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[Chinese consensus on diagnosis and treatment of bronchiolitis obliterans syndrome after hematopoietic stem cell transplantation (2022)]. ZHONGHUA XUE YE XUE ZA ZHI = ZHONGHUA XUEYEXUE ZAZHI 2022; 43:441-447. [PMID: 35968585 PMCID: PMC9800223 DOI: 10.3760/cma.j.issn.0253-2727.2022.06.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Figures] [Subscribe] [Scholar Register] [Received: 05/15/2022] [Indexed: 12/24/2022]
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Al Shamrani A, AlShammari A, AlAlkami H, AlShanwani J, Alharbi AS. When is asthma not guilty? Int J Pediatr Adolesc Med 2021; 8:203-211. [PMID: 34401444 PMCID: PMC8356124 DOI: 10.1016/j.ijpam.2020.10.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Revised: 09/12/2020] [Accepted: 10/18/2020] [Indexed: 11/20/2022]
Abstract
Asthma is a common childhood condition. Its prevalence in Saudi Arabia is high, increasing, and could exceed 20% at the current trajectory. Asthma is a syndrome with different clinical presentations and phenotypes. Many conditions are often misdiagnosed as asthma because they share the same symptoms, particularly coughing and shortness of breath; physical findings, such as wheezing; radiological findings, such as hyperinflation on chest X-ray; or even responses to asthma therapies, as in some patients with bronchiolitis. When treating the younger age group (>5 years old), there should be a high degree of suspicion of alternative causes when evaluating patients presenting with clinical features suggestive of asthma or patients who do not respond well to asthma therapies. This study will highlight common conditions that may mimic asthma and, as a result of incorrect treatment, unnecessarily expose patients to steroids and other therapies for extended periods. Furthermore, we seek to alert healthcare providers to common symptoms and signs that suggest a cause other than asthma and suggest when to refer the patient to subspecialists.
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Affiliation(s)
| | - Ayshah AlShammari
- Department of Pediatrics, Prince Sultan Military Medical City, Saudi Arabia
| | - Halima AlAlkami
- Department of Pediatrics, Prince Sultan Military Medical City, Saudi Arabia
| | - Jawaher AlShanwani
- Department of Pediatrics, Prince Sultan Military Medical City, Saudi Arabia
| | - Adel S. Alharbi
- Department of Pediatrics, Prince Sultan Military Medical City, Saudi Arabia
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Nathan S, Ustun C. Complications of Stem Cell Transplantation that Affect Infections in Stem Cell Transplant Recipients, with Analogies to Patients with Hematologic Malignancies. Infect Dis Clin North Am 2019; 33:331-359. [PMID: 30940464 DOI: 10.1016/j.idc.2019.01.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
This article discusses the complications of hematopoietic stem cell transplantion (HSCT) that affect infections in HSCT recipients, with analogies to patients with hematologic malignancies. Mucositis, with mucosal barrier disruption, is common and increases the risk of gram-positive and anaerobic bacterial, and fungal infections, and can evolve to typhlitis. Engraftment syndrome; graft-versus-host disease, hepatic sinusoidal obstruction syndrome; and posterior reversible encephalopathy syndrome can affect the infectious potential either directly from organ dysfunction or indirectly from specific treatment. Pulmonary infections can predispose to life threatening complications including diffuse alveolar hemorrhage, idiopathic pulmonary syndrome, bronchiolitis obliterans syndrome, and bronchiolitis obliterans with organizing pneumonia.
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Affiliation(s)
- Sunita Nathan
- Section of Bone Marrow Transplant and Cellular Therapy, Division of Hematology, Oncology and Cell Therapy, Rush University Medical Center, 1725 West Harrison Street, Suite 809, Chicago, IL 60612, USA
| | - Celalettin Ustun
- Section of Bone Marrow Transplant and Cellular Therapy, Division of Hematology, Oncology and Cell Therapy, Rush University Medical Center, 1725 West Harrison Street, Suite 809, Chicago, IL 60612, USA.
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Cengiz Seval G, Topçuoğlu P, Demirer T. Current Approach to Non-Infectious Pulmonary Complications of Hematopoietic Stem Cell Transplantation. Balkan Med J 2018; 35:131-140. [PMID: 29553463 PMCID: PMC5863250 DOI: 10.4274/balkanmedj.2017.1635] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
Hematopoietic stem cell transplantation is an established treatment for patients with a wide range of malignant and nonmalignant conditions. Noninfectious pulmonary complications still remain a leading cause of morbidity and mortality in these patients. Treating hematopoietic stem cell transplantation recipients with noninfectious pulmonary complications is still challenging, and the current treatment armamentarium and strategies are not adequate for patients receiving hematopoietic stem cell transplantation. Further trials are needed for a better description of the pathogenesis and the complete diagnostic criteria as well as for the development of effective therapeutic approaches for the management of noninfectious pulmonary complications of the hematopoietic stem cell transplantation. This review outlines the incidence, risk factors, pathogenesis, and clinical spectrum and discusses the current approaches to the management of noninfectious pulmonary complications of Hematopoietic stem cell transplantation.
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Affiliation(s)
- Güldane Cengiz Seval
- Department of Hematology, Ankara University School of Medicine, Cebeci Hospital, Ankara, Turkey
| | - Pervin Topçuoğlu
- Department of Hematology, Ankara University School of Medicine, Cebeci Hospital, Ankara, Turkey
| | - Taner Demirer
- Department of Hematology, Ankara University School of Medicine, Cebeci Hospital, Ankara, Turkey
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Wieruszewski PM, Herasevich S, Gajic O, Yadav H. Respiratory failure in the hematopoietic stem cell transplant recipient. World J Crit Care Med 2018; 7:62-72. [PMID: 30370228 PMCID: PMC6201323 DOI: 10.5492/wjccm.v7.i5.62] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2018] [Revised: 09/04/2018] [Accepted: 10/10/2018] [Indexed: 02/06/2023] Open
Abstract
The number of patients receiving hematopoietic stem cell transplantation (HSCT) is rapidly rising worldwide. Despite substantial improvements in peri-transplant care, pulmonary complications resulting in respiratory failure remain a major contributor to morbidity and mortality in the post-transplant period, and represent a major barrier to the overall success of HSCT. Infectious complications include pneumonia due to bacteria, viruses, and fungi, and most commonly occur during neutropenia in the early post-transplant period. Non-infectious complications include idiopathic pneumonia syndrome, peri-engraftment respiratory distress syndrome, diffuse alveolar hemorrhage, pulmonary veno-occlusive disease, delayed pulmonary toxicity syndrome, cryptogenic organizing pneumonia, bronchiolitis obliterans syndrome, and post-transplant lymphoproliferative disorder. These complications have distinct clinical features and risk factors, occur at differing times following transplant, and contribute to morbidity and mortality.
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Affiliation(s)
- Patrick M Wieruszewski
- Department of Pharmacy, Mayo Clinic, Rochester, MN 55905, United States
- Multidisciplinary Epidemiology and Translational Research in Intensive Care Group, Mayo Clinic, Rochester, MN 55905, United States
| | - Svetlana Herasevich
- Multidisciplinary Epidemiology and Translational Research in Intensive Care Group, Mayo Clinic, Rochester, MN 55905, United States
- Department of Anesthesiology, Mayo Clinic, Rochester, MN 55905, United States
| | - Ognjen Gajic
- Multidisciplinary Epidemiology and Translational Research in Intensive Care Group, Mayo Clinic, Rochester, MN 55905, United States
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN 55905, United States
| | - Hemang Yadav
- Multidisciplinary Epidemiology and Translational Research in Intensive Care Group, Mayo Clinic, Rochester, MN 55905, United States
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN 55905, United States
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Bergeron A, Cheng GS. Bronchiolitis Obliterans Syndrome and Other Late Pulmonary Complications After Allogeneic Hematopoietic Stem Cell Transplantation. Clin Chest Med 2017; 38:607-621. [PMID: 29128013 DOI: 10.1016/j.ccm.2017.07.003] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
As more individuals survive their hematologic malignancies after allogeneic hematopoietic stem cell transplantation (HSCT), there is growing appreciation of the late organ complications of this curative procedure for malignant and nonmalignant hematologic disorders. Late noninfectious pulmonary complications encompass all aspects of the bronchopulmonary anatomy. There have been recent advances in the diagnostic recognition and management of bronchiolitis obliterans syndrome, which is recognized as a pulmonary manifestation of chronic graft-versus-host disease. Organizing pneumonia and other interstitial lung diseases are increasingly recognized. This article provides an update on these entities as well as pleural and pulmonary vascular disease after allogeneic HSCT.
