Bronchoalveolar Lavage and Other Methods to Define the Human Respiratory Tract Milieu in Health and Disease

During fiber-optic bronchoscopy (FOB), surface sampling of the human respiratory airways and alveolar unit can be done with bronchoalveolar lavage (BAL), plus selective sites can be brushed for cells and transbronchial biopsies made in adjacent tissue. This permits analysis of the respiratory tract’s milieu in healthy normals, in those with disease, and in control subjects. These combined procedures have been an established approach for obtaining specimens for research and for clinical assessment for over four decades. However, now new less invasive sampling methods are emerging. This review emphasizes BAL and the cellular and noncellular components recovered in fluid that have contributed to improving knowledge of how the respiratory tree’s innate immunity can protect, and how airway structures can become deranged and manifest disease. After a discussion of training for FOB and procedural issues, a spectrum of respiratory diseases studied with BAL is presented, including airway illness (asthma and chronic obstructive pulmonary disease), diffuse interstitial lung diseases [idiopathic pulmonary fibrosis, rheumatoid interstitial lung disease (ILD), granulomatous ILDs], lung infections, lung malignancy, and upper and lower tract airway problems. Some recent studies with exhaled breath condensate analyses are given.

[1]  M. Raftery,et al.  Proteomics in detection and monitoring of asthma and smoking-related lung diseases , 2010, Expert review of proteomics.

[2]  D. Moller,et al.  Etiology of sarcoidosis. , 1997, Clinics in chest medicine.

[3]  R. Elashoff,et al.  Bronchoalveolar lavage and response to cyclophosphamide in scleroderma interstitial lung disease. , 2008, American journal of respiratory and critical care medicine.

[4]  H. Reynolds Bronchoalveolar lavage--obtaining biologic specimens from the respiratory tract surface. , 2008, Sarcoidosis, vasculitis, and diffuse lung diseases : official journal of WASOG.

[5]  W. MacNee,et al.  Update in chronic obstructive pulmonary disease 2007. , 2008, American journal of respiratory and critical care medicine.

[6]  H. Reynolds,et al.  Bronchoalveolar lavage cells and proteins in patients with the acquired immunodeficiency syndrome. An immunologic analysis. , 1985, Annals of internal medicine.

[7]  M. Fasano Combined airways: impact of upper airway on lower airway , 2010, Current opinion in otolaryngology & head and neck surgery.

[8]  R. Matthay,et al.  Bronchoalveolar lavage. Its safety in subjects with mild asthma. , 1984, Chest.

[9]  R. Baughman Technical aspects of bronchoalveolar lavage: recommendations for a standard procedure. , 2007, Seminars in respiratory and critical care medicine.

[10]  E. Danila,et al.  Diagnostic role of BAL fluid CD4/CD8 ratio in different radiographic and clinical forms of pulmonary sarcoidosis , 2009, The clinical respiratory journal.

[11]  E. Bargagli,et al.  Proteomic analysis in interstitial lung diseases: a review , 2009, Current opinion in pulmonary medicine.

[12]  A. Borczuk,et al.  Genomics of lung cancer. , 2009, Proceedings of the American Thoracic Society.

[13]  V. Poletti,et al.  Bronchoalveolar Lavage in Malignancy , 2007, Seminars in respiratory and critical care medicine.

[14]  Y. Lacasse,et al.  Hypersensitivity pneumonitis caused by fungi. , 2010, Proceedings of the American Thoracic Society.

[15]  P G Mulder,et al.  A computer program using BALF-analysis results as a diagnostic tool in interstitial lung diseases. , 1996, American journal of respiratory and critical care medicine.

[16]  Herbert Y. Reynolds M. D. Hypersensitivity pneumonitis: Correlation of cellular and immunologic changes with clinical phases of disease , 2007, Lung.

[17]  Symposium I: Pparγ: A Novel Molecular Target in Lung Disease , 2007, Journal of Investigative Medicine.

