1932

Abstract

Although the notion that “the normal lung is free from bacteria” remains common in textbooks, it is virtually always stated without citation or argument. The lungs are constantly exposed to diverse communities of microbes from the oropharynx and other sources, and over the past decade, novel culture-independent techniques of microbial identification have revealed that the lungs, previously considered sterile in health, harbor diverse communities of microbes. In this review, we describe the topography and population dynamics of the respiratory tract, both in health and as altered by acute and chronic lung disease. We provide a survey of current techniques of sampling, sequencing, and analysis of respiratory microbiota and review technical challenges and controversies in the field. We review and synthesize what is known about lung microbiota in various diseases and identify key lessons learned across disease states.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-physiol-021115-105238
2016-02-10
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/physiol/78/1/annurev-physiol-021115-105238.html?itemId=/content/journals/10.1146/annurev-physiol-021115-105238&mimeType=html&fmt=ahah

Literature Cited

  1. Lederberg J. 1.  2001. ‘Ome sweet ‘omics—a genealogical treasury of words. The Scientist April 2
  2. Cotran RS, Kumar V, Collins T, Robbins SL. 2.  1999. Robbins Pathologic Basis of Disease Philadelphia: Saunders
  3. Horikoshi K, Grant WD. 3.  1998. Extremophiles: Microbial Life in Extreme Environments New York: Wiley-Liss
  4. Hilty M, Burke C, Pedro H, Cardenas P, Bush A. 4.  et al. 2010. Disordered microbial communities in asthmatic airways. PLOS ONE 5:e8578 [Google Scholar]
  5. Pasteur L. 5.  1860. Expériences relatives aux générations dites spontanées. C. R. Hebd. Séances Acad. Sci. D 50:303–7 [Google Scholar]
  6. Hildebrandt G. 6.  1888. Experimentelle Untersuchungen über das Eindringen pathogener Mikroorganismen von den Luftwegen und der Lunge aus. Beitr. Pathol. Anat. Physiol. 3:411–50 [Google Scholar]
  7. Dürck H. 7.  1897. Studien über die Ätiologie und Histologie der Pneumonie im Kindesalter und der Pneumonie im Allgemeinen. Deutsch. Arch. klin. Med. 58:368 [Google Scholar]
  8. Quensel U. 8.  1902. Untersuchungen über das Vorkommen von Bakterien in den Lungen und bronchialen Lymphdrüsen gesunder Thiere. Z. Hyg. Infect. 40:505–21 [Google Scholar]
  9. Jones FS. 9.  1922. The source of the microorganisms in the lungs of normal animals. J. Exp. Med. 36:317–28 [Google Scholar]
  10. Thomson SC, Hewlett RT. 10.  1896. The fate of micro-organisms in inspired air. Lancet 147:86–87 [Google Scholar]
  11. Quinn LH, Meyer OO. 11.  1929. The relationship of sinusitis and bronchiectasis. Arch. Otolaryngol. 10:152–65 [Google Scholar]
  12. Dickson RP, Erb-Downward JR, Prescott HC, Martinez FJ, Curtis JL. 12.  et al. 2014. Analysis of culture-dependent versus culture-independent techniques for identification of bacteria in clinically obtained bronchoalveolar lavage fluid. J. Clin. Microbiol. 52:3605–13 [Google Scholar]
  13. Dickson RP, Erb-Downward JR, Huffnagle GB. 13.  2013. The role of the bacterial microbiome in lung disease. Expert Rev. Respir. Med. 7:245–57 [Google Scholar]
  14. Venkataraman A, Bassis CM, Beck JM, Young VB, Curtis JL. 14.  et al. 2015. Application of a neutral community model to assess structuring of the human lung microbiome. MBio 6:e02284–14 [Google Scholar]
  15. Bassis CM, Erb-Downward JR, Dickson RP, Freeman CM, Schmidt TM. 15.  et al. 2015. Analysis of the upper respiratory tract microbiotas as the source of the lung and gastric microbiotas in healthy individuals. MBio 6:e00037–15 [Google Scholar]