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Affiliation(s)
- Anne Bergeron
- Service de Pneumologie, AP-HP, Hôpital Saint-Louis, 1 Avenue Claude Vellefaux, 75010 Paris, France; Univ Paris Diderot, Sorbonne Paris Cité, UMR 1153 CRESS, Biostatistics and Clinical Epidemiology Research Team, Paris F-75010, France.
| | - Guang-Shing Cheng
- Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, D5-360, Seattle, WA 98105, USA; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington School of Medicine, 1959 NE Pacific, Campus Box 356522, Seattle, WA 98195-6522, USA
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Bergeron A. Late-Onset Noninfectious Pulmonary Complications After Allogeneic Hematopoietic Stem Cell Transplantation. Clin Chest Med 2017; 38:249-262. [DOI: 10.1016/j.ccm.2016.12.013] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
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Togni Filho PH, Casagrande JLM, Lederman HM. Utility of the inspiratory phase in high-resolution computed tomography evaluations of pediatric patients with bronchiolitis obliterans after allogeneic bone marrow transplant: reducing patient radiation exposure. Radiol Bras 2017; 50:90-96. [PMID: 28428651 PMCID: PMC5396998 DOI: 10.1590/0100-3984.2015.0181] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2015] [Accepted: 02/26/2016] [Indexed: 12/20/2022] Open
Abstract
OBJECTIVE To evaluate the utility of the inspiratory phase in high-resolution computed tomography (HRCT) of the chest for the diagnosis of post-bone marrow transplantation bronchiolitis obliterans. MATERIALS AND METHODS This was a retrospective, observational, cross-sectional study. We selected patients of either gender who underwent bone marrow transplantation and chest HRCT between March 1, 2002 and December 12, 2014. Ages ranged from 3 months to 20.7 years. We included all examinations in which the HRCT was performed appropriately. The examinations were read by two radiologists, one with extensive experience in pediatric radiology and another in the third year of residency, who determined the presence or absence of the following imaging features: air trapping, bronchiectasis, alveolar opacities, nodules, and atelectasis. RESULTS A total of 222 examinations were evaluated (mean, 5.4 ± 4.5 examinations per patient). The expiratory phase findings were comparable to those obtained in the inspiratory phase, except in one patient, in whom a small uncharacteristic nodule was identified only in the inspiratory phase. Air trapping was identified in a larger number of scans in the expiratory phase than in the inspiratory phase, as was atelectasis, although the difference was statistically significant only for air trapping. CONCLUSION In children being evaluated for post-bone marrow transplantation bronchiolitis obliterans, the inspiratory phase can be excluded from the chest HRCT protocol, thus reducing by half the radiation exposure in this population.
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Affiliation(s)
- Paulo Henrique Togni Filho
- MD, MSc, Attending Physician, Department of Diagnostic Imaging,
Escola Paulista de Medicina da Universidade Federal de São Paulo
(EPM-Unifesp), São Paulo, SP, Brazil
| | - João Luiz Marin Casagrande
- Radiologist, Fellow in Musculoskeletal Imaging, Instituto de
Radiologia do Hospital das Clínicas da Faculdade de Medicina da Universidade
de São Paulo (InRad/HC-FMUSP), São Paulo, SP, Brazil
| | - Henrique Manoel Lederman
- Tenured Full Professor, Department of Diagnostic Imaging, Escola
Paulista de Medicina da Universidade Federal de São Paulo (EPM-Unifesp),
São Paulo, SP, Brazil
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Kim SW, Rhee CK, Kim YJ, Lee S, Kim HJ, Lee JW. Therapeutic effect of budesonide/formoterol, montelukast and N-acetylcysteine for bronchiolitis obliterans syndrome after hematopoietic stem cell transplantation. Respir Res 2016; 17:63. [PMID: 27229850 PMCID: PMC4882858 DOI: 10.1186/s12931-016-0380-1] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2015] [Accepted: 05/18/2016] [Indexed: 01/16/2023] Open
Abstract
Background Bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic stem cell transplantation (HSCT) is currently treated with systemic corticosteroids despite poor efficacy and side effects. This study investigated the therapeutic effect of budesonide/formoterol, montelukast and n-acetylcysteine, which are suggested as treatment options for BOS after HSCT. Methods After diagnosis of BOS, 61 patients were treated with budesonide/formoterol, montelukast and n-acetylcysteine for 3 months. Pulmonary function test and COPD assessment test (CAT) were performed before and after the combination therapy. Therapeutic response was evaluated by changes in forced expiratory volume in 1 s (FEV1) or CAT score. Results After 3 months of combination treatment, mean FEV1 increased by 220 mL (p < 0.001) and residual volume decreased by 200 mL (p =0 .005). Median CAT score also significantly decreased from 15.5 to 11.0 (p = 0.001). The overall response rate to combination therapy was 82 %. Comparing the no-response group and the response group, the forced vital capacity (% predicted) decline between pre-HSCT and BOS diagnosis was significantly greater in the response group (p = 0.036). Conclusion Combination treatment with budesonide/formoterol, montelukast and n-acetylcysteine significantly improved lung function and respiratory symptoms in patients with BOS after allogeneic HSCT without serious side effects.
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Affiliation(s)
- Sei Won Kim
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Chin Kook Rhee
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Yoo Jin Kim
- Division of Hematology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Seok Lee
- Division of Hematology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Hee Je Kim
- Division of Hematology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jong Wook Lee
- Division of Hematology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
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Burgel PR, Bergeron A, Knoop C, Dusser D. [Small airway diseases and immune deficiency]. Rev Mal Respir 2016; 33:145-55. [PMID: 26854188 DOI: 10.1016/j.rmr.2015.11.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2014] [Accepted: 06/09/2015] [Indexed: 01/02/2023]
Abstract
INTRODUCTION Innate or acquired immune deficiency may show respiratory manifestations, often characterized by small airway involvement. The purpose of this article is to provide an overview of small airway disease across the major causes of immune deficiency. BACKGROUND In patients with common variable immune deficiency, recurrent lower airway infections may lead to bronchiolitis and bronchiectasis. Follicular and/or granulomatous bronchiolitis of unknown origin may also occur. Bronchiolitis obliterans is the leading cause of death after the first year in patients with lung transplantation. Bronchiolitis obliterans also occurs in patients with allogeneic haematopoietic stem cell transplantation, especially in the context of systemic graft-versus-host disease. VIEWPOINT AND CONCLUSION Small airway diseases have different clinical expression and pathophysiology across various causes of immune deficiency. A better understanding of small airways disease pathogenesis in these settings may lead to the development of novel targeted therapies.
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Affiliation(s)
- P-R Burgel
- Université Paris Descartes, Sorbonne Paris Cité, 75005 Paris, France; Service de pneumologie, hôpital Cochin, AP-HP, 27, rue du Faubourg-Saint-Jacques, 75014 Paris, France.
| | - A Bergeron
- Université Paris Diderot, Sorbonne Paris Cité, 75013 Paris, France; Service de pneumologie, hôpital Saint-Louis, AP-HP, 75010 Paris, France
| | - C Knoop
- Department of Chest Medicine, Erasme University Hospital, université libre de Bruxelles, Bruxelles, Belgique
| | - D Dusser
- Université Paris Descartes, Sorbonne Paris Cité, 75005 Paris, France; Service de pneumologie, hôpital Cochin, AP-HP, 27, rue du Faubourg-Saint-Jacques, 75014 Paris, France
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Bergeron A, Chevret S, Chagnon K, Godet C, Bergot E, Peffault de Latour R, Dominique S, de Revel T, Juvin K, Maillard N, Reman O, Contentin N, Robin M, Buzyn A, Socié G, Tazi A. Budesonide/Formoterol for Bronchiolitis Obliterans after Hematopoietic Stem Cell Transplantation. Am J Respir Crit Care Med 2015; 191:1242-9. [DOI: 10.1164/rccm.201410-1818oc] [Citation(s) in RCA: 76] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
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Pulmonary Manifestations of Hematological Malignancies: Focus on Pulmonary Chronic Graft-Versus Host Disease. ORPHAN LUNG DISEASES 2015. [PMCID: PMC7120310 DOI: 10.1007/978-1-4471-2401-6_32] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Advances in the management of patients in terms of the diagnosis and treatment of hematologic malignancies and treatment-related complications, especially infectious complications, have increased survival time. However, more than half of the patients treated for hematologic malignancies will develop a pulmonary complication during their follow-up, infectious pneumonia remaining the most common diagnosis that should be considered first in regard to its potential severity. Otherwise, new complications that may involve different organs, including the lungs, have been increasingly reported. Currently, over a quarter of lung infiltrates occurring in the context of hematological diseases are due to noninfectious causes. Thus, lung physicians may be increasingly confronted with these lung disorders. Various noninfectious pulmonary complications have been described in the different hematological malignancies; however, these complications are most often studied in the context of allogeneic hematopoietic stem cell transplantation (HSCT). In this chapter, we will briefly review the lung diseases associated with various hematological malignancies before focusing on noninfectious pulmonary complications following allogeneic HSCT.
