Advertisement

Lung

, Volume 189, Issue 2, pp 87–99 | Cite as

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

  • Herbert Y. ReynoldsEmail author
Article

Abstract

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.

Keywords

Bronchoalveolar lavage Connective tissue diseases Hypersensitivity pneumonitis Idiopathic pulmonary fibrosis Interstitial lung disease Sarcoidosis Scleroderma 

Notes

Acknowledgment

The preparation of the manuscript by Ms. Tracey Woodard was greatly appreciated.

References

  1. 1.
    Simmons JG (2002) Hippocrates: rational medicine (460–370 B.C.). In: Doctors and discoveries: lives that created today’s medicine. Houghton Mifflin, Boston, pp 29–33Google Scholar
  2. 2.
    Simmons JG (2002) Claude Bernard (1813–1878)—Medicine and modern experimental physiology. In: Doctors and discoveries: lives that created today’s medicine. Houghton Mifflin, Boston, pp 14–17Google Scholar
  3. 3.
    Reynolds HY (2004) President’s address: R.T.H. Laënnec, M.D.—clinicopathologic observations, using the stethoscope, made chest medicine more scientific. Trans Am Clin Climatol Assoc 115:1–29PubMedGoogle Scholar
  4. 4.
    Reynolds HY (1987) Bronchoalveolar lavage: state of art. Am Rev Respir Dis 135:250–263PubMedGoogle Scholar
  5. 5.
    Reynolds HY (2000) Use of bronchoalveolar lavage in humans—past necessity and future imperative. Lung 178:271–293PubMedCrossRefGoogle Scholar
  6. 6.
    Rottoli P, Bargagli E, Landi C, Magi B (2009) Proteomic analysis in interstitial lung diseases: a review. Curr Opin Pulm Med 15:470–478PubMedCrossRefGoogle Scholar
  7. 7.
    Reynolds HY (2001) Sampling local respiratory tract sites for inflammation. Sarcoidosis Vasc Diffuse Lung Dis 18:138–148PubMedGoogle Scholar
  8. 8.
    Reynolds HY, Newball HH (1974) Analysis of proteins and respiratory cells obtained from human lungs by bronchial lavage. J Lab Clin Med 84:559–573PubMedGoogle Scholar
  9. 9.
    Busse WW, Wanner A, Adams K, Reynolds HY, Castro M, Chowdhury B, Kraft M, Levine RJ, Peters SP, Sullivan EJ (2005) NHLBI/NIAID workshop: investigative bronchoprovocation and bronchoscopy in airway diseases. Am J Respir Crit Care Med 172:807–816PubMedCrossRefGoogle Scholar
  10. 10.
    Kazmierowski JA, Fauci AS, Reynolds HY (1976) Characterization of lymphocytes in bronchial lavage fluid from monkeys. J Immunol 116:615–618PubMedGoogle Scholar
  11. 11.
    Reynolds HY (2008) Bronchoalveolar lavage-obtaining biological specimens from the respiratory tract surface. Sarcoidosis Vasc Diff Lung Dis 25:5–9Google Scholar
  12. 12.
    Silvestri GA (2008) The evolution of bronchoscopy training (editorial). Respiration 76:19–20PubMedCrossRefGoogle Scholar
  13. 13.
    Wahidi MM, Silvestri GA, Coakley RD, Ferguson JS, Shepherd RW, Moses L, Confori J, Que LG, Anstrom KJ, McGuire F, Colt H, Downie GH (2010) A prospective multi-center study of competency metrics and educational interventions in the learning of bronchoscopy among starting pulmonary fellows. Chest 137:1040–1049PubMedCrossRefGoogle Scholar
  14. 14.
    Yoneda KY, Morrissey BM (2008) The technique of adult flexible bronchoscopy: part 1. J Respir Dis 29:423–428Google Scholar
  15. 15.
