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Kette S, Reccardini N, Salton F, Confalonieri P, Andrisano A, Chianese M, De Nes A, Maggisano M, Galantino A, Nicolosi S, Mari M, Salotti A, Angoni D, Chernovsky M, Hughes M, Confalonieri M, Mondini L, Ruaro B. The Impact of Comorbidities on the Discontinuation of Antifibrotic Therapy in Patients with Idiopathic Pulmonary Fibrosis. Pharmaceuticals (Basel) 2025; 18:411. [PMID: 40143187 PMCID: PMC11944575 DOI: 10.3390/ph18030411] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2025] [Revised: 03/02/2025] [Accepted: 03/12/2025] [Indexed: 03/28/2025] Open
Abstract
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease of unknown aetiology. Evidence on the progression of idiopathic pulmonary fibrosis (IPF) following the introduction of antifibrotic therapies still indicates a generally poor prognosis. IPF is associated with both respiratory and non-respiratory comorbidities, which can worsen symptoms and impact overall survival. Background/Objectives: The study aimed to investigate the effect of these comorbidities on the early and permanent discontinuation of pirfenidone or nintedanib in IPF patients. Methods: In this single-centre retrospective study, 101 patients diagnosed with IPF according to ATS/ERS/JRS/ALAT guidelines were treated with AFT. Clinical data were collected at 12 months prior to and up to 24 months following treatment initiation, including age, gender, smoking history, and the presence of respiratory and non-respiratory comorbidities. Results: The data showed that 21 patients (20.8%) discontinued treatment within the first 12 months. Additionally, pre-treatment comorbidities were not statistically correlated with the suspension of antifibrotic treatment. Among the overall cohort, 77 patients (76.2%) had at least one comorbidity and 27 (26.7%) had three or more comorbidities. Notably, 24 (23.8%) had respiratory comorbidities, while 75 (74.3%) had non-respiratory comorbidities. Conclusions: This real-life study emphasises the complexities involved in managing IPF, particularly regarding adherence to treatment when significant comorbidities are present. The evidence suggests that in patients with IPF, pre-treatment respiratory or non-respiratory conditions do not affect AFT discontinuation.
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Affiliation(s)
- Stefano Kette
- Pulmonology Unit, Department of Medical Surgical and Health Sciences, University of Trieste, Hospital of Cattinara, 34149 Trieste, Italy
| | - Nicolò Reccardini
- Pulmonology Unit, Department of Medical Surgical and Health Sciences, University of Trieste, Hospital of Cattinara, 34149 Trieste, Italy
| | - Francesco Salton
- Pulmonology Unit, Department of Medical Surgical and Health Sciences, University of Trieste, Hospital of Cattinara, 34149 Trieste, Italy
| | - Paola Confalonieri
- Pulmonology Unit, Department of Medical Surgical and Health Sciences, University of Trieste, Hospital of Cattinara, 34149 Trieste, Italy
| | - Alessia Andrisano
- Pulmonology Unit, Department of Cardio-Thoracic Surgery, Health Integrated Agency of Friuli Venezia Giulia, 33100 Udine, Italy
| | - Maria Chianese
- Pulmonology Unit, Department of Medical Surgical and Health Sciences, University of Trieste, Hospital of Cattinara, 34149 Trieste, Italy
| | - Anna De Nes
- Pulmonology Unit, Department of Medical Surgical and Health Sciences, University of Trieste, Hospital of Cattinara, 34149 Trieste, Italy
| | - Marta Maggisano
- Pulmonology Unit, Department of Medical Surgical and Health Sciences, University of Trieste, Hospital of Cattinara, 34149 Trieste, Italy
| | - Alessandra Galantino
- Pulmonology Unit, Department of Medical Surgical and Health Sciences, University of Trieste, Hospital of Cattinara, 34149 Trieste, Italy
| | - Salvatore Nicolosi
- Pulmonology Unit, Department of Medical Surgical and Health Sciences, University of Trieste, Hospital of Cattinara, 34149 Trieste, Italy
| | - Marco Mari
- Pulmonology Unit, Department of Medical Surgical and Health Sciences, University of Trieste, Hospital of Cattinara, 34149 Trieste, Italy
| | - Andrea Salotti
- Pulmonology Unit, Department of Medical Surgical and Health Sciences, University of Trieste, Hospital of Cattinara, 34149 Trieste, Italy
| | - Darina Angoni
- Pulmonology Unit, Department of Medical Surgical and Health Sciences, University of Trieste, Hospital of Cattinara, 34149 Trieste, Italy
| | - Maria Chernovsky
- Pulmonology Unit, Department of Medical Surgical and Health Sciences, University of Trieste, Hospital of Cattinara, 34149 Trieste, Italy
| | - Michael Hughes
- Division of Musculoskeletal and Dermatological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester & Salford Royal NHS Foundation Trust, Manchester M6 8HD, UK
| | - Marco Confalonieri
- Pulmonology Unit, Department of Medical Surgical and Health Sciences, University of Trieste, Hospital of Cattinara, 34149 Trieste, Italy
| | - Lucrezia Mondini
- Pulmonology Unit, Department of Medical Surgical and Health Sciences, University of Trieste, Hospital of Cattinara, 34149 Trieste, Italy
| | - Barbara Ruaro
- Pulmonology Unit, Department of Medical Surgical and Health Sciences, University of Trieste, Hospital of Cattinara, 34149 Trieste, Italy
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Joerns EK, Ghebranious MA, Adams TN, Makris UE. Evaluation of comorbidity burden on disease progression and mortality in patients with interstitial pneumonia with autoimmune features: A retrospective cohort study. PLoS One 2025; 20:e0316762. [PMID: 39903746 PMCID: PMC11793734 DOI: 10.1371/journal.pone.0316762] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Accepted: 12/16/2024] [Indexed: 02/06/2025] Open
Abstract
BACKGROUND Interstitial pneumonia with autoimmune features (IPAF) is a subset of interstitial lung disease that manifests with features of autoimmunity while not meeting classification criteria for a defined rheumatic disease. Comorbidity burden is an important prognostic indicator in various rheumatic and interstitial lung diseases, but few studies have commented on comorbidities in this population. This study was conducted to evaluate the association of individual comorbidities, the Charlson Comorbidity Index (CCI), and the Rheumatic Disease Comorbidity Index (RDCI) with lung disease progression and transplant/mortality outcomes in patients with IPAF. METHODS In a retrospective study, we evaluated the prevalence and severity of comorbidities in an institutional cohort of patients with IPAF. Using Cox regression, we correlated the association of individual comorbidities and comorbidity indices with time to lung disease progression (relative forced vital capacity decline of 10% or more) and with time to lung transplant/death. We compared the performance of CCI and RDCI in predicting outcomes. RESULTS History of cerebrovascular accident (CVA) or cardiovascular disease (CVD), moderate-severe chronic kidney disease, and fracture was associated with a faster onset of lung disease progression, while a history of gastroesophageal reflux was protective. History of CVA/CVD, diabetes mellitus, and lymphoma were associated with a faster onset of lung transplant/death. Both CCI and RDCI were associated with shorter time to lung disease progression and lung transplant/death in unadjusted analyses. However, only CCI was associated with shorter time to lung transplant/death in analyses adjusted for age, sex, pulmonary function, and radiographic pattern of lung lesion. CONCLUSIONS CCI and RDCI may be useful tools in assessing prognosis in patients with IPAF in terms of both lung disease progression and mortality. Prospective studies are needed to further evaluate the performance of CCI and RDCI and the impact of optimizing comorbid conditions that may mitigate poor outcomes among patients with IPAF.
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Affiliation(s)
| | - Michelle A. Ghebranious
- McGovern Medical School at University of Texas Houston, Houston, Texas, United States of America
| | - Traci N. Adams
- University of Texas Southwestern Medical Center, Dallas, Texas, United States of America
| | - Una E. Makris
- University of Texas Southwestern Medical Center, Dallas, Texas, United States of America
- Veterans Administration North Texas Health Care System, Dallas, Texas, United States of America
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Morgan AD, Massen GM, Whittaker HR, Stewart I, Jenkins G, George PM, Quint JK. Commonly prescribed medications and risk of pneumonia and all-cause mortality in people with idiopathic pulmonary fibrosis: a UK population-based cohort study. Pneumonia (Nathan) 2025; 17:2. [PMID: 39856755 PMCID: PMC11762896 DOI: 10.1186/s41479-024-00155-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Accepted: 10/16/2024] [Indexed: 01/27/2025] Open
Abstract
BACKGROUND A growing body of evidence suggests that prolonged use of inhaled corticosteroids (ICS) and proton pump inhibitors (PPIs) is associated with increased risks of pneumonia. A substantial proportion of people with idiopathic pulmonary fibrosis (IPF) are prescribed PPIs or ICS to treat common comorbidities, giving rise to concerns that use of these medications may be associated with potential harms in this patient population. METHODS We used UK Clinical Practice Research Datalink (CPRD) Aurum primary care data linked to national mortality and hospital admissions data to create a cohort of people diagnosed with IPF on or after 1 January 2010. Patients were assigned to one of three exposure categories according to their prescribing history in the 12 months prior to IPF diagnosis as follows: "regular" users (≥ 4 prescriptions), "irregular" users (1-3 prescriptions) and "non-users" (no prescriptions). We explored the association between PPI/ICS prescription and pneumonia hospitalisation and all-cause mortality using multinomial Cox regression models. RESULTS A total of 17,105 people met our study inclusion criteria; 62.6% were male and 15.9% were current smokers. Median age at IPF diagnosis was 76.7 years (IQR: 69.6-82.7). 19.9% were regularly prescribed PPIs, and 16.0% ICS, prior to IPF diagnosis. Regular prescribing of PPIs and ICS was positively associated with hospitalisation for pneumonia; the adjusted HR for pneumonia hospitalisation comparing regular PPI users with non-users was 1.14 (95%CI: 1.04-1.24); for regular ICS users the corresponding HR was 1.40 (95%CI: 1.25-1.55). We also observed a small increased risk for all-cause mortality in the "regular ICS user" group compared with the "non-user" control group (HRadj = 1.19, 1.06-1.33). We found no evidence of an association between PPI prescribing and all-cause mortality. CONCLUSION Prolonged prescription of medications used to treat common comorbidities in IPF may be associated with increased risks for severe respiratory infections. These findings point to a need to adopt an adequate risk-benefit balance approach to the prescribing of ICS-containing inhalers and PPIs in people with IPF without evidence of comorbidities, especially older patients and/or those with more advanced disease in whom respiratory infections are more likely to result in poorer outcomes.
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Affiliation(s)
- Ann D Morgan
- School of Public Health, Imperial College London, London, UK.
| | | | | | - Iain Stewart
- National Heart and Lung Institute, Imperial College London, London, UK
| | - Gisli Jenkins
- National Heart and Lung Institute, Imperial College London, London, UK
| | - Peter M George
- National Heart and Lung Institute, Imperial College London, London, UK
- Interstitial Lung Disease Unit, Royal Brompton Hospital and Harefield NHS Foundation Trust, London, UK
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Spagnolo P, Tonelli R, Mura M, Reisman W, Sotiropoulou V, Tzouvelekis A. Investigational gene expression inhibitors for the treatment of idiopathic pulmonary fibrosis. Expert Opin Investig Drugs 2025; 34:61-80. [PMID: 39916340 DOI: 10.1080/13543784.2025.2462592] [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: 07/15/2024] [Accepted: 01/31/2025] [Indexed: 02/12/2025]
Abstract
INTRODUCTION Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrosing interstitial lung disease of unknown cause that occurs primarily in older adults and is associated with poor quality of life and substantial healthcare utilization. IPF has a dismal prognosis. Indeed, first-line therapy, which includes nintedanib and pirfenidone, does not stop disease progression and is often associated with tolerability issues. Therefore, there remains a high medical need for more efficacious and better tolerated treatments. AREAS COVERED Gene therapy is a relatively unexplored field of research in IPF that has the potential to mitigate a range of profibrotic pathways by introducing genetic material into cells. Here, we summarize and critically discuss publications that have explored the safety and efficacy of gene therapy in experimentally-induced pulmonary fibrosis in animals, as clinical studies in humans have not been published yet. EXPERT OPINION The application of gene therapy in pulmonary fibrosis requires further investigation to address several technical and biological hurdles, improve vectors' design, drug delivery, and target selection, mitigate off-target effects and develop markers of gene penetration into target cells. Long-term clinical data are needed to bring gene therapy in IPF one step closer to practice.
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Affiliation(s)
- Paolo Spagnolo
- Respiratory Disease Unit, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Padova, Italy
| | - Roberto Tonelli
- Respiratory Disease Unit, Department of Medical and Surgical Sciences, University Hospital of Modena and Reggio Emilia, Modena, Italy
- Laboratory of Cell Therapies and Respiratory Medicine, Department of Medical and Surgical Sciences for Children and Adults, University Hospital of Modena, Modena, Italy
| | - Marco Mura
- Division of Respirology, Western University, London, Ontario, Canada
| | - William Reisman
- Division of Respirology, Western University, London, Ontario, Canada
| | | | - Argyrios Tzouvelekis
- Department of Respiratory Medicine, University Hospital of Patras, Patras, Greece
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Luppi F, Manfredi A, Faverio P, Franco G, Salvarani C, Bendstrup E, Sebastiani M. Treatment of acute exacerbation in interstitial lung disease secondary to autoimmune rheumatic diseases: More questions than answers. Autoimmun Rev 2024; 23:103668. [PMID: 39413945 DOI: 10.1016/j.autrev.2024.103668] [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: 08/01/2024] [Revised: 10/12/2024] [Accepted: 10/12/2024] [Indexed: 10/18/2024]
Abstract
Interstitial lung disease (ILD) is a relevant cause of morbidity and mortality in patients with autoimmune rheumatic diseases (ARDs). In the last years, an acute exacerbation (AE) - defined as an acute, clinically significant respiratory deterioration characterized by evidence of new widespread alveolar abnormality - has been reported to occur in virtually all ILD types, including ARD-ILD. The aim of this review is to describe the available and investigational treatments in patients affected by AE-ARD-ILD in light of the very low quality of evidence available. Currently, management consists of efforts to identify reversible triggers of respiratory decline, such as drugs effective in ARDs and infections, including opportunistic infections, together with supportive treatments. AE-ILD, AE-ARD-ILD and acute respiratory distress syndrome share histopathologically similar findings of diffuse alveolar damage in most cases. Identification of triggers and risk factors might contribute to early diagnosis and treatment of AE-ILD, before the alveolar damage becomes irreversible. In patients with acute respiratory distress syndrome, the role of steroids and immunosuppressants remains controversial. Also, many uncertainties characterize the management of AE-ARD-ILD because of the lack of evidence and of an unquestionable effective therapy. At this time, no effective evidence-based therapeutic strategies for AE-ARD-ILD are available. In clinical practice, AE-ARD-ILD is often empirically treated with high-dose systemic steroids and antibiotics, with or without immunosuppressive drugs. Randomized controlled trials are needed to better understand the efficacy of current and future drugs for the treatment of this clinical relevant condition.