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Takeuchi Y, Miyagawa-Hayashino A, Chen F, Kubo T, Handa T, Date H, Haga H. Pleuroparenchymal fibroelastosis and non-specific interstitial pneumonia: frequent pulmonary sequelae of haematopoietic stem cell transplantation. Histopathology 2014; 66:536-44. [PMID: 25234860 DOI: 10.1111/his.12553] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2014] [Accepted: 09/15/2014] [Indexed: 11/29/2022]
Abstract
AIMS Pulmonary sequelae, reported as chronic graft-versus-host disease (cGVHD), of haematopoietic stem cell transplantation (HSCT) include constrictive bronchiolitis obliterans (CBO), lymphocytic bronchiolitis (LB), and veno-occlusive disease (VOD); recently, pleuroparenchymal fibroelastosis (PPFE) has also been described in bone marrow transplant recipients. The histological features of pulmonary HSCT sequelae have not been described systematically. The aim of the study was to review and identify the histological features of PPFE after bone marrow transplant. METHODS AND RESULTS A retrospective review of 20 patients who underwent lung transplantation for pulmonary disease following HSCT between 2004 and 2013 was conducted. The patient age at transplantation ranged from 8 years to 57 years (median, 27.5 years). Fifteen patients had cGVHD in other organs (skin, nine; liver, six; salivary gland, six). Lung transplantation was performed at a median of 4.6 years (range, 1.2-14.8 years) post-HSCT. Histologically, all cases had CBO, with concurrent LB in 10, and VOD in three. PPFE was identified in 15 cases (75%), with subpleural (15), paraseptal (11) and centrilobular (13) distributions; and non-specific interstitial pneumonia (NSIP) was identified in 15 cases (75%), with fibrotic (nine) and cellular (six) patterns. PPFE was distributed in all lobes, with a predominance in the upper lobe. NSIP was mostly focal, with two cases having diffuse involvement. CONCLUSIONS PPFE and NSIP were frequently seen in HSCT patients. Possible causes may include reactions to drugs or radiation, or cGVHD.
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Affiliation(s)
- Yasuhide Takeuchi
- Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan
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Biopsy-verified bronchiolitis obliterans and other noninfectious lung pathologies after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2014; 21:531-8. [PMID: 25498923 DOI: 10.1016/j.bbmt.2014.12.004] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2014] [Accepted: 12/01/2014] [Indexed: 11/21/2022]
Abstract
Bronchiolitis obliterans (BO) is a serious complication of allogeneic hematopoietic stem cell transplantation (HSCT). Lung biopsy is the gold standard for diagnosis. This study describes the course of BO and assesses the congruity between biopsy-verified BO and a modified version of the National Institutes of Health's consensus criteria for BO syndrome (BOS) based exclusively on noninvasive measures. We included 44 patients transplanted between 2000 and 2010 who underwent lung biopsy for suspected BO. Of those, 23 were diagnosed with BO and 21 presented other noninfectious pulmonary pathologies, such as cryptogenic organizing pneumonia, diffuse alveolar damage, interstitial pneumonia, and nonspecific interstitial fibrosis. Compared with patients with other noninfectious pulmonary pathologies, BO patients had significantly lower values of forced expiratory volume in 1 second (FEV1), FEV1/forced vital capacity, and maximal mid-expiratory flow throughout follow-up, but there was no difference in the change in pulmonary function from the time of lung biopsy. The BO diagnosis was not associated with poorer overall survival. Fifty-two percent of patients with biopsy-verified BO and 24% of patients with other noninfectious pulmonary pathology fulfilled the BOS criteria. Pathological BO diagnosis was not superior to BOS criteria in predicting decrease in pulmonary function beyond the time of biopsy. A lung biopsy may provide a characterization of pathological patterns that can extend our knowledge on the pathophysiology of HSCT-related lung diseases.
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Peña E, Souza CA, Escuissato DL, Gomes MM, Allan D, Tay J, Dennie CJ. Noninfectious Pulmonary Complications after Hematopoietic Stem Cell Transplantation: Practical Approach to Imaging Diagnosis. Radiographics 2014; 34:663-83. [DOI: 10.1148/rg.343135080] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
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Vieira AG, Funke VAM, Nunes EC, Frare R, Pasquini R. Bronchiolitis obliterans in patients undergoing allogeneic hematopoietic SCT. Bone Marrow Transplant 2014; 49:812-7. [PMID: 24614836 DOI: 10.1038/bmt.2014.25] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2013] [Revised: 01/04/2014] [Accepted: 01/08/2014] [Indexed: 11/09/2022]
Abstract
Bronchiolitis obliterans (BO) is a severe pulmonary complication of allo-SCT. This study evaluated the incidence of BO in patients undergoing allo-SCT in Hospital Universitário da Universidade Federal do Paraná, risk factors for developing this complication and prognostic factors for those patients who developed this entity. The study included 1286 patients transplanted between 1979 and 2009 who survived for 100 days or more. We diagnosed 53 cases of BO. The cumulative incidence was 2.9% in 1 year and 3.7% in 3 years. Among patients with chronic GVHD, the cumulative incidence at the same intervals was 8.4% and 9.9%, respectively. The median time between transplantation and diagnosis of BO was 260 days (49-3877 days). In the multivariate analysis the risk factors for BO were female donor, older recipients and acute GVHD. The main prognostic factor was the severity of pulmonary impairment. Patients who developed BO earlier than 260 days had a worse prognosis than those who did so later. At least 80% of deaths were directly related to BO.
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Affiliation(s)
- A G Vieira
- Universidade Federal do Paraná, Curitiba, Brazil
| | - V A M Funke
- Universidade Federal do Paraná, Curitiba, Brazil
| | - E C Nunes
- Universidade Federal do Paraná, Curitiba, Brazil
| | - R Frare
- Universidade Federal do Paraná, Curitiba, Brazil
| | - R Pasquini
- Universidade Federal do Paraná, Curitiba, Brazil
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Chien JW. Preventing and managing bronchiolitis obliterans syndrome after allogeneic hematopoietic cell transplantation. Expert Rev Respir Med 2014; 5:127-35. [DOI: 10.1586/ers.10.79] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
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Yousef S, Benden C, Boyer D, Elidemir O, Frischer T, Goldfarb S, Lopez-Mitnik G, Mallory G, Visner G, Westall G, Schecter MG. Lung transplantation in children following bone marrow transplantation: a multi-center experience. Pediatr Transplant 2013; 17:231-6. [PMID: 23217003 DOI: 10.1111/petr.12023] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/02/2012] [Indexed: 12/19/2022]
Abstract
Allogenic BMT has been successfully performed as a treatment for hematologic diseases with an expected long-term survival. This survival is truncated by respiratory complications including airway obstruction especially BO. Chronic GVHD has been reported to precede almost all cases reported. LTx has become a therapeutic life-saving option for patients with end-stage lung disease that maybe offered for the treatment of GVHD. We report a multi-center experience of pediatric LTx following BMT in 11 patients age- and gender-matched with 11 controls who received LTx for end-stage lung disease secondary to CF. Overall death was 36.4% over a follow-up period of 19 months (range 3-36 months) for the cases and 27.3% for the control group followed for 17 months (range 8-32 months). Median FEV1 one yr post-transplant for the cases was 78% predicted compared with 67.3% predicted for the controls. The median for episodes of infection was comparable at a median of one episode per patient through the entire follow-up period among both groups. Acute rejection episodes were significantly higher in the control group with a median of one episode per patient in the control group compared to none within the cases. Our data suggest that LTx may be a valuable therapeutic option for children with end-stage lung disease post-BMT with comparable survival outcome to that after LTx in children for other indications such as CF. Hospital stay was significantly longer in our case group. Infection rate was comparable between groups albeit type of infection varied. Significantly and of interest is that acute rejection episodes were non-existent in these cases.
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Affiliation(s)
- S Yousef
- Division of Pediatric Pulmonology, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
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Khalid M, Aljurf M, Saleemi S, Khan MQ, Khan B, Ahmed S, Ibrahim KET, Mobeireek A, Al Mohareb F, Chaudhri N. Gastroesophageal reflux disease and its association with bronchiolitis obliterans syndrome in allogeneic hematopoietic stem cell transplant recipients. EXP CLIN TRANSPLANT 2013; 11:270-3. [PMID: 23530912 DOI: 10.6002/ect.2012.0207] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
OBJECTIVES Bronchiolitis obliterans syndrome is a significant postallogeneic hematopoietic stem cell transplant problem. Recent data in lung transplant patients suggest an association with gastroesophageal reflux disease and bronchiolitis obliterans syndrome. We studied posthematopoietic stem cell transplant patients with bronchiolitis obliterans syndrome for gastroesophageal reflux disease and its response to a proton pump inhibitor. MATERIALS AND METHODS Seven postallogeneic hematopoietic stem cell transplant patients with bronchiolitis obliterans syndrome were studied. Gastroesophageal reflux disease was assessed by 24-hour pH monitoring with a Bravo catheter-free radio pH capsule. Patients with positive gastroesophageal reflux disease were started on omeprazole. Pretreatment and posttreatment pulmonary function tests were done at 3-month intervals. RESULTS Of 7 patients, 5 had positive results for gastroesophageal reflux disease (71%). Omeprazole had a disease-stabilizing effect on the patients' pulmonary function tests. CONCLUSIONS Our study shows a significant association between bronchiolitis obliterans syndrome and gastroesophageal reflux disease in postallogeneic hematopoietic stem cell transplant patients. Use of omeprazole may have a disease-stabilizing effect in short-term follow-up.
