivors. In the multivariable Cox analysis, older age (hazard ratio [HR], 1.07; 95% confidence interval [CI], 1.01-1.14; p = 0.028) and higher BAL counts (HR, 1.09; 95% CI, 1.01-1.17; p = 0.015) were found to be the independent prognostic factors associated with mortality in patients with MPA-ILD. Conclusion: During the 6 years-follow-up, about half of patients with MPA-ILD died and approximately one-fifth experienced acute exacerbation. Our results suggest that older age and higher BAL neutrophil counts mean poor prognosis in patients with MPA-ILD.
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Affiliation(s)
- Min Jee Kim
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Donghee Lee
- University of Ulsan College of Medicine, Seoul, South Korea
| | - Jooae Choe
- Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Jin Woo Song
- Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea,*Correspondence: Jin Woo Song,
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22
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Pugashetti JV, Adegunsoye A, Wu Z, Lee CT, Srikrishnan A, Ghodrati S, Vo V, Renzoni EA, Wells AU, Garcia CK, Chua F, Newton CA, Molyneaux PL, Oldham JM. Validation of Proposed Criteria for Progressive Pulmonary Fibrosis. Am J Respir Crit Care Med 2023; 207:69-76. [PMID: 35943866 PMCID: PMC9952866 DOI: 10.1164/rccm.202201-0124oc] [Citation(s) in RCA: 76] [Impact Index Per Article: 38.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Accepted: 08/09/2022] [Indexed: 02/03/2023] Open
Abstract
Rationale: Criteria for progressive pulmonary fibrosis (PPF) have been proposed, but their prognostic value beyond categorical decline in FVC remains unclear. Objectives: To determine whether proposed PPF criteria predict transplant-free survival (TFS) in patients with non-idiopathic pulmonary fibrosis (IPF) forms of interstitial lung disease (ILD). Methods: A retrospective, multicenter cohort analysis was performed. Patients with diagnoses of fibrotic connective tissue disease-associated ILD, fibrotic hypersensitivity pneumonitis, and non-IPF idiopathic interstitial pneumonia from three U.S. centers and one UK center constituted the test and validation cohorts, respectively. Cox proportional hazards regression was used to test the association between 5-year TFS and ⩾10% FVC decline, followed by 13 additional PPF criteria satisfied in the absence of ⩾10% FVC decline. Measurements and Main Results: One thousand three hundred forty-one patients met the inclusion criteria. A ⩾10% relative FVC decline was the strongest predictor of reduced TFS and showed consistent TFS association across cohorts, ILD subtypes, and treatment groups, resulting in a phenotype that closely resembled IPF. Ten additional PPF criteria satisfied in the absence of 10% relative FVC decline were also associated with reduced TFS in the U.S. test cohort, with 6 maintaining TFS associations in the UK validation cohort. Validated PPF criteria requiring a combination of physiologic, radiologic, and symptomatic worsening performed similarly to their stand-alone components but captured a smaller number of patients. Conclusions: An FVC decline of ⩾10% and six additional PPF criteria satisfied in the absence of such decline identify patients with non-IPF ILD at increased risk for death or lung transplantation.
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Affiliation(s)
- Janelle Vu Pugashetti
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan
- Division of Pulmonary, Critical Care and Sleep Medicine, University of California, Davis, Davis, California
| | - Ayodeji Adegunsoye
- Section of Pulmonary and Critical Care Medicine, University of Chicago, Chicago, Illinois
| | - Zhe Wu
- National Heart and Lung Institute, Imperial College London, London, United Kingdom
- Royal Brompton and Harefield Hospitals, Guy’s and St. Thomas’ NHS Foundation Trust, London, United Kingdom
| | - Cathryn T. Lee
- Section of Pulmonary and Critical Care Medicine, University of Chicago, Chicago, Illinois
| | - Anand Srikrishnan
- Division of Pulmonary and Critical Care Medicine, University of Texas Southwestern Medical Center, Dallas, Texas; and
| | - Sahand Ghodrati
- Division of Pulmonary, Critical Care and Sleep Medicine, University of California, Davis, Davis, California
| | - Vivian Vo
- Division of Pulmonary, Critical Care and Sleep Medicine, University of California, Davis, Davis, California
| | - Elisabetta A. Renzoni
- National Heart and Lung Institute, Imperial College London, London, United Kingdom
- Royal Brompton and Harefield Hospitals, Guy’s and St. Thomas’ NHS Foundation Trust, London, United Kingdom
| | - Athol U. Wells
- National Heart and Lung Institute, Imperial College London, London, United Kingdom
- Royal Brompton and Harefield Hospitals, Guy’s and St. Thomas’ NHS Foundation Trust, London, United Kingdom
| | - Christine Kim Garcia
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Columbia University, New York, New York
| | - Felix Chua
- National Heart and Lung Institute, Imperial College London, London, United Kingdom
- Royal Brompton and Harefield Hospitals, Guy’s and St. Thomas’ NHS Foundation Trust, London, United Kingdom
| | - Chad A. Newton
- Division of Pulmonary and Critical Care Medicine, University of Texas Southwestern Medical Center, Dallas, Texas; and
| | - Philip L. Molyneaux
- National Heart and Lung Institute, Imperial College London, London, United Kingdom
- Royal Brompton and Harefield Hospitals, Guy’s and St. Thomas’ NHS Foundation Trust, London, United Kingdom
| | - Justin M. Oldham
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan
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23
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Bendstrup E, Kronborg-White S, Møller J, Prior TS. Current best clinical practices for monitoring of interstitial lung disease. Expert Rev Respir Med 2022; 16:1153-1166. [PMID: 36572644 DOI: 10.1080/17476348.2022.2162504] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
INTRODUCTION Interstitial lung diseases (ILDs) are a heterogeneous group of inflammatory and/or fibrotic conditions with variable outcome and often a dismal prognosis. Since many ILDs are progressive in nature, monitoring of signs and symptoms of progression is essential to inform treatment decisions and patient counseling. Monitoring of ILDs is a multimodality process and includes all aspects of the disease, e.g. measurement of pulmonary function and exercise capacity, symptom registration and quality of life (QoL), imaging, comorbidities and/or involvement of other organs to assess disease activity, symptom burden, treatment effects, adverse events, the need for supportive and palliative care, and lung transplantation. AREAS COVERED For this narrative review, we searched the PUBMED database to identify articles relevant for monitoring ILDs, including pulmonary function tests, exercise capacity, imaging, telemedicine, symptoms, and QoL. EXPERT OPINION Due to the high heterogeneity of the ILDs and their disease course, an individualized multimodality approach must be applied. Future strategies include use of telemedicine for home monitoring of lung function and symptoms, use of artificial intelligence to support automatized guidance of patients, computerized evaluation of ILD changes on imaging, and new imaging tools with less radiation dosage.
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Affiliation(s)
- Elisabeth Bendstrup
- Centre for Rare Lung Diseases, Department of Respiratory Diseases and Allergy, Aarhus University Hospital, Aarhus, Denmark
| | - Sissel Kronborg-White
- Centre for Rare Lung Diseases, Department of Respiratory Diseases and Allergy, Aarhus University Hospital, Aarhus, Denmark
| | - Janne Møller
- Centre for Rare Lung Diseases, Department of Respiratory Diseases and Allergy, Aarhus University Hospital, Aarhus, Denmark
| | - Thomas Skovhus Prior
- Centre for Rare Lung Diseases, Department of Respiratory Diseases and Allergy, Aarhus University Hospital, Aarhus, Denmark
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Cottin V, Bonniaud P, Cadranel J, Crestani B, Jouneau S, Marchand-Adam S, Nunes H, Wémeau-Stervinou L, Bergot E, Blanchard E, Borie R, Bourdin A, Chenivesse C, Clément A, Gomez E, Gondouin A, Hirschi S, Lebargy F, Marquette CH, Montani D, Prévot G, Quetant S, Reynaud-Gaubert M, Salaun M, Sanchez O, Trumbic B, Berkani K, Brillet PY, Campana M, Chalabreysse L, Chatté G, Debieuvre D, Ferretti G, Fourrier JM, Just N, Kambouchner M, Legrand B, Le Guillou F, Lhuillier JP, Mehdaoui A, Naccache JM, Paganon C, Rémy-Jardin M, Si-Mohamed S, Terrioux P. [French practical guidelines for the diagnosis and management of IPF - 2021 update, full version]. Rev Mal Respir 2022; 39:e35-e106. [PMID: 35752506 DOI: 10.1016/j.rmr.2022.01.014] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
Abstract
BACKGROUND Since the previous French guidelines were published in 2017, substantial additional knowledge about idiopathic pulmonary fibrosis has accumulated. METHODS Under the auspices of the French-speaking Learned Society of Pulmonology and at the initiative of the coordinating reference center, practical guidelines for treatment of rare pulmonary diseases have been established. They were elaborated by groups of writers, reviewers and coordinators with the help of the OrphaLung network, as well as pulmonologists with varying practice modalities, radiologists, pathologists, a general practitioner, a head nurse, and a patients' association. The method was developed according to rules entitled "Good clinical practice" in the overall framework of the "Guidelines for clinical practice" of the official French health authority (HAS), taking into account the results of an online vote using a Likert scale. RESULTS After analysis of the literature, 54 recommendations were formulated, improved, and validated by the working groups. The recommendations covered a wide-ranging aspects of the disease and its treatment: epidemiology, diagnostic modalities, quality criteria and interpretation of chest CT, indication and modalities of lung biopsy, etiologic workup, approach to familial disease entailing indications and modalities of genetic testing, evaluation of possible functional impairments and prognosis, indications for and use of antifibrotic therapy, lung transplantation, symptom management, comorbidities and complications, treatment of chronic respiratory failure, diagnosis and management of acute exacerbations of fibrosis. CONCLUSION These evidence-based guidelines are aimed at guiding the diagnosis and the management in clinical practice of idiopathic pulmonary fibrosis.
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Affiliation(s)
- V Cottin
- Centre national coordonnateur de référence des maladies pulmonaires rares, service de pneumologie, hôpital Louis-Pradel, Hospices Civils de Lyon (HCL), Lyon, France; UMR 754, IVPC, INRAE, Université de Lyon, Université Claude-Bernard Lyon 1, Lyon, France; Membre d'OrphaLung, RespiFil, Radico-ILD2, et ERN-LUNG, Lyon, France.