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Affiliation(s)
- Fabrizio Luppi
- Respiratory Diseases Unit, University of Milano-Bicocca, Fondazione IRCCS "San Gerardo dei Tintori", Monza, Italy.
| | - Andreina Manfredi
- Rheumatology Unit, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria Policlinico di Modena, Modena, Italy
| | - Paola Faverio
- Respiratory Diseases Unit, University of Milano-Bicocca, Fondazione IRCCS "San Gerardo dei Tintori", Monza, Italy
| | - Giovanni Franco
- Respiratory Diseases Unit, University of Milano-Bicocca, Fondazione IRCCS "San Gerardo dei Tintori", Monza, Italy
| | - Carlo Salvarani
- Rheumatology Unit, Dipartimento Medicina Interna e Specialità Mediche, Azienda Unità Sanitaria Locale di Reggio Emilia-Istituto di Ricerca e Cura a Carattere Scientifico, University of Modena and Reggio Emilia, Reggio Emilia, Italy
| | - Elisabeth Bendstrup
- Center for Rare Lung Disease, Department of Respiratory Medicine and Allergy, Aarhus University Hospital, Aarhus, Denmark
| | - Marco Sebastiani
- Rheumatology Unit, Azienda Unità Sanitaria Locale di Piacenza; Department of Medicine and Surgery, University of Parma, Italy
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Hung CF, Raghu G. Treatment of acute exacerbations of interstitial lung diseases with corticosteroids: Evidence? Respirology 2024; 29:747-750. [PMID: 38961640 PMCID: PMC11805574 DOI: 10.1111/resp.14788] [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: 06/18/2024] [Accepted: 06/24/2024] [Indexed: 07/05/2024]
Abstract
See related article
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Affiliation(s)
- Chi F. Hung
- Department of Medicine, Center for Interstitial Lung Diseases, University of Washington, Seattle, WA, USA
- Department of Laboratory Medicine and Pathology, Division of Pulmonary, Critical Care, and Sleep Medicine, University of Washington, Seattle, WA, USA
| | - Ganesh Raghu
- Department of Medicine, Center for Interstitial Lung Diseases, University of Washington, Seattle, WA, USA
- Department of Laboratory Medicine and Pathology, Division of Pulmonary, Critical Care, and Sleep Medicine, University of Washington, Seattle, WA, USA
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Knobler R, Geroldinger-Simić M, Kreuter A, Hunzelmann N, Moinzadeh P, Rongioletti F, Denton CP, Mouthon L, Cutolo M, Smith V, Gabrielli A, Bagot M, Olesen AB, Foeldvari I, Jalili A, Kähäri V, Kárpáti S, Kofoed K, Olszewska M, Panelius J, Quaglino P, Seneschal J, Sticherling M, Sunderkötter C, Tanew A, Wolf P, Worm M, Skrok A, Rudnicka L, Krieg T. Consensus statement on the diagnosis and treatment of sclerosing diseases of the skin, Part 1: Localized scleroderma, systemic sclerosis and overlap syndromes. J Eur Acad Dermatol Venereol 2024; 38:1251-1280. [PMID: 38456584 DOI: 10.1111/jdv.19912] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Accepted: 01/26/2024] [Indexed: 03/09/2024]
Abstract
The term 'sclerosing diseases of the skin' comprises specific dermatological entities, which have fibrotic changes of the skin in common. These diseases mostly manifest in different clinical subtypes according to cutaneous and extracutaneous involvement and can sometimes be difficult to distinguish from each other. The present consensus provides an update to the 2017 European Dermatology Forum Guidelines, focusing on characteristic clinical and histopathological features, diagnostic scores and the serum autoantibodies most useful for differential diagnosis. In addition, updated strategies for the first- and advanced-line therapy of sclerosing skin diseases are addressed in detail. Part 1 of this consensus provides clinicians with an overview of the diagnosis and treatment of localized scleroderma (morphea), and systemic sclerosis including overlap syndromes.
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Affiliation(s)
- R Knobler
- Department of Dermatology, Medical University of Vienna, Vienna, Austria
| | - M Geroldinger-Simić
- Department of Dermatology, Ordensklinikum Linz Elisabethinen, Linz, Austria
- Faculty of Medicine, Johannes Kepler University, Linz, Austria
| | - A Kreuter
- Department of Dermatology, Venereology and Allergology, HELIOS St. Elisabeth Klinik Oberhausen, University Witten-Herdecke, Oberhausen, Germany
| | - N Hunzelmann
- Department of Dermatology and Venereology, University of Cologne, Cologne, Germany
| | - P Moinzadeh
- Department of Dermatology and Venereology, University of Cologne, Cologne, Germany
| | - F Rongioletti
- Vita Salute University IRCSS San Raffaele Hospital, Milan, Italy
| | - C P Denton
- Center for Rheumatology, Royal Free and University College Medical School, London, UK
| | - L Mouthon
- Service de Médecine Interne, Centre de Référence Maladies Auto-Immunes et Systémiques Rares d'Ile de France, APHP-CUP, Hôpital Cochin, Paris, France
- Institut Cochin, Université de Paris Cité, Paris, France
| | - M Cutolo
- Laboratories for Experimental Rheumatology and Academic Division of Clinical Rheumatology, Department of Internal Medicine DiMI, University Medical School of Genoa, IRCCS San Martino Genoa, Genoa, Italy
| | - V Smith
- Department of Internal Medicine, Ghent University, Ghent, Belgium
- Department of Rheumatology, Ghent University Hospital, Ghent, Belgium
- Unit for Molecular Immunology and Inflammation, VIB Inflammation Research Center (IRC), Ghent, Belgium
| | - A Gabrielli
- Fondazione di Medicina Molecolare e Terapia Cellulare, Università Politecnica delle Marche, Ancona, Italy
| | - M Bagot
- Department of Dermatology, Hôpital Saint-Louis, Université Paris Cité, Paris, France
| | - A B Olesen
- Department of Dermatology, University Hospital of Aarhus, Aarhus, Denmark
| | - I Foeldvari
- Hamburg Centre for Pediatric and Adolescent Rheumatology, Schön Klinik Hamburg Eilbek, Hamburg, Germany
| | - A Jalili
- Dermatology & Skin Care Clinic, Buochs, Switzerland
| | - V Kähäri
- Department of Dermatology and Venereology, University of Turku and Turku University Hospital, Turku, Finland
| | - S Kárpáti
- Department of Dermatology, Venereology and Dermatooncology, Semmelweis University, Budapest, Hungary
| | - K Kofoed
- The Skin Clinic, Copenhagen, Denmark
| | - M Olszewska
- Department of Dermatology, Medical University of Warsaw, Warsaw, Poland
| | - J Panelius
- Department of Dermatology and Allergology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - P Quaglino
- Department of Medical Sciences, Dermatologic Clinic, University of Turin, Turin, Italy
| | - J Seneschal
- Department of Dermatology and Pediatric Dermatology, National Centre for Rare Skin Disorders, Hôpital Saint-Andre, University of Bordeaux, CNRS, Immuno CencEpT, UMR 5164, Bordeaux, France
| | - M Sticherling
- Department of Dermatology, Universitätsklinikum Erlangen, Erlangen, Germany
| | - C Sunderkötter
- Department of Dermatology and Venereology, University Hospital Halle, Halle (Saale), Germany
| | - A Tanew
- Private Practice, Vienna, Austria
| | - P Wolf
- Department of Dermatology, Medical University of Graz, Graz, Austria
| | - M Worm
- Division of Allergy and Immunology, Department of Dermatology, Venereology and Allergology, University Hospital Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - A Skrok
- Department of Dermatology, Medical University of Warsaw, Warsaw, Poland
| | - L Rudnicka
- Department of Dermatology, Medical University of Warsaw, Warsaw, Poland
| | - T Krieg
- Department of Dermatology and Venereology, and Translational Matrix Biology, University of Cologne, Cologne, Germany
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Fernandez AM, Chan WW. Update on extraesophageal manifestations of gastroesophageal reflux. Curr Opin Gastroenterol 2024; 40:305-313. [PMID: 38662405 DOI: 10.1097/mog.0000000000001037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/26/2024]
Abstract
PURPOSE OF REVIEW Symptoms/complications related to extraesophageal reflux (EER) are increasingly prevalent presentations and pose significant challenges for clinicians. We summarize and discuss clinical advances and developments in pathophysiology, testing and treatment algorithms of upper/lower airway manifestations of EER. RECENT FINDINGS Growing evidence supports likely multifactorial causes of laryngeal symptoms, including EER, oropharyngeal pathologies, allergic conditions, and cognitive-affective processes (brain-larynx interaction). Diagnostic paradigm for laryngopharyngeal reflux (LPR) is shifting towards a personalized approach with noninvasive strategies/prediction tools to risk-stratify patients for upfront reflux testing over empiric acid suppression trials. Management should be multipronged to include antireflux therapies and treatments targeting other causes. Lower airway complications of EER may result in lung dysfunction and poor transplant outcomes. Esophageal symptoms are often absent and routine esophageal/reflux testing to guide timely antireflux therapies may lead to improved outcomes. Modalities that leverage impedance technology may be important, given the potential role of nonacidic reflux. Novel impedance-based metrics such as mean nocturnal baseline impedance and postreflux swallow-induced peristaltic wave index may provide adjunctive diagnostic values. SUMMARY Standardized approach to diagnosis/management of EER should include multidisciplinary care teams and consider different phenotypes, nonreflux contributors, and the complex gut-airway relationships. Prompt antireflux therapies after careful candidate selection may improve outcomes of these airway complications.
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Affiliation(s)
- Annel M Fernandez
- Department of Medicine, Brigham and Women's Hospital
- Harvard Medical School
| | - Walter W Chan
- Department of Medicine, Brigham and Women's Hospital
- Harvard Medical School
- Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, Boston, Massachusetts, USA
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Enokido T, Hiraishi Y, Jo T, Urushiyama H, Saito A, Noguchi S, Hosoki K, Ishii T, Miyashita N, Fukuda K, Matsuki R, Minatsuki C, Shimamoto T, Kage H, Yamamichi N, Matsuzaki H. Endoscopic reflux esophagitis and decline in pulmonary function in nonsmokers: A retrospective cohort study. Respir Investig 2024; 62:599-605. [PMID: 38696950 DOI: 10.1016/j.resinv.2024.04.017] [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: 11/10/2023] [Revised: 03/31/2024] [Accepted: 04/18/2024] [Indexed: 05/04/2024]
Abstract
BACKGROUND The association between reflux esophagitis and pulmonary function remains controversial. Thus, evaluating the relationship between endoscopic reflux esophagitis and changes in pulmonary function over time in a nonsmoking population is an important clinical issue. METHODS In this single-center retrospective cohort study, a medical examination database at Kameda Medical Center Makuhari was employed to identify nonsmokers who underwent upper gastrointestinal endoscopy and spirometry in 2010 and were followed up in 2015. Gastroenterologists carefully double-checked the diagnosis of reflux esophagitis. Multiple linear regression analyses were performed to compare the decline in the percentage of predicted vital capacity (%VC), forced vital capacity (%FVC), and forced expiratory volume in 1 s (%FEV1) between participants with reflux esophagitis and those without. Furthermore, using multivariable logistic regression analyses, we evaluated the factors associated with rapid decline in %VC, %FVC, and %FEV1, which is defined as a decrease of >10% in each parameter over the 5-year observation period. RESULTS We identified 3098 eligible subjects, including 72 and 44 participants who had a Los Angeles classification grade A and B-C (severe) reflux esophagitis in 2010, respectively. The decline in %VC was significantly larger in the participants with severe reflux esophagitis than in the control subjects (standardized coefficient, -0.037; 95% confidence interval, -0.071 to -0.004). Moreover, reflux esophagitis was significantly associated with a rapid decline in %VC and %FVC but not in %FEV1 (P for trend: 0.009, 0.009, and 0.276, respectively). CONCLUSIONS Severe reflux esophagitis among nonsmokers had clinical disadvantages in terms of a decline in %VC.
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Affiliation(s)
- Takayoshi Enokido
- Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan
| | - Yoshihisa Hiraishi
- Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
| | - Taisuke Jo
- Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan; Department of Health Services Research, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan
| | - Hirokazu Urushiyama
- Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan
| | - Akira Saito
- Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan
| | - Satoshi Noguchi
- Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan
| | - Keisuke Hosoki
- Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan
| | - Takashi Ishii
- Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan; Division for Health Service Promotion, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan
| | - Naoya Miyashita
- Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan
| | - Kensuke Fukuda
- Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan
| | - Rei Matsuki
- Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan
| | - Chihiro Minatsuki
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan
| | - Takeshi Shimamoto
- Kameda Medical Center Makuhari, CD-2, 1-3, Nakase, Mihama-ku, Chiba, 261-0023, Japan
| | - Hidenori Kage
- Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan
| | - Nobutake Yamamichi
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan; Center for Epidemiology and Preventive Medicine, The University of Tokyo Hospital, Tokyo, 113-0033, Japan
| | - Hirotaka Matsuzaki
- Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan; Center for Epidemiology and Preventive Medicine, The University of Tokyo Hospital, Tokyo, 113-0033, Japan
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10
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Quinlivan A, Neuen D, Hansen D, Stevens W, Ross L, Ferdowsi N, Proudman SM, Walker JG, Sahhar J, Ngian GS, Apostolopoulos D, Host LV, Major G, Basnayake C, Morrisroe K, Nikpour M. The impact of gastroesophageal reflux disease and its treatment on interstitial lung disease outcomes. Arthritis Res Ther 2024; 26:124. [PMID: 38918847 PMCID: PMC11197189 DOI: 10.1186/s13075-024-03355-0] [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: 04/16/2024] [Accepted: 06/14/2024] [Indexed: 06/27/2024] Open
Abstract
BACKGROUND To determine the relationship between gastroesophageal reflux disease (GORD) and its treatment and interstitial lung disease in patients with systemic sclerosis (SSc). METHODS SSc patients from the Australian Scleroderma Cohort Study (ASCS) were included. GORD was defined as self-reported GORD symptoms, therapy with a proton pump inhibitor (PPI) or histamine 2 receptor antagonist (H2RA) and/or the presence of reflux oesophagitis diagnosed endoscopically. The impact of GORD and its treatment on ILD features (including severity and time to ILD development) and survival was evaluated. RESULTS GORD was a common manifestation affecting 1539/1632 (94%) of SSc patients. GORD affected 450/469 (96%) of those with SSc-ILD cohort. In SSc-ILD, there was no relationship between the presence of GORD or its treatment and time to ILD development or ILD severity. However, GORD treatment was associated with improved survival in those with ILD (p = 0.002). Combination therapy with both a PPI and a H2RA was associated with a greater survival benefit than single agent therapy with PPI alone (HR 0.3 vs 0.5 p < 0.050 respectively). CONCLUSION GORD is a common SSc disease manifestation. While the presence or treatment of GORD does not influence the development or severity of ILD, aggressive GORD treatment, in particular with a combination of PPI and H2RA, is associated with improved survival in those with SSc-ILD.