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Affiliation(s)
- Mohammed Khalid
- Department of Pulmonary Medicine and Gastroenterology, King Faisal Specialist Hospital and Research Centre, PO Box 3354, Riyadh 11211, Saudi Arabia.
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CD19(+)CD21(low) B cells and patients at risk for NIH-defined chronic graft-versus-host disease with bronchiolitis obliterans syndrome. Blood 2013; 121:1886-95. [PMID: 23303823 DOI: 10.1182/blood-2012-06-435008] [Citation(s) in RCA: 64] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Bronchiolitis obliterans syndrome (BOS), pathognomonic for chronic graft-versus-host disease (cGVHD) of the lung, is a progressive and often fatal complication after allogeneic hematopoietic cell transplantation (HCT). Biomarkers for the prediction and diagnosis of BOS are urgently needed to improve patients' prognosis. We prospectively evaluated B-cell subpopulations and B-cell activating factor (BAFF) in 136 patients (46 BOS, 41 no cGVHD, 49 cutaneous cGVHD) to define novel biomarkers for early diagnosis of National Institutes of Health-defined BOS diagnosed a median of 11 mo after HCT. Patients with newly diagnosed BOS had significantly higher percentages of CD19(+)CD21(low) B cells (25.5 versus 6.6%, P < .0001), BAFF (7.3 versus 3.5 ng/mL, P = .02), and BAFF/CD19(+) ratio (0.18 versus 0.02 ng/10(3) CD19(+) B cells, P 5 .007) compared with patients without cGVHD. The area under the receiver operating curve for CD19(+)CD21(low) B cells was 0.97 (95% confidence interval, 0.94-0.99) and a cutoff point >9% was optimal for diagnosing BOS in patients with first drop of pulmonary function tests with a sensitivity of 96% and a negative predictive value of 94%. Thus, elevated levels of CD19(+)CD21(low) B cells are a potential novel biomarker for HCT patients at risk for developing BOS at an early stage and could allow improvement of patient outcome.
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Bergeron A, Godet C, Chevret S, Lorillon G, Peffault de Latour R, de Revel T, Robin M, Ribaud P, Socié G, Tazi A. Bronchiolitis obliterans syndrome after allogeneic hematopoietic SCT: phenotypes and prognosis. Bone Marrow Transplant 2012. [PMID: 23208317 PMCID: PMC7091913 DOI: 10.1038/bmt.2012.241] [Citation(s) in RCA: 60] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic SCT (HSCT) is recognized as a new-onset obstructive lung defect (OLD) in pulmonary function testing and is related to pulmonary chronic GVHD. Little is known about the different phenotypes of patients with BOS and their outcomes. We reviewed the data of all allogeneic HSCT recipients referred to our pulmonary department for a non-infectious bronchial disease between 1999 and 2010. We identified 103 patients (BOS (n=77), asthma (n=11) and chronic bronchitis (n=15)). In patients with BOS, we identified two functional phenotypes: a typical OLD, that is, forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio <0.7 (n=53), and an atypical OLD with a concomitant decrease in the FEV1 <80% and FVC <80% predicted with a normal total lung capacity (n=24). The typical OLD was characterized by more severe FEV1 and fewer centrilobular nodules on the computed tomography scan. The FEV1 was not significantly affected during the follow-up, regardless of the phenotype. In addition to acute and extensive chronic GVHD, only the occurrence of BOS soon after transplantation and the intentional treatment of BOS with steroids were associated with a poor survival. The determination of patient subgroups should be explored to improve the management of this condition.
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Affiliation(s)
- A Bergeron
- Université Paris Diderot, Sorbonne Cité, Service de Pneumologie, AP-HP, Hôpital Saint Louis, Paris, France.
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Gassas A, Craig-Barnes H, Dell S, Doyle J, Schechter T, Sung L, Egeler M, Palaniyar N. Chest health surveillance utility in the early detection of bronchiolitis obliterans syndrome in children after allo-SCT. Bone Marrow Transplant 2012; 48:814-8. [DOI: 10.1038/bmt.2012.228] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
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Abstract
Bronchiolitis is a disease of the small airways accompanied by progressive and often irreversible airflow obstruction. Bronchiolitis can have several causes such as infection, toxic exposure, collagen vascular disease, post lung and stem cell transplant, and idiopathic etiology. Symptoms of cough and sputum production are often mistaken for chronic obstructive pulmonary disease or asthma, leading to a delay in diagnosis. Unfortunately, many types of bronchiolitis do not improve with therapy. Bronchiolitis following lung and stem cell transplant are the most common types seen in adults, and provide important insights into its pathogenesis.
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Affiliation(s)
- Brian T Garibaldi
- Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA
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24
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Late-onset noninfectious pulmonary complications in adult allogeneic hematopoietic cell transplant recipients. Transplantation 2011; 91:798-803. [PMID: 21403586 DOI: 10.1097/tp.0b013e31820c85fa] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Late-onset noninfectious pulmonary complications (LONIPCs) after allogeneic hematopoietic cell transplantation (HCT) contribute to posttransplant mortality, morbidity, and decreased quality of life. The effect of newer HCT approaches including reduced intensity and umbilical cord on the incidence and outcome of LONIPC has not been studied. We hereby present a study evaluating the incidence, risk factors, and outcomes of LONIPC in a recent cohort of allogeneic HCT recipients. METHODS We reviewed the incidence and outcomes of LONIPCs in 451 consecutive adult patients who received allogeneic HCT between 2002 and 2007 and survived for 80 days or more after transplant. RESULTS Seventy-four patients developed LONIPCs at a median of 177 days (range, 81-1017 days) after HCT. The 1-year cumulative incidence of LONIPCs was 13% (95% confidence interval, 10%-16%). Of the 451 patients, LONIPCs occurred in 21% receiving myeloablative vs. 12% with nonmyeloablative conditioning. Myeloablative conditioning and chronic graft-versus-host disease were associated with significantly higher risks of LONIPC, but age, graft type, and acute graft-versus-host disease were not identified as risk factors. LONIPCs manifest as diffuse alveolar hemorrhage (DAH, n=28), idiopathic pneumonia syndrome (IPS, n=19), bronchiolitis obliterans (n=22), and other uncommon syndromes (n=5). One-year survival was 77% for patients with bronchiolitis obliterans, 37% for patients with IPS, and 36% for patients with DAH. Three-year survival was significantly worse for recipients with LONIPCs compared with those without LONIPCs (34% vs. 57%, P<0.01). CONCLUSION LONIPCs in allogeneic HCT recipients include a heterogeneous group of diseases with varying clinical courses and prognosis. LONIPCs, particularly IPS or DAH, are associated with high mortality after HCT.
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25
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The spectrum of noninfectious pulmonary complications following hematopoietic stem cell transplantation. Hematol Oncol Stem Cell Ther 2011; 3:143-57. [PMID: 20890072 DOI: 10.1016/s1658-3876(10)50025-6] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
Hematopoietic stem cell transplantation (HSCT) is an established treatment for a variety of malignant and nonmalignant conditions. Pulmonary complications, infectious and noninfectious, are a major cause of morbidity and mortality in these patients. The recent advances in prophylaxis and treatment of infectious complications increased the significance of noninfectious pulmonary conditions. Acute lung injury due to diffuse alveolar hemorrhage or idiopathic pneumonia syndrome are the main acute complications, while bronchiolitis obliterans remains the most challenging pulmonary complications facing clinicians who are taking care of HSCT recipients. There are other noninfectious pulmonary complications following HSCT that are less frequent. This report provides a clinical update of the incidence, risk factors, pathogenesis, clinical characteristics and management of the main noninfectious pulmonary complications following HSCT.
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26
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Azoulay E. Fibrosing Alveolitis in Hematologic Malignancy Patients Undergoing Hematopoietic Cell Transplantation. PULMONARY INVOLVEMENT IN PATIENTS WITH HEMATOLOGICAL MALIGNANCIES 2011. [PMCID: PMC7123073 DOI: 10.1007/978-3-642-15742-4_42] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Although advances in antineoplastic therapy have considerably improved the survival of patients with hematological malignancies, current treatment modalities increase the risk of late complications. Several forms of chronic pulmonary dysfunction due to infectious or noninfectious causes commonly occur in the months to years after chemo-radiotherapy and can be fatal or result in long-term morbidity. The judicious use of prophylactic antimicrobial agents has tipped the balance toward noninfectious etiologies. Hence, while opportunistic infections still contribute to chronic lung disease, late sequelae resulting from antineoplastic therapy have been identified and reported. Patients who proceed to receive hematopoietic cell transplantation (HSCT) are particularly prone to developing lung complications. Pulmonary dysfunction occurring after HSCT may manifest with obstructive or restrictive pulmonary mechanics and may range in severity from subtle, subclinical functional changes to frank respiratory failure. Insights generated using animal models suggest that the immunologic mechanisms contributing to lung inflammation after HSCT may be similar to those responsible for graft-versus host disease. In sum, chronic fibrotic pulmonary dysfunction is a frequent and significant complication facing survivors of hematologic malignancies and their practitioners. The high incidence and suboptimal response to current support care and immunosuppressive therapy underscore the need for heightened awareness and continued research in this area.