    Buckley JD, Addrizzo-Harris DJ, Clay AS, Curtis JR, Kotloff RM, Lorin SM, Murin S, Sessler CN, Rogers PL, Rosen MJ, Spevetz A, King TE, Malhotra A, Parsons PE (2009) Multisociety task force recommendations of competencies in pulmonary and critical care medicine. Am J Respir Crit Care Med 180:290–295PubMedCrossRefGoogle Scholar
  16. 16.
    Silvestri GA, Vincent BD, Wahidi MM, Robinette E, Hansbrough JR, Downie GH (2009) A phase 3, randomized, double-blind study to access the efficacy and safety of fospropofol disodium injection for moderate sedation in patients undergoing flexible bronchoscopy. Chest 135:41–47PubMedCrossRefGoogle Scholar
  17. 17.
    Baughman RP (2007) Technical aspects of bronchoalveolar lavage: recommendations for a standard procedure. Semin Respir Crit Care Med 28:475–485PubMedCrossRefGoogle Scholar
  18. 18.
    Meyer KC (2007) Bronchoalveolar lavage as a diagnostic tool. Semin Respir Crit Care Med 28:546–560PubMedCrossRefGoogle Scholar
  19. 19.
    Rankin JA, Snyder PE, Schachter EN, Matthay RA (1984) Bronchoalveolar lavage. Its safety in subjects with mild asthma. Chest 85:723–728PubMedCrossRefGoogle Scholar
  20. 20.
    Metzger WJ, Richerson HB, Worden K, Monick M, Hunninghake GW (1986) Bronchoalveolar lavage of allergic asthmatic patients following allergen bronchoprovocation. Chest 89:477–483PubMedCrossRefGoogle Scholar
  21. 21.
    Metzger WJ, Nugent K, Richerson HB, Moseley P, Lakin R, Zavala D, Hunninghake GW (1985) Methods for bronchoalveolar lavage in asthmatic patients following bronchoprovocation and local antigen challenge. Chest 87(Suppl):16S–19SPubMedCrossRefGoogle Scholar
  22. 22.
    Bernstein IL, Boushey HA, Cherniack RM, other Workshop Participants (1985) NHLBI Workshop summary and recommendations of a workshop on the investigative use of fiberoptic bronchoscopy and bronchoalveolar lavage in asthmatics. Am Rev Respir Dis 132:180–182Google Scholar
  23. 23.
    Woodruff PG, Modrek B, Choy DF, Jia G, Abbas AR, Ellwanger A, Koth LL, Arron JR, Fahy JV (2009) T-helper type 2-driven inflammation defines major subphenotypes of asthma. Am J Respir Crit Care Med 180:388–395PubMedCrossRefGoogle Scholar
  24. 24.
    Thunberg S, Gafvelin G, Nord M, Grönneberg R, Grunewald J, Eklund A, van Hage M (2010) Allergen provocation increases Th2-cytokines and FOXP3 expression in the asthmatic lung. Allergy 65:311–318PubMedCrossRefGoogle Scholar
  25. 25.
    Punturieri A, Croxton TL, Weinmann G, Kiley JP (2007) The changing face of COPD (editorial). Am Fam Physician 75:315–316PubMedGoogle Scholar
  26. 26.
    Turner MC, Chen Y, Krewski D, Calle EE, Thun MJ (2007) Chronic obstructive pulmonary disease is associated with lung cancer mortality in a prospective study of never smokers. Am J Respir Crit Care Med 176:285–290PubMedCrossRefGoogle Scholar
  27. 27.
    Hogg JC, Chu F, Utokaparch S, Woods R, Elliott WM, Buzatu L, Cherniack RM, Rogers RM, Sciurba FC, Coxson HO, Paré PD (2004) The nature of small-airway obstruction in chronic obstructive pulmonary disease. New Engl J Med 350:2645–2653PubMedCrossRefGoogle Scholar
  28. 28.
    Curtis JL, Freeman CM, Hogg JC (2007) The immunopathogenesis of chronic obstructive pulmonary disease: insights from recent research. Proc Am Thorac Soc 4:512–521PubMedCrossRefGoogle Scholar