  16. Winslow CE. 16.  1908. A new method of enumerating bacteria in air. Science 28:28–31 [Google Scholar]
  17. Gleeson K, Eggli DF, Maxwell SL. 17.  1997. Quantitative aspiration during sleep in normal subjects. Chest 111:1266–72 [Google Scholar]
  18. Huxley EJ, Viroslav J, Gray WR, Pierce AK. 18.  1978. Pharyngeal aspiration in normal adults and patients with depressed consciousness. Am. J. Med. 64:564–68 [Google Scholar]
  19. Amberson JB. 19.  1954. A clinical consideration of abscesses and cavities of the lung. Bull. Johns Hopkins Hosp. 94:227–37 [Google Scholar]
  20. Dickson RP, Erb-Downward JR, Huffnagle GB. 20.  2014. Towards an ecology of the lung: new conceptual models of pulmonary microbiology and pneumonia pathogenesis. Lancet Respir. Med. 2:238–46 [Google Scholar]
  21. Dickson JL, Head JW, Levy JS, Marchant DR. 21.  2013. Don Juan Pond, Antarctica: near-surface CaCl2-brine feeding Earth's most saline lake and implications for Mars. Sci. Rep. 3:1166 [Google Scholar]
  22. Rogers GB, Carroll MP, Serisier DJ, Hockey PM, Jones G, Bruce KD. 22.  2004. Characterization of bacterial community diversity in cystic fibrosis lung infections by use of 16S ribosomal DNA terminal restriction fragment length polymorphism profiling. J. Clin. Microbiol. 42:5176–83 [Google Scholar]
  23. Rogers GB, Hart CA, Mason JR, Hughes M, Walshaw MJ, Bruce KD. 23.  2003. Bacterial diversity in cases of lung infection in cystic fibrosis patients: 16S ribosomal DNA (rDNA) length heterogeneity PCR and 16S rDNA terminal restriction fragment length polymorphism profiling. J. Clin. Microbiol. 41:3548–58 [Google Scholar]
  24. Hamady M, Knight R. 24.  2009. Microbial community profiling for human microbiome projects: tools, techniques, and challenges. Genome Res. 19:1141–52 [Google Scholar]
  25. Salter SJ, Cox MJ, Turek EM, Calus ST, Cookson WO. 25.  et al. 2014. Reagent and laboratory contamination can critically impact sequence-based microbiome analyses. BMC Biol. 12:87 [Google Scholar]
  26. Dickson RP, Erb-Downward JR, Prescott HC, Martinez FJ, Curtis JL. 26.  et al. 2014. Cell-associated bacteria in the human lung microbiome. Microbiome 2:28 [Google Scholar]
  27. Dickson RP, Erb-Downward JR, Freeman CM, Walker N, Scales BS. 27.  et al. 2014. Changes in the lung microbiome following lung transplantation include the emergence of two distinct Pseudomonas species with distinct clinical associations. PLOS ONE 9:e97214 [Google Scholar]
  28. Dickson RP, Martinez FJ, Huffnagle GB. 28.  2014. The role of the microbiome in exacerbations of chronic lung diseases. Lancet 384:691–702 [Google Scholar]
  29. Dickson RP, Erb-Downward JR, Freeman CM, McCloskey L, Beck JM. 29.  et al. 2015. Spatial variation in the healthy human lung microbiome and the adapted island model of lung biogeography. Ann. Am. Thorac. Soc. 12:821–30 [Google Scholar]
  30. Segal LN, Alekseyenko AV, Clemente JC, Kulkarni R, Wu B. 30.  et al. 2013. Enrichment of lung microbiome with supraglottic taxa is associated with increased pulmonary inflammation. Microbiome 1:19 [Google Scholar]
  31. Cox MJ, Allgaier M, Taylor B, Baek MS, Huang YJ. 31.  et al. 2010. Airway microbiota and pathogen abundance in age-stratified cystic fibrosis patients. PLOS ONE 5:e11044 [Google Scholar]
  32. Molyneaux PL, Mallia P, Cox MJ, Footitt J, Willis-Owen SA. 32.  et al. 2013. Outgrowth of the bacterial airway microbiome after rhinovirus exacerbation of chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 188:1224–31 [Google Scholar]