[18]  J. Grunewald,et al.  Löfgren's syndrome: human leukocyte antigen strongly influences the disease course. , 2009, American journal of respiratory and critical care medicine.

[19]  S. Hodge,et al.  Azithromycin improves macrophage phagocytic function and expression of mannose receptor in chronic obstructive pulmonary disease. , 2008, American journal of respiratory and critical care medicine.

[20]  H. Ortega,et al.  Needs and opportunities for research in hypersensitivity pneumonitis. , 2005, American journal of respiratory and critical care medicine.

[21]  Y. Lacasse,et al.  Classification of Hypersensitivity Pneumonitis , 2009, International Archives of Allergy and Immunology.

[22]  P. Paré,et al.  The nature of small-airway obstruction in chronic obstructive pulmonary disease. , 2004, The New England journal of medicine.

[23]  R. Crystal,et al.  Interstitial lung diseases of unknown cause. Disorders characterized by chronic inflammation of the lower respiratory tract. , 1984, The New England journal of medicine.

[24]  G. Silvestri The Evolution of Bronchoscopy Training , 2008, Respiration.

[25]  H. Collard,et al.  Undifferentiated Connective Tissue Disease-Associated Interstitial Lung Disease: Changes in Lung Function , 2010, Lung.

[26]  R. Golpe,et al.  Exhaled nitric oxide predicts control in patients with difficult-to-treat asthma , 2009, European Respiratory Journal.

[27]  D. Gail,et al.  Past achievements and future directions of sarcoidosis research: a NHLBI perspective. , 2006, Sarcoidosis, vasculitis, and diffuse lung diseases : official journal of WASOG.

[28]  C. Cordeiro,et al.  Bronchoalveolar lavage in occupational lung diseases. , 2007, Seminars in respiratory and critical care medicine.

[29]  M. Wolfgang,et al.  Detection of anaerobic bacteria in high numbers in sputum from patients with cystic fibrosis. , 2008, American journal of respiratory and critical care medicine.

[30]  Brian K. Schimmoller,et al.  The changing face , 2001 .

[31]  H. Reynolds Use of Bronchoalveolar Lavage in Humans—Past Necessity and Future Imperative , 2000, Lung.

[32]  S. Hurd,et al.  Summary and recommendations of a workshop on the investigative use of fiberoptic bronchoscopy and bronchoalveolar lavage in asthmatic patients. , 1985, Chest.

[33]  G. Hunninghake,et al.  Bronchoalveolar lavage of allergic asthmatic patients following allergen bronchoprovocation. , 1986, Chest.

[34]  A. Peters,et al.  Epithelium, inflammation, and immunity in the upper airways of humans: studies in chronic rhinosinusitis. , 2009, Proceedings of the American Thoracic Society.

[35]  T. Egan,et al.  Lung transplantation: opportunities for research and clinical advancement. , 2005, American journal of respiratory and critical care medicine.

[36]  H. Reynolds,et al.  Analysis of proteins and respiratory cells obtained from human lungs by bronchial lavage. , 1974, The Journal of laboratory and clinical medicine.

[37]  Barmak Modrek,et al.  T-helper type 2-driven inflammation defines major subphenotypes of asthma. , 2009, American journal of respiratory and critical care medicine.

[38]  T. Murphy,et al.  Pseudomonas aeruginosa in chronic obstructive pulmonary disease. , 2008, American journal of respiratory and critical care medicine.

[39]  B. Grant,et al.  Airway bacterial concentrations and exacerbations of chronic obstructive pulmonary disease. , 2007, American journal of respiratory and critical care medicine.

[40]  C. Deutschman,et al.  Plasma levels of receptor for advanced glycation end products, blood transfusion, and risk of primary graft dysfunction. , 2009, American journal of respiratory and critical care medicine.