  29. 29.
    Murphy TF, Brauer AL, Eschberger K, Lobbins P, Grove L, Cai X, Sethi S (2008) Pseudomonas aeruginosa in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 177:853–860PubMedCrossRefGoogle Scholar
  30. 30.
    Sethi S, Sethi R, Eschberger K, Lobbins P, Cai X, Grant BJ, Murphy TF (2007) Airway bacterial concentrations and exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 176:356–361PubMedCrossRefGoogle Scholar
  31. 31.
    MacNee W (2008) Update in chronic obstructive pulmonary disease 2007. Am J Respir Crit Care Med 177:820–829PubMedCrossRefGoogle Scholar
  32. 32.
    Hodge S, Hodge G, Jersmann H, Matthews G, Ahern J, Holmes M, Reynolds PN (2008) Azithromycin improves macrophage phagocytic function and expression of mannose receptor in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 178:139–148PubMedCrossRefGoogle Scholar
  33. 33.
    Crystal RG, Randall SH, Engelhardt JF, Voynow J, Sunday ME (2008) Airway epithelial cells—current concepts and challenges. Proc Am Thorac Soc 5:772–777PubMedCrossRefGoogle Scholar
  34. 34.
    Ammous Z, Hackett NR, Butler MW, Raman T, Dolgalev I, O’Connor TP, Harvey BG, Crystal RG (2008) Variability in small airway epithelial gene expression among normal smokers. Chest 133:1344–1353PubMedCrossRefGoogle Scholar
  35. 35.
    Hunninghake GW, Kawanami O, Ferrans VJ, Young RC Jr, Roberts WC, Crystal RG (1981) Characterization of inflammatory and immune effector cells in the lung parenchyma of patients with interstitial lung disease. Am Rev Respir Dis 123:407–412PubMedGoogle Scholar
  36. 36.
    Crystal RG, Bitterman PR, Rennard SI, Hance AJ, Keogh BA (1984) Interstitial lung diseases of unknown cause: disorders characterized by chronic inflammation of the lower respiratory tract. N Engl J Med 310:154–166, 235–244Google Scholar
  37. 37.
    Daniele RP, Elias JA, Epstein PE, Rossman MD (1985) Bronchoalveolar lavage: role in the pathogenesis, diagnosis, and management of interstitial lung disease. Ann Intern Med 102:93–108PubMedGoogle Scholar
  38. 38.
    Drent M, van Nierop MA, Gerritsen FA, Wouters EF, Mulder PG (1996) A computer program using BALF-analysis results as a diagnostic tool in interstitial lung diseases. Am J Respir Crit Care Med 153:736–741PubMedGoogle Scholar
  39. 39.
    Reynolds HY (2009) Present status of bronchoalveolar lavage in interstitial lung disease. Curr Opin Pulm Dis 15:479–485CrossRefGoogle Scholar
  40. 40.
    Wells AU, Hirani N (2008) Interstitial lung disease guideline. Thorax 63:V1–V58PubMedCrossRefGoogle Scholar
  41. 41.
    Kinder BW, Shariat C, Collard HR, Koth LL, Wolters PJ, Golden JA, Panos RJ, King TE Jr (2010) Undifferentiated connective tissue disease-associated interstitial lung disease: changes in lung function. Lung 188:143–149PubMedCrossRefGoogle Scholar
  42. 42.
    Reynolds HY (1998) Diagnostic and management strategies for diffuse interstitial lung disease. Chest 113:192–202PubMedCrossRefGoogle Scholar
  43. 43.
    Antin-Ozerkis D, Rubinowitz A (2008) Recognizing lung disease in patients with rheumatoid arthritis. Part 1: pleuropulmonary disease may be more common than you thought. J Respir Dis 29:274–280Google Scholar