| | - P Bonniaud
- Centre de référence constitutif des maladies pulmonaires rares, service de pneumologie et soins intensifs respiratoires, centre hospitalo-universitaire de Bourgogne et faculté de médecine et pharmacie, université de Bourgogne-Franche Comté, Dijon ; Inserm U123-1, Dijon, France
| | - J Cadranel
- Centre de référence constitutif des maladies pulmonaires rares, service de pneumologie et oncologie thoracique, Assistance publique-Hôpitaux de Paris (AP-HP), hôpital Tenon, Paris ; Sorbonne université GRC 04 Theranoscan, Paris, France
| | - B Crestani
- Centre de référence constitutif des maladies pulmonaires rares, service de pneumologie A, AP-HP, hôpital Bichat, Paris, France
| | - S Jouneau
- Centre de compétence pour les maladies pulmonaires rares de l'adulte, service de pneumologie, hôpital Pontchaillou, Rennes ; IRSET UMR1085, université de Rennes 1, Rennes, France
| | - S Marchand-Adam
- Centre de compétence pour les maladies pulmonaires rares de l'adulte, hôpital Bretonneau, service de pneumologie, CHRU, Tours, France
| | - H Nunes
- Centre de référence constitutif des maladies pulmonaires rares, service de pneumologie, AP-HP, hôpital Avicenne, Bobigny ; université Sorbonne Paris Nord, Bobigny, France
| | - L Wémeau-Stervinou
- Centre de référence constitutif des maladies pulmonaires rares, Institut Cœur-Poumon, service de pneumologie et immuno-allergologie, CHRU de Lille, Lille, France
| | - E Bergot
- Centre de compétence pour les maladies pulmonaires rares de l'adulte, service de pneumologie et oncologie thoracique, hôpital Côte de Nacre, CHU de Caen, Caen, France
| | - E Blanchard
- Centre de compétence pour les maladies pulmonaires rares de l'adulte, service de pneumologie, hôpital Haut Levêque, CHU de Bordeaux, Pessac, France
| | - R Borie
- Centre de référence constitutif des maladies pulmonaires rares, service de pneumologie A, AP-HP, hôpital Bichat, Paris, France
| | - A Bourdin
- Centre de compétence pour les maladies pulmonaires rares de l'adulte, département de pneumologie et addictologie, hôpital Arnaud-de-Villeneuve, CHU de Montpellier, Montpellier ; Inserm U1046, CNRS UMR 921, Montpellier, France
| | - C Chenivesse
- Centre de référence constitutif des maladies pulmonaires rares, service de pneumologie et d'immuno-allergologie, hôpital Albert Calmette ; CHRU de Lille, Lille ; centre d'infection et d'immunité de Lille U1019 - UMR 9017, Université de Lille, CHU Lille, CNRS, Inserm, Institut Pasteur de Lille, Lille, France
| | - A Clément
- Centre de ressources et de compétence de la mucoviscidose pédiatrique, centre de référence des maladies respiratoires rares (RespiRare), service de pneumologie pédiatrique, hôpital d'enfants Armand-Trousseau, CHU Paris Est, Paris ; Sorbonne université, Paris, France
| | - E Gomez
- Centre de compétence pour les maladies pulmonaires rares, département de pneumologie, hôpitaux de Brabois, CHRU de Nancy, Vandoeuvre-les Nancy, France
| | - A Gondouin
- Centre de compétence pour les maladies pulmonaires rares, service de pneumologie, CHU Jean-Minjoz, Besançon, France
| | - S Hirschi
- Centre de compétence pour les maladies pulmonaires rares, service de pneumologie, Nouvel Hôpital civil, Strasbourg, France
| | - F Lebargy
- Centre de compétence pour les maladies pulmonaires rares, service de pneumologie, CHU Maison Blanche, Reims, France
| | - C-H Marquette
- Centre de compétence pour les maladies pulmonaires rares, FHU OncoAge, département de pneumologie et oncologie thoracique, hôpital Pasteur, CHU de Nice, Nice cedex 1 ; Université Côte d'Azur, CNRS, Inserm, Institute of Research on Cancer and Aging (IRCAN), Nice, France
| | - D Montani
- Centre de compétence pour les maladies pulmonaires rares, centre national coordonnateur de référence de l'hypertension pulmonaire, service de pneumologie et soins intensifs pneumologiques, AP-HP, DMU 5 Thorinno, Inserm UMR S999, CHU Paris-Sud, hôpital de Bicêtre, Le Kremlin-Bicêtre ; Université Paris-Saclay, Faculté de médecine, Le Kremlin-Bicêtre, France
| | - G Prévot
- Centre de compétence pour les maladies pulmonaires rares, service de pneumologie, CHU Larrey, Toulouse, France
| | - S Quetant
- Centre de compétence pour les maladies pulmonaires rares, service de pneumologie et physiologie, CHU Grenoble Alpes, Grenoble, France
| | - M Reynaud-Gaubert
- Centre de compétence pour les maladies pulmonaires rares, service de pneumologie, AP-HM, CHU Nord, Marseille ; Aix Marseille Université, IRD, APHM, MEPHI, IHU-Méditerranée Infection, Marseille, France
| | - M Salaun
- Centre de compétence pour les maladies pulmonaires rares, service de pneumologie, oncologie thoracique et soins intensifs respiratoires & CIC 1404, hôpital Charles Nicole, CHU de Rouen, Rouen ; IRIB, laboratoire QuantiIF-LITIS, EA 4108, université de Rouen, Rouen, France
| | - O Sanchez
- Centre de compétence pour les maladies pulmonaires rares, service de pneumologie et soins intensifs, hôpital européen Georges-Pompidou, AP-HP, Paris, France
| | | | - K Berkani
- Clinique Pierre de Soleil, Vetraz Monthoux, France
| | - P-Y Brillet
- Université Paris 13, UPRES EA 2363, Bobigny ; service de radiologie, AP-HP, hôpital Avicenne, Bobigny, France
| | - M Campana
- Service de pneumologie et oncologie thoracique, CHR Orléans, Orléans, France
| | - L Chalabreysse
- Service d'anatomie-pathologique, groupement hospitalier est, HCL, Bron, France
| | - G Chatté
- Cabinet de pneumologie et infirmerie protestante, Caluire, France
| | - D Debieuvre
- Service de pneumologie, GHRMSA, hôpital Emile-Muller, Mulhouse, France
| | - G Ferretti
- Université Grenoble Alpes, Grenoble ; service de radiologie diagnostique et interventionnelle, CHU Grenoble Alpes, Grenoble, France
| | - J-M Fourrier
- Association Pierre-Enjalran Fibrose Pulmonaire Idiopathique (APEFPI), Meyzieu, France
| | - N Just
- Service de pneumologie, CH Victor-Provo, Roubaix, France
| | - M Kambouchner
- Service de pathologie, AP-HP, hôpital Avicenne, Bobigny, France
| | - B Legrand
- Cabinet médical de la Bourgogne, Tourcoing ; Université de Lille, CHU Lille, ULR 2694 METRICS, CERIM, Lille, France
| | - F Le Guillou
- Cabinet de pneumologie, pôle santé de l'Esquirol, Le Pradet, France
| | - J-P Lhuillier
- Cabinet de pneumologie, La Varenne Saint-Hilaire, France
| | - A Mehdaoui
- Service de pneumologie et oncologie thoracique, CH Eure-Seine, Évreux, France
| | - J-M Naccache
- Service de pneumologie, allergologie et oncologie thoracique, GH Paris Saint-Joseph, Paris, France
| | - C Paganon
- Centre national coordonnateur de référence des maladies pulmonaires rares, service de pneumologie, hôpital Louis-Pradel, Hospices Civils de Lyon (HCL), Lyon, France
| | - M Rémy-Jardin
- Institut Cœur-Poumon, service de radiologie et d'imagerie thoracique, CHRU de Lille, Lille, France
| | - S Si-Mohamed
- Département d'imagerie cardiovasculaire et thoracique, hôpital Louis-Pradel, HCL, Bron ; Université de Lyon, INSA-Lyon, Université Claude-Bernard Lyon 1, UJM-Saint Etienne, CNRS, Inserm, CREATIS UMR 5220, U1206, Villeurbanne, France
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French practical guidelines for the diagnosis and management of idiopathic pulmonary fibrosis - 2021 update. Full-length version. Respir Med Res 2022; 83:100948. [PMID: 36630775 DOI: 10.1016/j.resmer.2022.100948] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
BACKGROUND Since the latest 2017 French guidelines, knowledge about idiopathic pulmonary fibrosis has evolved considerably. METHODS Practical guidelines were drafted on the initiative of the Coordinating Reference Center for Rare Pulmonary Diseases, led by the French Language Pulmonology Society (SPLF), by a coordinating group, a writing group, and a review group, with the involvement of the entire OrphaLung network, pulmonologists practicing in various settings, radiologists, pathologists, a general practitioner, a health manager, and a patient association. The method followed the "Clinical Practice Guidelines" process of the French National Authority for Health (HAS), including an online vote using a Likert scale. RESULTS After a literature review, 54 guidelines were formulated, improved, and then validated by the working groups. These guidelines addressed multiple aspects of the disease: epidemiology, diagnostic procedures, quality criteria and interpretation of chest CT scans, lung biopsy indication and procedures, etiological workup, methods and indications for family screening and genetic testing, assessment of the functional impairment and prognosis, indication and use of antifibrotic agents, lung transplantation, management of symptoms, comorbidities and complications, treatment of chronic respiratory failure, diagnosis and management of acute exacerbations of fibrosis. CONCLUSION These evidence-based guidelines are intended to guide the diagnosis and practical management of idiopathic pulmonary fibrosis.
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Castro HM, Maritano Furcada J, Enghelmayer JI. Relative Versus Absolute Decline in Forced Vital Capacity in Progressive Pulmonary Fibrosis. Arch Bronconeumol 2022; 58:843-844. [DOI: 10.1016/j.arbres.2022.07.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2022] [Revised: 07/03/2022] [Accepted: 07/04/2022] [Indexed: 11/15/2022]
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Impact of the revised definition on incidence and outcomes of acute exacerbation of idiopathic pulmonary fibrosis. Sci Rep 2022; 12:8817. [PMID: 35614114 PMCID: PMC9130993 DOI: 10.1038/s41598-022-12693-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Accepted: 05/12/2022] [Indexed: 11/24/2022] Open
Abstract
The revised definition of acute exacerbation (AE) in idiopathic pulmonary fibrosis (IPF) was proposed in 2016, but changes in the incidence and impact on prognosis of the re-defined AE compared to those of the previous definition remain unclear. Clinical data of 445 patients with IPF (biopsy proven cases: 165) were retrospectively reviewed. The median follow-up period was 36.8 months and 17.5% (n = 78) experienced AE more than once. The 1- and 3-year incidence rates of AE were 6.7% and 16.6%, respectively, and idiopathic AE accounted for 82.1% of AE. Older age, lower diffusing capacity of the lung for carbon monoxide and 10% relative decline in forced vital capacity for 6 months were independently associated with AE. The in-hospital mortality rate following AE was 29.5%. In the multivariable analysis, AE was independently associated with poor prognosis in patients with IPF. Compared to the old definition, the revised definition relatively increased the incidence of AE by 20.4% and decreased the in-hospital mortality by 10.1%. Our results suggest that the revised definition affects approximately 20% increase in the incidences and 10% reduction in the in-hospital mortality of AE defined by the past definition.
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28
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Sgalla G, Wijsenbeek MS, Richeldi L. The Shorter, the Better: Can We Improve Efficiency of Idiopathic Pulmonary Fibrosis Trials? Am J Respir Crit Care Med 2022; 205:867-869. [PMID: 35134312 PMCID: PMC9838618 DOI: 10.1164/rccm.202201-0018ed] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Affiliation(s)
- Giacomo Sgalla
- Fondazione Policlinico Universitario A. Gemelli IRCCSUniversità Cattolica del Sacro CuoreRome, Italy
| | - Marlies S. Wijsenbeek
- Centre for Interstitial Lung Diseases and SarcoidosisErasmus University Medical Centre RotterdamRotterdam, the Netherlands
| | - Luca Richeldi
- Fondazione Policlinico Universitario A. Gemelli IRCCSUniversità Cattolica del Sacro CuoreRome, Italy
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29
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Conte P, Ascierto PA, Patelli G, Danesi R, Vanzulli A, Sandomenico F, Tarsia P, Cattelan A, Comes A, De Laurentiis M, Falcone A, Regge D, Richeldi L, Siena S. Drug-induced interstitial lung disease during cancer therapies: expert opinion on diagnosis and treatment. ESMO Open 2022; 7:100404. [PMID: 35219244 PMCID: PMC8881716 DOI: 10.1016/j.esmoop.2022.100404] [Citation(s) in RCA: 107] [Impact Index Per Article: 35.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Revised: 01/16/2022] [Accepted: 01/18/2022] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND Drug-induced interstitial lung disease (DIILD) is a form of interstitial lung disease resulting from exposure to drugs causing inflammation and possibly interstitial fibrosis. Antineoplastic drugs are the primary cause of DIILD, accounting for 23%-51% of cases, with bleomycin, everolimus, erlotinib, trastuzumab-deruxtecan and immune checkpoint inhibitors being the most common causative agents. DIILD can be difficult to identify and manage, and there are currently no specific guidelines on the diagnosis and treatment of DIILD caused by anticancer drugs. OBJECTIVE To develop recommendations for the diagnosis and management of DIILD in cancer patients. METHODS Based on the published literature and their clinical expertise, a multidisciplinary group of experts in Italy developed recommendations stratified by DIILD severity, based on the Common Terminology Criteria for Adverse Events. RESULTS The recommendations highlight the importance of multidisciplinary interaction in the diagnosis and management of DIILD. Important components of the diagnostic process are physical examination and careful patient history-taking, measurement of vital signs (particularly respiratory rate and arterial oxygen saturation), relevant laboratory tests, respiratory function testing with spirometry and diffusing capacity of the lung for carbon monoxide and computed tomography/imaging. Because the clinical and radiological signs of DIILD are often similar to those of pneumonias or interstitial lung diseases, differential diagnosis is important, including microbial and serological testing to exclude or confirm infectious causes. In most cases, management of DIILD requires the discontinuation of the antineoplastic agent and the administration of short-term steroids. Steroid tapering must be undertaken slowly to prevent reactivation of DIILD. Patients with severe and very severe (grade 3 and 4) DIILD will require hospitalisation and often need oxygen and non-invasive ventilation. Decisions about invasive ventilation should take into account the patient's cancer prognosis. CONCLUSIONS These recommendations provide a structured step-by-step diagnostic and therapeutic approach for each grade of suspected cancer-related DIILD.