  33. Rogers GB, van der Gast CJ, Cuthbertson L, Thomson SK, Bruce KD. 33.  et al. 2013. Clinical measures of disease in adult non-CF bronchiectasis correlate with airway microbiota composition. Thorax 68:731–37 [Google Scholar]
  34. Zhao J, Murray S, Lipuma JJ. 34.  2014. Modeling the impact of antibiotic exposure on human microbiota. Sci. Rep. 4:4345 [Google Scholar]
  35. Zhao J, Schloss PD, Kalikin LM, Carmody LA, Foster BK. 35.  et al. 2012. Decade-long bacterial community dynamics in cystic fibrosis airways. PNAS 109:5809–14 [Google Scholar]
  36. Rogers GB, Zain NM, Bruce KD, Burr LD, Chen AC. 36.  et al. 2014. A novel microbiota stratification system predicts future exacerbations in bronchiectasis. Ann. Am. Thorac. Soc. 11:496–503 [Google Scholar]
  37. Hasleton PS. 37.  1972. The internal surface area of the adult human lung. J. Anat. 112:391–400 [Google Scholar]
  38. Helander HF, Fandriks L. 38.  2014. Surface area of the digestive tract—revisited. Scand. J. Gastroenterol. 49:681–89 [Google Scholar]
  39. Policard J, Galy P. 39.  1945. Les bronches: structures et mécanismes à l'état normal et pathologique Paris: Masson & Cie
  40. Wu H, Kuzmenko A, Wan S, Schaffer L, Weiss A. 40.  et al. 2003. Surfactant proteins A and D inhibit the growth of Gram-negative bacteria by increasing membrane permeability. J. Clin. Investig. 111:1589–602 [Google Scholar]
  41. Lighthart B. 41.  2000. Mini-review of the concentration variations found in the alfresco atmospheric bacterial populations. Aerobiologia 16:7–16 [Google Scholar]
  42. Munyard P, Bush A. 42.  1996. How much coughing is normal?. Arch. Dis. Child 74:531–34 [Google Scholar]
  43. Hatch TF. 43.  1961. Distribution and deposition of inhaled particles in respiratory tract. Bacteriol. Rev. 25:237–40 [Google Scholar]
  44. Ingenito EP, Solway J, McFadden ER Jr, Pichurko B, Bowman HF. 44.  et al. 1987. Indirect assessment of mucosal surface temperatures in the airways: theory and tests. J. Appl. Physiol. 63:2075–83 [Google Scholar]
  45. West JB. 45.  1978. Regional differences in the lung. Chest 74:426–37 [Google Scholar]
  46. MacArthur RH, Wilson EO. 46.  1963. An equilibrium theory of insular zoogeography. Evolution 17:373–87 [Google Scholar]
  47. D'Ovidio F, Singer LG, Hadjiliadis D, Pierre A, Waddell TK. 47.  et al. 2005. Prevalence of gastroesophageal reflux in end-stage lung disease candidates for lung transplant. Ann. Thorac. Surg. 80:1254–60 [Google Scholar]
  48. Raghu G, Freudenberger TD, Yang S, Curtis JR, Spada C. 48.  et al. 2006. High prevalence of abnormal acid gastro-oesophageal reflux in idiopathic pulmonary fibrosis. Eur. Respir. J. 27:136–42 [Google Scholar]
  49. Coxson HO, Hogg JC, Mayo JR, Behzad H, Whittall KP. 49.  et al. 1997. Quantification of idiopathic pulmonary fibrosis using computed tomography and histology. Am. J. Respir. Crit. Care Med. 155:1649–56 [Google Scholar]
  50. Coxson HO, Rogers RM, Whittall KP, D'Yachkova Y, Pare PD. 50.  et al. 1999. A quantification of the lung surface area in emphysema using computed tomography. Am. J. Respir. Crit. Care Med. 159:851–56 [Google Scholar]
  51. Molyneaux PL, Cox MJ, Willis-Owen SA, Mallia P, Russell KE. 51.  et al. 2014. The role of bacteria in the pathogenesis and progression of idiopathic pulmonary fibrosis. Am. J. Respir. Crit. Care Med. 190:906–13 [Google Scholar]
  52. Worlitzsch D, Tarran R, Ulrich M, Schwab U, Cekici A. 52.  et al. 2002. Effects of reduced mucus oxygen concentration in airway Pseudomonas infections of cystic fibrosis patients. J. Clin. Investig. 109:317–25 [Google Scholar]
  53. Schmidt A, Belaaouaj A, Bissinger R, Koller G, Malleret L. 53.  et al. 2014. Neutrophil elastase–mediated increase in airway temperature during inflammation. J. Cyst. Fibros. 13:623–31 [Google Scholar]