  44. 44.
    Antin-Ozerkis D, Rubinowitz A (2008) Recognizing lung disease in patients with rheumatoid arthritis. Part 2. J Respir Dis 29:318–324Google Scholar
  45. 45.
    Tashkin DP, Elashoff R, Clements PJ, Golden J, Roth MD, Furst DE, Arriola E, Silver R, Strange C, Bolster M, Seibold JR, Riley DJ, Hsu VM, Varga J, Schraufnagel DE, Theodore A, Simms R, Wise R, Wigley F, White B, Steen V, Read C, Mayes M, Parsley E, Mubarak K, Connolly MK, Golden J, Olman M, Fessler B, Rothfield N, Metersky M, Scleroderma Lung Study Research Group (2006) Cyclophosphamide versus placebo in scleroderma lung disease. N Engl J Med 354:2655–2666PubMedCrossRefGoogle Scholar
  46. 46.
    Strange C, Bolster MB, Roth MD, Silver RM, Theodore A, Goldin J, Clements P, Chung J, Elashoff RM, Suh R, Smith EA, Furst DE, Tashkin DP, Scleroderma Lung Study Reserch Group (2008) Bronchoalveolar lavage and response to cyclophosphamide in scleroderma interstitial lung disease. Am J Respir Crit Care Med 177:91–98PubMedCrossRefGoogle Scholar
  47. 47.
    Nagai S, Handa T, Ito Y, Takeuchi M, Izumi T (2007) Bronchoalveolar lavage in idiopathic interstitial lung diseases. Semin Respir Crit Care Med 28:496–503PubMedCrossRefGoogle Scholar
  48. 48.
    Wang Y, Kuan PJ, Xing C, Cronkhite JT, Torres F, Rosenblatt RL, DiMaio JM, Kinch LN, Grishin NV, Garcia CK (2009) Genetic defects in surfactant protein A2 are associated with pulmonary fibrosis and lung cancer. Am J Hum Genet 84:52–59PubMedCrossRefGoogle Scholar
  49. 49.
    Rosas IO, Richards TJ, Konishi K, Zhang Y, Gibson K, Lokshin AE, Lindell KO, Cisneros J, Macdonald SD, Pardo A, Sciurba F, Dauber J, Selman M, Gochuico BR, Kaminski N (2008) MMP1 and MMP7 as potential peripheral blood biomarkers in idiopathic pulmonary fibrosis. PLoS Med 5:623–633CrossRefGoogle Scholar
  50. 50.
    Vasakova M, Sterclova M, Kolesart L, Slavcev A, Pohunek P, Sulc J, Skibova J, Striz I (2009) Bronchoalveolar lavage fluid cellular characteristics, functional parameters and cytokine and chemokine levels in interstitial lung diseases. Scand J Immunol 69:268–274PubMedCrossRefGoogle Scholar
  51. 51.
    Shinoda H, Tasaka S, Fujishima S, Yamasawa W, Miyamoto K, Nakano Y, Kamata H, Hasegawa N, Ishizaka A (2009) Elevated CC chemokine levels in bronchoalveolar lavage fluid is predictive of a poor outcome of idiopathic pulmonary fibrosis. Respiration 78:285–292PubMedCrossRefGoogle Scholar
  52. 52.
    Ohshimo S, Bonella F, Cui A, Beume M, Kohno N, Guzman J, Costabel U (2009) Significance of bronchoalveolar lavage for the diagnosis of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 179:1043–1047PubMedCrossRefGoogle Scholar
  53. 53.
    Kawabata Y, Takermura T, Hebisawa A, Ogura T, Yamaguchi T, Kuriyama T, Nagai S, Sakatani M, Chida K, Sakai F, Park J, Colby TV (2008) Eosinophilia in bronchoalveolar lavage fluid and architectural destruction are features of desquamative interstitial pneumonia. Histopathology 52:194–202PubMedCrossRefGoogle Scholar
  54. 54.
    Reynolds HY (2008) Respiratory structure and function: mechanisms and testing. In: Goldman L, Ausiello D (eds) Cecil medicine, 23rd edn. Saunders Elsevier, Philadelphia, pp 602–609Google Scholar