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Affiliation(s)
- P Conte
- DiSCOG, University of Padova and Medical Oncology 2, IOV-Istituto Oncologico Veneto IRCCS, Padua, Italy
| | - P A Ascierto
- Department of Melanoma, Cancer Immunotherapy and Development Therapeutics, Istituto Nazionale Tumori IRCCS Fondazione Pascale, Naples, Italy
| | - G Patelli
- Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, Milan, Italy; Department of Hematology, Oncology and Molecular Medicine, Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - R Danesi
- Unit of Clinical Pharmacology and Pharmacogenetics, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - A Vanzulli
- Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, Milan, Italy; Radiology Department, Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - F Sandomenico
- Radiology Unit, Buon Consiglio Fatebenefratelli Hospital, Naples, Italy
| | - P Tarsia
- Pneumology Unit, Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - A Cattelan
- Tropical and Infectious Diseases Unit, Padua University Hospital, Padua, Italy
| | - A Comes
- Unità Operativa Complessa di Pneumologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - M De Laurentiis
- Department of Breast and Thoracic Oncology, Istituto Nazionale Tumori IRCCS Fondazione Pascale, Naples, Italy
| | - A Falcone
- Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
| | - D Regge
- Department of Radiology, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Turin, Italy; Department of Surgical Sciences, University of Turin, Turin, Italy
| | - L Richeldi
- Unità Operativa Complessa di Pneumologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - S Siena
- Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, Milan, Italy; Department of Hematology, Oncology and Molecular Medicine, Grande Ospedale Metropolitano Niguarda, Milan, Italy.
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30
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Takei R, Brown KK, Yamano Y, Kataoka K, Yokoyama T, Matsuda T, Kimura T, Suzuki A, Furukawa T, Fukuoka J, Johkoh T, Goto Y, Kondoh Y. Prevalence and prognosis of chronic fibrosing interstitial lung diseases with a progressive phenotype. Respirology 2022; 27:333-340. [PMID: 35293077 DOI: 10.1111/resp.14245] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2021] [Revised: 02/17/2022] [Accepted: 03/01/2022] [Indexed: 01/04/2023]
Abstract
BACKGROUND AND OBJECTIVE The development of clinically progressive fibrosis complicates a wide array of interstitial lung diseases (ILDs). However, there are limited data regarding its prevalence and prognosis. METHODS We analysed consecutive patients seen for initial evaluation of a fibrosing form of ILD (FILD). Patients were evaluated for evidence of progressive fibrosis over the first 24 months of follow-up. We defined a progressive phenotype as the presence of at least one of the following: a relative decline in forced vital capacity (FVC) of ≥10%; a relative decline in FVC of ≥5%-<10% with a relative decline in diffusing capacity of the lung for carbon monoxide of ≥15%, increased fibrosis on HRCT or progressive symptoms. RESULTS Eight hundred and forty-four patients (397 with idiopathic pulmonary fibrosis [IPF] and 447 non-IPF FILD) made up the final analysis cohort. Three hundred and fifty-five patients (42.1%) met the progressive phenotype criteria (59.4% of IPF patients and 26.6% of non-IPF FILD patients, p <0.01). In both IPF and non-IPF FILD, transplantation-free survival differed between patients with a progressive phenotype and those without (p <0.01). Multivariable analysis showed that a progressive phenotype was an independent predictor of transplantation-free survival (hazard ratio [HR]: 3.36, 95% CI: 2.68-4.23, p <0.01). Transplantation-free survival did not differ between non-IPF FILD with a progressive phenotype and IPF (HR: 1.12, 95% CI: 0.85-1.48, p = 0.42). CONCLUSION Over one-fourth of non-IPF FILD patients develop a progressive phenotype compared to approximately 60% of IPF patients. The survival of non-IPF FILD patients with a progressive phenotype is similar to IPF.
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Affiliation(s)
- Reoto Takei
- Department of Respiratory Medicine and Allergy, Tosei General Hospital, Seto, Japan
| | - Kevin K Brown
- Department of Medicine, National Jewish Health, Denver, Colorado, USA
| | - Yasuhiko Yamano
- Department of Respiratory Medicine and Allergy, Tosei General Hospital, Seto, Japan
| | - Kensuke Kataoka
- Department of Respiratory Medicine and Allergy, Tosei General Hospital, Seto, Japan
| | - Toshiki Yokoyama
- Department of Respiratory Medicine and Allergy, Tosei General Hospital, Seto, Japan
| | - Toshiaki Matsuda
- Department of Respiratory Medicine and Allergy, Tosei General Hospital, Seto, Japan
| | - Tomoki Kimura
- Department of Respiratory Medicine and Allergy, Tosei General Hospital, Seto, Japan
| | - Atsushi Suzuki
- Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Taiki Furukawa
- Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.,Department of Medical IT Center, Nagoya University Hospital, Nagoya, Japan
| | - Junya Fukuoka
- Department of Laboratory of Pathology, Nagasaki University Hospital, Nagasaki, Japan
| | - Takeshi Johkoh
- Department of Radiology, Kansai Rosai Hospital, Amagasaki, Japan
| | - Yoshihito Goto
- Department of Health Informatics, Kyoto University School of Public Health, Kyoto, Japan
| | - Yasuhiro Kondoh
- Department of Respiratory Medicine and Allergy, Tosei General Hospital, Seto, Japan
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31
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Brown KK, Inoue Y, Flaherty KR, Martinez FJ, Cottin V, Bonella F, Cerri S, Danoff SK, Jouneau S, Goeldner R, Schmidt M, Stowasser S, Schlenker‐Herceg R, Wells AU. Predictors of mortality in subjects with progressive fibrosing interstitial lung diseases. Respirology 2022; 27:294-300. [PMID: 35224814 PMCID: PMC9306931 DOI: 10.1111/resp.14231] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Revised: 12/13/2021] [Accepted: 02/08/2022] [Indexed: 01/15/2023]
Abstract
Background and objective Demographic and clinical variables, measured at baseline or over time, have been associated with mortality in subjects with progressive fibrosing interstitial lung diseases (ILDs). We used data from the INPULSIS trials in subjects with idiopathic pulmonary fibrosis (IPF) and the INBUILD trial in subjects with other progressive fibrosing ILDs to assess relationships between demographic/clinical variables and mortality. Methods The relationships between baseline variables and time‐varying covariates and time to death over 52 weeks were analysed using pooled data from the INPULSIS trials and, separately, the INBUILD trial using a Cox proportional hazards model. Results Over 52 weeks, 68/1061 (6.4%) and 33/663 (5.0%) subjects died in the INPULSIS and INBUILD trials, respectively. In the INPULSIS trials, a relative decline in forced vital capacity (FVC) >10% predicted within 12 months (hazard ratio [HR] 3.77) and age (HR 1.03 per 1‐year increase) were associated with increased risk of mortality, while baseline FVC % predicted (HR 0.97 per 1‐unit increase) and diffusing capacity of the lungs for carbon monoxide (DLCO) % predicted (HR 0.77 per 1‐unit increase) were associated with lower risk. In the INBUILD trial, a relative decline in FVC >10% predicted within 12 months (HR 2.60) and a usual interstitial pneumonia‐like fibrotic pattern on HRCT (HR 2.98) were associated with increased risk of mortality, while baseline DLCO % predicted (HR 0.95 per 1‐unit increase) was associated with lower risk. Conclusion These data support similarity in the course of lung injury between IPF and other progressive fibrosing ILDs and the value of FVC decline as a predictor of mortality. We assessed relationships between baseline and time‐varying factors and mortality over 52 weeks in 1061 subjects with idiopathic pulmonary fibrosis (IPF) and 663 subjects with other progressive fibrosing interstitial lung diseases (ILDs). Our findings support similarity in the course of IPF and ILD and an association between decline in forced vital capacity and mortality.
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Affiliation(s)
- Kevin K. Brown
- Department of Medicine National Jewish Health Denver Colorado USA
| | - Yoshikazu Inoue
- Clinical Research Center National Hospital Organization Kinki‐Chuo Chest Medical Center Sakai City Japan
| | - Kevin R. Flaherty
- Division of Pulmonary and Critical Care Medicine University of Michigan Ann Arbor Michigan USA
| | | | - Vincent Cottin
- National Reference Centre for Rare Pulmonary Diseases, Louis Pradel Hospital, Hospices Civils de Lyon Claude Bernard University Lyon 1 Lyon France
| | - Francesco Bonella
- Center for Interstitial and Rare Lung Diseases, Department of Pneumology, Ruhrlandklinik University Hospital University of Duisburg‐Essen Essen Germany
| | - Stefania Cerri
- Center for Rare Lung Disease Azienda Ospedaliero‐Universitaria Policlinico di Modena Modena Italy
| | | | - Stephane Jouneau
- Department of Respiratory Medicine Competences Centre for Rare Pulmonary Diseases, CHU Rennes, IRSET UMR 1085, Univ Rennes Rennes France
| | | | - Martin Schmidt
- Boehringer Ingelheim Pharma GmbH Ingelheim am Rhein Germany
| | | | | | - Athol U. Wells
- National Institute for Health Research Respiratory Biomedical Research Unit, Royal Brompton and Harefield NHS Foundation Trust, and National Heart and Lung Institute Imperial College London UK
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Prasad JD, Paul E, Holland AE, Glaspole IN, Westall GP. Physical activity decline is disproportionate to decline in pulmonary physiology in IPF. Respirology 2021; 26:1152-1159. [PMID: 34448321 DOI: 10.1111/resp.14137] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2020] [Revised: 06/13/2021] [Accepted: 08/02/2021] [Indexed: 12/01/2022]
Abstract
BACKGROUND AND OBJECTIVE Patients with idiopathic pulmonary fibrosis (IPF) have reduced levels of daily physical activity (DPA); however, little is known about how DPA changes as disease progresses. We aimed to (i) describe change in DPA over 12 months, (ii) analyse its association with conventional markers of disease severity and quality of life and (iii) assess DPA as a prognostic tool. METHODS A total of 54 patients with IPF had DPA monitored at baseline and at 6 and 12 months with a SenseWear armband for 7 consecutive days. Participants completed the Hospital Anxiety and Depression scale, St George's Respiratory Questionnaire and Leicester Cough Questionnaire at each time point and provided clinical data including forced vital capacity (FVC), diffusion capacity of carbon monoxide and 6-min walk distance (6MWD). RESULTS Baseline and 12-month daily step count (DSC) were 3887 (395) and 3326 (419), respectively. A significant reduction in DSC (mean = 645 [260], p = 0.02) and total energy expenditure (mean = 486 kJ [188], p = 0.01) was demonstrated at 12 months. The decline in DSC over 12 months was proportionally larger than decline in lung function. Annual change in DPA had weak to moderate correlation with annual change in FVC % predicted and 6MWD (range r = 0.34-0.45). Change in physical activity was not associated with long-term survival. CONCLUSION In IPF, decline in DPA over 12 months is significant and disproportionate to decline in pulmonary physiology and may be a useful tool for assessment of disease progression.
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Affiliation(s)
- Jyotika D Prasad
- Lung Fibrosis Service, Department of General Respiratory Medicine and Lung Transplantation, Alfred Hospital, Melbourne, Victoria, Australia.,Central Clinical School, Monash University, Melbourne, Victoria, Australia
| | - Eldho Paul
- Australian and New Zealand Intensive Care Research Centre (ANZIC-RC), Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia
| | - Anne E Holland
- Central Clinical School, Monash University, Melbourne, Victoria, Australia.,Physiotherapy Department, Alfred Hospital, Melbourne, Victoria, Australia.,Institute for Breathing and Sleep, Melbourne, Victoria, Australia
| | - Ian N Glaspole
- Lung Fibrosis Service, Department of General Respiratory Medicine and Lung Transplantation, Alfred Hospital, Melbourne, Victoria, Australia.,Central Clinical School, Monash University, Melbourne, Victoria, Australia
| | - Glen P Westall
- Lung Fibrosis Service, Department of General Respiratory Medicine and Lung Transplantation, Alfred Hospital, Melbourne, Victoria, Australia.,Central Clinical School, Monash University, Melbourne, Victoria, Australia
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Juge PA, Solomon JJ, van Moorsel CHM, Garofoli R, Lee JS, Louis-Sydney F, Rojas-Serrano J, González-Pérez MI, Mejia M, Buendia-Roldán I, Falfán-Valencia R, Ambrocio-Ortiz E, Manali E, Papiris SA, Karageorgas T, Boumpas D, Antoniou KM, Sidiropoulos P, Trachalaki A, van der Vis JJ, Jamnitski A, Grutters JC, Kannengiesser C, Borie R, Kawano-Dourado L, Wemeau-Stervinou L, Flipo RM, Nunes H, Uzunhan Y, Valeyre D, Saidenberg-Kermanac'h N, Boissier MC, Richez C, Schaeverbeke T, Doyle T, Wolters PJ, Debray MP, Boileau C, Porcher R, Schwartz DA, Crestani B, Dieudé P. MUC5B promoter variant rs35705950 and rheumatoid arthritis associated interstitial lung disease survival and progression. Semin Arthritis Rheum 2021; 51:996-1004. [PMID: 34411838 DOI: 10.1016/j.semarthrit.2021.07.002] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Revised: 06/19/2021] [Accepted: 07/05/2021] [Indexed: 10/20/2022]
Abstract
BACKGROUND The major risk factor for idiopathic pulmonary fibrosis (IPF), MUC5B rs35705950, was found to be associated with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Whilst the MUC5B rs35705950 T risk allele has been associated with better survival in IPF, its impact on RA-ILD prognosis remains to be determined. Our objective was to explore the influence of MUC5B rs35705950 on survival and progression in RA-ILD. METHODS Through an international retrospective observational study, patients with RA-ILD were genotyped for the MUC5B rs35705950 variant and consecutive pulmonary function tests (PFTs) findings were collected. Longitudinal data up to a 10-year follow-up were considered and analyzed using mixed regression models. Proportional hazards and joint proportional hazards models were used to analyze the association of baseline and longitudinal variables with lung transplant-free survival. Significant progression of RA-ILD was defined as at least an absolute or relative 10% decline of forced vital capacity at 2 years from baseline. RESULTS Out of 321 registered patients, 261 were included in the study: 139 women (53.3%), median age at RA-ILD diagnosis 65 years (interquartile range [IQR] 57 to 71), 151 ever smokers (59.2%). Median follow-up was 3.5 years (IQR 1.3 to 6.6). Mortality rate was 32% (95%CI 19 to 42) at 10 years. The MUC5B rs35705950 variant did not impact lung transplant-free survival (HR for the T risk allele carriers=1.26; 95%CI 0.61 to 2.62; P=0.53). Decline in pulmonary function at 2 years was not influenced by MUC5B rs35705950 (OR=0.95; 95%CI 0.44 to 2.05; P=0.89), irrespective of the HRCT pattern. CONCLUSION In this study, the MUC5B rs35705950 promoter variant did not influence transplant- free survival or decline in pulmonary function in patients with RA-ILD.