  54. Konstan MW, Hilliard KA, Norvell TM, Berger M. 54.  1994. Bronchoalveolar lavage findings in cystic fibrosis patients with stable, clinically mild lung disease suggest ongoing infection and inflammation. Am. J. Respir. Crit. Care Med. 150:448–54 [Google Scholar]
  55. Papi A, Bellettato CM, Braccioni F, Romagnoli M, Casolari P. 55.  et al. 2006. Infections and airway inflammation in chronic obstructive pulmonary disease severe exacerbations. Am. J. Respir. Crit. Care Med. 173:1114–21 [Google Scholar]
  56. Soler N, Ewig S, Torres A, Filella X, Gonzalez J, Zaubet A. 56.  1999. Airway inflammation and bronchial microbial patterns in patients with stable chronic obstructive pulmonary disease. Eur. Respir. J. 14:1015–22 [Google Scholar]
  57. Finlay BB, McFadden G. 57.  2006. Anti-immunology: evasion of the host immune system by bacterial and viral pathogens. Cell 124:767–82 [Google Scholar]
  58. Freestone PP, Hirst RA, Sandrini SM, Sharaff F, Fry H. 58.  et al. 2012. Pseudomonas aeruginosa–catecholamine inotrope interactions: a contributory factor in the development of ventilator-associated pneumonia?. Chest 142:1200–10 [Google Scholar]
  59. Kanangat S, Meduri GU, Tolley EA, Patterson DR, Meduri CU. 59.  et al. 1999. Effects of cytokines and endotoxin on the intracellular growth of bacteria. Infect. Immun. 67:2834–40 [Google Scholar]
  60. Kaza SK, McClean S, Callaghan M. 60.  2011. IL-8 released from human lung epithelial cells induced by cystic fibrosis pathogens Burkholderia cepacia complex affects the growth and intracellular survival of bacteria. Int. J. Med. Microbiol. 301:26–33 [Google Scholar]
  61. Porat R, Clark BD, Wolff SM, Dinarello CA. 61.  1991. Enhancement of growth of virulent strains of Escherichia coli by interleukin-1. Science 254:430–32 [Google Scholar]
  62. Marks LR, Davidson BA, Knight PR, Hakansson AP. 62.  2013. Interkingdom signaling induces Streptococcus pneumoniae biofilm dispersion and transition from asymptomatic colonization to disease. MBio 4:e00438–13 [Google Scholar]
  63. Aagaard K, Ma J, Antony KM, Ganu R, Petrosino J, Versalovic J. 63.  2014. The placenta harbors a unique microbiome. Sci. Transl. Med. 6:237ra65 [Google Scholar]
  64. DiGiulio DB. 64.  2012. Diversity of microbes in amniotic fluid. Semin. Fetal Neonatal Med. 17:2–11 [Google Scholar]
  65. Dominguez-Bello MG, Costello EK, Contreras M, Magris M, Hidalgo G. 65.  et al. 2010. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. PNAS 107:11971–75 [Google Scholar]
  66. Capone KA, Dowd SE, Stamatas GN, Nikolovski J. 66.  2011. Diversity of the human skin microbiome early in life. J. Investig. Dermatol. 131:2026–32 [Google Scholar]
  67. Yatsunenko T, Rey FE, Manary MJ, Trehan I, Dominguez-Bello MG. 67.  et al. 2012. Human gut microbiome viewed across age and geography. Nature 486:222–27 [Google Scholar]
  68. Biesbroek G, Tsivtsivadze E, Sanders EA, Montijn R, Veenhoven RH. 68.  et al. 2014. Early respiratory microbiota composition determines bacterial succession patterns and respiratory health in children. Am. J. Respir. Crit. Care Med. 190:1283–92 [Google Scholar]
  69. Teo Shu M, Mok D, Pham K, Kusel M, Serralha M. 69.  et al. 2015. The infant nasopharyngeal microbiome impacts severity of lower respiratory infection and risk of asthma development. Cell Host Microbe 17:704–15 [Google Scholar]
  70. Morris A, Beck JM, Schloss PD, Campbell TB, Crothers K. 70.  et al. 2013. Comparison of the respiratory microbiome in healthy nonsmokers and smokers. Am. J. Respir. Crit. Care Med. 187:1067–75 [Google Scholar]