  55. 55.
    Reynolds HY, Fulmer JD, Kazmierowski JA, Roberts WC, Frank MM, Crystal RG (1977) Analysis of cellular and protein content of bronchoalveolar lavage fluid from patients with idiopathic pulmonary fibrosis and chronic hypersensitivity pneumonitis. J Clin Invest 59:165–175PubMedCrossRefGoogle Scholar
  56. 56.
    Drake WP, Newman LS (2006) Mycobacterial antigens may be important in sarcoidosis pathogenesis. Curr Opin Pulm Med 12:359–363PubMedCrossRefGoogle Scholar
  57. 57.
    Chen ES, Moller DR (2008) Etiology of sarcoidosis. Clin Chest Med 29:365–377PubMedCrossRefGoogle Scholar
  58. 58.
    Reynolds HY (2002) Sarcoidosis: impact of other illness on the presentation and management of multiorgan disease. Lung 180:281–299PubMedCrossRefGoogle Scholar
  59. 59.
    Grunewald J, Eklund A (2009) Löfgren’s syndrome: human leukocyte antigen strongly influences the disease course. Am J Respir Crit Care Med 179:301–312Google Scholar
  60. 60.
    Reynolds HY, Peavy HH, Gail DB, Kiley JP (2006) Review: past achievements and future directions of sarcoidosis research: a NHLBI perspective. Sarcoidosis Vasc Diffuse Lung Dis 23:83–91PubMedGoogle Scholar
  61. 61.
    Drent M, Mansour K, Linssen C (2007) Bronchoalveolar lavage in sarcoidosis. Semin Respir Crit Care Med 28:486–495PubMedCrossRefGoogle Scholar
  62. 62.
    Culver DA, Barna BP, Raychaudhuri B, Bonifield TL, Abraham S, Malur A, Farver CF, Kavuru MS, Thomassen MJ (2004) Peroxisome proliferator-activated receptor-gamma activity is deficient in alveolar macrophages in pulmonary sarcoidosis. Am J Respir Cell Mol Biol 30:1–5PubMedCrossRefGoogle Scholar
  63. 63.
    Hart CM, Roman J, Reddy R, Sime PJ (2008) PPARγ: a novel molecular target in lung disease. J Invest Med 56:515–517Google Scholar
  64. 64.
    Bonfield TL, Farver CF, Barna BP, Malur A, Abraham S, Raychaudhuri B, Kavuru MS, Thomassen MJ (2003) Peroxisome proliferator-activated receptor-gamma is deficient in alveolar macrophages from patients with alveolar proteinosis. Am J Respir Cell Mol Biol 29:677–682PubMedCrossRefGoogle Scholar
  65. 65.
    Ichikawa H, Kataoka M, Hiramatsu J, Ohmori M, Tanimoto Y, Kanehiro A, Nakata Y, Tanimoto M (2008) Quantitative analysis of propionibacterial DNA in bronchoalveolar lavage cells from patients with sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis 25:15–20PubMedGoogle Scholar
  66. 66.
    Danila E, Norkūniene J, Jurgauskiene L, Malickaite R (2009) Diagnostic role of BAL fluid CD4/CD8 ratio in different radiographic and clinical forms of pulmonary sarcoidosis. Clin Respir J 3:214–221Google Scholar
  67. 67.
    Piotrowski WJ, Kurmanowska Z, Antczak A, Marczak J, Ciebiada M, Górski P (2010) Exhaled 8-isoprostane in sarcoidosis: relation to superoxide anion production by bronchoalveolar lavage cells. Inflamm Res 59:1027–1032PubMedCrossRefGoogle Scholar
  68. 68.
    Lockstone HE, Sanderson S, Kulakova N, Baban D, Leonard A, Kok WL, McGowan S, McMichael AJ, Ho LP (2010) Gene set analysis of lung samples provides insight into pathogenesis of progressive, fibrotic pulomonary sarcoidosis. Am J Respir Crit Care Med 181(12):1367–1375PubMedCrossRefGoogle Scholar
  69. 69.