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Affiliation(s)
- A Quinlivan
- Department of Rheumatology, St Vincent's Hospital (Melbourne), 35 Victoria Parade, Fitzroy, Victoria, 3065, Australia
- Department of Medicine, The University of Melbourne at St Vincent's Hospital (Melbourne), 41 Victoria Parade, Fitzroy, Victoria, 3065, Australia
| | - D Neuen
- Department of Rheumatology, Liverpool Hospital, Corner of Elizabeth St and Goulburn St, Liverpool, 2170 NSW, Australia
| | - D Hansen
- Department of Rheumatology, St Vincent's Hospital (Melbourne), 35 Victoria Parade, Fitzroy, Victoria, 3065, Australia
| | - W Stevens
- Department of Rheumatology, St Vincent's Hospital (Melbourne), 35 Victoria Parade, Fitzroy, Victoria, 3065, Australia
| | - L Ross
- Department of Rheumatology, St Vincent's Hospital (Melbourne), 35 Victoria Parade, Fitzroy, Victoria, 3065, Australia
- Department of Medicine, The University of Melbourne at St Vincent's Hospital (Melbourne), 41 Victoria Parade, Fitzroy, Victoria, 3065, Australia
| | - N Ferdowsi
- Department of Rheumatology, St Vincent's Hospital (Melbourne), 35 Victoria Parade, Fitzroy, Victoria, 3065, Australia
- Department of Medicine, The University of Melbourne at St Vincent's Hospital (Melbourne), 41 Victoria Parade, Fitzroy, Victoria, 3065, Australia
| | - S M Proudman
- Rheumatology Unit, Royal Adelaide Hospital (Adelaide), Port Rd, Adelaide, South Australia, 5000, Australia
- Discipline of Medicine, University of Adelaide (Adelaide), North Terrace, Adelaide, South Australia, 5000, Australia
| | - J G Walker
- Rheumatology Unit, Royal Adelaide Hospital (Adelaide), Port Rd, Adelaide, South Australia, 5000, Australia
- Rheumatology Unit, Flinders Medical Centre (Adelaide), Flinders Drive, Bedford Park, South Australia, 5042, Australia
- Immunology, Allergy and Arthritis Department, Flinders University (Adelaide), Sturt Road, Bedford Park, South Australia, 5042, Australia
| | - J Sahhar
- Department of Rheumatology, Monash Health (Melbourne), 246 Clayton Rd, ClaytonVictoria, 3168, Australia
- Department of Medicine, Monash University (Melbourne), Wellington Rd, ClaytonVictoria, 3168, Australia
| | - G-S Ngian
- Department of Rheumatology, Monash Health (Melbourne), 246 Clayton Rd, ClaytonVictoria, 3168, Australia
- Department of Medicine, Monash University (Melbourne), Wellington Rd, ClaytonVictoria, 3168, Australia
| | - D Apostolopoulos
- Department of Rheumatology, Monash Health (Melbourne), 246 Clayton Rd, ClaytonVictoria, 3168, Australia
- School of Clinical Sciences, Monash University Faculty of Medicine Nursing and Health Sciences, Clayton, VIC, Australia
| | - L V Host
- Department of Rheumatology, Fiona Stanley Hospital (Perth), 11 Robin Warren Drive, Murdoch, WA, 6150, Australia
| | - G Major
- Department of Rheumatology, Royal Newcastle Centre, John Hunter Hospital, 2 Lookout Rd, New Lambton Heights, New South Wales, 2305, Australia
- Faculty of Medicine, University of Newcastle, University Drive, Callaghan, New South Wales, 2308, Australia
| | - C Basnayake
- Department of Medicine, The University of Melbourne at St Vincent's Hospital (Melbourne), 41 Victoria Parade, Fitzroy, Victoria, 3065, Australia
- Department of Gastroenterology, St Vincent's Hospital (Melbourne), 35 Victoria Parade, Fitzroy, Victoria, 3065, Australia
| | - K Morrisroe
- Department of Rheumatology, St Vincent's Hospital (Melbourne), 35 Victoria Parade, Fitzroy, Victoria, 3065, Australia
- Department of Medicine, The University of Melbourne at St Vincent's Hospital (Melbourne), 41 Victoria Parade, Fitzroy, Victoria, 3065, Australia
| | - M Nikpour
- Department of Rheumatology, St Vincent's Hospital (Melbourne), 35 Victoria Parade, Fitzroy, Victoria, 3065, Australia.
- Department of Medicine, The University of Melbourne at St Vincent's Hospital (Melbourne), 41 Victoria Parade, Fitzroy, Victoria, 3065, Australia.
- School of Public Health, University of Sydney, Edward Ford Building, Fisher Road, Camperdown, NSW, 2006, Australia.
- Department of Rheumatology, Royal Prince Alfred Hospital, 50 Missenden Road, Camperdown, NSW, 2050, Australia.
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11
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Naqvi M, Hannah J, Lawrence A, Myall K, West A, Chaudhuri N. Antifibrotic therapy in progressive pulmonary fibrosis: a review of recent advances. Expert Rev Respir Med 2024; 18:397-407. [PMID: 39039699 DOI: 10.1080/17476348.2024.2375420] [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: 03/27/2024] [Accepted: 06/28/2024] [Indexed: 07/24/2024]
Abstract
INTRODUCTION Progressive pulmonary fibrosis (PPF) is a manifestation of a heterogenous group of underlying interstitial lung disease (ILD) diagnoses, defined as non-idiopathic pulmonary fibrosis (IPF) progressive fibrotic ILD meeting at least two of the following criteria in the previous 12 months: worsening respiratory symptoms, absolute decline in forced vital capacity (FVC) more than or equal to 5% and/or absolute decline in diffusing capacity for carbon monoxide (DLCO) more than or equal to 10% and/or radiological progression. AREAS COVERED The authors subjectively reviewed a synthesis of literature from PubMed to identify recent advances in the diagnosis and characterisation of PPF, treatment recommendations, and management challenges. This review provides a comprehensive summary of recent advances and highlights future directions for the diagnosis, management, and treatment of PPF. EXPERT OPINION Recent advances in defining the criteria for PPF diagnosis and licensing of treatment are likely to support further characterisation of the PPF patient population and improve our understanding of prevalence. The diagnosis of PPF remains challenging with the need for a specialised ILD multidisciplinary team (MDT) approach. The evidence base supports the use of immunomodulatory therapy to treat inflammatory ILDs and antifibrotic therapy where PPF develops. Treatment needs to be tailored to the specific underlying disease and determined on a case-by-case basis.
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Affiliation(s)
- Marium Naqvi
- Guy's and St Thomas' NHS Trust, Guy's Hospital, London, UK
| | - Jennifer Hannah
- Department of Rheumatology, Kings' College Hospitals NHS Trust, Orpington Hospital, Orpington, UK
| | | | - Katherine Myall
- Department of Respiratory Medicine, King's College London, London, UK
| | - Alex West
- Guy's and St Thomas' NHS Trust, Guy's Hospital, London, UK
| | - Nazia Chaudhuri
- Department of Health and Life Sciences, School of Medicine, Ulster University, Derry-Londonderry, UK
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12
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Bae S, Loloci G, Lee DY, Jang HJ, Jeong J, Choi WI. Association between Antacid Exposure and Risk of Interstitial Lung Diseases. Tuberc Respir Dis (Seoul) 2024; 87:185-193. [PMID: 38111098 PMCID: PMC10990614 DOI: 10.4046/trd.2023.0093] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Revised: 10/07/2023] [Accepted: 12/17/2023] [Indexed: 12/20/2023] Open
Abstract
BACKGROUND The mechanisms leading to lung fibrosis are still under investigation. This study aimed to demonstrate whether antacids could prevent the development of interstitial lung disease (ILD). METHODS This population-based longitudinal cohort study was conducted between January 2006 and December 2010 in South Korea. Eligible subjects were ≥40 years of age, exposed to proton pump inhibitors (PPI)±histamine-2 receptor antagonists (H-2 blockers) or H-2 blockers only, and had no history of ILD between 2004 and 2005. Exposure to antacids was defined as the administration of either PPI or H-2 receptor antagonists for >14 days, whereas underexposure was defined as antacid treatment administered for less than 14 days. Newly developed ILDs, including idiopathic pulmonary fibrosis (IPF), were counted during the 5-year observation period. The association between antacid exposure and ILD development was evaluated using adjusted Cox regression models with variables, such as age, sex, smoking history, and comorbidities. RESULTS The incidence rates of ILD with/without antacid use were 43.2 and 33.8/100,000 person-years, respectively and those of IPF were 14.9 and 22.9/100,000 person-years, respectively. In multivariable analysis, exposure to antacid before the diagnosis of ILD was independently associated with a reduced development of ILD (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.45 to 0.71; p<0.001), while antacid exposure was not associated with development of IPF (HR, 0.88; 95% CI, 0.72 to 1.09; p=0.06). CONCLUSION Antacid exposure may be independently associated with a decreased risk of ILD development.
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Affiliation(s)
- Soohyun Bae
- Department of Internal Medicine, Myongji Hospital, Hanyang University College of Medicine, Goyang, Republic of Korea
| | - Gjustina Loloci
- Department of Internal Medicine, Myongji Hospital, Hanyang University College of Medicine, Goyang, Republic of Korea
- German Hospital of Tirana, Tirana, Albania
| | - Dong Yoon Lee
- Department of Internal Medicine, Myongji Hospital, Hanyang University College of Medicine, Goyang, Republic of Korea
| | - Hye Jin Jang
- Department of Internal Medicine, Myongji Hospital, Hanyang University College of Medicine, Goyang, Republic of Korea
| | - Jihyeon Jeong
- Department of Statistics, Kyungpook National University, Daegu, Republic of Korea
| | - Won-Il Choi
- Department of Internal Medicine, Myongji Hospital, Hanyang University College of Medicine, Goyang, Republic of Korea
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13
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Iftikhar S, Alhaddad SF, Paulsingh CN, Riaz MF, Garg G, Umeano L, Hamid P. The Role of Proton Pump Inhibitors in the Realm of Idiopathic Pulmonary Fibrosis and its Associated Comorbidities: A Systematic Review. Cureus 2024; 16:e55980. [PMID: 38606271 PMCID: PMC11008918 DOI: 10.7759/cureus.55980] [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: 02/03/2024] [Accepted: 03/10/2024] [Indexed: 04/13/2024] Open
Abstract
As the global incidence of idiopathic pulmonary fibrosis (IPF) is on the rise, there is a need for better diagnostic criteria, better treatment options, early and appropriate diagnosis, adequate care, and a multidisciplinary approach to the management of patients. This systematic review explores the role of proton pump inhibitors (PPIs) in IPF and answers the question, "Does proton pump inhibitor improve only the prognosis of gastroesophageal associated idiopathic pulmonary fibrosis or for other types of idiopathic pulmonary fibrosis too?" We used PubMed (PMC) and Google Scholar for data collection for this systematic review and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for conducting this review. After in-depth literature screening and quality appraisal, 12 articles were selected for this systematic review. On the one hand, the efficacy of PPI therapy is supported by research such as the CAPACITY and ASCEND trials, a pilot randomized control trial (RCT) investigating the role of omeprazole in IPF and a bidirectional two-sample Mendelian randomization (MR) study, respectively. On the other hand, a systematic review and meta-analysis on antacid and antireflux surgery in IPF negate these results and show no statistical significance. Questions regarding the efficacy of PPI therapy must be dealt with in an adequately powered multicenter and double-blinded randomized control trial. The anti-inflammatory properties of antacids can serve as the cornerstone for future trials. In the following systematic review, antacid, antireflux therapy, omeprazole, and proton pump therapy are synonymous with stomach acid suppression therapy.
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Affiliation(s)
- Sadaf Iftikhar
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Sarah F Alhaddad
- Pediatrics, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Christian N Paulsingh
- Pathology, St. George's University School of Medicine, St. Georges, GRD
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Muhammad Faisal Riaz
- Internal Medicine, Rawalpindi Medical University, Rawalpindi, PAK
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Gourav Garg
- Orthopaedics, Kings Mill Hospital, Sutton in Ashfield, GBR
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Lotanna Umeano
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Pousette Hamid
- Neurology, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
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14
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Sun D, Ye Q. Mendelian randomization analysis suggests no causal influence of gastroesophageal reflux disease on the susceptibility and prognosis of idiopathic pulmonary fibrosis. BMC Pulm Med 2023; 23:517. [PMID: 38129814 PMCID: PMC10740234 DOI: 10.1186/s12890-023-02788-8] [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: 07/26/2023] [Accepted: 11/26/2023] [Indexed: 12/23/2023] Open
Abstract
BACKGROUND The relationship between gastroesophageal reflux disease (GERD) and the susceptibility as well as the prognosis of idiopathic pulmonary fibrosis (IPF) has been previously suggested, with the potential confounding factor of smoking not adequately addressed. In light of this, we conducted a Mendelian randomization (MR) study to investigate the causal effects of GERD on the susceptibility and prognosis of IPF while excluding smoking. METHODS We chose GERD as the exposure variable and employed genome-wide association data to examine its association with susceptibility, forced vital capacity (FVC), diffusing capacity of the lung for carbon monoxide (DLco), and transplant-free survival (TFS) in patients with IPF as the outcome variables. MR analyses were performed using the inverse variance weighted (IVW) method, and sensitivity analyses were conducted using the MR-PRESSO outlier test, Cochran's Q test, MR-Egger intercept test, and leave-one-out sensitivity analysis. Additionally, to mitigate the potential effects of smoking on our MR estimates, we conducted a multivariable MR (MVMR) analysis by adjusting for smoking. RESULTS The univariable MR analysis demonstrated no causal effect of GERD on FVC (βIVW = 26.63, SE = 48.23, P = 0.581), DLco (βIVW = 0.12, SE = 0.12, P = 0.319), and TFS (HRIVW = 0.87, 95% CI = 0.56 to 1.35, P = 0.533) in patients with IPF. Furthermore, sensitivity analysis revealed no evidence of heterogeneity, horizontal pleiotropy, or outlier single nucleotide polymorphisms. The MVMR analysis showed no causal effect of GERD on susceptibility to IPF after adjusting for smoking (ORIVW = 1.30, 95% CI = 0.93 to 1.68, P = 0.071). These findings were consistent in the replication cohort. CONCLUSIONS The link between GERD and its potential impact on susceptibility to IPF may not be of a direct causal nature and could be influenced by factors such as smoking. Our findings did not reveal any evidence of a causal relationship between GERD and the FVC, DLco, and TFS of patients with IPF.