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Affiliation(s)
- Elie Azoulay
- Service de Réanimation Médicale, Hôpital Saint Louis, Avenue Claude Vellefaux 1, Paris, 75010 France
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Fluticasone, azithromycin and montelukast therapy in reducing corticosteroid exposure in bronchiolitis obliterans syndrome after allogeneic hematopoietic SCT: a case series of eight patients. Bone Marrow Transplant 2010; 46:1369-73. [PMID: 21132024 PMCID: PMC3987109 DOI: 10.1038/bmt.2010.311] [Citation(s) in RCA: 56] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
Bronchiolitis obliterans syndrome (BOS) is a devastating pulmonary complication affecting long-term survivors of allogeneic hematopoietic cell transplantation. Treatment of BOS with prolonged courses of high dose corticosteroids is often associated with significant morbidity. Reducing the exposure to corticosteroids may reduce treatment-related morbidity. Our institution has recently begun to treat patients with emerging therapies in an effort to diminish corticosteroid exposure. We retrospectively reviewed the 6-month corticosteroid exposure, lung function and failure rates in eight patients with newly diagnosed BOS who were treated with a combination of fluticasone, azithromycin and montelukast (FAM) and a rapid corticosteroid taper. These patients were compared with 14 matched historical patients who received high-dose corticosteroids, followed by a standard taper. The median 6-month prednisone exposure in FAM-treated patients was 1819 mg (0-4036 mg) compared with 7163 mg (6551-7829 mg) in the control group (P=0.002). The median forced expiratory volume in 1 s (FEV(1)) change in FAM-treated patients was 2% (-3 to 4%] compared with 1% (-4 to 5%) in the control group (P=1.0). Prednisone exposure in FAM patients was one quarter that of a retrospective-matched group of patients, with minimal change in median FEV(1), suggesting that BOS may be spared of the morbidities associated with long-term corticosteroid use by using alternative agents with less side effects.
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Au BKC, Au MA, Chien JW. Bronchiolitis obliterans syndrome epidemiology after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant 2010; 17:1072-8. [PMID: 21126596 DOI: 10.1016/j.bbmt.2010.11.018] [Citation(s) in RCA: 153] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2010] [Accepted: 11/17/2010] [Indexed: 02/06/2023]
Abstract
Bronchiolitis obliterans syndrome (BOS) is a pulmonary complication of allogeneic hematopoietic cell transplantation (aHCT). Recent National Institutes of Health consensus diagnostic criteria for BOS have not been assessed in a clinical setting. Modified National Institutes of Health diagnostic consensus criteria for BOS were applied to evaluate its prevalence, risk factors, and outcomes in the modern era of aHCT. Pulmonary function tests from 1145 patients were screened to identify patients with new-onset airflow obstruction. Clinical records were reviewed to exclude pulmonary infection and other causes. The overall prevalence of BOS among all transplanted patients was 5.5%, and 14% among patients with chronic graft-versus-host disease (cGVHD). The median time from transplant to meeting spirometric criteria for BOS was 439 days (range: 274-1690). Although many previously identified risk factors were not significantly associated, lower baseline FEV(1)/FVC ratio (P = .006), non-Caucasian race (P = .014), lower circulating IgG level (P = .010), and presence of cGVHD (P < 0.001) were associated with an increase in risk, with the latter associated with a 10-fold increase in risk. Multivariate analysis indicated that BOS conferred a 1.6-fold increase in risk for mortality after diagnosis. These results suggest that the National Institutes of Health diagnostic criteria can reliably identify BOS, and that it is more prevalent than previously suggested. Spirometric monitoring of high-risk patients with cGVHD may permit earlier detection and intervention for this often-fatal disease.
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Affiliation(s)
- Brandon K C Au
- John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii, USA
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29
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Kinnier CV, Martinu T, Gowdy KM, Nugent JL, Kelly FL, Palmer SM. Innate immune activation by the viral PAMP poly I:C potentiates pulmonary graft-versus-host disease after allogeneic hematopoietic cell transplant. Transpl Immunol 2010; 24:83-93. [PMID: 21070856 DOI: 10.1016/j.trim.2010.11.004] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2010] [Accepted: 11/04/2010] [Indexed: 12/18/2022]
Abstract
Respiratory viral infections cause significant morbidity and increase the risk for chronic pulmonary graft-versus-host disease (GVHD) after hematopoietic cell transplantation (HCT). Our overall hypothesis is that local innate immune activation potentiates adaptive alloimmunity. In this study, we hypothesized that a viral pathogen-associated molecular pattern (PAMP) alone can potentiate pulmonary GVHD after allogeneic HCT. We, therefore, examined the effect of pulmonary exposure to polyinosinic:polycytidylic acid (poly I:C), a viral mimetic that activates innate immunity, in an established murine HCT model. Poly I:C-induced a marked pulmonary T cell response in allogeneic HCT mice as compared to syngeneic HCT, with increased CD4+ cells in the lung fluid and tissue. This lymphocytic inflammation persisted at 2 weeks post poly I:C exposure in allogeneic mice and was associated with CD3+ cell infiltration into the bronchiolar epithelium and features of epithelial injury. In vitro, poly I:C enhanced allospecific proliferation in a mixed lymphocyte reaction. In vivo, poly I:C exposure was associated with an early increase in pulmonary monocyte recruitment and activation as well as a decrease in CD4+FOXP3+ regulatory T cells in allogeneic mice as compared to syngeneic. In contrast, intrapulmonary poly I:C did not alter the extent of systemic GVHD in either syngeneic or allogeneic mice. Collectively, our results suggest that local activation of pulmonary innate immunity by a viral molecular pattern represents a novel pathway that contributes to pulmonary GVHD after allogeneic HCT, through a mechanism that includes increased recruitment and maturation of intrapulmonary monocytes.
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Affiliation(s)
- Christine V Kinnier
- Department of Medicine, Duke University Medical Center, 106 Research Drive, Building MSRB2 Room 2100B, Durham, NC 27710, USA
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Duncan CN, Barry EV, Lehmann LE. Tolerability of pravastatin in pediatric hematopoietic stem cell transplant patients with bronchiolitis obliterans. J Pediatr Hematol Oncol 2010; 32:185-8. [PMID: 20186101 DOI: 10.1097/mph.0b013e3181d32184] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Pravachol and other statins have immune modulatory effects and have been shown to decrease the incidence of bronchiolitis obliterans (BrOb) in lung transplant recipients. It may also be useful in the treatment or prevention of hematopoietic stem cell transplant (HSCT) associated bronchiolitis obliterans. However, the safety of pravachol has not been shown in pediatric patients with BrOb after HSCT. We report on the safety and tolerability in 5 pediatric HSCT patients with established BrOb. All participants tolerated the drug without difficulty and there were no pravachol-associated adverse effects. Changes in creatine kinase (CK) and transaminases were minimal in 4 patients. One patient experienced increased CK and alanine aminotransferase, and a decrease in platelet count in the setting of severe systemic illness. No other patient had a clinically relevant change in white blood cell count, platelet count, or hemoglobin. Pravachol was well tolerated and safe in this group of patients, and merits further study in this patient population.
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31
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Outcome and treatment of late-onset noninfectious pulmonary complications after allogeneic haematopoietic SCT. Bone Marrow Transplant 2010; 45:1719-27. [DOI: 10.1038/bmt.2010.48] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
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Bergeron A, Chagnon K, Feuillet S, Chevret S, Tazi A. [Prospective evaluation of the efficacy of the combination of budesonide/formoterol in obstructive airway disease after allogeneic hematopoietic stem cell transplantation]. Rev Mal Respir 2010; 26:794-800. [PMID: 19953024 PMCID: PMC7126391 DOI: 10.1016/s0761-8425(09)72433-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
État des connaissances La survenue d’un trouble ventilatoire obstructif au décours d’une allogreffe de cellules souches hématopoïétiques est attribuée à une réaction de greffon contre l’hôte pulmonaire et menace le pronostic des patients. La prise en charge thérapeutique consiste habituellement en une intensification du traitement immunosuppresseur systémique. Cette attitude non validée entraîne de nombreuses complications, notamment infectieuses, encourageant l’évaluation de traitements plus ciblés. Nous avons récemment rapporté de façon rétrospective notre expérience de l’efficacité du budésonide/ formotérol inhalés dans cette pathologie. Méthodes Il s’agit d’une étude prospective, multicentrique, randomisée, en double aveugle contre placebo qui évaluera l’efficacité de l’association budésonide/formotérol (400/12 µg 2 inhalations matin et soir) chez des patients ayant développé un trouble ventilatoire obstructif modéré à sévère après allogreffe de cellules souches hématopoïétiques. Le critère d’évaluation principal sera la variation absolue du VEMS après 1 mois de traitement. Les critères d’évaluation secondaires seront basés sur l’évolution de la symptomatologie clinique et de la fonction respiratoire après 6 mois de traitement. Résultats attendus L’hypothèse émise est que le traitement inhalé de budésonide/formotérol améliore de façon significative la fonction et les symptômes respiratoires dès le premier mois de traitement dans le groupe de patients étudié.