[41]  W. Drake,et al.  Mycobacterial antigens may be important in sarcoidosis pathogenesis , 2006, Current opinion in pulmonary medicine.

[42]  B. Thiers Cyclophosphamide versus Placebo in Scleroderma Lung Disease , 2007 .

[43]  Ami N. Rubinowitz,et al.  Recognizing lung disease in patients with rheumatoid arthritis, part 2 , 2008 .

[44]  P. Mahesh,et al.  Time Interval and the Factors Associated with the Development of Asthma in Patients with Allergic Rhinitis , 2009, Lung.

[45]  A. Fauci,et al.  Characterization of lymphocytes in bronchial lavage fluid from monkeys. , 1976, Journal of immunology.

[46]  K. Meyer,et al.  Bronchoalveolar lavage as a diagnostic tool. , 2007, Seminars in respiratory and critical care medicine.

[47]  J. Curtis,et al.  The immunopathogenesis of chronic obstructive pulmonary disease: insights from recent research. , 2007, Proceedings of the American Thoracic Society.

[48]  R. Crystal,et al.  Airway epithelial cells: current concepts and challenges. , 2008, Proceedings of the American Thoracic Society.

[49]  Sharon Sanderson,et al.  Gene set analysis of lung samples provides insight into pathogenesis of progressive, fibrotic pulmonary sarcoidosis. , 2010, American journal of respiratory and critical care medicine.

[50]  H. Reynolds,et al.  Sarcoidosis: Impact of Other Illnesses on the Presentation and Management of Multi-Organ Disease , 2002, Lung.

[51]  X. Muñoz,et al.  Bird Fancier's Lung: A Series of 86 Patients , 2008, Medicine.

[52]  M. Iannuzzi,et al.  Recent advances in sarcoidosis. , 2011, Chest.

[53]  V. Poletti,et al.  Bronchoalveolar lavage in bronchiolitis obliterans organizing pneumonia primed by radiation therapy to the breast. , 2000, The Journal of allergy and clinical immunology.

[54]  V. Lama Update in lung transplantation 2008. , 2009, American journal of respiratory and critical care medicine.

[55]  S. Nava,et al.  Comparison between exhaled and bronchoalveolar lavage levels of hydrogen peroxide in patients with diffuse interstitial lung diseases. , 2008, Acta bio-medica : Atenei Parmensis.

[56]  I. Horváth,et al.  Adenosine triphosphate concentration of exhaled breath condensate in asthma. , 2010, Chest.

[57]  Kevin J Anstrom,et al.  A prospective multicenter study of competency metrics and educational interventions in the learning of bronchoscopy among new pulmonary fellows. , 2010, Chest.

[58]  J. Simmons Doctors and Discoveries: Lives That Created Today's Medicine , 2002 .

[59]  J. Elias,et al.  Bronchoalveolar lavage: role in the pathogenesis, diagnosis, and management of interstitial lung disease. , 1985, Annals of internal medicine.

[60]  A. Boyle,et al.  Update on chronic obstructive pulmonary disease. , 2004, Medsurg nursing : official journal of the Academy of Medical-Surgical Nurses.

[61]  Ken Y. Yoneda,et al.  The technique of adult flexible bronchoscopy: Part 1 , 2008 .

[62]  R. Effros Exhaled breath condensate: delusion or dilution? , 2010, Chest.

[63]  B. Barna,et al.  Peroxisome proliferator-activated receptor-gamma is deficient in alveolar macrophages from patients with alveolar proteinosis. , 2003, American journal of respiratory cell and molecular biology.

[64]  F. Bonella,et al.  Bronchoalveolar lavage in other interstitial lung diseases. , 2007, Seminars in respiratory and critical care medicine.

[65]  M. Drent,et al.  Bronchoalveolar lavage in sarcoidosis. , 2007, Seminars in respiratory and critical care medicine.