  71. Lozupone C, Cota-Gomez A, Palmer BE, Linderman DJ, Charlson ES. 71.  et al. 2013. Widespread colonization of the lung by Tropheryma whipplei in HIV infection. Am. J. Respir. Crit. Care Med. 187:1110–17 [Google Scholar]
  72. Sullivan CE, Murphy E, Kozar LF, Phillipson EA. 72.  1978. Waking and ventilatory responses to laryngeal stimulation in sleeping dogs. J. Appl. Physiol. Respir. Environ. Exerc. Physiol. 45:681–89 [Google Scholar]
  73. Goddard AF, Staudinger BJ, Dowd SE, Joshi-Datar A, Wolcott RD. 73.  et al. 2012. Direct sampling of cystic fibrosis lungs indicates that DNA-based analyses of upper-airway specimens can misrepresent lung microbiota. PNAS 109:13769–74 [Google Scholar]
  74. Willner D, Haynes MR, Furlan M, Schmieder R, Lim YW. 74.  et al. 2012. Spatial distribution of microbial communities in the cystic fibrosis lung. ISME J. 6:471–74 [Google Scholar]
  75. Erb-Downward JR, Thompson DL, Han MK, Freeman CM, McCloskey L. 75.  et al. 2011. Analysis of the lung microbiome in the “healthy” smoker and in COPD. PLOS ONE 6:e16384 [Google Scholar]
  76. Huang YJ, Nelson CE, Brodie EL, Desantis TZ, Baek MS. 76.  et al. 2011. Airway microbiota and bronchial hyperresponsiveness in patients with suboptimally controlled asthma. J. Allergy Clin. Immunol. 127:372–81.e1–3 [Google Scholar]
  77. Goleva E, Jackson LP, Harris JK, Robertson CE, Sutherland ER. 77.  et al. 2013. The effects of airway microbiome on corticosteroid responsiveness in asthma. Am. J. Respir. Crit. Care Med. 188:1193–201 [Google Scholar]
  78. Marri PR, Stern DA, Wright AL, Billheimer D, Martinez FD. 78.  2013. Asthma-associated differences in microbial composition of induced sputum. J. Allergy Clin. Immunol. 131:346–52e1–3 [Google Scholar]
  79. Slater M, Rivett DW, Williams L, Martin M, Harrison T. 79.  et al. 2013. The impact of azithromycin therapy on the airway microbiota in asthma. Thorax 69:673–74 [Google Scholar]
  80. Green BJ, Wiriyachaiporn S, Grainge C, Rogers GB, Kehagia V. 80.  et al. 2014. Potentially pathogenic airway bacteria and neutrophilic inflammation in treatment resistant severe asthma. PLOS ONE 9:e100645 [Google Scholar]
  81. Ege MJ, Mayer M, Normand AC, Genuneit J, Cookson WO. 81.  et al. 2011. Exposure to environmental microorganisms and childhood asthma. N. Engl. J. Med. 364:701–9 [Google Scholar]
  82. Noverr MC, Noggle RM, Toews GB, Huffnagle GB. 82.  2004. Role of antibiotics and fungal microbiota in driving pulmonary allergic responses. Infect. Immun. 72:4996–5003 [Google Scholar]
  83. Trompette A, Gollwitzer ES, Yadava K, Sichelstiel AK, Sprenger N. 83.  et al. 2014. Gut microbiota metabolism of dietary fiber influences allergic airway disease and hematopoiesis. Nat. Med. 20:159–66 [Google Scholar]
  84. Green RH, Brightling CE, Woltmann G, Parker D, Wardlaw AJ, Pavord ID. 84.  2002. Analysis of induced sputum in adults with asthma: identification of subgroup with isolated sputum neutrophilia and poor response to inhaled corticosteroids. Thorax 57:875–79 [Google Scholar]
  85. Essilfie AT, Horvat JC, Kim RY, Mayall JR, Pinkerton JW. 85.  et al. 2015. Macrolide therapy suppresses key features of experimental steroid-sensitive and steroid-insensitive asthma. Thorax 70:458–67 [Google Scholar]
  86. Simpson JL, Powell H, Boyle MJ, Scott RJ, Gibson PG. 86.  2008. Clarithromycin targets neutrophilic airway inflammation in refractory asthma. Am. J. Respir. Crit. Care Med. 177:148–55 [Google Scholar]
  87. Sze MA, Abbasi M, Hogg JC, Sin DD. 87.  2014. A comparison between droplet digital and quantitative PCR in the analysis of bacterial 16S load in lung tissue samples from control and COPD GOLD 2. PLOS ONE 9:e110351 [Google Scholar]