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Affiliation(s)
- A Bergeron
- Service de Pneumologie, Hôpital Saint-Louis, Assistance Publique- Hôpitaux de Paris, Université Denis Diderot, Paris 7, Paris, France.
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Bronchiolitis obliterans syndrome after allogeneic hematopoietic stem cell transplantation-an increasingly recognized manifestation of chronic graft-versus-host disease. Biol Blood Marrow Transplant 2009; 16:S106-14. [PMID: 19896545 DOI: 10.1016/j.bbmt.2009.11.002] [Citation(s) in RCA: 134] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
Bronchiolitis obliterans syndrome (BOS) is a progressive, insidious, and often fatal lung alloreaction that can occur following allogeneic hematopoietic stem cell transplantation (HSCT) or allogeneic lung transplantation. Current estimates in the literature suggest that approximately 2% to 3% of all allogeneic HSCT recipients and 6% of patients who develop chronic graft-versus-host disease (cGVHD) will develop this syndrome. However, based on newer data it is likely that the true incidence of BOS is higher. Unfortunately, the survival and treatment of patients with BOS after HSCT has not improved over the last 20 years. Attempts at clinical trials have been hindered by the lack of uniform diagnostic criteria and inability to detect the syndrome at a reversible stage in its natural history. Recently, the National Institutes of Health (NIH) consensus project for criteria in cGVHD has made recommendations regarding the diagnosis of BOS and monitoring of lung disease among long-term survivors. Although a rare and poorly understood manifestation of cGVHD, BOS occurs commonly after lung transplantation and is similar in pathology, clinical presentation, radiographic presentation, and presumed immunologic pathogenesis. This review describes the current understanding of the epidemiology and pathogenesis of BOS and presents information on evaluations and therapies for patients with BOS after HSCT.
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Pandya CM, Soubani AO. Bronchiolitis obliterans following hematopoietic stem cell transplantation: a clinical update. Clin Transplant 2009; 24:291-306. [PMID: 19849704 DOI: 10.1111/j.1399-0012.2009.01122.x] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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Williams KM, Chien JW, Gladwin MT, Pavletic SZ. Bronchiolitis obliterans after allogeneic hematopoietic stem cell transplantation. JAMA 2009; 302:306-14. [PMID: 19602690 PMCID: PMC7357209 DOI: 10.1001/jama.2009.1018] [Citation(s) in RCA: 158] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/14/2022]
Abstract
With improvements in supportive care, both long-term survival following allogeneic hematopoietic stem cell transplantations (HSCTs) and the indications for this procedure have increased. As a result, the number of patients living with long-term toxic effects due to HSCT has increased. A once rare condition of the donor immune cells attacking healthy host tissues, termed chronic graft-vs-host disease, has become a more common phenomenon. When chronic graft-vs-host disease affects the lung tissue, bronchiolitis obliterans syndrome ensues. Recent data suggest that bronchiolitis obliterans syndrome may affect up to 6% of HSCT recipients and dramatically alters survival, with overall survival of only 13% at 5 years. These statistics have not improved since the first presentation of this disease over 20 years ago. Challenges to the progress of medical management of bronchiolitis obliterans syndrome include difficulties and delays in diagnosis and a paucity of data on pathogenesis to direct new therapies. This article critically evaluates the current diagnostic criteria for bronchiolitis obliterans syndrome and reviews the epidemiology, pathogenesis, and available treatments. Improvements in survival will likely require early disease recognition, allowing for therapeutic modulation of disease prior to the development of irreversible airway obliteration.
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Affiliation(s)
- Kirsten M Williams
- Experimental Transplantation and Immunology Branch, National Cancer Institute, Bldg 10 CRC, Room 3-3288, 10 Center Dr, Bethesda, MD 20892, USA.
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Macrolides in the treatment of bronchiolitis obliterans in allograft recipients. Bone Marrow Transplant 2009; 44:69-73. [PMID: 19430505 DOI: 10.1038/bmt.2009.106] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Bronchiolitis obliterans (BO) is a serious complication of hematopoietic SCT (HSCT). The condition is believed to be the result of an inflammatory part of the GVHD. Although many BO patients receive immunosuppressive therapy, there is no clear evidence that therapeutic interventions have a positive impact. In the last 20 years, it has been recognized that macrolides have immunomodulatory effects beyond their antibiotic effect. Recent data suggest also that the use of macrolides in BO post HSCT may halt disease progression. Our objectives are to give the readers information on the background of BO post HSCT, to review the immunomodulatory properties of macrolides in general and specifically in pulmonary diseases, and to summarize the current knowledge of macrolide benefits in BO therapy. Research into macrolide immunomodulation for chronic pulmonary disorders, such as diffuse panbronchiolitis and cystic fibrosis, shows consistent positive effects. The use of macrolides for other types of pulmonary inflammatory complications is yet to be proved. The benefit for BO post HSCT was shown only in a small non-randomized trial. Additional in vivo research is needed before developing any firm conclusions.
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High-resolution CT findings of bronchiolitis obliterans syndrome after hematopoietic stem cell transplantation. J Thorac Imaging 2009; 23:244-50. [PMID: 19204468 DOI: 10.1097/rti.0b013e3181809df0] [Citation(s) in RCA: 65] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE To describe the high-resolution computed tomography (CT) findings occurring in bronchiolitis obliterans syndrome (BOS) after hematopoietic stem cell transplantation (HSCT) and to determine the relationship between pulmonary function tests (PFTs) and air trapping detected on expiratory CT. MATERIALS AND METHODS The high-resolution CT scans of 33 patients who underwent HSCT and subsequently developed BOS were evaluated by 2 observers blinded to PFT results. Scans were ranked for degree of air trapping and scored for findings of bronchial wall thickening, bronchiectasis, and centrilobular opacities. Air-trapping rank was correlated with the degree of airflow obstruction as determined by PFTs. RESULTS The ranking of air trapping correlated significantly with 1-second forced expiratory volume (P=0.001), 1-second forced expiratory volume/forced vital capacity (P<0.001), residual volume (P<0.001), carbon monoxide diffusion capacity (P=0.023), but not forced vital capacity (P=0.14) or total lung capacity (P=0.07). Bronchial wall thickening occurred in 73.0%, predominantly in lower lobes (P=0.007), but was mild. Bronchiectasis occurred in 42.4% and centrilobular opacities in 39.4%. CONCLUSIONS In BOS developing after HSCT, air trapping is the principal finding on CT, and its severity correlates with PFTs. Bronchial wall thickening is common, but almost always mild; bronchiectasis and centrilobular opacities occur in less than half of cases and are also mild.
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Bergeron A, Feuillet S, Meignin V, Socie G, Tazi A. Les complications pulmonaires tardives non infectieuses après allogreffe de cellules souches hématopoïétiques. Rev Mal Respir 2008; 25:173-83. [DOI: 10.1016/s0761-8425(08)71515-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
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Yoshihara S, Yanik G, Cooke KR, Mineishi S. Bronchiolitis obliterans syndrome (BOS), bronchiolitis obliterans organizing pneumonia (BOOP), and other late-onset noninfectious pulmonary complications following allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2008; 13:749-59. [PMID: 17580252 DOI: 10.1016/j.bbmt.2007.05.001] [Citation(s) in RCA: 106] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2007] [Accepted: 05/01/2007] [Indexed: 12/19/2022]
Abstract
Pulmonary dysfunction is a significant complication following allogeneic hematopoietic stem cell transplantation (HSCT), and is associated with significant morbidity and mortality. Effective antimicrobial prophylaxis and treatment strategies have increased the incidence of noninfectious lung injury, which can occur in the early posttransplant period or in the months and years that follow. Late-onset noninfectious pulmonary complications are frequently encountered, but diagnostic criteria and terminology for these disorders can be confusing and therapeutic approaches are suboptimal. As a consequence, inaccurate diagnosis of these conditions may hamper the appropriate data collection, enrollment into clinical trials, and appropriate patient care. The purpose of this review is to clarify the pathogenesis and diagnostic criteria of representative conditions, such as bronchiolitis obliterans syndrome and bronchiolitis obliterans organizing pneumonia, and to discuss the appropriate diagnostic strategies and treatment options.