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Affiliation(s)
- Pierre-Antoine Juge
- Université de Paris, AP-HP, Hôpital Bichat Claude-Bernard, Service de Rhumatologie, DMU Locomotion, INSERM UMR1152, Paris, France
| | - Joshua J Solomon
- Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, National Jewish Health, Denver, CO, United States
| | - Coline H M van Moorsel
- St Antonius ILD center of excellence, St Antonius ziekenhuis, Nieuwegein, the Netherlands
| | - Romain Garofoli
- Université de Paris, AP-HP, Hôpital Bichat Claude-Bernard, Service de Rhumatologie, DMU Locomotion, INSERM UMR1152, Paris, France
| | - Joyce S Lee
- Department of Medicine, University of Colorado School of Medicine, Aurora, CO, United States
| | - Fabienne Louis-Sydney
- Université de Paris, AP-HP, Hôpital Bichat Claude-Bernard, Service de Rhumatologie, DMU Locomotion, INSERM UMR1152, Paris, France
| | - Jorge Rojas-Serrano
- Interstitial Lung Disease & Rheumatology Unit, Instituto Nacional de Enfermedades Respiratorias, Ismael Cosío Villegas, México City, México
| | - Montserrat I González-Pérez
- Interstitial Lung Disease & Rheumatology Unit, Instituto Nacional de Enfermedades Respiratorias, Ismael Cosío Villegas, México City, México
| | - Mayra Mejia
- Interstitial Lung Disease & Rheumatology Unit, Instituto Nacional de Enfermedades Respiratorias, Ismael Cosío Villegas, México City, México
| | - Ivette Buendia-Roldán
- Interstitial Lung Disease & Rheumatology Unit, Instituto Nacional de Enfermedades Respiratorias, Ismael Cosío Villegas, México City, México
| | - Ramcés Falfán-Valencia
- HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas. Mexico City, Mexico
| | - Enrique Ambrocio-Ortiz
- HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas. Mexico City, Mexico
| | - Effrosyni Manali
- 2nd Pulmonary Medicine Department, University Hospital of Athens "Attikon", National and Kapodistrian University of Athens, Athens, Greece
| | - Spyros A Papiris
- 2nd Pulmonary Medicine Department, University Hospital of Athens "Attikon", National and Kapodistrian University of Athens, Athens, Greece
| | - Theofanis Karageorgas
- Rheumatology and Clinical Immunology Unit, 4th Department of Internal Medicine, University Hospital of Athens "Attikon", National and Kapodistrian University of Athens, Athens, Greece
| | - Dimitrios Boumpas
- Rheumatology and Clinical Immunology Unit, 4th Department of Internal Medicine, University Hospital of Athens "Attikon", National and Kapodistrian University of Athens, Athens, Greece
| | - Katarina M Antoniou
- PS Department of Respiratory Medicine & Laboratory of Molecular & Cellular Pneumonology, Faculty of Medicine, University of Crete, Crete, Greece
| | | | - Athina Trachalaki
- Internal Medecine, University College of London, London, United Kingdom
| | - Joanne J van der Vis
- St Antonius ILD center of excellence, St Antonius ziekenhuis, Nieuwegein, the Netherlands
| | - Anna Jamnitski
- St Antonius ILD center of excellence, St Antonius ziekenhuis, Nieuwegein, the Netherlands
| | - Jan C Grutters
- St Antonius ILD center of excellence, St Antonius ziekenhuis, Nieuwegein, the Netherlands
| | - Caroline Kannengiesser
- Université de Paris, AP-HP, Hôpital Bichat Claude-Bernard, Service de Génétique, INSERM UMR1152, Paris, France
| | - Raphaël Borie
- Université de Paris, AP-HP, Hôpital Bichat Claude-Bernard, Service de Pneumologie, DMU Victoire, INSERM UMR1152, Paris, France
| | - Leticia Kawano-Dourado
- Université de Paris, AP-HP, Hôpital Bichat Claude-Bernard, Service de Pneumologie, DMU Victoire, INSERM UMR1152, Paris, France
| | - Lidwine Wemeau-Stervinou
- CHRU de Lille, Service de Pneumologie et Immuno-Allergologie, Centre de compétence des maladies pulmonaires rares, FHU IMMINENT, Lille, France
| | | | - Hilario Nunes
- Université de Paris, AP-HP, Hôpital Avicenne, Service de Pneumologie, Bobigny, France
| | - Yurdagul Uzunhan
- Université de Paris, AP-HP, Hôpital Avicenne, Service de Pneumologie, Bobigny, France
| | - Dominique Valeyre
- Université de Paris, AP-HP, Hôpital Avicenne, Service de Pneumologie, Bobigny, France
| | | | | | - Christophe Richez
- CHU de Bordeaux, service de rhumatologie, Bordeaux, France; Immuno ConcEpT, CNRS UMR_5164, Bordeaux, France
| | - Thierry Schaeverbeke
- CHU de Bordeaux, service de rhumatologie, Bordeaux, France; Immuno ConcEpT, CNRS UMR_5164, Bordeaux, France
| | - Tracy Doyle
- Department of Medicine, Brigham and Women's Hospital, Boston, MA, United States
| | - Paul J Wolters
- Department of Medicine, University of California, San Francisco, CA, United States
| | - Marie-Pierre Debray
- Université de Paris, AP-HP, Hôpital Bichat Claude-Bernard, Service de Radiologie, Paris, France
| | - Catherine Boileau
- Université de Paris, AP-HP, Hôpital Bichat Claude-Bernard, Service de Génétique, INSERM UMR1152, Paris, France
| | - Raphaël Porcher
- Université de Paris, CRESS, INSERM, INRA, F-75004 Paris, France; Centre d'Épidémiologie Clinique, AP-HP, Hôpital Hôtel-Dieu, F-75004 Paris, France
| | - David A Schwartz
- Department of Medicine, University of Colorado School of Medicine, Aurora, CO, United States
| | - Bruno Crestani
- Université de Paris, AP-HP, Hôpital Bichat Claude-Bernard, Service de Pneumologie, DMU Victoire, INSERM UMR1152, Paris, France
| | - Philippe Dieudé
- Université de Paris, AP-HP, Hôpital Bichat Claude-Bernard, Service de Rhumatologie, DMU Locomotion, INSERM UMR1152, Paris, France.
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Ueyama M, Hashimoto S, Takeda A, Maruguchi N, Yamamoto R, Matsumura K, Nakamura S, Terada S, Inao T, Kaji Y, Yasuda T, Hajiro T, Tanaka E, Taguchi Y, Noma S. Prediction of forced vital capacity with dynamic chest radiography in interstitial lung disease. Eur J Radiol 2021; 142:109866. [PMID: 34365304 DOI: 10.1016/j.ejrad.2021.109866] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Revised: 07/06/2021] [Accepted: 07/13/2021] [Indexed: 10/20/2022]
Abstract
PURPOSE The pulmonary function test (PFT) has played an essential role in diagnosing and managing interstitial lung disease (ILD) but has its contraindications and difficult conditions to perform. Therefore, the present study aimed to evaluate dynamic chest radiography (DCR) ability to predict forced vital capacity (FVC) and other PFT parameters of ILD patients. METHOD The prospective observational study included 97 patients who underwent DCR at Tenri Hospital (Tenri, Japan) between June 2019 and April 2020. Twenty-five patients with stable disease status underwent DCR twice to evaluate test-retest reliability using the intraclass correlation coefficient. From the lung field areas measured by DCR, lung volumes at maximum inspiration (V.ins) and expiration (V.exp) were estimated. Correlation coefficients between the measured values of DCR and PFT parameters were calculated. Multilinear models for predicting FVC and other PFT parameters were developed. RESULTS Intraclass correlation coefficients between first and second measurements of V.ins and V.exp were 0.94 (95% CI: 0.89-0.97, p < 0.001) and 0.88 (95% CI: 0.78-0.94, p < 0.001), respectively. The correlation coefficient between V.ins and FVC was 0.86 (95% CI: 0.79-0.90, p < 0.001). A multilinear model for predicting FVC was developed using V.ins, V.exp, age, sex, and body mass index as predictor variables, wherein the adjusted coefficient of determination was 0.814. CONCLUSIONS Lung volumes measured by DCR correlated with the lung function of ILD patients. Prediction models with high predictive power and internal validity were developed, suggesting that DCR can predict FVC and other PFT parameters of ILD patients.
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Affiliation(s)
- Masakuni Ueyama
- Department of Respiratory Medicine, Tenri Hospital, 200 Mishima-cho Tenri-shi, Nara 632-8552, Japan.
| | - Seishu Hashimoto
- Department of Respiratory Medicine, Tenri Hospital, 200 Mishima-cho Tenri-shi, Nara 632-8552, Japan
| | - Atsushi Takeda
- Department of Respiratory Medicine, Tenri Hospital, 200 Mishima-cho Tenri-shi, Nara 632-8552, Japan
| | - Naoto Maruguchi
- Department of Respiratory Medicine, Tenri Hospital, 200 Mishima-cho Tenri-shi, Nara 632-8552, Japan
| | - Ryo Yamamoto
- Department of Respiratory Medicine, Tenri Hospital, 200 Mishima-cho Tenri-shi, Nara 632-8552, Japan
| | - Kazuki Matsumura
- Department of Respiratory Medicine, Tenri Hospital, 200 Mishima-cho Tenri-shi, Nara 632-8552, Japan
| | - Satoshi Nakamura
- Department of Respiratory Medicine, Tenri Hospital, 200 Mishima-cho Tenri-shi, Nara 632-8552, Japan
| | - Satoru Terada
- Department of Respiratory Medicine, Kyoto University, Yoshida-honmachi Sakyo-ku Kyoto-shi, Kyoto 606-8501, Japan
| | - Takashi Inao
- Department of Respiratory Medicine, Shinko Hospital, 1-4-47 Wakinohama-cho Chuo-ku Kobe-shi, Hyogo 651-0072, Japan
| | - Yusuke Kaji
- Department of Respiratory Medicine, Tenri Hospital, 200 Mishima-cho Tenri-shi, Nara 632-8552, Japan
| | - Takehiro Yasuda
- Department of Respiratory Medicine, Tenri Hospital, 200 Mishima-cho Tenri-shi, Nara 632-8552, Japan
| | - Takashi Hajiro
- Department of Respiratory Medicine, Tenri Hospital, 200 Mishima-cho Tenri-shi, Nara 632-8552, Japan
| | - Eisaku Tanaka
- Department of Respiratory Medicine, Tenri Hospital, 200 Mishima-cho Tenri-shi, Nara 632-8552, Japan
| | - Yoshio Taguchi
- Department of Respiratory Medicine, Tenri Hospital, 200 Mishima-cho Tenri-shi, Nara 632-8552, Japan
| | - Satoshi Noma
- Department of Radiology, Tenri Hospital, 200 Mishima-cho Tenri-shi, Nara 632-8552, Japan
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McErlean P, Bell CG, Hewitt RJ, Busharat Z, Ogger PP, Ghai P, Albers GJ, Calamita E, Kingston S, Molyneaux PL, Beck S, Lloyd CM, Maher TM, Byrne AJ. DNA Methylome Alterations are Associated with Airway Macrophage Differentiation and Phenotype During Lung Fibrosis. Am J Respir Crit Care Med 2021; 204:954-966. [PMID: 34280322 DOI: 10.1164/rccm.202101-0004oc] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
RATIONALE Airway macrophages (AMs) are key regulators of the lung environment and are implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF), a fatal respiratory disease with no cure. However, knowledge of epigenetics of AMs in IPF are limited. METHODS We undertook DNA methylation profiling using Illumina EPIC (850k) arrays in sorted AMs from Healthy (n=14) and IPF (n=30) donors. Cell-type deconvolution was performed using reference myeloid-cell DNA methylomes. MEASUREMENTS AND MAIN RESULTS Our analysis revealed epigenetic heterogeneity was a key characteristic of IPF-AMs. DNAm 'clock' analysis indicated epigenetic alterations in IPF-AMs was not associated with accelerated ageing. In differential DNAm analysis, we identified numerous differentially methylated positions (DMPs, n=11) and regions (DMRs, n=49) between healthy and IPF AMs respectively. DMPs and DMRs encompassed genes involved in lipid (LPCAT1) and glucose (PFKFB3) metabolism and importantly, DNAm status was associated with disease severity in IPF. CONCLUSIONS Collectively, our data identify that changes in the epigenome are associated with development and function of AMs in the IPF lung.