    Cordeiro CR, Jones JC, Alfaro T, Ferreina AJ (2007) Bronchoalveolar lavage in occupational lung diseases. Semin Respir Crit Care Med 28:504–513PubMedCrossRefGoogle Scholar
  70. 70.
    Selman M, Lacasse Y, Pardo A, Cormier Y (2010) Hypersensitivity pneumonitis caused by fungi. Proc Am Thorac Soc 7:229–236PubMedCrossRefGoogle Scholar
  71. 71.
    Reynolds HY (1988) Hypersensitivity pneumonitis: correlation of cellular and immunologic changes with clinical phases of disease. Lung 166:189–208PubMedCrossRefGoogle Scholar
  72. 72.
    Fink JN, Ortega HG, Reynolds HY, Cormier Y, Fan LL, Franks TJ, Kreiss K, Kunkel S, Lynch D, Quirce S, Rose C, Schleimer RP, Schuyler MR, Selman M, Trout D, Yoshizawa Y (2005) NHLBI workshop: needs and opportunities for research in hypersensitivity pneumonitis. Am J Respir Crit Care Med 171:792–798PubMedCrossRefGoogle Scholar
  73. 73.
    Lacasse Y, Selman M, Costabel U, Dalphin JC, Morell F, Erkinjuntti-Pekkanen R, Mueller NL, Colby TV, Schuyler M, Jomphe V, Cormier Y, Study Group HP (2009) Classification of hypersensitivity pneumonitis: a hypothesis. Int Arch Allergy Immunol 149:161–166PubMedCrossRefGoogle Scholar
  74. 74.
    Morell F, Roger A, Reyes L, Cruz MJ, Murio C, Muñoz X (2008) Bird fancier’s lung: a series of 86 patients. Medicine 87:110–130PubMedCrossRefGoogle Scholar
  75. 75.
    Costabel U, Guzman J, Bonella F, Oshimo S (2007) Bronchoalveolar lavage in other interstitial lung diseases. Semin Respir Crit Care Med 28:514–524PubMedCrossRefGoogle Scholar
  76. 76.
    Majori M, Poletti V, Curti A, Corradi M, Falcone F, Pesci A (2000) Bronchoalveolar lavage in bronchiolitis obliterans organizing pneumonia primed by radiation therapy to the breast. J Allergy Clin Immunol 105:239–244PubMedCrossRefGoogle Scholar
  77. 77.
    Poletti V, Poletti G, Murer B, Saragoni L, Chilosi M (2007) Bronchoalveolar lavage in malignancy. Semin Respir Crit Care Med 28:534–545PubMedCrossRefGoogle Scholar
  78. 78.
    Borczuk AC, Toonkel RL, Powell CA (2009) Genomics of lung cancer. Proc Am Thorac Soc 6:152–158PubMedCrossRefGoogle Scholar
  79. 79.
    Wilkes DS, Egan TM, Reynolds HY (2005) NHLBI Workshop: lung transplantation—opportunities for research and clinical advancement. Am J Respir Crit Care Med 172:944–955PubMedCrossRefGoogle Scholar
  80. 80.
    Lama VN (2009) Update in lung transplantation 2008. Am J Respir Crit Care Med 179:759–764PubMedCrossRefGoogle Scholar
  81. 81.
    Iacono AT, Johnson BA, Grgurich WF, Youssef JG, Corcoran TE, Seiler DA, Dauber JH, Smaldone GC, Zeevi A, Yousem SA, Fung JJ, Burckart GJ, McCurry KR, Griffith BP (2006) A randomized trial of inhaled cyclosporine in lung-transplant recipients. N Engl J Med 354:141–150PubMedCrossRefGoogle Scholar
  82. 82.
    Belperio JA, Weigt SS, Fishbein MC, Lynch JP III (2009) Chronic lung allograft rejection: mechanisms and therapy. Proc Am Thorac Soc 6:108–121PubMedCrossRefGoogle Scholar
  83. 83.
    Muylem AV, Knoop C, Estenne M (2007) Early detection of chronic pulmonary allograft dysfunction by exhaled biomarkers. Am J Respir Crit Care Med 175:731–736PubMedCrossRefGoogle Scholar
  84. 84.