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Affiliation(s)
- Satoshi Yoshihara
- Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan
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Bergeron A, Belle A, Chevret S, Ribaud P, Devergie A, Esperou H, Ades L, Gluckman E, Socié G, Tazi A. Combined inhaled steroids and bronchodilatators in obstructive airway disease after allogeneic stem cell transplantation. Bone Marrow Transplant 2007; 39:547-53. [PMID: 17351647 DOI: 10.1038/sj.bmt.1705637] [Citation(s) in RCA: 51] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Bronchiolitis obliterans (BO) is a potentially life-threatening complication following allogeneic stem cell transplantation (SCT) and usually carries a poor prognosis. Immunosuppressive medications are the main treatment, but are rarely effective, especially when the disease is severe. Thus, both early detection and alternative therapeutic approaches of post SCT BO are needed. We report our experience with Budesonide/Formoterol, an inhaled steroid and long-acting bronchodilatator combination, in a group of patients with mild to moderately severe BO after SCT whose systemic immunosuppressive treatment had not been modified. Thirteen patients were treated. The diagnosis of BO was based on the presence of respiratory symptoms and air-trapping on expiratory lung high-resolution computed tomography in all patients, associated with irreversible airflow obstruction in seven cases. The median follow-up was 12.8 months (range: 5-29 months). All patients improved clinically, and both forced expiratory volume in 1 (FEV(1)) and mean expiratory flow values increased significantly during follow-up (534+/-268 ml in absolute values and 36+/-27% compared to pretreatment values for FEV(1); P<0.02). These encouraging results provide new insights in the therapeutic approach of BO after SCT and require confirmation in a larger group of patients with a longer follow-up.
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Affiliation(s)
- A Bergeron
- Service de Pneumologie, Hôpital Saint-Louis, Université Paris 7, UFR Denis Diderot, Assistance Publique-Hôpitaux de Paris, Paris, France
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Abstract
Tens of thousands of patients undergo hematopoietic stem cell transplantation (HSCT) each year, mainly for hematologic disorders. In addition to the underlying diseases, the chemotherapy and radiation therapy that HSCT recipients receive can result in damage to multiple organ systems. Pulmonary complications develop in 30% to 60% of HSCT recipients. With the widespread use of prophylaxis for certain infections, the spectrum of pulmonary complications after HSCT has shifted from more infectious to noninfectious complications. This article reviews some of the noninfectious, chronic pulmonary complications.
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Affiliation(s)
- Bekele Afessa
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
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Chien JW, Zhao LP, Hansen JA, Fan WH, Parimon T, Clark JG. Genetic variation in bactericidal/permeability-increasing protein influences the risk of developing rapid airflow decline after hematopoietic cell transplantation. Blood 2005; 107:2200-7. [PMID: 16304058 PMCID: PMC1895720 DOI: 10.1182/blood-2005-06-2338] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Innate immunity is involved in the biology of graft versus host disease and common airway diseases. We screened 15 genes in this pathway using a linkage disequilibrium-based approach to identify potential candidate genes that may be involved in the development of airflow obstruction after hematopoietic cell transplantation. Sixty-nine single-nucleotide polymorphisms were selected for assessment in a discovery cohort (n = 363). Significant associations were validated in a validation cohort (n = 209). Expression of the candidate gene was demonstrated by detecting gene transcript and protein in malignant and normal small airway epithelial cells. In the discovery cohort, 133 patients developed significant airflow decline. Four patient and donor bactericidal/permeability-increasing (BPI) haplotypes were associated with a 2-fold to 3-fold increased risk of developing significant airflow decline (P values, .004-.038). This association was confirmed in the validation cohort, which had 66 patients with significant airflow decline, with 9 significant haplotypes (P values, .013-.043). BPI gene transcript and protein were detected in airway epithelial cells. These results suggest mutations in the BPI gene significantly influence the risk of developing rapid airflow decline after hematopoietic cell transplantation and may represent a novel therapeutic target for this form of airway disease.
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Affiliation(s)
- Jason W Chien
- Pulmonary and Critical Care Section, Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave North, D5-280, Seattle, WA 98109-1024, USA.
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Yoshihara S, Tateishi U, Ando T, Kunitoh H, Suyama H, Onishi Y, Tanosaki R, Mineishi S. Lower incidence of Bronchiolitis obliterans in allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning compared with myeloablative conditioning. Bone Marrow Transplant 2005; 35:1195-200. [PMID: 15852024 DOI: 10.1038/sj.bmt.1704985] [Citation(s) in RCA: 50] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
Bronchiolitis obliterans (BO) is one of the most devastating complications after allogeneic stem cell transplantation (HSCT). However, its true pathogenesis is still to be elucidated. We conducted this study to find whether tissue damage due to high-dose chemo-radiotherapy is related to its pathogenesis. In all, 144 patients who received allogeneic HSCT between May 1999 and October 2001, and survived more than 80 days after transplant, were analyzed. Clinical course, pulmonary function tests, imaging studies including CT scan, and pathology results were reviewed. The overall incidence of BO was 9.7% (14/144). The cumulative incidence of BO at 2 years after transplant was 17% with myeloablative conditioning, and 2.3% with reduced intensity conditioning (P=0.024). Multivariate analysis showed that myeloablative conditioning was the only factor which affected the incidence of BO. Development of BO did not significantly affect the overall survival of patients. However, if they developed BO earlier than 200 days post transplant, the prognosis was significantly worse than if they developed it later than 200 days post transplant (P=0.003) or if they did not develop BO (P=0.002). Our results imply that tissue damage secondary to intensive chemo-radiotherapy may contribute to the pathogenesis of BO.
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Affiliation(s)
- S Yoshihara
- Stem Cell Transplant Unit, National Cancer Center Hospital, Tokyo, Japan.
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Santo Tomas LH, Loberiza FR, Klein JP, Layde PM, Lipchik RJ, Rizzo JD, Bredeson CN, Horowitz MM. Risk Factors for Bronchiolitis Obliterans in Allogeneic Hematopoietic Stem-Cell Transplantation for Leukemia. Chest 2005; 128:153-61. [PMID: 16002929 DOI: 10.1378/chest.128.1.153] [Citation(s) in RCA: 127] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022] Open
Abstract
STUDY OBJECTIVES Reported risk factors for bronchiolitis obliterans (BO) in allogeneic hematopoietic stem-cell transplant recipients come from modest-sized studies and are limited to experiences of single institutions. We sought to identify risk factors for BO using data from the International Bone Marrow Transplant Registry. METHODS Registry data on 6,275 adult patients with leukemia who received human leukocyte antigen-identical sibling transplants from 1989 to 1997 and survived at least 100 days after transplantation were evaluated for the study. Risk factors for BO were analyzed using proportional hazards regression. RESULTS Seventy-six patients were found to have BO, with an incidence rate of 1.7% at 2 years after transplantation. The Kaplan-Meier estimate of median time to onset of BO was 431 days. Histologic evaluation was performed in 36 patients (47%). In 28 patients (37%), diagnosis was based on pulmonary function tests, CT scans of the chest, or a combination of both. On multivariate analysis, the factors that were associated with an increased risk for BO included the following: peripheral blood-derived stem cell, a busulfan-based conditioning regimen, interval from diagnosis to transplant > or = 14 months, female donor to male recipient sex match, prior interstitial pneumonitis, and an episode of moderate-to-severe acute graft-vs-host disease (GVHD). CONCLUSION In addition to corroborating previously reported risk factors, such as acute GVHD and a busulfan-based conditioning regimen, we found that peripheral blood stem-cell transplantation, long duration to transplant, female donor to male recipient, and a prior episode of interstitial pneumonitis are associated with an increased risk for BO.
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Affiliation(s)
- Linus H Santo Tomas
- Division of Pulmonary and Critical Care Medicine, Medical College of Wisconsin, 9200 West Wisconsin Ave, Milwaukee, WI 53226, USA.
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Chien JW, Martin PJ, Flowers ME, Nichols WG, Clark JG. Implications of early airflow decline after myeloablative allogeneic stem cell transplantation. Bone Marrow Transplant 2004; 33:759-64. [PMID: 14968136 DOI: 10.1038/sj.bmt.1704422] [Citation(s) in RCA: 55] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The clinical significance of early airflow decline after myeloablative allogeneic hematopoietic SCT is uncertain. We performed a retrospective cohort analysis to determine if airflow decline by day 100 is associated with later development of transplant-related airflow obstruction (AFO) and increased mortality risk. Overall, 750 (40%) patients had airflow decline by day 100. Development of airflow decline by day 100 was associated with an increased risk for AFO at 1 year (relative risk 2.6, 95% confidence interval 2.1-3.1) but not with an increase in mortality risk (hazard ratio (HR) 0.86, P=0.05). However, patients with the fastest rate of decline between day 100 and 1 year (12.5% per year +/-24) had the highest mortality risk (HR 3.2, P<0.001). In conclusion, airflow measurements made on day 100 do not predict the rate of airflow decline between day 100 and 1 year, and therefore are not useful as a single measurement for determining mortality risk associated with development of AFO. Closer monitoring of the rate of airflow decline during the first year may facilitate the timely detection and treatment of early airflow decline and prevent the development of fixed AFO and increased mortality risk after hematopoietic stem cell transplant.