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Affiliation(s)
- Peter McErlean
- Imperial College London, 4615, London, United Kingdom of Great Britain and Northern Ireland
| | - Christopher G Bell
- William Harvey Research Institute, 105713, London, United Kingdom of Great Britain and Northern Ireland
| | - Richard J Hewitt
- National Heart and Lung Institute, Inflammation, Repair & Development, London, United Kingdom of Great Britain and Northern Ireland
| | - Zabreen Busharat
- Imperial College London, London, United Kingdom of Great Britain and Northern Ireland
| | - Patricia P Ogger
- Imperial College London, London, United Kingdom of Great Britain and Northern Ireland
| | - Poonam Ghai
- Imperial College London, London, United Kingdom of Great Britain and Northern Ireland
| | - Gesa J Albers
- Imperial College London, London, United Kingdom of Great Britain and Northern Ireland
| | - Emily Calamita
- Imperial College London, 4615, London, United Kingdom of Great Britain and Northern Ireland
| | - Shaun Kingston
- Royal Brompton Hospital, 156726, Interstitial Lung Disease Unit, London, United Kingdom of Great Britain and Northern Ireland
| | - Philip L Molyneaux
- Imperial College London, National Heart and Lung Institute, London, United Kingdom of Great Britain and Northern Ireland
| | - Stephan Beck
- University College London, 4919, London, United Kingdom of Great Britain and Northern Ireland
| | - Clare M Lloyd
- Imperial College, Leukocyte Biology, London, United Kingdom of Great Britain and Northern Ireland
| | - Toby M Maher
- Royal Brompton Hospital, 156726, Interstitial Lung Disease Unit, London, United Kingdom of Great Britain and Northern Ireland;
| | - Adam J Byrne
- Imperial College London, London, United Kingdom of Great Britain and Northern Ireland
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Shebl E, Hamdy T. Evaluation of the efficacy of pirfenidone in progressive chronic hypersensitivity pneumonitis. THE EGYPTIAN JOURNAL OF BRONCHOLOGY 2021. [DOI: 10.1186/s43168-021-00065-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
The present data about the treatment of progressive CHP are few and largely based on observational studies and expert opinion. It is suggested that pirfenidone may slow disease progression in cases of CHP as it has some anti-inflammatory in addition to antifibrotic effects, so this study aimed to evaluate the efficacy of pirfenidone in chronic hypersensitivity pneumonitis. This study included 40 adult patients (≥ 18 years) with a diagnosis of chronic progressive hypersensitivity pneumonitis. The included patients were divided into 2 groups 20 patients in each one.
Group 1 received pirfenidone in addition to the conventional treatment
Group 2 was maintained on conventional treatment.
Forced vital capacity (FVC), 6-min walking test (6MWT), oxygen tension in the arterial blood (PaO2), and St. George’s Respiratory Questionnaire (SGRQ) were measured before and after 6 months of a pirfenidone treatment trial.
Results
The present study showed that in patients with progressive chronic hypersensitivity pneumonitis, adding pirfenidone to their conventional treatment was associated with significantly higher FVC, 6MWT, SaO2, and PaO2, and significant lower SGRQ score compared to patients who were maintained only on their conventional treatment at 6 months after treatment
Conclusion
Pirfenidone can reduce the progression of chronic hypersensitivity pneumonitis and so it can be considered a therapeutic option in its treatment.
Trial registration
ClinicalTrials.gov, NCT04675619.
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Aussedat PH, Chebib N, Ahmad K, Glerant JC, Drevet G, Grima R, Maury JM, Nasser M, Thivolet-Bejui F, Traclet J, Turquier S, Chalabreysse L, Tronc F, Cottin V. Impact of Lung Biopsy on Lung Function in Idiopathic Pulmonary Fibrosis. Respiration 2020; 99:1101-1108. [PMID: 33260187 DOI: 10.1159/000509557] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2020] [Accepted: 06/18/2020] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Video-assisted surgical lung biopsy (SLB) is performed in 10-30% of cases to establish the diagnosis of idiopathic pulmonary fibrosis (IPF). OBJECTIVES The aim of the study was to analyze the impact of SLB on lung function in patients eventually diagnosed with IPF. METHODS This is an observational, retrospective, monocentric study of all consecutive patients eventually diagnosed with IPF in multidisciplinary discussion who underwent SLB over 10 years in a specialized center. The primary end point was the variation in forced vital capacity (FVC) before and after the SLB. The secondary end points were the variations in forced expiratory volume in one second (FEV1), total lung capacity (TLC), carbon monoxide diffusion capacity (DLCO), and morbidity and mortality associated with the SLB. RESULTS In 118 patients who underwent SLB and were diagnosed with IPF, a relative decrease in FVC of 4.8% (p < 0.001) was found between measurements performed before and after the procedure. The mean FVC decrease was 156 ± 386 mL in an average period of 185 days, representing an annualized decline of 363 ± 764 mL/year. A significant decrease was also observed after SLB in FEV1, TLC, and DLCO. Complications within 30 days of SLB occurred in 14.4% of patients. Two patients (1.7%) died within 30 days, where one of them had poor lung function. Survival at 1 year was significantly poorer in patients with FVC <50% at baseline. CONCLUSION In this uncontrolled study in patients ultimately diagnosed with IPF, SLB was followed by a significant decline in FVC, which appears to be numerically greater than the average decline in the absence of treatment in the literature. Summary at a Glance: This study evaluated the change in lung function in 118 consecutive patients diagnosed with idiopathic pulmonary fibrosis by surgical lung biopsy. Forced vital capacity decreased by 156 ± 386 mL in a mean of 185 days between the last measurement before and first measurement after biopsy, representing an annualized decline of 363 ± 764 mL/year.
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Affiliation(s)
- Pierre-Henri Aussedat
- Service de pneumologie, Centre national coordinateur de référence des maladies pulmonaires rares, Groupement Hospitalier Est, Hospices civils de Lyon, UMR 754, INRAE, Université Claude Bernard Lyon 1, Lyon, France
| | - Nader Chebib
- Service de pneumologie, Centre national coordinateur de référence des maladies pulmonaires rares, Groupement Hospitalier Est, Hospices civils de Lyon, UMR 754, INRAE, Université Claude Bernard Lyon 1, Lyon, France
| | - Kais Ahmad
- Service de pneumologie, Centre national coordinateur de référence des maladies pulmonaires rares, Groupement Hospitalier Est, Hospices civils de Lyon, UMR 754, INRAE, Université Claude Bernard Lyon 1, Lyon, France
| | | | - Gabrielle Drevet
- Service de chirurgie thoracique, transplantation pulmonaire et cardio-pulmonaire, Groupement Hospitalier Est, Lyon, France
| | - Renaud Grima
- Service de chirurgie thoracique, transplantation pulmonaire et cardio-pulmonaire, Groupement Hospitalier Est, Lyon, France
| | - Jean-Michel Maury
- Service de chirurgie thoracique, transplantation pulmonaire et cardio-pulmonaire, Groupement Hospitalier Est, Lyon, France
| | - Mouhamad Nasser
- Service de pneumologie, Centre national coordinateur de référence des maladies pulmonaires rares, Groupement Hospitalier Est, Hospices civils de Lyon, UMR 754, INRAE, Université Claude Bernard Lyon 1, Lyon, France
| | | | - Julie Traclet
- Service de pneumologie, Centre national coordinateur de référence des maladies pulmonaires rares, Groupement Hospitalier Est, Hospices civils de Lyon, UMR 754, INRAE, Université Claude Bernard Lyon 1, Lyon, France
| | | | | | - François Tronc
- Service de chirurgie thoracique, transplantation pulmonaire et cardio-pulmonaire, Groupement Hospitalier Est, Lyon, France
| | - Vincent Cottin
- Service de pneumologie, Centre national coordinateur de référence des maladies pulmonaires rares, Groupement Hospitalier Est, Hospices civils de Lyon, UMR 754, INRAE, Université Claude Bernard Lyon 1, Lyon, France,
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Marcos Ribes B, Sancho-Chust JN, Talens A, Arlandis M, Herraiz P, Chiner E, Aznar T. Effectiveness and safety of pirfenidone for idiopathic pulmonary fibrosis. Eur J Hosp Pharm 2020; 27:350-354. [PMID: 33020058 PMCID: PMC7856155 DOI: 10.1136/ejhpharm-2018-001806] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2018] [Revised: 03/02/2019] [Accepted: 03/12/2019] [Indexed: 11/03/2022] Open
Abstract
OBJECTIVES To assess the long-term effectiveness of pirfenidone in idiopathic pulmonary fibrosis (IPF) treatment and to establish its adverse effects profile. METHODS Retrospective observational study in patients with IPF who initiated treatment with pirfenidone between 2011 and 2016. We collected demographic variables (age, sex); date of first and last treatment; reason for discontinuation; pulmonary function measures (forced vital capacity (FVC), carbon monoxide diffusion capacity (DLCO), and 6 min walk test (6MWT)) at treatment initiation (baseline) and at 1, 2 and 3 year follow-up; adherence to pirfenidone treatment; recorded adverse effects; and mortality. RESULTS Thirty-one patients treated with pirfenidone were included; mean±SD age was 69±8 years, 74% were men, and 59% had a smoking history. Mean baseline values were: FVC 2.43±0.66 L (61.8±12.1%); DLCO 46.1±19.4%; and 6MWT 334±125 m. Median duration of treatment was 14±13 months, and treatment was discontinued in 58% of patients. The most frequently observed adverse effects were gastrointestinal disturbances and photosensitivity. Twenty (65%) patients were evaluated at 1 year, when mean FVC was 2.41±0.86 L (64.7±20.3%); DLCO 50.8±26.8%; and 6MWT 341±139 m. At 2 years' follow-up, 11 patients (36%) who were still taking pirfenidone were evaluated. Mean FVC was 2.34±0.79 L (66.2±14.7%); DLCO 50.0±28.3%; and 6MWT 265±121 m. At 3 years, five patients were still taking the treatment. Mean FVC was 2.71±0.84 L (71.0±24.7%); DLCO 52.6±26.7%; and 6MWT 286±139 m. Nineteen per cent of patients were non-adherent to treatment. CONCLUSIONS Pirfenidone seems to be effective for long-term control of IPF despite substantial variability in response among individual patients. The most frequent adverse effects were digestive and cutaneous, prompting in some cases a reduction in dose or even discontinuation of the treatment.