[66]  I. Stříž,et al.  Bronchoalveolar Lavage Fluid Cellular Characteristics, Functional Parameters and Cytokine and Chemokine Levels in Interstitial Lung Diseases , 2009, Scandinavian journal of immunology.

[67]  Y. Kawabata,et al.  Eosinophilia in bronchoalveolar lavage fluid and architectural destruction are features of desquamative interstitial pneumonia , 2007, Histopathology.

[68]  Niki Fens,et al.  Exhaled breath profiling enables discrimination of chronic obstructive pulmonary disease and asthma. , 2009, American journal of respiratory and critical care medicine.

[69]  M. Tanimoto,et al.  Quantitative analysis of propionibacterial DNA in bronchoalveolar lavage cells from patients with sarcoidosis. , 2008, Sarcoidosis, vasculitis, and diffuse lung diseases : official journal of WASOG.

[70]  P. Moseley,et al.  Methods for bronchoalveolar lavage in asthmatic patients following bronchoprovocation and local antigen challenge. , 1985, Chest.

[71]  M. Estenne,et al.  Early detection of chronic pulmonary allograft dysfunction by exhaled biomarkers. , 2007, American journal of respiratory and critical care medicine.

[72]  R. Crystal,et al.  Variability in small airway epithelial gene expression among normal smokers. , 2008, Chest.

[73]  W. Roberts,et al.  Characterization of the inflammatory and immune effector cells in the lung parenchyma of patients with interstitial lung disease. , 2015, The American review of respiratory disease.

[74]  H. Reynolds,et al.  Respiratory tract fluids: analysis of content and contemporary use in understanding lung diseases. , 1984, Disease-a-month : DM.

[75]  M. Thun,et al.  Chronic obstructive pulmonary disease is associated with lung cancer mortality in a prospective study of never smokers. , 2007, American journal of respiratory and critical care medicine.

[76]  A. Fisher,et al.  An update on lung transplantation , 2013, Breathe.

[77]  A. Ishizaka,et al.  Elevated CC Chemokine Level in Bronchoalveolar Lavage Fluid Is Predictive of a Poor Outcome of Idiopathic Pulmonary Fibrosis , 2009, Respiration.

[78]  N. Grishin,et al.  Genetic defects in surfactant protein A2 are associated with pulmonary fibrosis and lung cancer. , 2009, American journal of human genetics.

[79]  P. Senthil Kumar,et al.  Whole lung lavage for pulmonary alveolar proteinosis , 2010, Lung India : official organ of Indian Chest Society.

[80]  D. Moller Etiology of sarcoidosis. , 1997, Clinics in chest medicine.

[81]  B. Barna,et al.  Peroxisome proliferator-activated receptor gamma activity is deficient in alveolar macrophages in pulmonary sarcoidosis. , 2004, American journal of respiratory cell and molecular biology.

[82]  A. Ghio,et al.  Mass spectrometric analysis of biomarkers and dilution markers in exhaled breath condensate reveals elevated purines in asthma and cystic fibrosis. , 2009, American journal of physiology. Lung cellular and molecular physiology.

[83]  Naftali Kaminski,et al.  MMP1 and MMP7 as Potential Peripheral Blood Biomarkers in Idiopathic Pulmonary Fibrosis , 2008, PLoS medicine.

[84]  N. Kohno,et al.  Significance of bronchoalveolar lavage for the diagnosis of idiopathic pulmonary fibrosis. , 2009, American journal of respiratory and critical care medicine.

[85]  E. Bargagli,et al.  Exhaled carbon monoxide in sarcoidosis. , 2008, Sarcoidosis, vasculitis, and diffuse lung diseases : official journal of WASOG.

[86]  M. Fishbein,et al.  Chronic lung allograft rejection: mechanisms and therapy. , 2009, Proceedings of the American Thoracic Society.

[87]  H. Reynolds Sampling local respiratory tract sites for inflammation. , 2001, Sarcoidosis Vasculities and Diffuse Lung Diseases.