  88. Sze MA, Utokaparch S, Elliott WM, Hogg JC, Hegele RG. 88.  2015. Loss of GD1-positive Lactobacillus correlates with inflammation in human lungs with COPD. BMJ Open 5:e006677 [Google Scholar]
  89. Garcia-Nuñez M, Millares L, Pomares X, Ferrari R, Pérez-Brocal V. 89.  et al. 2014. Severity-related changes of bronchial microbiome in chronic obstructive pulmonary disease. J. Clin. Microbiol. 52:4217–23 [Google Scholar]
  90. Wu D, Hou C, Li Y, Zhao Z, Liu J. 90.  et al. 2014. Analysis of the bacterial community in chronic obstructive pulmonary disease sputum samples by denaturing gradient gel electrophoresis and real-time PCR. BMC Pulm. Med. 14:179 [Google Scholar]
  91. Sze MA, Dimitriu PA, Hayashi S, Elliott WM, McDonough JE. 91.  et al. 2012. The lung tissue microbiome in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 185:1073–80 [Google Scholar]
  92. Morris A, Sciurba FC, Lebedeva IP, Githaiga A, Elliott WM. 92.  et al. 2004. Association of chronic obstructive pulmonary disease severity and Pneumocystis colonization. Am. J. Respir. Crit. Care Med. 170:408–13 [Google Scholar]
  93. Cui L, Lucht L, Tipton L, Rogers MB, Fitch A. 93.  et al. 2015. Topographic diversity of the respiratory tract mycobiome and alteration in HIV and lung disease. Am. J. Respir. Crit. Care Med. 191:932–42 [Google Scholar]
  94. Bafadhel M, McKenna S, Agbetile J, Fairs A, Desai D. 94.  et al. 2014. Aspergillus fumigatus during stable state and exacerbations of COPD. Eur. Respir. J. 43:64–71 [Google Scholar]
  95. 95. Cystic Fibrosis Foundation 2014. Patient registry annual data report 2014 https://www.cff.org/2014_CFF_Annual_Data_Report_to_the_Center_Directors.pdf/
  96. Hurley MN, Ariff AH, Bertenshaw C, Bhatt J, Smyth AR. 96.  2012. Results of antibiotic susceptibility testing do not influence clinical outcome in children with cystic fibrosis. J. Cyst. Fibros. 11:288–92 [Google Scholar]
  97. Smith AL, Fiel SB, Mayer-Hamblett N, Ramsey B, Burns JL. 97.  2003. Susceptibility testing of Pseudomonas aeruginosa isolates and clinical response to parenteral antibiotic administration: lack of association in cystic fibrosis. Chest 123:1495–502 [Google Scholar]
  98. Gold R, Overmeyer A, Knie B, Fleming PC, Levison H. 98.  1985. Controlled trial of ceftazidime versus ticarcillin and tobramycin in the treatment of acute respiratory exacerbations in patients with cystic fibrosis. Pediatr. Infect. Dis. 4:172–77 [Google Scholar]
  99. Rogers GB, Carroll MP, Serisier DJ, Hockey PM, Kehagia V. 99.  et al. 2005. Bacterial activity in cystic fibrosis lung infections. Respir. Res. 6:49 [Google Scholar]
  100. Sibley CD, Parkins MD, Rabin HR, Duan K, Norgaard JC, Surette MG. 100.  2008. A polymicrobial perspective of pulmonary infections exposes an enigmatic pathogen in cystic fibrosis patients. PNAS 105:15070–75 [Google Scholar]
  101. Bruzzese E, Raia V, Spagnuolo MI, Volpicelli M, De Marco G. 101.  et al. 2007. Effect of Lactobacillus GG supplementation on pulmonary exacerbations in patients with cystic fibrosis: a pilot study. Clin. Nutr. 26:322–28 [Google Scholar]
  102. Weiss B, Bujanover Y, Yahav Y, Vilozni D, Fireman E, Efrati O. 102.  2010. Probiotic supplementation affects pulmonary exacerbations in patients with cystic fibrosis: a pilot study. Pediatr. Pulmonol. 45:536–40 [Google Scholar]
  103. Madan JC, Koestler DC, Stanton BA, Davidson L, Moulton LA. 103.  et al. 2012. Serial analysis of the gut and respiratory microbiome in cystic fibrosis in infancy: interaction between intestinal and respiratory tracts and impact of nutritional exposures. MBio 3:e00251–12 [Google Scholar]