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Affiliation(s)
- J W Chien
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.
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46
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Jung JI, Jung WS, Hahn ST, Min CK, Kim CC, Park SH. Bronchiolitis obliterans after allogenic bone marrow transplantation: HRCT findings. Korean J Radiol 2004; 5:107-13. [PMID: 15235235 PMCID: PMC2698138 DOI: 10.3348/kjr.2004.5.2.107] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Abstract
Objective To evaluate the high resolution computed tomography (HRCT) findings of bronchiolitis obliterans (BO) after bone marrow transplantation (BMT). Materials and Methods During the past three years, 11 patients were diagnosed as having BO after BMT when they developed irreversible air flow obstruction, with an FEV1 value of less than 80% of the baseline value, without any clinical evidence of infection. All 11 patients underwent HRCT, of whom eight also underwent follow-up HRCT. The HRCT images were assessed retrospectively for the presence of decreased lung attenuation, segmental or subsegmental bronchial dilatation, diminution of peripheral vascularity, centrilobular nodules, and branching linear structure on the inspiratory images. The lobar distribution of the decreased lung attenuation and bronchial dilatation was also examined. The presence of air trapping was investigated on the expiratory images. The interval changes of the HRCT findings were evaluated in those patients who had follow-up images. Results Abnormal HRCT findings were present in all cases; the most common abnormalities were decreased lung attenuation (n=11), subsegmental bronchial dilatation (n=6), diminution of peripheral vascularity (n=6), centrilobular nodules or branching linear structure (n=3), and segmental bronchial dilatation (n=3). Expiratory air trapping was noted in all patients. The decreased lung attenuation and bronchial dilatations were more frequent or extensive in the lower lobes. Interval changes were found in all patients with follow-up HRCT: increased extent of decreased lung attenuation (n=7); newly developed or progressed bronchial dilatation (n=4); and increased lung volume (n=3). Conclusion HRCT scans are abnormal in patients with BO, with the most commonly observed finding being areas of decreased lung attenuation. While the HRCT findings are not specific, it is believed that their common features can assist in the diagnosis of BO in BMT recipients.
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Affiliation(s)
- Jung Im Jung
- Department of Radiology, St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
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Dudek AZ, Mahaseth H, DeFor TE, Weisdorf DJ. Bronchiolitis obliterans in chronic graft-versus-host disease: analysis of risk factors and treatment outcomes. Biol Blood Marrow Transplant 2004; 9:657-66. [PMID: 14569562 DOI: 10.1016/s1083-8791(03)00242-8] [Citation(s) in RCA: 188] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Bronchiolitis obliterans (BrOb), a late complication of bone marrow transplantation (BMT), is associated with chronic graft-versus-host disease (GVHD) and is frequently fatal. To identify the risk factors associated with BrOb, the factors affecting survival, treatment outcomes, and causes of death of patients with BrOb, we retrospectively analyzed 2859 BMT recipients. No cases of BrOb occurred among 1070 autologous BMT recipients. Among 1789 allogeneic BMT recipients, we identified 47 patients with BrOb. In multivariate analysis, older recipients or donors and acute GVHD were significantly associated with the development of BrOb. Among patients with BrOb, 5-year survival from the time of transplantation was only 10%, versus 40% among allogeneic BMT recipients without BrOb. The clinical course of BrOb had a significant effect on survival: 79% survived 5 years from the time of BrOb diagnosis if BrOb improved versus 13% if there was no improvement after the first-line therapy. Predictors of response included older donors and recipients, a previous diagnosis of chronic GVHD, and diagnosis of BrOb 6 months after transplantation; each of these significantly increased the likelihood of a favorable response to treatment. BrOb had high mortality rate of 55%, and pulmonary failure was the leading cause of death. More effective BrOb therapy is needed, especially for patients with unfavorable presentation.
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Affiliation(s)
- Arkadiusz Z Dudek
- Bone Marrow Transplantation Program, University of Minnesota Health Sciences Center, 420 Delaware Street SE, MMC 480, Minneapolis, MN 55455, USA.
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Kotloff RM, Ahya VN, Crawford SW. Pulmonary complications of solid organ and hematopoietic stem cell transplantation. Am J Respir Crit Care Med 2004; 170:22-48. [PMID: 15070821 DOI: 10.1164/rccm.200309-1322so] [Citation(s) in RCA: 231] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
The ability to successfully transplant solid organs and hematopoietic stem cells represents one of the landmark medical achievements of the twentieth century. Solid organ transplantation has emerged as the standard of care for select patients with severe vital organ dysfunction and hematopoietic stem cell transplantation has become an important treatment option for patients with a wide spectrum of nonmalignant and malignant hematologic disorders, genetic disorders, and solid tumors. Although advances in surgical techniques, immunosuppressive management, and prophylaxis and treatment of infectious diseases have made long-term survival an achievable goal, transplant recipients remain at high risk for developing a myriad of serious and often life-threatening complications. Paramount among these are pulmonary complications, which arise as a consequence of the immunosuppressed status of the recipient as well as from such factors as the initial surgical insult of organ transplantation, the chemotherapy and radiation conditioning regimens that precede hematopoietic stem cell transplantation, and alloimmune mechanisms mediating host-versus-graft and graft-versus-host responses. As the population of transplant recipients continues to grow and as their care progressively shifts from the university hospital to the community setting, knowledge of the pulmonary complications of transplantation is increasingly germane to the contemporary practice of pulmonary medicine.
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Affiliation(s)
- Robert M Kotloff
- Section of Advanced Lung Disease and Lung Transplantation, Pulmonary, Allergy, and Critical Care Division, University of Pennsylvania Medical Center, 838 West Gates, 3400 Spruce Street, Philadelphia, PA 19027, USA.
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49
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Shin HJ, Park CY, Park YH, Kim YJ, Min CK, Lee S, Kim DW, Lee JW, Min WS, Kim CC. Spontaneous Pneumothorax Developed in Patients with Bronchiolitis Obliterans after Unrelated Hematopoietic Stem Cell Transplantation: Case Report and Review of the Literature. Int J Hematol 2004; 79:298-302. [PMID: 15168602 DOI: 10.1532/ijh97.a10302] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Spontaneous pneumothorax following unrelated hematopoietic stem cell transplantation developed in our 2 patients with bronchiolitis obliterans. Bronchiolitis obliterans is a form of obstructive airway disease and is considered a manifestation of chronic graft-versus-host disease (GVHD). Both of the patients were the recipients of marrow from HLA-matched unrelated donors after a preparative regimen with total body irradiation. Chronic GVHD after transplantation is a common feature in these cases. In contrast to other patients with pneumothorax described in the literature, our patients did not develop bullae. We describe a pneumothorax secondary to bronchiolitis obliterans that complicated the posttransplantation course.
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Affiliation(s)
- Ho-Jin Shin
- Department of Internal Medicine, College of Medicine, Pusan National University, Busan, Korea
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Freudenberger TD, Madtes DK, Curtis JR, Cummings P, Storer BE, Hackman RC. Association between acute and chronic graft-versus-host disease and bronchiolitis obliterans organizing pneumonia in recipients of hematopoietic stem cell transplants. Blood 2003; 102:3822-8. [PMID: 12869516 DOI: 10.1182/blood-2002-06-1813] [Citation(s) in RCA: 125] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Bronchiolitis obliterans organizing pneumonia (BOOP) has been reported following hematopoietic stem cell (HSC) transplantation, but the clinical features and risk factors for this disorder have not been well characterized. This case-control study of 49 patients with histologic BOOP and 161 control subjects matched by age and year of transplantation describes the clinical features and analyzes the risk factors for BOOP following HSC transplantation. Data on clinical features and outcome were collected by chart review. Odds ratios, estimating the relative risk of BOOP in allogeneic HSC recipients, were calculated by conditional logistic regression with adjustment for potential confounding factors. Clinical features of BOOP in this population were similar to idiopathic BOOP and BOOP occurring in other disease settings. There was an association between acute and chronic graft-versus-host disease (GVHD) and the subsequent development of BOOP (odds ratios, 3.8 [95% CI, 1.2 to 12.3] and 3.1 [95% CI, 1.1 to 9.2], respectively). Patients with BOOP were more likely to have acute GVHD involving the skin (odds ratio, 4.6; P =.005) and chronic GVHD involving the gut (odds ratio, 6.6; P =.018) and oral cavity (odds ratio, 5.9; P =.026). This study shows that histologic BOOP following HSC transplantation has clinical features that resemble idiopathic BOOP and is strongly associated with prior acute and chronic GVHD. These results have important implications for the care of patients who develop respiratory symptoms after HSC transplantation and may help elucidate the pathogenesis of idiopathic BOOP.
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Affiliation(s)
- Todd D Freudenberger
- Department of Medicine, School of Public Health and Community Medicine, University of Washington, Seattle, WA, USA
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