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Affiliation(s)
- Di Sun
- Department of Occupational Medicine and Toxicology, Clinical Center for Interstitial Lung Diseases, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, China
| | - Qiao Ye
- Department of Occupational Medicine and Toxicology, Clinical Center for Interstitial Lung Diseases, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, China.
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15
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Newton CA, Noth I, Raghu G. Gastro-oesophageal reflux and idiopathic pulmonary fibrosis: sorting the chicken and the egg by genetic link. Eur Respir J 2023; 62:2301878. [PMID: 38128953 PMCID: PMC10990001 DOI: 10.1183/13993003.01878-2023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Accepted: 11/08/2023] [Indexed: 12/23/2023]
Affiliation(s)
- Chad A Newton
- Division of Pulmonary and Critical Care Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Imre Noth
- Division of Pulmonary and Critical Care Medicine, University of Virginia, Charlottesville, VA, USA
| | - Ganesh Raghu
- Center for Interstitial Lung Diseases, University of Washington Medical Center, Seattle, WA, USA
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16
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Yu Z, Xu C, Song B, Zhang S, Chen C, Li C, Zhang S. Tissue fibrosis induced by radiotherapy: current understanding of the molecular mechanisms, diagnosis and therapeutic advances. J Transl Med 2023; 21:708. [PMID: 37814303 PMCID: PMC10563272 DOI: 10.1186/s12967-023-04554-0] [Citation(s) in RCA: 43] [Impact Index Per Article: 21.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2023] [Accepted: 09/22/2023] [Indexed: 10/11/2023] Open
Abstract
Cancer remains the leading cause of death around the world. In cancer treatment, over 50% of cancer patients receive radiotherapy alone or in multimodal combinations with other therapies. One of the adverse consequences after radiation exposure is the occurrence of radiation-induced tissue fibrosis (RIF), which is characterized by the abnormal activation of myofibroblasts and the excessive accumulation of extracellular matrix. This phenotype can manifest in multiple organs, such as lung, skin, liver and kidney. In-depth studies on the mechanisms of radiation-induced fibrosis have shown that a variety of extracellular signals such as immune cells and abnormal release of cytokines, and intracellular signals such as cGAS/STING, oxidative stress response, metabolic reprogramming and proteasome pathway activation are involved in the activation of myofibroblasts. Tissue fibrosis is extremely harmful to patients' health and requires early diagnosis. In addition to traditional serum markers, histologic and imaging tests, the diagnostic potential of nuclear medicine techniques is emerging. Anti-inflammatory and antioxidant therapies are the traditional treatments for radiation-induced fibrosis. Recently, some promising therapeutic strategies have emerged, such as stem cell therapy and targeted therapies. However, incomplete knowledge of the mechanisms hinders the treatment of this disease. Here, we also highlight the potential mechanistic, diagnostic and therapeutic directions of radiation-induced fibrosis.
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Affiliation(s)
- Zuxiang Yu
- Laboratory of Radiation Medicine, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, 610041, China
| | - Chaoyu Xu
- Laboratory of Radiation Medicine, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, 610041, China
| | - Bin Song
- Laboratory of Radiation Medicine, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, 610041, China
- The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, Chengdu, 610051, China
- NHC Key Laboratory of Nuclear Technology Medical Transformation (Mianyang Central Hospital), Mianyang, 621099, China
| | - Shihao Zhang
- Laboratory of Radiation Medicine, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, 610041, China
| | - Chong Chen
- Department of Gastroenterology, The First People's Hospital of Xuzhou, Xuzhou Municipal Hospital Affiliated to Xuzhou Medical University, Xuzhou, 221200, China
| | - Changlong Li
- Laboratory of Radiation Medicine, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, 610041, China.
- Department of Molecular Biology and Biochemistry, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, China.
| | - Shuyu Zhang
- Laboratory of Radiation Medicine, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, 610041, China.
- The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, Chengdu, 610051, China.
- NHC Key Laboratory of Nuclear Technology Medical Transformation (Mianyang Central Hospital), Mianyang, 621099, China.
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17
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Aoki A, Hara Y, Fujii H, Murohashi K, Nagasawa R, Tagami Y, Enomoto T, Matsumoto Y, Masuda M, Watanabe K, Horita N, Kobayashi N, Kudo M, Ogura T, Kaneko T. The clinical impact of comorbidities among patients with idiopathic pulmonary fibrosis undergoing anti-fibrotic treatment: A multicenter retrospective observational study. PLoS One 2023; 18:e0291489. [PMID: 37725604 PMCID: PMC10508598 DOI: 10.1371/journal.pone.0291489] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Accepted: 08/31/2023] [Indexed: 09/21/2023] Open
Abstract
BACKGROUND Among patients with idiopathic pulmonary fibrosis (IPF), few studies have investigated the clinical impact of anti-fibrotic treatment (AFT) with and without comorbidities. The aim of the study was to determine whether Charlson Comorbidity Index score (CCIS) can predict the efficacy of AFT in patients with IPF. METHODS We retrospectively assessed data extracted from the medical records of IPF patients who received anti-fibrotic agents between 2009 and 2019. The collected data included age, sex, CCIS, pulmonary function test, high-resolution computed tomography (HRCT) pattern, gender/age/physiology (GAP) score, and 3-year IPF-related events defined as the first acute exacerbation or death within 3 years after starting AFT. RESULTS We assessed 130 patients (median age, 74 years) who received nintedanib (n = 70) or pirfenidone (n = 60). Median duration of AFT was 425 days. Patients were categorized into high (≥ 3 points) and low (≤ 2 points) CCIS groups. There was no significant difference between the groups in terms of age, sex, duration of AFT, GAP score, or incidence of usual interstitial pneumonia pattern on HRCT except percentage predicted diffusion capacity of lung for carbon monoxide. Also, significant difference was not seen between the groups for 3-year IPF-related events (P = 0.75). Especially, in the low CCIS group but not the high CCIS group, the longer duration of AFT had better disease outcome. CONCLUSION In the present study, we could not show any relation between CCIS and IPF disease outcomes in patients undergoing AFT, though the longer duration of AFT might be beneficial for IPF outcomes among patients with low CCIS.
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Affiliation(s)
- Ayako Aoki
- Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Yu Hara
- Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Hiroaki Fujii
- Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
- Department of Pulmonology, Yokohama Minami Kyousai Hospital, Yokohama, Japan
| | - Kota Murohashi
- Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Ryo Nagasawa
- Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan
| | - Yoichi Tagami
- Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Tatsuji Enomoto
- Department of Respiratory Medicine, Ofuna Chuo Hospital, Kamakura, Japan
| | - Yutaka Matsumoto
- Department of Respiratory Medicine, Yamato Municipal Hospital, Yamato, Japan
| | - Makoto Masuda
- Department of Respiratory Medicine, Ofuna Chuo Hospital, Kamakura, Japan
- Department of Respiratory Medicine, Fujisawa City Hospital, Fujisawa, Japan
| | - Keisuke Watanabe
- Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Nobuyuki Horita
- Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Nobuaki Kobayashi
- Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Makoto Kudo
- Respiratory Disease Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Takashi Ogura
- Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan
| | - Takeshi Kaneko
- Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
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18
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Elkhatib WY, Helgeson SA, Baig HZ, Lee AS. Impact of concomitant gastroesophageal reflux disease symptomology on prognosis and pulmonary function of chronic hypersensitivity pneumonitis. Lung India 2023; 40:406-411. [PMID: 37787352 PMCID: PMC10553774 DOI: 10.4103/lungindia.lungindia_107_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Revised: 06/07/2023] [Accepted: 06/17/2023] [Indexed: 10/04/2023] Open
Abstract
Background and Objectives Comorbid risk factors in chronic hypersensitivity pneumonitis (CHP) are poorly characterised. Gastroesophageal reflux disease (GERD) is linked to interstitial lung diseases like idiopathic pulmonary fibrosis (IPF), but its association and treatment in CHP is less understood. This study aims to understand the role and prevalence of GERD in CHP, plus the effect of GERD treatment on lung function and mortality. Methods A tertiary referral centre panel was retrospectively reviewed for 214 patients diagnosed with CHP based on clinical history, bronchoalveolar lavage fluid analysis, imaging and histopathology. GERD diagnostic criteria included symptomology, acid suppressive therapy use and diagnostic testing. CHP patients with GERD (n = 89) and without GERD (n = 125) were compared via descriptive statistical analysis. Pulmonary function, GERD diagnosis plus treatment and other comorbidities were evaluated against CHP outcomes. Results Respective differences between diagnosis and study termination dates in the GERD population versus without GERD for functional vital capacity (FVC) were - 1 L vs - 2.5 L, diffusing capacity of the lungs for carbon monoxide (DLCO) were - 2 mL/min/mmHg versus - 1 mL/min/mmHg, per cent alive at the time of study 88% versus 81%, median date of survival 574.5 versus 850 and supplemental oxygen requirement 41% versus 37%. GERD prevalence was higher in CHP patients relative to the general population. No statistical significance was found between survival curves, oxygen requirement, smoking history, FVC, or DLCO. Conclusions GERD could be a harmful comorbidity in CHP though may not necessarily affect survival or functional outcomes. This aligns with previous IPF studies, though remains controversial. Further research is needed regarding this association and treatment benefit.
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Affiliation(s)
| | - Scott A. Helgeson
- Department of Pulmonary and Critical Care Medicine, Mayo Clinic Florida, USA
| | - Hassan Z. Baig
- Department of Pulmonary and Critical Care Medicine, Mayo Clinic Florida, USA
| | - Augustine S. Lee
- Department of Pulmonary and Critical Care Medicine, Mayo Clinic Florida, USA
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19
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Kreuter M, Bonella F, Blank N, Riemekasten G, Müller-Ladner U, Henes J, Siegert E, Günther C, Kötter I, Pfeiffer C, Schmalzing M, Zeidler G, Korsten P, Susok L, Juche A, Worm M, Jandova I, Ehrchen J, Sunderkötter C, Keyßer G, Ramming A, Schmeiser T, Kreuter A, Kuhr K, Lorenz HM, Moinzadeh P, Hunzelmann N. Anti-acid therapy in SSc-associated interstitial lung disease: long-term outcomes from the German Network for Systemic Sclerosis. Rheumatology (Oxford) 2023; 62:3067-3074. [PMID: 36708008 PMCID: PMC10473195 DOI: 10.1093/rheumatology/kead023] [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: 04/21/2022] [Revised: 12/20/2022] [Accepted: 01/06/2023] [Indexed: 01/29/2023] Open
Abstract
OBJECTIVES Gastroesophageal reflux disease (GERD) occurs frequently in patients with SSc. We investigated whether the presence of GERD and/or the use of anti-acid therapy, specifically proton-pump inhibitors (PPIs), are associated with long-term outcomes, especially in SSc-associated interstitial lung disease (SSc-ILD). METHODS We retrospectively analysed patients with SSc and SSc-ILD from the German Network for Systemic Sclerosis (DNSS) database (2003 onwards). Kaplan-Meier analysis compared overall survival (OS) and progression-free survival (PFS) in patients with GERD vs without GERD (SSc and SSc-ILD), and PPI vs no PPI use (SSc-ILD only). Progression was defined as a decrease in either percentage predicted forced vital capacity of ≥10% or single-breath diffusing capacity for carbon monoxide of ≥15%, or death. RESULTS It was found that 2693/4306 (63%) registered patients with SSc and 1204/1931 (62%) with SSc-ILD had GERD. GERD was not associated with decreased OS or decreased PFS in patients in either cohort. In SSc-ILD, PPI use was associated with improved OS vs no PPI use after 1 year [98.4% (95% CI: 97.6, 99.3); n = 760 vs 90.8% (87.9-93.8); n = 290] and after 5 years [91.4% (89.2-93.8); n = 357 vs 70.9% (65.2-77.1); n = 106; P < 0.0001]. PPI use was also associated with improved PFS vs no PPI use after 1 year [95.9% (94.6-97.3); n = 745 vs 86.4% (82.9-90.1); n = 278] and after 5 years [66.8% (63.0-70.8); n = 286 vs 45.9% (39.6-53.2); n = 69; P < 0.0001]. CONCLUSION GERD had no effect on survival in SSc or SSc-ILD. PPIs improved survival in patients with SSc-ILD. Controlled, prospective trials are needed to confirm this finding.