  104. Carmody LA, Zhao J, Kalikin LM, LeBar W, Simon RH. 104.  et al. 2015. The daily dynamics of cystic fibrosis airway microbiota during clinical stability and at exacerbation. Microbiome 3:12 [Google Scholar]
  105. Zhao J, Evans CR, Carmody LA, LiPuma JJ. 105.  2015. Impact of storage conditions on metabolite profiles of sputum samples from persons with cystic fibrosis. J. Cyst. Fibros. 14:468–73 [Google Scholar]
  106. Maughan H, Cunningham KS, Wang PW, Zhang Y, Cypel M. 106.  et al. 2012. Pulmonary bacterial communities in surgically resected noncystic fibrosis bronchiectasis lungs are similar to those in cystic fibrosis. Pulm. Med. 2012:746358 [Google Scholar]
  107. Tunney MM, Einarsson GG, Wei L, Drain M, Klem ER. 107.  et al. 2013. Lung microbiota and bacterial abundance in patients with bronchiectasis when clinically stable and during exacerbation. Am. J. Respir. Crit. Care Med. 187:1118–26 [Google Scholar]
  108. Taylor SL, Rogers GB, Chen AC, Burr LD, McGuckin MA, Serisier DJ. 108.  2015. Matrix metalloproteinases vary with airway microbiota composition and lung function in non–cystic fibrosis bronchiectasis. Ann. Am. Thorac. Soc. 2: 701–7
  109. Young LR, Hadjiliadis D, Davis RD, Palmer SM. 109.  2003. Lung transplantation exacerbates gastroesophageal reflux disease. Chest 124:1689–93 [Google Scholar]
  110. Yusen RD, Edwards LB, Kucheryavaya AY, Benden C, Dipchand AI. 110.  et al. 2014. The registry of the International Society for Heart and Lung Transplantation: thirty-first adult lung and heart-lung transplant report—2014; focus theme: retransplantation. J. Heart Lung Transplant. 33:1009–24 [Google Scholar]
  111. Botha P, Archer L, Anderson RL, Lordan J, Dark JH. 111.  et al. 2008. Pseudomonas aeruginosa colonization of the allograft after lung transplantation and the risk of bronchiolitis obliterans syndrome. Transplantation 85:771–74 [Google Scholar]
  112. Gottlieb J, Mattner F, Weissbrodt H, Dierich M, Fuehner T. 112.  et al. 2009. Impact of graft colonization with gram-negative bacteria after lung transplantation on the development of bronchiolitis obliterans syndrome in recipients with cystic fibrosis. Respir. Med. 103:743–49 [Google Scholar]
  113. Vos R, Vanaudenaerde BM, Geudens N, Dupont LJ, Van Raemdonck DE, Verleden GM. 113.  2008. Pseudomonal airway colonisation: risk factor for bronchiolitis obliterans syndrome after lung transplantation?. Eur. Respir. J. 31:1037–45 [Google Scholar]
  114. Borewicz K, Pragman AA, Kim HB, Hertz M, Wendt C, Isaacson RE. 114.  2012. Longitudinal analysis of the lung microbiome in lung transplantation. FEMS Microbiol. Lett. 339:57–65 [Google Scholar]
  115. Charlson ES, Diamond JM, Bittinger K, Fitzgerald AS, Yadav A. 115.  et al. 2012. Lung-enriched organisms and aberrant bacterial and fungal respiratory microbiota after lung transplant. Am. J. Respir. Crit. Care Med. 186:536–45 [Google Scholar]
  116. Willner DL, Hugenholtz P, Yerkovich ST, Tan ME, Daly JN. 116.  et al. 2013. Re-establishment of recipient-associated microbiota in the lung allograft is linked to reduced risk of bronchiolitis obliterans syndrome. Am. J. Respir. Crit. Care Med. 187:640–47 [Google Scholar]
  117. Scales BS, Dickson RP, LiPuma JJ, Huffnagle GB. 117.  2014. Microbiology, genomics, and clinical significance of the Pseudomonas fluorescens species complex, an unappreciated colonizer of humans. Clin. Microbiol. Rev. 27:927–48 [Google Scholar]
  118. Shulgina L, Cahn AP, Chilvers ER, Parfrey H, Clark AB. 118.  et al. 2013. Treating idiopathic pulmonary fibrosis with the addition of co-trimoxazole: a randomised controlled trial. Thorax 68:155–62 [Google Scholar]