[88]  Jin-liang Kong,et al.  Accuracy of BAL galactomannan in diagnosing invasive aspergillosis: a bivariate metaanalysis and systematic review. , 2010, Chest.

[89]  M. Wahidi,et al.  A phase 3, randomized, double-blind study to assess the efficacy and safety of fospropofol disodium injection for moderate sedation in patients undergoing flexible bronchoscopy. , 2009, Chest.

[90]  R. Eberhardt,et al.  Bronchoalveolar lavage enzyme-linked immunospot for a rapid diagnosis of tuberculosis: a Tuberculosis Network European Trialsgroup study. , 2009, American journal of respiratory and critical care medicine.

[91]  J. Grunewald,et al.  Allergen provocation increases TH2‐cytokines and FOXP3 expression in the asthmatic lung , 2010, Allergy.

[92]  I. Pavord,et al.  Exhaled nitric oxide in pulmonary diseases: a comprehensive review. , 2010, Chest.

[93]  A. Wells,et al.  Interstitial lung disease guideline , 2008, Thorax.

[94]  W. Busse,et al.  Investigative bronchoprovocation and bronchoscopy in airway diseases. , 2005, American journal of respiratory and critical care medicine.

[95]  J. Cooper,et al.  Lung transplantation: opportunities for research and clinical advancement. , 2005, American journal of respiratory and critical care medicine.

[96]  H. Reynolds,et al.  Diagnostic and management strategies for diffuse interstitial lung disease. , 1998, Chest.

[97]  H. Reynolds,et al.  Airway changes in young smokers that may antedate chronic obstructive lung disease. , 1981, The Medical clinics of North America.

[98]  D. Ojcius,et al.  The oral microbiota: living with a permanent guest. , 2009, DNA and cell biology.

[99]  S. Nagai,et al.  Bronchoalveolar lavage in idiopathic interstitial lung diseases. , 2007, Seminars in respiratory and critical care medicine.

[100]  A. Malhotra,et al.  Multisociety task force recommendations of competencies in Pulmonary and Critical Care Medicine. , 2009, American journal of respiratory and critical care medicine.

[101]  G. Lefranc,et al.  Update in chronic obstructive pulmonary disease: role of antioxidant and metabolizing gene polymorphisms , 2011, Experimental lung research.

[102]  H. Reynolds Present status of bronchoalveolar lavage in interstitial lung disease. , 2009, Current opinion in pulmonary medicine.

[103]  D. Wilkes Primary graft dysfunction: it's all the RAGE. , 2009, American journal of respiratory and critical care medicine.

[104]  Scott H Randell,et al.  Resident cellular components of the human lung: current knowledge and goals for research on cell phenotyping and function. , 2008, Proceedings of the American Thoracic Society.

[105]  R. Machado,et al.  Identifying chronic obstructive pulmonary disease and asthma by exhaled breath analysis: does the (e)Nose know? , 2009, American journal of respiratory and critical care medicine.

[106]  M. Ranson,et al.  Interstitial Lung Disease in Lung Cancer , 2005, Drug safety.

[107]  Z. Kurmanowska,et al.  Exhaled 8-isoprostane in sarcoidosis: relation to superoxide anion production by bronchoalveolar lavage cells , 2010, Inflammation Research.

[108]  B. Griffith,et al.  A randomized trial of inhaled cyclosporine in lung-transplant recipients. , 2006, The New England journal of medicine.

[109]  W. Roberts,et al.  Analysis of cellular and protein content of broncho-alveolar lavage fluid from patients with idiopathic pulmonary fibrosis and chronic hypersensitivity pneumonitis. , 1977, The Journal of clinical investigation.

[110]  R. Crystal,et al.  Interstitial lung diseases of unknown cause. Disorders characterized by chronic inflammation of the lower respiratory tract (first of two parts). , 1984, The New England journal of medicine.