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Affiliation(s)
- Borja Marcos Ribes
- Department of Pharmacy, Hospital Universitari Sant Joan d'Alacant, Sant Joan d'Alacant, Spain
| | - José N Sancho-Chust
- Department of Pneumology, Hospital Universitari Sant Joan d'Alacant, Sant Joan d'Alacant, Spain
| | - Amparo Talens
- Department of Pharmacy, Hospital Universitari Sant Joan d'Alacant, Sant Joan d'Alacant, Spain
| | - Mar Arlandis
- Department of Pneumology, Hospital Universitari Sant Joan d'Alacant, Sant Joan d'Alacant, Spain
| | - Paola Herraiz
- Department of Pharmacy, Hospital Universitari Sant Joan d'Alacant, Sant Joan d'Alacant, Spain
| | - Eusebi Chiner
- Department of Pneumology, Hospital Universitari Sant Joan d'Alacant, Sant Joan d'Alacant, Spain
| | - Teresa Aznar
- Department of Pharmacy, Hospital Universitari Sant Joan d'Alacant, Sant Joan d'Alacant, Spain
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Veit T, Barnikel M, Crispin A, Kneidinger N, Ceelen F, Arnold P, Munker D, Schmitzer M, Barton J, Schiopu S, Schiller HB, Frankenberger M, Milger K, Behr J, Neurohr C, Leuschner G. Variability of forced vital capacity in progressive interstitial lung disease: a prospective observational study. Respir Res 2020; 21:270. [PMID: 33076914 PMCID: PMC7574190 DOI: 10.1186/s12931-020-01524-8] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2020] [Accepted: 09/25/2020] [Indexed: 11/28/2022] Open
Abstract
Background Fibrotic interstitial lung disease (ILD) is often associated with poor outcomes, but has few predictors of progression. Daily home spirometry has been proposed to provide important information about the clinical course of idiopathic pulmonary disease (IPF). However, experience is limited, and home spirometry is not a routine component of patient care in ILD. Using home spirometry, we aimed to investigate the predictive potential of daily measurements of forced vital capacity (FVC) in fibrotic ILD. Methods In this prospective observational study, patients with fibrotic ILD and clinical progression were provided with home spirometers for daily measurements over 6 months. Hospital based spirometry was performed after three and 6 months. Disease progression, defined as death, lung transplantation, acute exacerbation or FVC decline > 10% relative was assessed in the cohort. Results From May 2017 until August 2018, we included 47 patients (IPF n = 20; non-IPF n = 27). Sufficient daily measurements were performed by 85.1% of the study cohort. Among these 40 patients (IPF n = 17; non-IPF n = 23), who had a mean ± SD age of 60.7 ± 11.3 years and FVC 64.7 ± 21.7% predicted (2.4 ± 0.8 L), 12 patients experienced disease progression (death: n = 2; lung transplantation: n = 3; acute exacerbation: n = 1; FVC decline > 10%: n = 6). Within the first 28 days, a group of patients had high daily variability in FVC, with 60.0% having a variation ≥5%. Patients with disease progression had significantly higher FVC variability than those in the stable group (median variability 8.6% vs. 4.8%; p = 0.002). Cox regression identified FVC variability as independently associated with disease progression when controlling for multiple confounding variables (hazard ratio: 1.203; 95% CI:1.050–1.378; p = 0.0076). Conclusions Daily home spirometry is feasible in IPF and non-IPF ILD and facilitates the identification of FVC variability, which was associated with disease progression.
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Affiliation(s)
- Tobias Veit
- Department of Internal Medicine V, Ludwig-Maximilian University Munich, Marchioninistrasse 15, 81377, Munich, Germany.,Comprehensive Pneumology Center (CPC-M), Ludwig-Maximilian University, and Helmholtz Center Munich, Member of the German Center for Lung Research (DZL), Munich, Germany
| | - Michaela Barnikel
- Department of Internal Medicine V, Ludwig-Maximilian University Munich, Marchioninistrasse 15, 81377, Munich, Germany.,Comprehensive Pneumology Center (CPC-M), Ludwig-Maximilian University, and Helmholtz Center Munich, Member of the German Center for Lung Research (DZL), Munich, Germany
| | - Alexander Crispin
- IBE - Institute for Medical Information Processing, Biometry and Epidemiology, Ludwig-Maximilian University Munich, Munich, Germany
| | - Nikolaus Kneidinger
- Department of Internal Medicine V, Ludwig-Maximilian University Munich, Marchioninistrasse 15, 81377, Munich, Germany.,Comprehensive Pneumology Center (CPC-M), Ludwig-Maximilian University, and Helmholtz Center Munich, Member of the German Center for Lung Research (DZL), Munich, Germany
| | - Felix Ceelen
- Department of Internal Medicine V, Ludwig-Maximilian University Munich, Marchioninistrasse 15, 81377, Munich, Germany.,Comprehensive Pneumology Center (CPC-M), Ludwig-Maximilian University, and Helmholtz Center Munich, Member of the German Center for Lung Research (DZL), Munich, Germany
| | - Paola Arnold
- Department of Internal Medicine V, Ludwig-Maximilian University Munich, Marchioninistrasse 15, 81377, Munich, Germany.,Comprehensive Pneumology Center (CPC-M), Ludwig-Maximilian University, and Helmholtz Center Munich, Member of the German Center for Lung Research (DZL), Munich, Germany
| | - Dieter Munker
- Department of Internal Medicine V, Ludwig-Maximilian University Munich, Marchioninistrasse 15, 81377, Munich, Germany.,Comprehensive Pneumology Center (CPC-M), Ludwig-Maximilian University, and Helmholtz Center Munich, Member of the German Center for Lung Research (DZL), Munich, Germany
| | - Magdalena Schmitzer
- Department of Internal Medicine V, Ludwig-Maximilian University Munich, Marchioninistrasse 15, 81377, Munich, Germany.,Comprehensive Pneumology Center (CPC-M), Ludwig-Maximilian University, and Helmholtz Center Munich, Member of the German Center for Lung Research (DZL), Munich, Germany
| | - Jürgen Barton
- Department of Internal Medicine V, Ludwig-Maximilian University Munich, Marchioninistrasse 15, 81377, Munich, Germany.,Comprehensive Pneumology Center (CPC-M), Ludwig-Maximilian University, and Helmholtz Center Munich, Member of the German Center for Lung Research (DZL), Munich, Germany
| | - Sanziana Schiopu
- Department of Internal Medicine V, Ludwig-Maximilian University Munich, Marchioninistrasse 15, 81377, Munich, Germany.,Comprehensive Pneumology Center (CPC-M), Ludwig-Maximilian University, and Helmholtz Center Munich, Member of the German Center for Lung Research (DZL), Munich, Germany
| | - Herbert B Schiller
- Comprehensive Pneumology Center (CPC-M), Ludwig-Maximilian University, and Helmholtz Center Munich, Member of the German Center for Lung Research (DZL), Munich, Germany
| | - Marion Frankenberger
- Comprehensive Pneumology Center (CPC-M), Ludwig-Maximilian University, and Helmholtz Center Munich, Member of the German Center for Lung Research (DZL), Munich, Germany
| | - Katrin Milger
- Department of Internal Medicine V, Ludwig-Maximilian University Munich, Marchioninistrasse 15, 81377, Munich, Germany.,Comprehensive Pneumology Center (CPC-M), Ludwig-Maximilian University, and Helmholtz Center Munich, Member of the German Center for Lung Research (DZL), Munich, Germany
| | - Jürgen Behr
- Department of Internal Medicine V, Ludwig-Maximilian University Munich, Marchioninistrasse 15, 81377, Munich, Germany.,Comprehensive Pneumology Center (CPC-M), Ludwig-Maximilian University, and Helmholtz Center Munich, Member of the German Center for Lung Research (DZL), Munich, Germany.,Department of Pneumology, Asklepios Fachkliniken Muenchen-Gauting, Academic Teaching Hospital of the University of Munich, Gauting, Germany
| | - Claus Neurohr
- Department of Pneumology and Respiratory Medicine, Hospital Schillerhoehe, Academic Teaching Hospital of the University of Tuebingen, Gerlingen, Germany
| | - Gabriela Leuschner
- Department of Internal Medicine V, Ludwig-Maximilian University Munich, Marchioninistrasse 15, 81377, Munich, Germany. .,Comprehensive Pneumology Center (CPC-M), Ludwig-Maximilian University, and Helmholtz Center Munich, Member of the German Center for Lung Research (DZL), Munich, Germany.
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Lancaster L, Goldin J, Trampisch M, Kim GH, Ilowite J, Homik L, Hotchkin DL, Kaye M, Ryerson CJ, Mogulkoc N, Conoscenti CS. Effects of Nintedanib on Quantitative Lung Fibrosis Score in Idiopathic Pulmonary Fibrosis. Open Respir Med J 2020; 14:22-31. [PMID: 33088361 PMCID: PMC7539538 DOI: 10.2174/1874306402014010022] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Revised: 06/17/2020] [Accepted: 07/02/2020] [Indexed: 12/19/2022] Open
Abstract
Background: Nintedanib slows disease progression in patients with Idiopathic Pulmonary Fibrosis (IPF) by reducing decline in Forced Vital Capacity (FVC). The effects of nintedanib on abnormalities on high-resolution computed tomography scans have not been previously studied. Objective: We conducted a Phase IIIb trial to assess the effects of nintedanib on changes in Quantitative Lung Fibrosis (QLF) score and other measures of disease progression in patients with IPF. Methods: 113 patients were randomized 1:1 to receive nintedanib 150 mg bid or placebo double-blind for ≥6 months, followed by open-label nintedanib. The primary endpoint was the relative change from baseline in QLF score (%) at month 6. Analyses were descriptive and exploratory. Results: Adjusted mean relative changes from baseline in QLF score at month 6 were 11.4% in the nintedanib group (n=42) and 14.6% in the placebo group (n=45) (difference 3.2% [95% CI: −9.2, 15.6]). Adjusted mean absolute changes from baseline in QLF score at month 6 were 0.98% and 1.33% in these groups, respectively (difference 0.35% [95% CI: −1.27, 1.96]). Adjusted mean absolute changes from baseline in FVC at month 6 were −14.2 mL and −83.2 mL in the nintedanib (n=54) and placebo (n=54) groups, respectively (difference 69.0 mL [95% CI: −8.7, 146.8]). Conclusion: Exploratory data suggest that in patients with IPF, 6 months’ treatment with nintedanib was associated with a numerically smaller degree of fibrotic change in the lungs and reduced FVC decline versus placebo. These data support previous findings that nintedanib slows the progression of IPF.
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Affiliation(s)
- Lisa Lancaster
- Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Jonathan Goldin
- Department of Radiology, University of California, Los Angeles, California, USA
| | | | - Grace Hyun Kim
- Department of Radiology, University of California, Los Angeles, California, USA.,Department of Biostatistics, University of California, Los Angeles, California, USA
| | - Jonathan Ilowite
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Hofstra North Shore-LIJ School of Medicine, New Hyde Park, New York
| | - Lawrence Homik
- Department of Respiratory Medicine and Bronchoscopy, Winnipeg Clinic, Winnipeg, Manitoba, Canada
| | - David L Hotchkin
- The Oregon Clinic, Division of Pulmonary, Critical Care & Sleep Medicine, Portland, Oregon, USA
| | - Mitchell Kaye
- Department of Pulmonary Medicine, Minnesota Lung Center, Ltd., Minneapolis, Minnesota, USA
| | - Christopher J Ryerson
- Department of Medicine & Centre for Heart Lung Innovation, University of British Columbia, Vancouver, Canada
| | - Nesrin Mogulkoc
- Department of Pulmonology, Ege University Hospital, Bornova, Izmir, Turkey
| | - Craig S Conoscenti
- Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut, USA
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Sgalla G, Larici AR, Golfi N, Calvello M, Farchione A, Del Ciello A, Varone F, Iovene B, Manfredi R, Richeldi L. Mediastinal lymph node enlargement in idiopathic pulmonary fibrosis: relationships with disease progression and pulmonary function trends. BMC Pulm Med 2020; 20:249. [PMID: 32957969 PMCID: PMC7507660 DOI: 10.1186/s12890-020-01289-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Accepted: 09/15/2020] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND AND OBJECTIVES Evidence of mediastinal Lymph Node Enlargement (LNE) on CT scan is a common finding in idiopathic pulmonary fibrosis (IPF). We sought to investigate whether the involvement of mediastinal lymph nodes is associated with accelerated disease progression, and explored the changes occurring in mediastinal lymph nodes during the radiological follow up of these patients. METHODS This retrospective study included IPF patients referred to a single ILD centre in Italy. A consensus-based assessment of mediastinal LNE on chest CT scan was performed by two thoracic radiologists. Kaplan-Meier curves and multivariate Cox proportional hazards regression were used to assess hazard ratios for mortality and disease progression (defined as categorical FVC decline ≥10%). The annualized rates of change in functional parameters for each patient were calculated using mixed linear models. RESULTS The study population consisted of 152 IPF patients, of whom 135 (89%) received antifibrotic treatment for IPF during the study follow up. Patients having evidence of 3 or more enlarged mediastinal lymph nodes on baseline CT scan showed increased rates of mortality (HR 5.03, 95% CI 1.86-13.62, p ≤ 0.001) and significant disease progression (HR 2.99, 95% CI 1.22-7.33, p = 0.17) as compared to patients without LNE, after adjusting for GAP stage. Among 62 patients with LNE who underwent a follow up CT scan of the chest and received antifibrotic treatment, 57 (92%) maintained evidence mediastinal LNE over time. CONCLUSIONS Diffuse mediastinal lymph node involvement predicts clinically meaningful functional deterioration in patients with IPF.