  119. Raghu G, Anstrom KJ, King TE Jr, Lasky JA, Martinez FJ. 119.  2012. Prednisone, azathioprine, and N-acetylcysteine for pulmonary fibrosis. N. Engl. J. Med. 366:1968–77 [Google Scholar]
  120. Han MK, Zhou Y, Murray S, Tayob N, Noth I. 120.  et al. 2014. Lung microbiome and disease progression in idiopathic pulmonary fibrosis: an analysis of the COMET study. Lancet Respir. Med. 2:548–56 [Google Scholar]
  121. Molyneaux PL, Cox MJ, Willis-Owen SA, Mallia P, Russell KE. 121.  et al. 2014. The role of bacteria in the pathogenesis and progression of idiopathic pulmonary fibrosis. Am. J. Respir. Crit. Care Med. 190:906–13 [Google Scholar]
  122. Flaherty KR, Andrei AC, Murray S, Fraley C, Colby TV. 122.  et al. 2006. Idiopathic pulmonary fibrosis: prognostic value of changes in physiology and six-minute-walk test. Am. J. Respir. Crit. Care Med. 174:803–9 [Google Scholar]
  123. Peljto AL, Zhang Y, Fingerlin TE, Ma SF, Garcia JG. 123.  et al. 2013. Association between the MUC5B promoter polymorphism and survival in patients with idiopathic pulmonary fibrosis. JAMA 309:2232–39 [Google Scholar]
  124. Iwai S, Huang D, Fong S, Jarlsberg LG, Worodria W. 124.  et al. 2014. The lung microbiome of Ugandan HIV-infected pneumonia patients is compositionally and functionally distinct from that of San Franciscan patients. PLOS ONE 9:e95726 [Google Scholar]
  125. Toma I, Siegel MO, Keiser J, Yakovleva A, Kim A. 125.  et al. 2014. Single-molecule long-read 16S sequencing to characterize the lung microbiome from mechanically ventilated patients with suspected pneumonia. J. Clin. Microbiol. 52:3913–21 [Google Scholar]
  126. Lyte M, Ernst S. 126.  1992. Catecholamine induced growth of gram negative bacteria. Life Sci. 50:203–12 [Google Scholar]
  127. Dickson RP, Erb-Downward JR, Prescott HC, Martinez FJ, Curtis JL. 127.  et al. 2015. Intraalveolar catecholamines and the human lung microbiome. Am. J. Respir. Crit. Care Med. 192:257–59 [Google Scholar]
  128. Casadevall A, Pirofski LA. 128.  2003. The damage-response framework of microbial pathogenesis. Nat. Rev. Microbiol. 1:17–24 [Google Scholar]
  129. Carmody LA, Zhao J, Schloss PD, Petrosino JF, Murray S. 129.  et al. 2013. Changes in cystic fibrosis airway microbiota at pulmonary exacerbation. Ann. Am. Thorac. Soc. 10:179–87 [Google Scholar]
  130. Huang YJ, Sethi S, Murphy T, Nariya S, Boushey HA, Lynch SV. 130.  2014. Airway microbiome dynamics in exacerbations of chronic obstructive pulmonary disease. J. Clin. Microbiol. 52:2813–23 [Google Scholar]
  131. Millares L, Ferrari R, Gallego M, Garcia-Nuñez M, Pérez-Brocal V. 131.  et al. 2014. Bronchial microbiome of severe COPD patients colonised by Pseudomonas aeruginosa. Eur. J. Clin. Microbiol. Infect. Dis. 33:1101–11 [Google Scholar]
  132. Price KE, Hampton TH, Gifford AH, Dolben EL, Hogan DA. 132.  et al. 2013. Unique microbial communities persist in individual cystic fibrosis patients throughout a clinical exacerbation. Microbiome 1:27 [Google Scholar]
  133. Stressmann FA, Rogers GB, Marsh P, Lilley AK, Daniels TW. 133.  et al. 2011. Does bacterial density in cystic fibrosis sputum increase prior to pulmonary exacerbation?. J. Cyst. Fibros. 10:357–65 [Google Scholar]
  134. Page SE. 134.  2010. Diversity and Complexity Princeton, NJ: Princeton Univ. Press
  135. Holland JH. 135.  2006. Studying complex adaptive systems. J. Syst. Sci. Complex. 19:1–8 [Google Scholar]
/content/journals/10.1146/annurev-physiol-021115-105238
Loading
/content/journals/10.1146/annurev-physiol-021115-105238
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error