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Affiliation(s)
- Michael Kreuter
- Center for Interstitial and Rare Lung Diseases, Department of Pneumology, Thoraxklinik, University of Heidelberg, German Center for Lung Research, Heidelberg, Germany
| | - Francesco Bonella
- Center for Interstitial and Rare Lung Diseases, Ruhrlandklinik, Pneumonology Department, University of Duisburg-Essen, Essen, Germany
| | - Norbert Blank
- Division of Rheumatology, Department of Internal Medicine V, University Hospital Heidelberg, Heidelberg, Germany
| | - Gabriela Riemekasten
- Clinic for Rheumatology and Clinical Immunology, University Hospital Schleswig-Holstein, University of Lübeck, Lübeck, Germany
| | | | - Jörg Henes
- Centre for Interdisciplinary Rheumatology, Immunology and Auto-inflammatory Diseases and Department of Internal Medicine 2, University Hospital Tübingen, Tübingen, Germany
| | - Elise Siegert
- Department of Rheumatology and Clinical Immunology, Charité – Universitaetsmedizin Berlin, Berlin, Germany
- Berlin Institute of Health, Berlin, Germany
| | - Claudia Günther
- Department of Dermatology, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany
| | - Ina Kötter
- Division of Rheumatology and Systemic Inflammatory Diseases, University Hospital Hamburg, Rheumatology Clinic, Bad Bramstedt, Germany
| | - Christiane Pfeiffer
- Department of Dermatology and Allergology, University Hospital of Munich (LMU), Munich, Germany
| | - Marc Schmalzing
- Rheumatology/Clinical Immunology, Department of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany
| | - Gabriele Zeidler
- Department of Rheumatology, Osteology and Pain Therapy, Center for Rheumatology Brandenburg, Johanniter-Hospital Treuenbrietzen, Treuenbrietzen, Germany
| | - Peter Korsten
- Department of Nephrology and Rheumatology, University Medical Center Göttingen, Göttingen, Germany
| | - Laura Susok
- Department of Dermatology, Venereology and Allergology, St. Josef Hospital Bochum, Bochum, Germany
| | - Aaron Juche
- Department of Rheumatology, Immanuel Hospital Berlin-Buch, Berlin, Germany
| | - Margitta Worm
- Department of Dermatology, Venereology and Allergology, Charité – Universitaetsmedizin Berlin, Berlin, Germany
| | - Ilona Jandova
- Rheumatology and Clinical Immunology, University Medical Center Freiburg, Freiburg, Germany
| | - Jan Ehrchen
- Department of Dermatology, University Hospital Münster, Münster, Germany
| | - Cord Sunderkötter
- Department of Dermatology, University Hospital Halle (Saale), Halle, Germany
| | - Gernot Keyßer
- Department of Internal Medicine, Division of Rheumatology, University Hospital Halle (Saale), Halle, Germany
| | - Andreas Ramming
- Department of Internal Medicine 3, Rheumatology & Immunology, Friedrich-Alexander-University (FAU) Erlangen-Nürnberg and University Hospital Erlangen, Erlangen, Germany
| | - Tim Schmeiser
- Department for Rheumatology, Immunology and Osteology, St. Josef Hospital Wuppertal, Wuppertal, Germany
| | - Alexander Kreuter
- Department of Dermatology, Venereology and Allergology, Helios St Elisabeth Hospital Oberhausen, University Witten/Herdecke, Oberhausen, Germany
| | - Kathrin Kuhr
- Institute of Medical Statistics and Computational Biology (IMSB), University Hospital Cologne, Cologne, Germany
| | - Hanns-Martin Lorenz
- Center for Interstitial and Rare Lung Diseases, Ruhrlandklinik, Pneumonology Department, University of Duisburg-Essen, Essen, Germany
| | - Pia Moinzadeh
- Department of Dermatology and Venereology, University Hospital Cologne, Cologne, Germany
| | - Nicolas Hunzelmann
- Department of Dermatology and Venereology, University Hospital Cologne, Cologne, Germany
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20
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Koudstaal T, Wijsenbeek MS. Idiopathic pulmonary fibrosis. Presse Med 2023; 52:104166. [PMID: 37156412 DOI: 10.1016/j.lpm.2023.104166] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Revised: 03/14/2023] [Accepted: 05/02/2023] [Indexed: 05/10/2023] Open
Abstract
Idiopathic pulmonary fibrosis (IPF) is a progressive devastating lung disease with substantial morbidity. It is associated with cough, dyspnea and impaired quality of life. If left untreated, IPF has a median survival of 3 years. IPF affects ∼3 million people worldwide, with increasing incidence in older patients. The current concept of pathogenesis is that pulmonary fibrosis results from repetitive injury to the lung epithelium, with fibroblast accumulation, myofibroblast activation, and deposition of matrix. These injuries, in combination with innate and adaptive immune responses, dysregulated wound repair and fibroblast dysfunction, lead to recurring tissue remodeling and self-perpetuating fibrosis as seen in IPF. The diagnostic approach includes the exclusion of other interstitial lung diseases or underlying conditions and depends on a multidisciplinary team-based discussion combining radiological and clinical features and well as in some cases histology. In the last decade, considerable progress has been made in the understanding of IPF clinical management, with the availability of two drugs, pirfenidone and nintedanib, that decrease pulmonary lung function decline. However, current IPF therapies only slow disease progression and prognosis remains poor. Fortunately, there are multiple clinical trials ongoing with potential new therapies targeting different disease pathways. This review provides an overview of IPF epidemiology, current insights in pathophysiology, diagnostic and therapeutic management approaches. Finally, a detailed description of current and evolving therapeutic approaches is also provided.
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Affiliation(s)
- Thomas Koudstaal
- Center for Interstitial Lung Diseases and Sarcoidosis, Department of Pulmonary Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands.
| | - Marlies S Wijsenbeek
- Center for Interstitial Lung Diseases and Sarcoidosis, Department of Pulmonary Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands
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21
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Guo H, Sun J, Zhang S, Nie Y, Zhou S, Zeng Y. Progress in understanding and treating idiopathic pulmonary fibrosis: recent insights and emerging therapies. Front Pharmacol 2023; 14:1205948. [PMID: 37608885 PMCID: PMC10440605 DOI: 10.3389/fphar.2023.1205948] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2023] [Accepted: 07/28/2023] [Indexed: 08/24/2023] Open
Abstract
Idiopathic pulmonary fibrosis (IPF) is a long-lasting, continuously advancing, and irrevocable interstitial lung disorder with an obscure origin and inadequately comprehended pathological mechanisms. Despite the intricate and uncharted causes and pathways of IPF, the scholarly consensus upholds that the transformation of fibroblasts into myofibroblasts-instigated by injury to the alveolar epithelial cells-and the disproportionate accumulation of extracellular matrix (ECM) components, such as collagen, are integral to IPF's progression. The introduction of two novel anti-fibrotic medications, pirfenidone and nintedanib, have exhibited efficacy in decelerating the ongoing degradation of lung function, lessening hospitalization risk, and postponing exacerbations among IPF patients. Nonetheless, these pharmacological interventions do not present a definitive solution to IPF, positioning lung transplantation as the solitary potential curative measure in contemporary medical practice. A host of innovative therapeutic strategies are presently under rigorous scrutiny. This comprehensive review encapsulates the recent advancements in IPF research, spanning from diagnosis and etiology to pathological mechanisms, and introduces a discussion on nascent therapeutic methodologies currently in the pipeline.
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Affiliation(s)
| | | | | | | | | | - Yulan Zeng
- Department of Respiratory Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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22
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Zhu J, Zhou D, Wang J, Yang Y, Chen D, He F, Li Y. A Causal Atlas on Comorbidities in Idiopathic Pulmonary Fibrosis: A Bidirectional Mendelian Randomization Study. Chest 2023; 164:429-440. [PMID: 36870387 DOI: 10.1016/j.chest.2023.02.038] [Citation(s) in RCA: 26] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Revised: 02/21/2023] [Accepted: 02/24/2023] [Indexed: 03/06/2023] Open
Abstract
BACKGROUND Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease with a high burden of both pulmonary and extrapulmonary comorbidities. RESEARCH QUESTION Do these comorbidities have causal relationships with IPF? STUDY DESIGN AND METHODS We searched PubMed to pinpoint possible IPF-related comorbid conditions. Bidirectional Mendelian randomization (MR) was performed using summary statistics from the largest genome-wide association studies for these diseases to date in a two-sample setting. Findings were verified using multiple MR approaches under different model assumptions, replication datasets for IPF, and secondary phenotypes. RESULTS A total of 22 comorbidities with genetic data available were included. Bidirectional MR analyses showed convincing evidence for two comorbidities and suggestive evidence for four comorbidities. Gastroesophageal reflux disease, VTE, and hypothyroidism were associated causally with an increased risk of IPF, whereas COPD was associated causally with a decreased risk of IPF. For the reverse direction, IPF showed causal associations with a higher risk of lung cancer, but a reduced risk of hypertension. Follow-up analyses of pulmonary function parameters and BP measures supported the causal effect of COPD on IPF and the causal effect of IPF on hypertension. INTERPRETATION The present study suggested the causal associations between IPF and certain comorbidities from a genetic perspective. Further research is needed to understand the mechanisms of these associations.
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Affiliation(s)
- Jiahao Zhu
- Department of Epidemiology and Health Statistics, School of Public Health, Hangzhou Medical College, Hangzhou, China
| | - Dan Zhou
- School of Public Health and the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN
| | - Jing Wang
- Department of Epidemiology and Health Statistics, School of Public Health, Hangzhou Medical College, Hangzhou, China
| | - Ye Yang
- Department of Epidemiology and Health Statistics, School of Public Health, Hangzhou Medical College, Hangzhou, China
| | - Dingwan Chen
- Research Center on Primary Health of Zhejiang Province, School of Public Health, Hangzhou Medical College, Hangzhou, China
| | - Fan He
- Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, China
| | - Yingjun Li
- Department of Epidemiology and Health Statistics, School of Public Health, Hangzhou Medical College, Hangzhou, China.
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23
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Khor YH, Cottin V, Holland AE, Inoue Y, McDonald VM, Oldham J, Renzoni EA, Russell AM, Strek ME, Ryerson CJ. Treatable traits: a comprehensive precision medicine approach in interstitial lung disease. Eur Respir J 2023; 62:2300404. [PMID: 37263752 PMCID: PMC10626565 DOI: 10.1183/13993003.00404-2023] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Accepted: 05/16/2023] [Indexed: 06/03/2023]
Abstract
Interstitial lung disease (ILD) is a diverse group of inflammatory and fibrotic lung conditions causing significant morbidity and mortality. A multitude of factors beyond the lungs influence symptoms, health-related quality of life, disease progression and survival in patients with ILD. Despite an increasing emphasis on multidisciplinary management in ILD, the absence of a framework for assessment and delivery of comprehensive patient care poses challenges in clinical practice. The treatable traits approach is a precision medicine care model that operates on the premise of individualised multidimensional assessment for distinct traits that can be targeted by specific interventions. The potential utility of this approach has been described in airway diseases, but has not been adequately considered in ILD. Given the similar disease heterogeneity and complexity between ILD and airway diseases, we explore the concept and potential application of the treatable traits approach in ILD. A framework of aetiological, pulmonary, extrapulmonary and behavioural and lifestyle treatable traits relevant to clinical care and outcomes for patients with ILD is proposed. We further describe key research directions to evaluate the application of the treatable traits approach towards advancing patient care and health outcomes in ILD.
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Affiliation(s)
- Yet H Khor
- Respiratory Research@Alfred, Central Clinical School, Monash University, Melbourne, Australia
- Department of Respiratory and Sleep Medicine, Austin Health, Heidelberg, Australia
- Institute for Breathing and Sleep, Heidelberg, Australia
- Faculty of Medicine, University of Melbourne, Melbourne, Australia
| | - Vincent Cottin
- National Coordinating Reference Centre for Rare Pulmonary Diseases, OrphaLung, Louis Pradel Hospital, Hospices Civils de Lyon, ERN-LUNG, Lyon, France
- UMR 754, Claude Bernard University Lyon 1, INRAE, Lyon, France
| | - Anne E Holland
- Respiratory Research@Alfred, Central Clinical School, Monash University, Melbourne, Australia
- Institute for Breathing and Sleep, Heidelberg, Australia
- Department of Respiratory and Sleep Medicine, Alfred Health, Melbourne, Australia
- Department of Physiotherapy, Alfred Health, Melbourne, Australia
| | - Yoshikazu Inoue
- Clinical Research Center, National Hospital Organization Kinki-Chuo Chest Medical Center, Sakai City, Japan
| | - Vanessa M McDonald
- National Health and Medical Research Council Centre for Research Excellence in Treatable Traits, New Lambton Heights, Australia
- Asthma and Breathing Research Centre, Hunter Medical Research Institute, New Lambton Heights, Australia
- School of Nursing and Midwifery, College of Health, Medicine and Wellbeing, The University of Newcastle, Callaghan, Australia
| | - Justin Oldham
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
- Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA
| | - Elisabetta A Renzoni
- Interstitial Lung Disease Unit, Royal Brompton and Harefield Clinical Group, Guy's and St Thomas' NHS Foundation Trust, London, UK
- Margaret Turner Warwick Centre for Fibrosing Lung Disease, National Heart and Lung Institute, Imperial College London, London, UK
| | - Anne Marie Russell
- Exeter Respiratory Innovation Centre, University of Exeter, Exeter, UK
- Royal Devon University Hospitals, NHS Foundation Trust, Devon, UK
- Faculty of Medicine, Imperial College Healthcare NHS Trust, London, UK
| | - Mary E Strek
- Pulmonary and Critical Care Medicine, University of Chicago, Chicago, IL, USA
| | - Christopher J Ryerson
- Department of Medicine, University of British Columbia, Vancouver, BC, Canada
- Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, BC, Canada
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24
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Hayat Syed MK, Bruck O, Kumar A, Surani S. Acute exacerbation of interstitial lung disease in the intensive care unit: Principles of diagnostic evaluation and management. World J Crit Care Med 2023; 12:153-164. [PMID: 37397591 PMCID: PMC10308341 DOI: 10.5492/wjccm.v12.i3.153] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Revised: 04/18/2023] [Accepted: 05/17/2023] [Indexed: 06/08/2023] Open
Abstract
Interstitial lung disease (ILD) is typically managed on an outpatient basis. Critical care physicians manage patients with ILD in the setting of an acute exacerbation (ILD flare) causing severe hypoxia. The principles of management of acute exacerbation of ILD are different from those used to manage patients with acute respiratory distress syndrome from sepsis, etc. Selected patients may be candidates for aggressive measures like extracorporeal membrane oxygenation and lung transplantation, while almost all patients will benefit from early palliative care. This review focused on the types of ILD, diagnosis, and management pathways for this challenging condition.