    Christie JD, Shah CV, Kawut SM, Mangalmurti N, Lederer DJ, Sonett JR, Ahya VN, Palmer SM, Wille K, Lama V, Shah PD, Shah A, Weinacker A, Deutschman CS, Kohl BA, Demissie E, Bellamy S, Ware LB, Lung Transplant Outcomes Group (2009) Plasma levels of receptor for advanced glycation end products, blood transfusion, and risk of primary graft dysfunction. Am J Respir Crit Care Med 180:1010–1015PubMedCrossRefGoogle Scholar
  85. 85.
    Wilkes DS (2009) Primary graft dysfunction: it’s all the RAGE (editorial). Am J Respir Crit Care Med 180:915–919PubMedCrossRefGoogle Scholar
  86. 86.
    Avila M, Ojcius DM, Yilmaz Ö (2009) The oral microbiota: living with a permanent guest. DNA Cell Biol 25:405–411CrossRefGoogle Scholar
  87. 87.
    Young KR Jr, Rankin JA, Naegel GP, Paul ES, Reynolds HY (1985) Bronchoalveolar lavage cells and proteins in patients with the acquired immunodeficiency syndrome. Ann Intern Med 103:522–533PubMedGoogle Scholar
  88. 88.
    Jafari C, Thijsen S, Sotgiu G, Goletti D, Benítez JA, Losi M, Eberhardt R, Kirsten D, Kalsdorf B, Bossink A, Latorre I, Migliori GB, Strassburg A, Winteroll S, Greinert U, Richeldi L, Ernst M, Lange C, Tuberculosis Network European Trialsgroup (2009) Bronchoalveolar lavage enzyme-linked immunospot for rapid diagnosis of tuberculosis (A Tuberculosis Network European Trials Group Study). Am J Respir Crit Care Med 180:666–673PubMedCrossRefGoogle Scholar
  89. 89.
    Tunney MM, Field TR, Moriarty TF, Patrick S, Doering G, Muhlebach MS, Wolfgang MC, Boucher R, Gilpin DF, McDowell A, Elborn JS (2008) Detection of anaerobic bacteria in high numbers in sputum from patients with cystic fibrosis. Am J Respir Crit Care Med 177:995–1001PubMedCrossRefGoogle Scholar
  90. 90.
    Fasano MB (2010) Combined airway: impact of upper airway on lower airway. Curr Opin Otolaryngol Head Neck Surg 18:15–20PubMedCrossRefGoogle Scholar
  91. 91.
    Boujaoude ZC, Bartter TC, Pratter MR, Fasano MB (2008) Tips on the management of rhinosinusitis. J Respir Dis 29:353–359Google Scholar
  92. 92.
    Mahesh PA, Vedanthan PK, Holla AD (2009) Time interval and the factors associated with the development of asthma in patients with allergic rhinitis. Lung 187:393–400PubMedCrossRefGoogle Scholar
  93. 93.
    Schleimer RP, Kato A, Peters A, Conley D, Kim J, Liu MC, Harris KE, Kuperman DA, Chandra R, Favoreto S Jr, Avila PC, Grammer LC, Kern RC (2009) Epithelium, inflammation, and immunity in the upper airways of humans. Proc Am Thorac Soc 6:288–294PubMedCrossRefGoogle Scholar
  94. 94.
    Ciarleglio G, Refini RM, Pieroni MG, Martino VA, Bargagli E, Rottoli P, Sestini P (2008) Exhaled carbon monoxide in sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis 25:46–50PubMedGoogle Scholar
  95. 95.
    Corradi M, Pignatti P, Brunetti G, Goldoni M, Caglieri A, Nava S, Moscato G, Balbi B (2008) Comparison between exhaled and bronchoalveolar lavage levels of hydrogen peroxide in patients with diffuse interstitial lung diseases. ACTA Biomed 79(suppl):73–78PubMedGoogle Scholar
  96. 96.
    Pérez-de-Llano LA, Carballada F, Castro Añón O, Pizarro M, Golpe R, Baloira A, Vázquez Caruncho M, Boquete M (2010) Exhaled nitric oxide predicts controls in patients with difficult-to-treat asthma. Eur Respir J 35(6):1221–1227PubMedCrossRefGoogle Scholar
  97. 97.