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Affiliation(s)
- Giacomo Sgalla
- Dipartimento Scienze Gastroenterologiche, Endocrino-Metaboliche e Nefro-Urologiche, Unità Operativa Complessa di Pneumologia, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy.
| | - Anna Rita Larici
- Dipartimento Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- Dipartimento Universitario Scienze Radiologiche ed Ematologiche, Sezione di Radiologia, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Nicoletta Golfi
- Dipartimento Scienze Gastroenterologiche, Endocrino-Metaboliche e Nefro-Urologiche, Unità Operativa Complessa di Pneumologia, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy
| | - Mariarosaria Calvello
- Dipartimento Scienze Gastroenterologiche, Endocrino-Metaboliche e Nefro-Urologiche, Unità Operativa Complessa di Pneumologia, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy
| | - Alessandra Farchione
- Dipartimento Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Annemilia Del Ciello
- Dipartimento Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Francesco Varone
- Dipartimento Scienze Gastroenterologiche, Endocrino-Metaboliche e Nefro-Urologiche, Unità Operativa Complessa di Pneumologia, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy
| | - Bruno Iovene
- Dipartimento Scienze Gastroenterologiche, Endocrino-Metaboliche e Nefro-Urologiche, Unità Operativa Complessa di Pneumologia, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy
| | - Riccardo Manfredi
- Dipartimento Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- Dipartimento Universitario Scienze Radiologiche ed Ematologiche, Sezione di Radiologia, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Luca Richeldi
- Dipartimento Scienze Gastroenterologiche, Endocrino-Metaboliche e Nefro-Urologiche, Unità Operativa Complessa di Pneumologia, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy
- Università Cattolica del Sacro Cuore, Rome, Italy
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Brown KK, Martinez FJ, Walsh SLF, Thannickal VJ, Prasse A, Schlenker-Herceg R, Goeldner RG, Clerisme-Beaty E, Tetzlaff K, Cottin V, Wells AU. The natural history of progressive fibrosing interstitial lung diseases. Eur Respir J 2020; 55:13993003.00085-2020. [PMID: 32217654 PMCID: PMC7315005 DOI: 10.1183/13993003.00085-2020] [Citation(s) in RCA: 159] [Impact Index Per Article: 31.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2020] [Accepted: 02/20/2020] [Indexed: 12/31/2022]
Abstract
We used data from the INBUILD and INPULSIS trials to investigate the natural history of progressive fibrosing interstitial lung diseases (ILDs). Subjects in the two INPULSIS trials had a clinical diagnosis of idiopathic pulmonary fibrosis (IPF) while subjects in the INBUILD trial had a progressive fibrosing ILD other than IPF and met protocol-defined criteria for ILD progression despite management. Using data from the placebo groups, we compared the rate of decline in forced vital capacity (FVC) (mL·year−1) and mortality over 52 weeks in the INBUILD trial with pooled data from the INPULSIS trials. The adjusted mean annual rate of decline in FVC in the INBUILD trial (n=331) was similar to that observed in the INPULSIS trials (n=423) (−192.9 mL·year−1 and −221.0 mL·year−1, respectively; nominal p-value=0.19). The proportion of subjects who had a relative decline in FVC >10% predicted at Week 52 was 48.9% in the INBUILD trial and 48.7% in the INPULSIS trials, and the proportion who died over 52 weeks was 5.1% in the INBUILD trial and 7.8% in the INPULSIS trials. A relative decline in FVC >10% predicted was associated with an increased risk of death in the INBUILD trial (hazard ratio 3.64) and the INPULSIS trials (hazard ratio 3.95). These findings indicate that patients with fibrosing ILDs other than IPF, who are progressing despite management, have a subsequent clinical course similar to patients with untreated IPF, with a high risk of further ILD progression and early mortality. Analyses of data from the INBUILD and INPULSIS trials suggest that progressive fibrosing ILDs other than IPF have a clinical course similar to IPF, irrespective of underlying ILD diagnosis or the fibrotic pattern on HRCThttp://bit.ly/3apG0Q5
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Affiliation(s)
- Kevin K Brown
- Dept of Medicine, National Jewish Health, Denver, CO, USA
| | | | - Simon L F Walsh
- National Heart and Lung Institute, Imperial College, London, UK
| | - Victor J Thannickal
- Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Antje Prasse
- Dept of Respiratory Medicine, MHH Hannover Medical School and Biomedical Research in Endstage and Obstructive Lung Disease (BREATH), Deutsches Zentrum für Lungenforschung (DZL), Hannover, Germany
| | | | | | | | - Kay Tetzlaff
- Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany.,Dept of Sports Medicine, University of Tübingen, Tübingen, Germany
| | - Vincent Cottin
- National Reference Centre for Rare Pulmonary Diseases, Louis Pradel Hospital, Hospices Civils de Lyon, UMR 754, Claude Bernard University Lyon 1, Lyon, France
| | - Athol U Wells
- National Heart and Lung Institute, Imperial College, London, UK.,National Institute for Health Research Respiratory Biomedical Research Unit, Royal Brompton and Harefield NHS Foundation Trust, London, UK
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Taha N, D'Amato D, Hosein K, Ranalli T, Sergiacomi G, Zompatori M, Mura M. Longitudinal functional changes with clinically significant radiographic progression in idiopathic pulmonary fibrosis: are we following the right parameters? Respir Res 2020; 21:119. [PMID: 32429952 PMCID: PMC7238541 DOI: 10.1186/s12931-020-01371-7] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Accepted: 04/23/2020] [Indexed: 02/02/2023] Open
Abstract
Background Progression of the disease in idiopathic pulmonary fibrosis (IPF) is difficult to predict, due to its variable and heterogenous course. The relationship between radiographic progression and functional decline in IPF is unclear. We sought to confirm that a simple HRCT fibrosis visual score is a reliable predictor of mortality in IPF, when longitudinally followed; and to ascertain which pulmonary functional variables best reflect clinically significant radiographic progression. Methods One-hundred-twenty-three consecutive patients with IPF from 2 centers were followed for an average of 3 years. Longitudinal changes of HRCT fibrosis scores, forced vital capacity (FVC), total lung capacity and diffusing lung capacity for carbon monoxide were considered. HRCTs were scored by 2 chest radiologists. The primary outcome was lung transplant (LTx)-free survival after the follow-up HRCT. Results During the follow-up period, 43 deaths and 11 LTx occurred. On average, the HRCT fibrosis score increased significantly, and a longitudinal increase > 7% predicted LTx-free survival significantly, with good specificity, but limited sensitivity. The correlation between radiographic and functional progression was moderately significant. HRCT progression and FVC decline predicted LTx-free survival independently and significantly, with better sensitivity, but worse specificity for a ≥ 5% decline of FVC. However, the area under the curve towards LTx-survival were only 0.61 and 0.62, respectively. Conclusions The HRCT fibrosis visual score is a reliable and responsive tool to detect clinically meaningful disease progression. Although no individual pulmonary function test closely reflects radiographic progression, a longitudinal FVC decline improves sensitivity in the detection of clinically significant disease progression. However, the accuracy of these methods remains limited, and better prognostication models need to be found.
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Affiliation(s)
- Nada Taha
- Division of Respirology, Western University, London, Ontario, Canada
| | - Dejanira D'Amato
- Diagnostica per Immagini e Radiologia Interventistica, Policlinico Tor Vergata, University of Rome "Tor Vergata", Rome, Italy
| | - Karishma Hosein
- Division of Respirology, Western University, London, Ontario, Canada
| | - Tiziana Ranalli
- Diagnostica per Immagini e Radiologia Interventistica, Policlinico Tor Vergata, University of Rome "Tor Vergata", Rome, Italy
| | - Gianluigi Sergiacomi
- Diagnostica per Immagini e Radiologia Interventistica, Policlinico Tor Vergata, University of Rome "Tor Vergata", Rome, Italy
| | - Maurizio Zompatori
- Radiologia, MultiMedica Group, I.R.C.C.S. San Giuseppe Hospital, Milan, Italy
| | - Marco Mura
- Division of Respirology, Western University, London, Ontario, Canada. .,London Health Science Centre, Victoria Hospital, 800 Commissioners Road East Room E6-203, London, Ontario, N6A 5W9, Canada.
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Safety and Efficacy of Pirfenidone in Advanced Idiopathic Pulmonary Fibrosis: A Nationwide Post-Marketing Surveillance Study in Korean Patients. Adv Ther 2020; 37:2303-2316. [PMID: 32297284 PMCID: PMC7467484 DOI: 10.1007/s12325-020-01328-8] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2020] [Indexed: 12/12/2022]
Abstract
Aim The efficacy and safety of pirfenidone have been previously demonstrated in patients with mild-to-moderate idiopathic pulmonary fibrosis (IPF). However, the effect of pirfenidone in patients with advanced IPF remains unclear. Here, we investigated the effects of pirfenidone against advanced IPF in a real-world setting. Methods A prospective nationwide post-marketing study was conducted on 258 patients from 10 Korean institutions. Patients with a predicted forced vital capacity (FVC) less than 50% or a diffusing capacity of the lung for carbon monoxide (DLco) less than 35% at baseline were classified as the advanced IPF group. Results Of 219 patients included in the analysis, the majority were male (76.3%); the mean age was 67.3 years, and the advanced group accounted for 17.8% of the patients. The median treatment duration was 298 days. Among the subjects, 86.3% experienced adverse events (AEs), of which a decreased appetite (32.4%) and a photosensitivity reaction (13.7%) were the most frequent. The incidence of AEs was similar between the advanced and non-advanced groups (92.3% vs. 85.0%, respectively; p = 0.229). Although the overall discontinuation rate was higher in the advanced group than in the non-advanced group (74.4% vs. 50.0%, respectively; p = 0.006), the percentages of the patients who discontinued treatment as a result of AEs were similar in both groups (20.5% vs. 23.3%, respectively; p = 0.704). In all patients, the rates of decline in the predicted FVC and DLco over 48 weeks were − 4.3 ± 1.3% and − 4.4 ± 1.7%, respectively. There was no between-group difference in the rate of lung function decline. Conclusions Pirfenidone used for the treatment of patients with IPF in a real-world setting was well tolerated, with an acceptable safety profile and a consistent therapeutic effect, regardless of the disease severity. Trial Registration ClinicalTrials.gov NCT03761082; the trial was retrospectively registered on December 3, 2018. Electronic supplementary material The online version of this article (10.1007/s12325-020-01328-8) contains supplementary material, which is available to authorized users.
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45
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Kishaba T. Clinical staging of idiopathic pulmonary fibrosis. Respir Investig 2020; 58:81-82. [PMID: 31892464 DOI: 10.1016/j.resinv.2019.12.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Revised: 11/14/2019] [Accepted: 12/03/2019] [Indexed: 06/10/2023]
Affiliation(s)
- Tomoo Kishaba
- Department of Respiratory Medicine, Okinawa Chubu Hospital, Miyazato 281, Uruma, Okinawa, Japan.
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Higo H, Miyahara N, Taniguchi A, Senoo S, Itano J, Watanabe H, Oda N, Kayatani H, Ichikawa H, Shibayama T, Kajimoto K, Tanimoto Y, Kanehiro A, Maeda Y, Kiura K. Deterioration of high-resolution computed tomography findings predicts disease progression after initial decline in forced vital capacity in idiopathic pulmonary fibrosis patients treated with pirfenidone. Respir Investig 2020; 58:185-189. [PMID: 32102769 DOI: 10.1016/j.resinv.2019.12.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2019] [Revised: 11/23/2019] [Accepted: 12/10/2019] [Indexed: 11/24/2022]
Abstract
BACKGROUND Pirfenidone suppresses the decline of forced vital capacity (FVC) in patients with idiopathic pulmonary fibrosis (IPF). However, IPF progresses in some patients despite treatment. We analyzed patients with meaningful FVC declines during pirfenidone treatment and explored the factors predictive of disease progression after FVC decline. METHODS This study was a retrospective, multicenter, observational study conducted by the Okayama Respiratory Disease Study Group. We defined initial decline in %FVC as 5% or greater per 6-month period during pirfenidone treatment. IPF patients who were treated with pirfenidone and experienced an initial decline from December 2008 to September 2017 were enrolled. RESULTS We analyzed 21 patients with IPF. After the initial decline, 4 (19.0%) patients showed improvement in disease, 11 (52.4%) showed stable disease, and 6 (28.6%) showed progressive disease. There was no significant correlation between %FVC reduction on initial decline and subsequent %FVC change (p = 0.475). Deterioration of high-resolution computed tomography (HRCT) findings on initial decline was observed significantly more often in the progressive versus improved/stable disease groups (100% vs 20.0%, p = 0.009). CONCLUSIONS We revealed that deterioration of HRCT findings may predict disease progression after the initial decline in %FVC in IPF patients treated with pirfenidone.