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Affiliation(s)
- Muhammad K Hayat Syed
- Pulmonary and Critical Care Medicine, Baylor College of Medicine, Houston, TX 77030, United States
| | - Or Bruck
- Pulmonary and Critical Care Medicine, Baylor College of Medicine, Houston, TX 77030, United States
| | - Anupam Kumar
- Pulmonary and Critical Care Medicine, Baylor College of Medicine, Houston, TX 77030, United States
| | - Salim Surani
- Department of Medicine and Pharmacology, Texas A&M University, College Station, TX 77843, United States
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25
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Trachalaki A, Sultana N, Wells AU. An update on current and emerging drug treatments for idiopathic pulmonary fibrosis. Expert Opin Pharmacother 2023:1-18. [PMID: 37183672 DOI: 10.1080/14656566.2023.2213436] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/16/2023]
Abstract
INTRODUCTION Idiopathic Pulmonary Fibrosis (IPF) is a progressive and devastating lung disease, characterized by progressive lung scarring. AREAS COVERED Prior to antifibrotic therapy (pirfenidone and nintedanib), there was no validated pharmaceutical therapy for IPF. Both antifibrotics can slow disease progression, however, IPF remains a detrimental disease with poor prognosis and treated survival rates of less than 7 years from diagnosis. Despite their effect the disease remains non-reversible and progressing whilst their side effect profile is often challenging. Treatment of comorbidities is also crucial. In this review, we discuss the current pharmacological management as well as management of comorbidities and symptoms. We also reviewed clinicaltrials.gov and summarised all the mid to late stage clinical trials (phase II and III) registered in IPF over the last 7 years and discuss the most promising drugs in clinical development. EXPERT OPINION Future for IPF management will need to focus on current unresolved issues. First a primary pathogenetic pathway has not been clearly identified. Future management may involve a combination of brushstroke approach with antifibrotics with targeted treatments for specific pathways in patient subsets following an 'oncological' approach. Another unmet need is management of exacerbations, which are deathly in most cases as well as either treating or preventing lung cancer.
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Affiliation(s)
- Athina Trachalaki
- The Margaret Turner Warwick Centre for Fibrosing Lung Diseases, Imperial College London National Heart and Lung Institute, Imperial College, London, UK
- Imperial College NHS Hospitals, London UK
| | | | - Athol Umfrey Wells
- Interstitial Lung Disease Unit, Royal Brompton & Harefield Hospitals, London, UK
- The Margaret Turner Warwick Centre for Fibrosing Lung Diseases, Imperial College London National Heart and Lung Institute, Imperial College, London, UK
- Imperial College NHS Hospitals, London UK
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26
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Molina-Molina M. The relationship between gastro-oesophageal reflux and pulmonary fibrosis: a never-ending story. Eur Respir J 2023; 61:61/5/2300566. [PMID: 37230505 DOI: 10.1183/13993003.00566-2023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2023] [Accepted: 04/18/2023] [Indexed: 05/27/2023]
Affiliation(s)
- Maria Molina-Molina
- Interstitial Lung Disease (ILD) Unit, Respiratory Department, University Hospital of Bellvitge, IDIBELL, UB, Barcelona, Spain
- National Research Network in Respiratory Disease (CIBERES), Spain
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27
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Zhou JC, Gavini S, Chan WW, Lo WK. Relationship Between Esophageal Disease and Pulmonary Fibrosis. Dig Dis Sci 2023; 68:1096-1105. [PMID: 36918450 DOI: 10.1007/s10620-023-07908-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Accepted: 02/27/2023] [Indexed: 03/16/2023]
Abstract
Esophageal disorders are prevalent among patients with chronic lung diseases, including idiopathic pulmonary fibrosis (IPF). Gastroesophageal reflux disease (GERD) has been associated with IPF prevalence, severity, and respiratory decline. The pathophysiologic relationship between GERD and IPF is likely bidirectional, with aspiration of refluxate leading to lung inflammation and fibrosis, while the restrictive pulmonary physiology may contribute to altered transdiaphragmatic pressure gradient and increased reflux. Esophageal symptoms are frequently absent and do not predict esophageal dysfunction or pathologic reflux in patients with IPF, and objective diagnostic tools including upper endoscopy, ambulatory reflux monitoring, and high-resolution manometry are often needed. Impedance-based testing that identifies both weakly/non-acidic and acid reflux may provide important additional diagnostic value beyond pH-based acid testing alone. Novel metrics and maneuvers, including advanced impedance measures on impedance-pH study and provocative testing on HRM, may hold promise to future diagnostic advancements. The main treatment options include medical therapy with acid suppressants and anti-reflux surgery, although their potential benefits in pulmonary outcomes of IPF require further validations. Future directions of research include identifying phenotypes of IPF patients who may benefit from esophageal testing and treatment, determining the optimal testing strategy and protocol, and prospectively assessing the value of different esophageal therapies to improve outcomes while minimizing risks. This review will discuss the pathophysiology, evaluation, and management of esophageal diseases, particularly GERD, in patients with IPF, as informed by the most recent publications in the field, in hopes of identifying targets for future study and research.
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Affiliation(s)
- Joyce C Zhou
- Department of Medicine, Massachusetts General Hospital, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Sravanya Gavini
- Division of Digestive and Liver Diseases, The University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Walter W Chan
- Harvard Medical School, Boston, MA, USA.
- Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA.
| | - Wai-Kit Lo
- Harvard Medical School, Boston, MA, USA
- Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA
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28
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Berger K, Kaner RJ. Diagnosis and Pharmacologic Management of Fibrotic Interstitial Lung Disease. Life (Basel) 2023; 13:599. [PMID: 36983755 PMCID: PMC10055741 DOI: 10.3390/life13030599] [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: 12/26/2022] [Revised: 02/15/2023] [Accepted: 02/16/2023] [Indexed: 02/23/2023] Open
Abstract
Interstitial lung disease is an umbrella term that encompasses a spectrum of parenchymal lung pathologies affecting the gas exchanging part of the lung. While many of these disease entities are not fibrotic in nature, a number can lead to pulmonary fibrosis which may or may not progress over time. Idiopathic pulmonary fibrosis is the prototypical, progressive fibrotic interstitial lung disease, which can lead to worsening hypoxemic respiratory failure and mortality within a number of years from the time of diagnosis. The importance of an accurate and timely diagnosis of interstitial lung diseases, which is needed to inform prognosis and guide clinical management, cannot be overemphasized. Developing a consensus diagnosis requires the incorporation of a variety of factors by a multidisciplinary team, which then may or may not determine a need for tissue sampling. Clinical management can be challenging given the heterogeneity of disease behavior and the paucity of controlled trials to guide decision making. This review addresses current paradigms and recent updates in the diagnosis and pharmacologic management of these fibrotic interstitial lung diseases.
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Affiliation(s)
- Kristin Berger
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Weill Cornell Medicine, New York, NY 10021, USA
| | - Robert J. Kaner
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Weill Cornell Medicine, New York, NY 10021, USA
- Department of Genetic Medicine, Weill Cornell Medicine, New York, NY 10021, USA
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29
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Thong L, McElduff EJ, Henry MT. Trials and Treatments: An Update on Pharmacotherapy for Idiopathic Pulmonary Fibrosis. Life (Basel) 2023; 13:486. [PMID: 36836843 PMCID: PMC9963632 DOI: 10.3390/life13020486] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Revised: 02/07/2023] [Accepted: 02/08/2023] [Indexed: 02/12/2023] Open
Abstract
Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive fibrosing interstitial lung disease that occurs predominantly in the older population. There is increasing incidence and prevalence in IPF globally. The emergence of anti-fibrotic therapies in the last decade have improved patient survival though a cure is yet to be developed. In this review article, we aim to summarize the existing and novel pharmacotherapies for the treatment of IPF (excluding treatments for acute exacerbations), focusing on the current knowledge on the pathophysiology of the disease, mechanism of action of the drugs, and clinical trials.
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Affiliation(s)
- Lorraine Thong
- Department of Clinical Medicine, Trinity College Dublin, D08 W9RT Dublin, Ireland
| | - Enda James McElduff
- Department of Clinical Medicine, Royal College of Surgeons Ireland, D02 YN77 Dublin, Ireland
| | - Michael Thomas Henry
- Department of Respiratory Medicine, Cork University Hospital, T12 YE02 Cork, Ireland
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Ebrahimpour A, Ahir M, Wang M, Jegga AG, Bonnen MD, Eissa NT, Montesi SB, Raghu G, Ghebre YT. Combination of esomeprazole and pirfenidone enhances antifibrotic efficacy in vitro and in a mouse model of TGFβ-induced lung fibrosis. Sci Rep 2022; 12:20668. [PMID: 36450789 PMCID: PMC9712660 DOI: 10.1038/s41598-022-24985-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Accepted: 11/23/2022] [Indexed: 12/03/2022] Open
Abstract
Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease of unknown etiology. Currently, pirfenidone and nintedanib are the only FDA-approved drugs for the treatment of IPF and are now the standard of care. This is a significant step in slowing down the progression of the disease. However, the drugs are unable to stop or reverse established fibrosis. Several retrospective clinical studies indicate that proton pump inhibitors (PPIs; FDA-approved to treat gastroesophageal reflux) are associated with favorable outcomes in patients with IPF, and emerging preclinical studies report that PPIs possess antifibrotic activity. In this study, we evaluated the antifibrotic efficacy of the PPI esomeprazole when combined with pirfenidone in vitro and in vivo. In cell culture studies of IPF lung fibroblasts, we assessed the effect of the combination on several fibrosis-related biological processes including TGFβ-induced cell proliferation, cell migration, cell contraction, and collagen production. In an in vivo study, we used mouse model of TGFβ-induced lung fibrosis to evaluate the antifibrotic efficacy of esomeprazole/pirfenidone combination. We also performed computational studies to understand the molecular mechanisms by which esomeprazole and/or pirfenidone regulate lung fibrosis. We found that esomeprazole significantly enhanced the anti-proliferative effect of pirfenidone and favorably modulated TGFβ-induced cell migration and contraction of collagen gels. We also found that the combination significantly suppressed collagen production in response to TGFβ in comparison to pirfenidone monotherapy. In addition, our animal study demonstrated that the combination therapy effectively inhibited the differentiation of lung fibroblasts into alpha smooth muscle actin (αSMA)-expressing myofibroblasts to attenuate the progression of lung fibrosis. Finally, our bioinformatics study of cells treated with esomeprazole or pirfenidone revealed that the drugs target several extracellular matrix (ECM) related pathways with esomeprazole preferentially targeting collagen family members while pirfenidone targets the keratins. In conclusion, our cell biological, computational, and in vivo studies show that the PPI esomeprazole enhances the antifibrotic efficacy of pirfenidone through complementary molecular mechanisms. This data supports the initiation of prospective clinical studies aimed at repurposing PPIs for the treatment of IPF and other fibrotic lung diseases where pirfenidone is prescribed.
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Affiliation(s)
- Afshin Ebrahimpour
- Department of Radiation Oncology, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA
| | - Manisha Ahir
- Department of Radiation Oncology, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA
| | - Min Wang
- Department of Radiation Oncology, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA
| | - Anil G Jegga
- Division of Biomedical Informatics, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, 45229, USA
| | - Mark D Bonnen
- Department of Radiation Oncology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, USA
| | - N Tony Eissa
- Department of Medicine, University of California, Irvine School of Medicine, Irvine, CA, 92697, USA
| | - Sydney B Montesi
- Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA
| | - Ganesh Raghu
- Division of Pulmonary and Critical Care Medicine, Center for Interstitial Lung Disease, University of Washington, Seattle, WA, 98195, USA
| | - Yohannes T Ghebre
- Department of Radiation Oncology, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA.
- Department of Radiation Oncology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, USA.
- Department of Medicine, Section on Pulmonary and Critical Care Medicine, Baylor College of Medicine, Houston, TX, 77030, USA.
- Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA.
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Patel H, Shah JR, Patel DR, Avanthika C, Jhaveri S, Gor K. Idiopathic pulmonary fibrosis: Diagnosis, biomarkers and newer treatment protocols. Dis Mon 2022:101484. [DOI: 10.1016/j.disamonth.2022.101484] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
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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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Lee J, White E, Freiheit E, Scholand MB, Strek ME, Podolanczuk AJ, Patel NM. Cough-Specific Quality of Life Predicts Disease Progression Among Patients With Interstitial Lung Disease: Data From the Pulmonary Fibrosis Foundation Patient Registry. Chest 2022; 162:603-613. [PMID: 35337809 PMCID: PMC9808640 DOI: 10.1016/j.chest.2022.03.025] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Revised: 03/02/2022] [Accepted: 03/16/2022] [Indexed: 01/13/2023] Open
Abstract
BACKGROUND Cough is a common symptom of interstitial lung disease (ILD) and negatively impacts health-related quality of life (QOL). Previous studies have shown that among patients with idiopathic pulmonary fibrosis, cough may predict progression of lung disease and perhaps even respiratory hospitalizations and mortality. RESEARCH QUESTION Does cough-specific QOL predict disease progression, respiratory hospitalization, lung transplantation, and death among patients with ILD? STUDY DESIGN AND METHODS We analyzed data from the Pulmonary Fibrosis Foundation Registry, which comprises a multicenter population of well-characterized patients with ILD. We first examined associations between patient factors and baseline scores on the Leicester Cough Questionnaire (LCQ), a cough-specific QOL tool, using a proportional odds model. Next, we examined associations between baseline LCQ scores and patient-centered clinical outcomes, as well as pulmonary function parameters, using a univariable and multivariable proportional hazards model that was adjusted for clinically relevant variables, including measures of disease severity. RESULTS One thousand four hundred forty-seven patients with ILD were included in our study. In the multivariable proportional odds model, we found that the following patient factors were associated with worse cough-specific QOL: younger age, diagnosis of "other ILD," gastroesophageal reflux disease, and lower FVC % predicted. Multivariable Cox regression models, adjusting for several variables including baseline disease severity, showed that a 1-point decrease in LCQ score (indicating lower cough-specific QOL) was associated with a 6.5% higher risk of respiratory-related hospitalization (hazard ratio [HR], 1.065; 95% CI, 1.025-1.107), a 7.4% higher risk of death (HR, 1.074; 95% CI, 1.020-1.130), and an 8.7% higher risk of lung transplantation (HR, 1.087; 95% CI, 1.022-1.156). INTERPRETATION Among a large population of well-characterized patients with ILD, cough-specific QOL was associated independently with respiratory hospitalization, death, and lung transplantation.
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Affiliation(s)
- Janet Lee
- Section of Pulmonary and Critical Care Medicine, University of Utah, Salt Lake City, UT.
| | - Emily White
- Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI
| | - Elizabeth Freiheit
- Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI
| | - Mary Beth Scholand
- Section of Pulmonary and Critical Care Medicine, University of Utah, Salt Lake City, UT
| | - Mary E Strek
- Section of Pulmonary and Critical Care Medicine, University of Chicago, Chicago, IL
| | - Anna J Podolanczuk
- Division of Pulmonary and Critical Care Medicine, Weill Cornell Medical Center, New York, NY
| | - Nina M Patel
- Division of Pulmonary, Allergy and Critical Care Medicine, Columbia University Medical Center, New York, NY; Boehringer-Inghelheim, Ridgefield, CT.