    Esther CR Jr, Boysen G, Olsen BM, Collins LB, Ghio AJ, Swenberg JW, Boucher RC (2009) Mass spectrometric analysis of biomarkers and dilution markers in exhaled breath condensate reveals elevated purines in asthma and cystic fibrosis. Am J Physiol Lung Cell Mol Physiol 296:L987–L993PubMedCrossRefGoogle Scholar
  98. 98.
    Fens N, Zwinderman AH, Van der Schee MP, de Nijs SB, Dijkers E, Roldaan AC, Cheung D, Bel EH, Sterk PJ (2009) Exhaled breath profiling enables discrimination of chronic obstructive pulmonary disease and asthma. Am J Respir Crit Care Med 180:1076–1082PubMedCrossRefGoogle Scholar
  99. 99.
    Machado RF (2009) Identifying chronic obstructive pulmonary disease and asthma by exhaled breath analysis (editorial). Am J Respir Crit Care Med 180:1038–1039PubMedCrossRefGoogle Scholar
  100. 100.
    Effros RM (2010) Exhaled breath condensate: delusion or dilution? Chest 138:471–472PubMedCrossRefGoogle Scholar
  101. 101.
    Barnes PJ, Dweik RA, Gelb AF, Gibson PG, George SC, Grasemann H, Pavord ID, Ratjen F, Silkoff PE, Taylor DR, Zamel N (2010) Exhaled nitric oxide in pulmonary diseases: a comprehensive review. Chest 138:682–692PubMedCrossRefGoogle Scholar
  102. 102.
    Lázár Z, Cervenak L, Orosz M, Gálffy G, Komlósi ZI, Bikov A, Losonczy G, Horváth I (2010) Adenosine triphosphate concentration of exhaled breath condensate in asthma. Chest 138:536–542PubMedCrossRefGoogle Scholar
  103. 103.
    Lin JL, Bonnichsen MH, Nogeh EU, Raftery MJ, Thomas PS (2010) Proteomics in detection and monitoring of asthma and smoking-related lung diseases. Expert Rev Proteomics 7(3):361–372PubMedCrossRefGoogle Scholar
  104. 104.
    Reynolds HY, Chrétien J (1984) Respiratory tract fluids: analysis of content and contemporary use in understanding lung diseases. Dis Mon 30(5):3–103Google Scholar
  105. 105.
    Reynolds HY, Merrill WW (1981) Airway changes in young smokers that may antedate chronic obstructive lung disease. Med Clin North Am 65:667–689PubMedGoogle Scholar
  106. 106.
    Morgenthau AS, Iannuzzi MC (2011) Recent advances in sarcoidosis. Chest 139:174–182PubMedCrossRefGoogle Scholar
  107. 107.
    Franks TJ, Colby TV, Travis WD, Tuder RM, Reynolds HY, Brody AR, Cardoso WV, Crystal RG, Drake CJ, Engelhardt J, Frid M, Herzog E, Mason R, Phan SH, Randell SH, Rose MC, Stevens T, Serge J, Sunday ME, Voynow JA, Weinstein BM, Whitsett J, Williams MC (2008) Resident cellular components of the human lung: current knowledge and goals for research on cell phenotyping and function. Proc Am Thorac Soc 5:763–766PubMedCrossRefGoogle Scholar
  108. 108.
    Guo YL, Chen YQ, Wang K, Qin SM, Wu C, Kong JL (2010) Accuracy of BAL galactomannan in diagnosing invasive aspergillosis: a bivariate metaanalysis and systemic review. Chest 138:817–824PubMedCrossRefGoogle Scholar
  109. 109.
    Jayaraman S, Gayathri AR, Kumar PS, Santosham R, Santosham R, Narasimhan R (2010) Whole lung lavage for pulmonary alveolar proteinosis. Lung India 27:33–36PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC (outside the USA) 2011

Authors and Affiliations

  1. 1.Lung Biology and Disease Branch, Division of Lung DiseasesNational Heart, Lung & Blood InstituteBethesdaUSA

Personalised recommendations