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Affiliation(s)
- Hisao Higo
- Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
| | - Nobuaki Miyahara
- Department of Allergy and Respiratory Medicine, Okayama University Hospital, Okayama, Japan; Department of Medical Technology, Okayama University Graduate School of Health Sciences, Okayama, Japan.
| | - Akihiko Taniguchi
- Department of Allergy and Respiratory Medicine, Okayama University Hospital, Okayama, Japan.
| | - Satoru Senoo
- Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
| | - Junko Itano
- Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
| | - Hiromi Watanabe
- Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
| | - Naohiro Oda
- Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
| | - Hiroe Kayatani
- Department of Respiratory Medicine, National Hospital Organization Okayama Medical Center, Okayama, Japan.
| | - Hirohisa Ichikawa
- Department of Respiratory Medicine, KKR Takamatsu Hospital, Takamatsu, Japan.
| | - Takuo Shibayama
- Department of Respiratory Medicine, National Hospital Organization Okayama Medical Center, Okayama, Japan.
| | - Kazuhiro Kajimoto
- Department of Respiratory Medicine, Kobe Red Cross Hospital, Kobe, Japan.
| | - Yasushi Tanimoto
- Department of Respiratory Medicine, National Hospital Organization Minami-Okayama Medical Center, Okayama, Japan.
| | - Arihiko Kanehiro
- Department of Allergy and Respiratory Medicine, Okayama Rosai Hospital, Okayama, Japan.
| | - Yoshinobu Maeda
- Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
| | - Katsuyuki Kiura
- Department of Allergy and Respiratory Medicine, Okayama University Hospital, Okayama, Japan.
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Maher TM, Corte TJ, Fischer A, Kreuter M, Lederer DJ, Molina-Molina M, Axmann J, Kirchgaessler KU, Samara K, Gilberg F, Cottin V. Pirfenidone in patients with unclassifiable progressive fibrosing interstitial lung disease: a double-blind, randomised, placebo-controlled, phase 2 trial. THE LANCET RESPIRATORY MEDICINE 2020; 8:147-157. [DOI: 10.1016/s2213-2600(19)30341-8] [Citation(s) in RCA: 417] [Impact Index Per Article: 83.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/16/2019] [Revised: 08/30/2019] [Accepted: 09/02/2019] [Indexed: 01/03/2023]
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Kreuter M, Wuyts WA, Wijsenbeek M, Bajwah S, Maher TM, Stowasser S, Male N, Stansen W, Schoof N, Orsatti L, Swigris J. Health-related quality of life and symptoms in patients with IPF treated with nintedanib: analyses of patient-reported outcomes from the INPULSIS® trials. Respir Res 2020; 21:36. [PMID: 32000772 PMCID: PMC6990488 DOI: 10.1186/s12931-020-1298-1] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2019] [Accepted: 01/16/2020] [Indexed: 02/07/2023] Open
Abstract
Background In the Phase III INPULSIS® trials, treatment of patients with idiopathic pulmonary fibrosis (IPF) with nintedanib significantly reduced the annual rate of decline in forced vital capacity (FVC) versus placebo, consistent with slowing disease progression. However, nintedanib was not associated with a benefit in health-related quality of life (HRQoL) assessed using the St George’s respiratory questionnaire (SGRQ). We aimed to further examine the impact of IPF progression on HRQoL and symptoms, and to explore the effect of nintedanib on HRQoL in patients from the INPULSIS® trials stratified by clinical factors associated with disease progression. Methods Patient-reported outcome (PRO) data from the INPULSIS® trials were included in three post hoc analyses. Two analyses used the pooled data set to examine PRO changes from baseline to week 52 according to 1) decline in FVC and 2) occurrence of acute exacerbations. In the third analysis, patients were stratified based on clinical indicators of disease progression (gender, age and physiology [GAP] stage; FVC % predicted; diffusing capacity of the lung for carbon monoxide [DLCO] % predicted; composite physiologic index [CPI]; and SGRQ total score) at baseline; median change from baseline was measured at 52 weeks and treatment groups were compared using the Wilcoxon two-sample test. Results Data from 1061 patients (638 nintedanib, 423 placebo) were analyzed. Greater categorical decline from baseline in FVC % predicted over 52 weeks was associated with significant worsening of HRQoL and symptoms across all PRO measures. Acute exacerbations were associated with deterioration in HRQoL and worsened symptoms. In general, patients with advanced disease at baseline (defined as GAP II/III, FVC ≤ 80%, DLCO ≤ 40%, CPI > 45, or SGRQ > 40) experienced greater deterioration in PROs than patients with less-advanced disease. Among patients with advanced disease, compared with placebo, nintedanib slowed deterioration in several PROs; benefit was most apparent on the SGRQ (total and activity scores). Conclusions In patients with advanced IPF, compared with placebo, nintedanib slowed deterioration in HRQoL and symptoms as assessed by several PROs. HRQoL measures have a higher responsiveness to change in advanced disease and may lack sensitivity to capture change in patients with less-advanced IPF.
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Affiliation(s)
- Michael Kreuter
- Center for Interstitial and Rare Lung Diseases, Pneumology, Thoraxklinik, Heidelberg University Hospital, Röntgenstraße 1, 69126, Heidelberg, Germany. .,German Center for Lung Research, Gießen, Germany.
| | - Wim A Wuyts
- Unit for Interstitial Lung Diseases, Department of Pulmonary Medicine, University Hospitals Leuven, Leuven, Belgium
| | | | | | - Toby M Maher
- National Heart and Lung Institute, Imperial College, London, UK.,Interstitial Lung Disease Unit, Royal Brompton Hospital, London, UK
| | - Susanne Stowasser
- Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany
| | - Natalia Male
- Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany
| | - Wibke Stansen
- Boehringer Ingelheim GmbH & Co KG, Ingelheim am Rhein, Germany
| | - Nils Schoof
- Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany
| | - Leticia Orsatti
- Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany
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Mori Y, Nishikiori H, Chiba H, Yamada G, Kuronuma K, Takahashi H. Respiratory reactance in forced oscillation technique reflects disease stage and predicts lung physiology deterioration in idiopathic pulmonary fibrosis. Respir Physiol Neurobiol 2020; 275:103386. [PMID: 31931177 DOI: 10.1016/j.resp.2020.103386] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2019] [Accepted: 01/08/2020] [Indexed: 01/21/2023]
Abstract
BACKGROUND Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease. Although pulmonary function test (PFT) is useful for evaluating the progression of IPF, obtaining adequate results in advanced cases can be challenging. Conversely, the forced oscillation technique (FOT) can be noninvasively performed, even in patients with severely deteriorated lung function. In this study, the usefulness of FOT for the evaluation of IPF disease status was investigated. METHODS We analyzed the PFT and FOT data of 97 patients with IPF. RESULTS The respiratory reactance (Xrs) components of FOT, especially in the inspiratory phase, correlated with the PFT values. Patients with advanced disease had significantly lower reactance at 5 Hz (X5), higher resonant frequency (Fres) and low-frequency reactance area (ALX). The longitudinal deterioration of Xrs was also observed. Moreover, X5 in the inspiratory phase predicted subsequent lung capacity deterioration. CONCLUSION The Xrs components of FOT, especially in the inspiratory phase, reflected restrictive ventilatory impairment and disease severity in patients with IPF.
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Affiliation(s)
- Yuki Mori
- Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, South-1 West-16, Chuo-ku, Sapporo, Hokkaido 060-8543, Japan.
| | - Hirotaka Nishikiori
- Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, South-1 West-16, Chuo-ku, Sapporo, Hokkaido 060-8543, Japan.
| | - Hirofumi Chiba
- Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, South-1 West-16, Chuo-ku, Sapporo, Hokkaido 060-8543, Japan.
| | - Gen Yamada
- Department of Respiratory Medicine, Teine Keijinkai Hospital, 1-12 Maeda, Teineku, Sapporo, Hokkaido 006-8555, Japan.
| | - Koji Kuronuma
- Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, South-1 West-16, Chuo-ku, Sapporo, Hokkaido 060-8543, Japan.
| | - Hiroki Takahashi
- Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, South-1 West-16, Chuo-ku, Sapporo, Hokkaido 060-8543, Japan.
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Asai Y, Chiba H, Nishikiori H, Kamekura R, Yabe H, Kondo S, Miyajima S, Shigehara K, Ichimiya S, Takahashi H. Aberrant populations of circulating T follicular helper cells and regulatory B cells underlying idiopathic pulmonary fibrosis. Respir Res 2019; 20:244. [PMID: 31694639 PMCID: PMC6836348 DOI: 10.1186/s12931-019-1216-6] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2019] [Accepted: 10/15/2019] [Indexed: 12/17/2022] Open
Abstract
Background T follicular helper (Tfh) cells have been identified as a new category of helper T cells, which express CXCR5 on their surface and induce the production of antigen-specific antibodies. Many investigations have found morbid proliferation and/or activation of Tfh cells in systemic autoimmune and allergic diseases. It is also known that Tfh cells are regulated by regulatory B (Breg) cells in the deteriorating such diseases. Recently, CXCL13, a ligand of CXCR5, has been reported to increase in the peripheral blood and lungs of patients with idiopathic pulmonary fibrosis (IPF). This study aimed to investigate the involvement of Tfh cells and Breg cells in IPF. Methods Peripheral blood samples were obtained from 18 patients with IPF. We isolated heparinized peripheral blood mononuclear cells and investigated the proportions of Breg cells, Tfh cells, PD-1+ICOS+ Tfh cells (activated form of Tfh cells), and the Tfh-cell subsets by flow cytometry. These cell profiles were compared with those of 21 healthy controls. Furthermore, we investigated the correlations between profiles of lymphocytes and lung physiology. Results The median proportions of Tfh cells per total CD4+ T cells and of PD-1+ICOS+ proportion of Tfh cells per total Tfh cells was significantly more in the IPF patients (20.4 and 5.2%, respectively) compared with healthy controls (15.4 and 2.1%, respectively; p = 0.042 and p = 0.004, respectively). The proportion of Tfh2 cells per total Tfh cells was significantly higher and the proportion of Tfh17 was smaller in the IPF patients than healthy controls. The percentage of Breg cells to total B cells was significantly decreased in the IPF patients (median, 8.5%) compared with that in the controls (median, 19.7%; p < 0.001). The proportion of Breg cells was positively correlated with the annual relative change in diffusing capacity of the lungs for carbon monoxide in the IPF patients (r = 0.583, p = 0.018). Conclusion Proliferation and activation of Tfh cells and a decrease in Breg cells were observed in the peripheral blood of patients with IPF. The profile of the Tfh-cell subset also changed. Specific humoral immunity aberration would likely underlie complicated pathophysiology of IPF.
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Affiliation(s)
- Yuichiro Asai
- Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, 1-37, South 1-West 16, Chuo-ku, Sapporo, Hokkaido, 060-8543, Japan
| | - Hirofumi Chiba
- Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, 1-37, South 1-West 16, Chuo-ku, Sapporo, Hokkaido, 060-8543, Japan.
| | - Hirotaka Nishikiori
- Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, 1-37, South 1-West 16, Chuo-ku, Sapporo, Hokkaido, 060-8543, Japan
| | - Ryuta Kamekura
- Department of Human Immunology, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.,Department of Otolaryngology, Sapporo Medical University School of Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Hayato Yabe
- Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, 1-37, South 1-West 16, Chuo-ku, Sapporo, Hokkaido, 060-8543, Japan.,Department of Human Immunology, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Shun Kondo
- Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, 1-37, South 1-West 16, Chuo-ku, Sapporo, Hokkaido, 060-8543, Japan
| | - Satsuki Miyajima
- Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, 1-37, South 1-West 16, Chuo-ku, Sapporo, Hokkaido, 060-8543, Japan
| | - Katsunori Shigehara
- Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, 1-37, South 1-West 16, Chuo-ku, Sapporo, Hokkaido, 060-8543, Japan.,Department of Human Immunology, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Shingo Ichimiya
- Department of Human Immunology, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Hiroki Takahashi
- Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, 1-37, South 1-West 16, Chuo-ku, Sapporo, Hokkaido, 060-8543, Japan
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