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Mucke HA. Drug Repurposing Patent Applications March–June 2022. Assay Drug Dev Technol 2022; 20:286-293. [DOI: 10.1089/adt.2022.065] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
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Gastroesophageal Reflux Disease in Idiopathic Pulmonary Fibrosis: Viewer or Actor? To Treat or Not to Treat? Pharmaceuticals (Basel) 2022; 15:ph15081033. [PMID: 36015181 PMCID: PMC9412643 DOI: 10.3390/ph15081033] [Citation(s) in RCA: 38] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Revised: 08/14/2022] [Accepted: 08/19/2022] [Indexed: 02/07/2023] Open
Abstract
Background: Idiopathic pulmonary fibrosis (IPF) is a rare and severe disease with a median survival of ∼3 years. Several risk factors have been identified, such as age, genetic predisposition, tobacco exposure, and gastro-oesophageal reflux disease (GERD). Prevalence of GERD in IPF is high and may affect 87% of patients, of whom only half (47%) report symptoms. Objective: The aim of this study is to review current evidence regarding the correlation between GERD and IPF and to evaluate the current studies regarding treatments for GERD-IPF. Methods: A review to identify research papers documenting an association between GERD and IPF was performed. Results: We identified several studies that have confirmed the association between GERD and IPF, with an increased acid exposure, risk of gastric aspiration and bile acids levels in these patients. Few studies focused their attention on GERD treatment, showing how antiacid therapy was not able to change IPF evolution. Conclusions: This review investigating the correlation between GERD and IPF has confirmed the hypothesized association. However, further large prospective studies are needed to corroborate and elucidate these findings with a focus on preventative and treatment strategies.
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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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Impact of gastroesophageal reflux disease on idiopathic pulmonary fibrosis and lung transplant recipients. Curr Opin Gastroenterol 2022; 38:411-416. [PMID: 35762701 DOI: 10.1097/mog.0000000000000841] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
PURPOSE OF REVIEW Idiopathic pulmonary fibrosis (IPF) is a prevalent subset of interstitial lung disease (ILD) that often progresses to require lung transplantation. Gastroesophageal reflux disease (GERD) is common in the IPF population, and GER-related micro-aspiration appears to be an important risk factor for IPF pathogenesis and for the deterioration of transplanted lung function. RECENT FINDINGS Many patients with IPF have elevated esophageal acid exposure on reflux testing despite having no or minimal symptoms. Studies on the effects of medical GERD therapy on IPF-related outcomes have had mixed results. Antireflux surgery is safe in appropriately selected IPF patients, and appears to have potential for slowing the decline of lung function. GERD can persist, improve or develop after lung transplantation, and the presence of GERD is associated with allograft injury and pulmonary function decline in lung transplant recipients. SUMMARY Clinicians should have a low threshold to assess for objective evidence of GERD in IPF patients. Antireflux surgery in IPF patients with GERD appears to improve lung function, but further studies are needed before surgical treatment can be recommended routinely in this setting. In lung transplant recipients, reflux testing after transplant is the most accurate way to guide GERD treatment decisions.
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Hashemi-Bajgani SM, Samareh-Fekri M, Paghaleh AJ, Yazdani R, Zarandi MA, Shafahi A. Prevalence of Micro-Aspiration of Bile Acids in Patients with Primary Lung Cancer: A Cross-Sectional Study. Ethiop J Health Sci 2022; 32:715-722. [PMID: 35950065 PMCID: PMC9341028 DOI: 10.4314/ejhs.v32i4.7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Accepted: 03/25/2022] [Indexed: 11/17/2022] Open
Abstract
Background Lung cancer remains a serious public health problem and is the first cause of cancer-related death worldwide. There is some evidence suggests that bile acid micro-aspiration may contribute to the development of lung diseases. This study aimed to assess the prevalence of micro-aspiration of bile acids in patients with primary lung cancer. Methods In a cross-sectional study, 52 patients with primary lung cancer referred to a teaching hospital affiliated with Kerman University of Medical Sciences, Kerman, Iran were enrolled. Patients with pathology-confirmed lung cancer who did not receive specific treatment were included in the present study. All patients underwent bronchoscopy and the levels of bile acid was assessed in their Broncho-Alveolar Lavage (BAL) samples. Results According to the results, 53.85% of patients were in the age group of 40 to 59 years. Of the participants, 88.46% were male, 82.69% were smokers, and 69.23% were opium addicted. The most common presenting clinical symptoms of patients were heartburn (61.55%), hoarseness (17.31%), and epigastric pain (9.61%), respectively. Ninety-two point thirty-two percent of patients had endobronchial lesions in bronchoscopy. Squamous cell carcinoma, small-cell lung carcinoma and adenocarcinoma accounts for 48.08%, 34.61% and 17.31% of all cases of lung cancer, respectively. Bile acids were found in the BAL sample of all patients with primary lung cancer. The mean Bile acids levels in patients were 63.42 (SD=7.03) µmol/Lit. Conclusion According to the results of present study, there was a micro-aspiration of bile acids in all patients with primary lung cancer that may participate in shaping early events in the etiology of primary lung cancer. It seems that developing clinical strategies preventing the micro-aspiration of bile acids into the lungs could remove a key potential trigger in this process.
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Affiliation(s)
| | - Mitra Samareh-Fekri
- Cardiovascular Research Center, Basic and Clinical Institute of Physiology, Kerman University of Medical Sciences, Kerman, Iran
| | - Arshia Jamali Paghaleh
- Afzalipour Hospital Research Center, Kerman University of Medical Sciences, Kerman, Iran
| | - Rostam Yazdani
- Afzalipour Hospital Research Center, Kerman University of Medical Sciences, Kerman, Iran
| | - Mahboobe Asadi Zarandi
- Afzalipour Hospital Research Center, Kerman University of Medical Sciences, Kerman, Iran
| | - Ahmad Shafahi
- Afzalipour Hospital Research Center, Kerman University of Medical Sciences, Kerman, Iran
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Liu GY, Budinger GRS, Dematte JE. Advances in the management of idiopathic pulmonary fibrosis and progressive pulmonary fibrosis. BMJ 2022; 377:e066354. [PMID: 36946547 DOI: 10.1136/bmj-2021-066354] [Citation(s) in RCA: 44] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
Similarly to idiopathic pulmonary fibrosis (IPF), other interstitial lung diseases can develop progressive pulmonary fibrosis (PPF) characterized by declining lung function, a poor response to immunomodulatory therapies, and early mortality. The pathophysiology of disordered lung repair involves common downstream pathways that lead to pulmonary fibrosis in both IPF and PPF. The antifibrotic drugs, such as nintedanib, are indicated for the treatment of IPF and PPF, and new therapies are being evaluated in clinical trials. Clinical, radiographic, and molecular biomarkers are needed to identify patients with PPF and subgroups of patients likely to respond to specific therapies. This article reviews the evidence supporting the use of specific therapies in patients with IPF and PPF, discusses agents being considered in clinical trials, and considers potential biomarkers based on disease pathogenesis that might be used to provide a personalized approach to care.
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Affiliation(s)
- Gabrielle Y Liu
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University, Chicago, IL, USA
| | - G R Scott Budinger
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University, Chicago, IL, USA
| | - Jane E Dematte
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University, Chicago, IL, USA
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Ma H, Liu S, Li S, Xia Y. Targeting Growth Factor and Cytokine Pathways to Treat Idiopathic Pulmonary Fibrosis. Front Pharmacol 2022; 13:918771. [PMID: 35721111 PMCID: PMC9204157 DOI: 10.3389/fphar.2022.918771] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Accepted: 05/06/2022] [Indexed: 02/05/2023] Open
Abstract
Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease of unknown origin that usually results in death from secondary respiratory failure within 2–5 years of diagnosis. Recent studies have identified key roles of cytokine and growth factor pathways in the pathogenesis of IPF. Although there have been numerous clinical trials of drugs investigating their efficacy in the treatment of IPF, only Pirfenidone and Nintedanib have been approved by the FDA. However, they have some major limitations, such as insufficient efficacy, undesired side effects and poor pharmacokinetic properties. To give more insights into the discovery of potential targets for the treatment of IPF, this review provides an overview of cytokines, growth factors and their signaling pathways in IPF, which have important implications for fully exploiting the therapeutic potential of targeting cytokine and growth factor pathways. Advances in the field of cytokine and growth factor pathways will help slow disease progression, prolong life, and improve the quality of life for IPF patients in the future.
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Affiliation(s)
- Hongbo Ma
- Department of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu, China.,West China School of Pharmacy, Sichuan University, Chengdu, China
| | - Shengming Liu
- Department of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu, China.,West China School of Pharmacy, Sichuan University, Chengdu, China
| | - Shanrui Li
- Department of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu, China.,West China School of Pharmacy, Sichuan University, Chengdu, China
| | - Yong Xia
- Department of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu, China.,Key Laboratory of Rehabilitation Medicine in Sichuan Province/Rehabilitation Medicine Research Institute, Chengdu, China
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Cao M, Gu L, Guo L, Liu M, Wang T, Zhang J, Zhang H, Zhang Y, Shi Y, Zhao Y, Qiu X, Gui X, Ma M, Tian Y, Liu X, Meng F, Xiao Y, Sun L. Elevated Expression of Growth Differentiation Factor-15 Is Associated With Acute Exacerbation of Idiopathic Pulmonary Fibrosis. Front Immunol 2022; 13:891448. [PMID: 35784345 PMCID: PMC9241490 DOI: 10.3389/fimmu.2022.891448] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Accepted: 05/04/2022] [Indexed: 11/13/2022] Open
Abstract
Backgrounds Growth differentiation factor 15 (GDF-15) is a highly divergent member of the TGF-β superfamily and has been implicated in various biological functions. However, the expression of GDF-15 in patients with acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is unclear. Method The study included 47 AE-IPF patients, 61 stable IPF (S-IPF) subjects, and 31 healthy controls (HCs). Serum GDF-15 levels and their expression in the lung were measured. The correlation between serum GDF-15 and other clinical parameters and the risk factors for AE occurrence and the survival of IPF patients were analyzed. Results Serum GDF-15 levels were significantly elevated in AE-IPF patients (1279.22 ± 540.02 pg/ml) as compared with HCs (891.30 ± 479.90 pg/ml) or S-IPF subjects (107.82 ± 14.21 pg/ml) (both p < 0.001). The protein and mRNA expressions of GDF-15 in the lung of AE-IPF patients were significantly increased as compared with S-IPF cases (p = 0.007 and p = 0.026, respectively). The serum GDF-15 level was correlated with the clinical variables of inflammation, metabolism, and disease severity in IPF subjects (all p < 0.05). The GDF-15 serum concentration was significantly higher in decedents than in survivors (p = 0.005). A serum GDF-15 level above 989.3 pg/ml was a risk factor for AE occurrence (p = 0.04), and the level above 1,075.76 pg/ml was an independent predictor for survival in IPF cases (p = 0.007). Conclusions The GDF-15 level was significantly elevated in subjects with AE-IPF. GDF-15 could be a promising biomarker for AE occurrence and survival in IPF patients.
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Affiliation(s)
- Mengshu Cao
- Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
- Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
- Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China
| | - Lina Gu
- Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Lili Guo
- Department of Clinical Laboratory, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Mengying Liu
- Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China
| | - Tianzhen Wang
- Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China
| | - Ji Zhang
- Wuxi Transplant Center, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, China
| | - Huizhe Zhang
- Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Yufeng Zhang
- Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Yanchen Shi
- Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Yichao Zhao
- Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Xiaohua Qiu
- Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Xianhua Gui
- Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Miao Ma
- Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Yaqiong Tian
- Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Xiaoqin Liu
- Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Fanqing Meng
- Department of Pathology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
- *Correspondence: Lingyun Sun, ; Yonglong Xiao, ; Fanqing Meng,
| | - Yonglong Xiao
- Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
- *Correspondence: Lingyun Sun, ; Yonglong Xiao, ; Fanqing Meng,
| | - Lingyun Sun
- Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
- *Correspondence: Lingyun Sun, ; Yonglong Xiao, ; Fanqing Meng,
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Evaluation of Proteasome Inhibitors in the Treatment of Idiopathic Pulmonary Fibrosis. Cells 2022; 11:cells11091543. [PMID: 35563849 PMCID: PMC9099509 DOI: 10.3390/cells11091543] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Revised: 04/22/2022] [Accepted: 05/03/2022] [Indexed: 11/16/2022] Open
Abstract
Idiopathic pulmonary fibrosis (IPF) is the most common form of idiopathic interstitial pneumonia, and it has a worse prognosis than non-small cell lung cancer. The pathomechanism of IPF is not fully understood, but it has been suggested that repeated microinjuries of epithelial cells induce a wound healing response, during which fibroblasts differentiate into myofibroblasts. These activated myofibroblasts express α smooth muscle actin and release extracellular matrix to promote matrix deposition and tissue remodeling. Under physiological conditions, the remodeling process stops once wound healing is complete. However, in the lungs of IPF patients, myofibroblasts re-main active and deposit excess extracellular matrix. This leads to the destruction of alveolar tissue, the loss of lung elastic recoil, and a rapid decrease in lung function. Some evidence has indicated that proteasomal inhibition combats fibrosis by inhibiting the expressions of extracellular matrix proteins and metalloproteinases. However, the mechanisms by which proteasome inhibitors may protect against fibrosis are not known. This review summarizes the current research on proteasome inhibitors for pulmonary fibrosis, and provides a reference for whether proteasome inhibitors have the potential to become new drugs for the treatment of pulmonary fibrosis.
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Raghu G, Remy-Jardin M, Richeldi L, Thomson CC, Inoue Y, Johkoh T, Kreuter M, Lynch DA, Maher TM, Martinez FJ, Molina-Molina M, Myers JL, Nicholson AG, Ryerson CJ, Strek ME, Troy LK, Wijsenbeek M, Mammen MJ, Hossain T, Bissell BD, Herman DD, Hon SM, Kheir F, Khor YH, Macrea M, Antoniou KM, Bouros D, Buendia-Roldan I, Caro F, Crestani B, Ho L, Morisset J, Olson AL, Podolanczuk A, Poletti V, Selman M, Ewing T, Jones S, Knight SL, Ghazipura M, Wilson KC. Idiopathic Pulmonary Fibrosis (an Update) and Progressive Pulmonary Fibrosis in Adults: An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med 2022; 205:e18-e47. [PMID: 35486072 PMCID: PMC9851481 DOI: 10.1164/rccm.202202-0399st] [Citation(s) in RCA: 1342] [Impact Index Per Article: 447.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
Background: This American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana de Tórax guideline updates prior idiopathic pulmonary fibrosis (IPF) guidelines and addresses the progression of pulmonary fibrosis in patients with interstitial lung diseases (ILDs) other than IPF. Methods: A committee was composed of multidisciplinary experts in ILD, methodologists, and patient representatives. 1) Update of IPF: Radiological and histopathological criteria for IPF were updated by consensus. Questions about transbronchial lung cryobiopsy, genomic classifier testing, antacid medication, and antireflux surgery were informed by systematic reviews and answered with evidence-based recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. 2) Progressive pulmonary fibrosis (PPF): PPF was defined, and then radiological and physiological criteria for PPF were determined by consensus. Questions about pirfenidone and nintedanib were informed by systematic reviews and answered with evidence-based recommendations using the GRADE approach. Results:1) Update of IPF: A conditional recommendation was made to regard transbronchial lung cryobiopsy as an acceptable alternative to surgical lung biopsy in centers with appropriate expertise. No recommendation was made for or against genomic classifier testing. Conditional recommendations were made against antacid medication and antireflux surgery for the treatment of IPF. 2) PPF: PPF was defined as at least two of three criteria (worsening symptoms, radiological progression, and physiological progression) occurring within the past year with no alternative explanation in a patient with an ILD other than IPF. A conditional recommendation was made for nintedanib, and additional research into pirfenidone was recommended. Conclusions: The conditional recommendations in this guideline are intended to provide the basis for rational, informed decisions by clinicians.
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Antacid Medication and Antireflux Surgery in Patients with Idiopathic Pulmonary Fibrosis: A Systematic Review and Meta-Analysis. Ann Am Thorac Soc 2022; 19:833-844. [PMID: 35486080 DOI: 10.1513/annalsats.202102-172oc] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
Rationale: Idiopathic pulmonary fibrosis (IPF) is a fibrosing interstitial pneumonia with impaired survival. Previous guidelines recommend antacid medication to improve respiratory outcomes in patients with IPF. Objectives: This systematic review was undertaken during the development of an American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax guideline. The clinical question was, "Should patients with IPF who have documented abnormal gastroesophageal reflux (GER) with or without symptoms of GER disease 1) be treated with antacid medication or 2) undergo antireflux surgery to improve respiratory outcomes?" Methods: Medline, Embase, the Cochrane Central Register of Controlled Trials, and the gray literature were searched through June 30, 2020. Studies that enrolled patients with IPF and 1) compared antacid medication to placebo or no medication or 2) compared antireflux surgery to no surgery were selected. Meta-analyses were performed when possible. Outcomes included disease progression, mortality, exacerbations, hospitalizations, lung function, respiratory symptoms, GER severity, and adverse effects/complications. Results: For antacid medication, when two studies were aggregated, there was no statistically significant effect on disease progression, defined as a 10% or more decline in FVC, more than 50-m decline in 6-minute walking distance, or death (risk ratio [RR], 0.88; 95% confidence interval [CI], 0.76-1.03). A separate study that could not be included in the meta-analysis found no statistically significant effect on disease progression when defined as a 5% or more decline in FVC or death (RR, 1.10; 95% CI, 1.00-1.21) and an increase in disease progression when defined as a 10% or more decline in FVC or death (RR, 1.28; 95% CI, 1.08-1.51). For antireflux surgery, there was also no statistically significant effect on disease progression (RR, 0.29; 95% CI, 0.06-1.26). Neither antacid medications nor antireflux surgery was associated with improvements in the other outcomes. Conclusions: There is insufficient evidence to conclude that antacid medication or antireflux surgery improves respiratory outcomes in patients with IPF, most of whom had not had abnormal GER confirmed. Well-designed and adequately powered prospective studies with objective evaluation for GER are critical to elucidate the role of antacid medication and antireflux surgery for respiratory outcomes in patients with IPF.
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Pang Q, Li G, Cao F, Liu H, Wei W, Jiao Y. Clinical efficacy of Chinese herbs for supplementing qi and activating blood circulation combined with N-acetylcysteine in the treatment of idiopathic pulmonary fibrosis: A systematic review and network meta-analysis. PLoS One 2022; 17:e0265006. [PMID: 35245333 PMCID: PMC8896725 DOI: 10.1371/journal.pone.0265006] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Accepted: 02/21/2022] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND Chinese herbs for supplementing qi and activating blood circulation (CH) combined with N-acetylcysteine (NAC) is widely used for idiopathic pulmonary fibrosis (IPF) in China, but there is a lack of literature to evaluate its efficacy and clinical value. PURPOSE This study compared CH + NAC with other treatments by network meta-analysis to clarify its clinical value. METHODS Cochrane Library, PubMed, Embase, Web of Science, China National Knowledge Infrastructure, WanFang Data, VIP Database, and China Biology Medicine were searched. Outcomes included lung function (DLCO (%), VC (%), FVC (%), FVC (L)), 6-min walking distance (6MWD), score of St George's respiratory questionnaire (SGRQ), blood gas analysis (PaO2, PaCO2). The data were analyzed by Review Manager 5.4, Stata 12.0 and ADDIS 1.16.5. RESULTS 23 studies including 1390 patients (702 in intervention group and 688 in control group) were collected to compare 8 outcome indicators among different treatments involving CH, CH+NAC, CH+PFD, NAC, PFD and PFD+NAC on IPF. Network meta-analysis showed that CH was better than NAC in terms of DLCO (%) (MD = 5.14, 95%CI: 1.01 to 8.68) and 6MWD (MD = 49.17, 95%CI: 25.97 to 71.36) as well as PFD + NAC was better than NAC in terms of FVC (L) (MD = -0.56, 95%CI: -0.83 to -0.31). In rankings results, CH + NAC is the best in terms of FVC (%), SGRQ, PaO2 and PaCO2; CH is the best in terms of DLCO (%), VC (%) and 6MWD; CH + PFD is the best in terms of FVC (L). CONCLUSION CH related treatments may have advantages in the treatment of IPF and CH + NAC may have clinical application value. However, limited by the quality and quantity of researches included, more rational and scientific randomized controlled trials containing large sample sizes need to be conducted to further verify our conclusions.
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Affiliation(s)
- Qinglu Pang
- Department of Internal Medicine of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Guodong Li
- Department of Respiratory, Beijing Changping Hospital of Integrated traditional Chinese and Western Medicine, Beijing, China
| | - Fang Cao
- Department of Geriatrics, Dongfang Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, China
| | - Haoge Liu
- Department of Internal Medicine of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Wan Wei
- Department of Geriatrics, Dongfang Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, China
- * E-mail: (YJ); (WW)
| | - Yang Jiao
- Department of Respiratory, Dongfang Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, China
- * E-mail: (YJ); (WW)
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Snyder DL, Katzka DA. Complex Gastroesophageal Reflux Disease. GASTRO HEP ADVANCES 2022; 1:420-430. [PMID: 39131678 PMCID: PMC11307939 DOI: 10.1016/j.gastha.2022.02.014] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/27/2021] [Accepted: 02/15/2022] [Indexed: 08/13/2024]
Abstract
Gastroesophageal reflux disease (GERD) is the most prevalent gastrointestinal disorder posing diagnostic and therapeutic challenges. Diagnosis should be objectively defined with endoscopy and pH testing, while novel metrics may augment diagnosis for inconclusive GERD cases, including the postreflux swallow-induced peristaltic wave index and esophageal mucosal impedance. Conditions that overlap with or mimic GERD should be considered such as achalasia, rumination, and eosinophilic esophagitis. Genetic testing for proton pump inhibitor metabolism is an option for precision therapy in complex persistent GERD. Proton pump inhibitor refractory GERD may require medical, surgical, or endoscopic therapies. The presence of GERD should be objectively evaluated in achalasia patients treated with peroral endoscopic myotomy, and further studies are needed to determine timing of this evaluation. Patients with scleroderma are at a high risk for GERD owing to abnormal esophageal motility and should be managed with aggressive medical therapy and lifestyle changes given the high prevalence of esophagitis and Barrett's esophagus in this population. Further studies are needed to understand the complex mechanisms of GERD in idiopathic pulmonary fibrosis and lung transplantation.
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Prior TS, Hyldgaard C, Torrisi SE, Kronborg-White S, Ganter C, Bendstrup E, Kreuter M. Comorbidities in unclassifiable interstitial lung disease. Respir Res 2022; 23:59. [PMID: 35296320 PMCID: PMC8925215 DOI: 10.1186/s12931-022-01981-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Accepted: 03/08/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Comorbidities are common in interstitial lung diseases (ILD) and have an important association with survival, but the frequency and prognostic impact of comorbidities in unclassifiable interstitial lung disease (uILD) remains elusive. We aimed to describe the prevalence of comorbidities and assess the impact on survival in patients with uILD. Furthermore, we aimed to identify and characterize potential phenotypes based on clusters of comorbidities and examine their association with disease progression and survival. METHODS Incident patients diagnosed with uILD were identified at two ILD referral centers in Denmark and Germany from 2003 to 2018. The diagnosis uILD was based on multidisciplinary team meetings. Clinical characteristics and comorbidities were extracted from ILD registries and patient case files. Survival analyses were performed using Cox regression analyses, disease progression was analyzed by linear mixed effects models, and clusters of comorbidities were analyzed using self-organizing maps. RESULTS A total of 249 patients with uILD were identified. The cohort was dominated by males (60%), former (49%) or current (15%) smokers, median age was 70 years, mean FVC was 75.9% predicted, and mean DLCO was 49.9% predicted. One-year survival was 89% and three-year survival was 73%. Eighty-five percent of the patients had ≥ 1 comorbidities, 33% had ≥ 3 comorbidities and 9% had ≥ 5 comorbidities. The only comorbidity associated with excess mortality was dyslipidemia. No association between survival and number of comorbidities or the Charlson comorbidity index was observed. Three clusters with different comorbidities profiles and clinical characteristics were identified. A significant annual decline in FVC and DLCO % predicted was observed in cluster 1 and 2, but not in cluster 3. No difference in mortality was observed between the clusters. CONCLUSIONS The comorbidity burden in uILD is lower than reported in other types of ILD and the impact of comorbidities on mortality needs further clarification. Three clusters with distinct comorbidity profiles were identified and could represent specific phenotypes. No difference in mortality was observed between clusters, but slower disease progression was observed in cluster 3. Better understanding of disease behavior and mortality will require further studies of subgroups of uILD with longer observation time.
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Affiliation(s)
- Thomas Skovhus Prior
- Centre for Rare Lung Diseases, Department of Respiratory Diseases and Allergy, Aarhus University Hospital, Aarhus, Denmark.
| | - Charlotte Hyldgaard
- Diagnostic Center, University Research Clinic for Innovative Patient Pathways, Silkeborg Regional Hospital, Silkeborg, Denmark
| | - Sebastiano Emanuele Torrisi
- Centre for Interstitial and Rare Lung Diseases, Pneumology, Thoraxklinik, University of Heidelberg and German Centre for Lung Research, Heidelberg, Germany
| | - Sissel Kronborg-White
- Centre for Rare Lung Diseases, Department of Respiratory Diseases and Allergy, Aarhus University Hospital, Aarhus, Denmark
| | - Claudia Ganter
- Centre for Interstitial and Rare Lung Diseases, Pneumology, Thoraxklinik, University of Heidelberg and German Centre for Lung Research, Heidelberg, Germany
| | - Elisabeth Bendstrup
- Centre for Rare Lung Diseases, Department of Respiratory Diseases and Allergy, Aarhus University Hospital, Aarhus, Denmark
| | - Michael Kreuter
- Centre for Interstitial and Rare Lung Diseases, Pneumology, Thoraxklinik, University of Heidelberg and German Centre for Lung Research, Heidelberg, Germany
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Novel Advanced Impedance Metrics on Impedance-pH Testing Predict Lung Function Decline in Idiopathic Pulmonary Fibrosis. Am J Gastroenterol 2022; 117:405-412. [PMID: 34934030 DOI: 10.14309/ajg.0000000000001577] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Accepted: 11/02/2021] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Gastroesophageal reflux has been associated with idiopathic pulmonary fibrosis (IPF). Mean nocturnal baseline impedance (MNBI) is a marker of esophageal mucosal integrity, whereas postreflux swallow-induced peristaltic wave (PSPW) index reflects esophageal chemical clearance. Both metrics offer novel ways to assess reflux burden on multichannel intraluminal impedance-pH testing (MII-pH), but their role in extraesophageal reflux remains unclear. We aimed to evaluate the relationship between these novel metrics and lung function decline in patients with IPF. METHODS Adults with IPF undergoing prelung transplant MII-pH were enrolled. All patients completed pulmonary function testing (PFT) at the time of MII-pH and at the 1-year follow-up. MNBI was calculated by averaging baseline impedance at three 10-minute intervals (1 AM/2 AM/3 AM). PSPW index was the proportion of all reflux episodes, followed by a peristaltic swallow within 30 seconds. Univariate (Student t-test/Pearson correlation) and multivariable (general linear regression) analyses were performed. RESULTS One hundred twenty-five subjects (mean age = 61.7 years, 62% men) were included. Forced expiratory volume in one second and forced vital capacity declined more significantly over 12 months in subjects with lower distal MNBI, proximal MNBI, and PSPW index (all P < 0.05). On multivariable analyses adjusting for age, sex, proton pump inhibitor use, and baseline lung function, distal MNBI (β = -10.86, P = 0.024; β = -8.03, P = 0.045), proximal MNBI (β = -13.5, P = 0.0068; β = -9.80, P = 0.025), and PSPW index (β = -18.1, P = 0.010; β = -12.55, P = 0.050) remained predictive of greater forced expiratory volume in one second and forced vital capacity decline. DISCUSSION Low distal MNBI, proximal MNBI, and PSPW index independently predicted more severe lung function decline over 1 year in patients with IPF. These impedance metrics may have prognostic value and support a role for reflux in IPF pathogenesis.
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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, short version]. Rev Mal Respir 2022; 39:275-312. [PMID: 35304014 DOI: 10.1016/j.rmr.2022.01.005] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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
- Service de pneumologie et soins intensifs respiratoires, centre de référence constitutif des maladies pulmonaires rares, centre hospitalo-universitaire de Bourgogne et faculté de médecine et pharmacie, université de Bourgogne-Franche Comté, Dijon ; Inserm U123-1, Dijon, France
| | - J Cadranel
- Service de pneumologie et oncologie thoracique, centre de référence constitutif des maladies pulmonaires rares, 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 compétences 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, unité 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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