The role of acute and chronic respiratory colonization and infections in the pathogenesis of COPD

Janice M Leung, Pei Yee Tiew, Micheál Mac Aogáin, Kurtis F Budden, Valerie Fei Lee Yong, Sangeeta S Thomas, Kevin Pethe, Philip M Hansbro, Sanjay H Chotirmall, Janice M Leung, Pei Yee Tiew, Micheál Mac Aogáin, Kurtis F Budden, Valerie Fei Lee Yong, Sangeeta S Thomas, Kevin Pethe, Philip M Hansbro, Sanjay H Chotirmall

Abstract

COPD is a major global concern, increasingly so in the context of ageing populations. The role of infections in disease pathogenesis and progression is known to be important, yet the mechanisms involved remain to be fully elucidated. While COPD pathogens such as Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae are strongly associated with acute exacerbations of COPD (AECOPD), the clinical relevance of these pathogens in stable COPD patients remains unclear. Immune responses in stable and colonized COPD patients are comparable to those detected in AECOPD, supporting a role for chronic colonization in COPD pathogenesis through perpetuation of deleterious immune responses. Advances in molecular diagnostics and metagenomics now allow the assessment of microbe-COPD interactions with unprecedented personalization and precision, revealing changes in microbiota associated with the COPD disease state. As microbial changes associated with AECOPD, disease severity and therapeutic intervention become apparent, a renewed focus has been placed on the microbiology of COPD and the characterization of the lung microbiome in both its acute and chronic states. Characterization of bacterial, viral and fungal microbiota as part of the lung microbiome has the potential to reveal previously unrecognized prognostic markers of COPD that predict disease outcome or infection susceptibility. Addressing such knowledge gaps will ultimately lead to a more complete understanding of the microbe-host interplay in COPD. This will permit clearer distinctions between acute and chronic infections and more granular patient stratification that will enable better management of these features and of COPD.

Keywords: acute exacerbations of chronic obstructive pulmonary disease; chronic obstructive pulmonary disease; colonization; infection; microbiome.

© 2017 Asian Pacific Society of Respirology.

Figures

Figure 1
Figure 1
Microbial factors affecting COPD disease pathogenesis and progression. Pathogenic microbes associated with acute and chronic COPD infection influence disease progression. Increasingly, the role of the microbiome and its associated virome and mycobiome is recognized. As microbiome architecture is profoundly altered by COPD therapy, dynamic interaction between microbiology, infection and therapy likely occurs during COPD disease progression. LTB4, leukotriene B4; MDR, multidrug resistance; MMP, matrix metalloproteinase; MPO, myeloperoxidase; NE, neutrophil elastase; TLR, Toll‐like receptor.
Figure 2
Figure 2
A proposed schematic representation of the interactions between COPD and tuberculosis (TB). While both conditions share a number of risk factors, TB may contribute to the development of COPD through matrix metalloproteinase‐mediated lung remodelling. COPD may also contribute to TB infection by impairing immune responses, ciliary function and through exposure to inhaled corticosteroids.
Figure 3
Figure 3
Role of the microbiome in COPD pathogenesis and progression. Bacteria, viruses and fungi enter the lung through breathing and microaspiration of oral microbes. In the healthy lung, homeostasis is achieved through an appropriate immune response and pathogen clearance. In COPD, an increased abundance of pathogenic organisms and oral taxa is seen in association with reduced overall bacterial diversity. Consequently, perpetuation of a deleterious immune response occurs with associated COPD progression. Host–microbe dialogue may also proceed via the gut–lung axis further exacerbating disease symptoms as demonstrated in other chronic respiratory disease states. IPA, invasive pulmonary aspergillosis; Th, T‐helper.

References

    1. Fletcher C, Peto R. The natural history of chronic airflow obstruction. Br. Med. J. 1977; 1: 1645–8.
    1. Anthonisen NR. The British hypothesis revisited. Eur. Respir. J. 2004; 23: 657–8.
    1. Papi A, Bellettato CM, Braccioni F, Romagnoli M, Casolari P, Caramori G, Fabbri LM, Johnston SL. Infections and airway inflammation in chronic obstructive pulmonary disease severe exacerbations. Am. J. Respir. Crit. Care Med. 2006; 173: 1114–21.
    1. Bafadhel M, McKenna S, Terry S, Mistry V, Reid C, Haldar P, McCormick M, Haldar K, Kebadze T, Duvoix A et al. Acute exacerbations of chronic obstructive pulmonary disease: identification of biologic clusters and their biomarkers. Am. J. Respir. Crit. Care Med. 2011; 184: 662–71.
    1. Berenson CS, Kruzel RL, Eberhardt E, Dolnick R, Minderman H, Wallace PK, Sethi S. Impaired innate immune alveolar macrophage response and the predilection for COPD exacerbations. Thorax 2014; 69: 811–8.
    1. Taylor AE, Finney‐Hayward TK, Quint JK, Thomas CM, Tudhope SJ, Wedzicha JA, Barnes PJ, Donnelly LE. Defective macrophage phagocytosis of bacteria in COPD. Eur. Respir. J. 2010; 35: 1039–47.
    1. King PT, Sharma R, O'Sullivan K, Selemidis S, Lim S, Radhakrishna N, Lo C, Prasad J, Callaghan J, McLaughlin P et al. Nontypeable Haemophilus influenzae induces sustained lung oxidative stress and protease expression. PLoS One 2015; 10: e0120371.
    1. Hsu AC, Starkey MR, Hanish I, Parsons K, Haw TJ, Howland LJ, Barr I, Mahony JB, Foster PS, Knight DA et al. Targeting PI3K‐p110alpha suppresses influenza virus infection in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 2015; 191: 1012–23.
    1. Hsu AC, Parsons K, Barr I, Lowther S, Middleton D, Hansbro PM, Wark PA. Critical role of constitutive type I interferon response in bronchial epithelial cell to influenza infection. PLoS One 2012; 7: e32947.
    1. Hsu AC, Parsons K, Moheimani F, Knight DA, Hansbro PM, Fujita T, Wark PA. Impaired antiviral stress granule and IFN‐beta enhanceosome formation enhances susceptibility to influenza infection in chronic obstructive pulmonary disease epithelium. Am. J. Respir. Cell Mol. Biol. 2016; 55: 117–27.
    1. Bauer CM, Dewitte‐Orr SJ, Hornby KR, Zavitz CC, Lichty BD, Stampfli MR, Mossman KL. Cigarette smoke suppresses type I interferon‐mediated antiviral immunity in lung fibroblast and epithelial cells. J. Interferon Cytokine Res. 2008; 28: 167–79.
    1. Simet SM, Sisson JH, Pavlik JA, Devasure JM, Boyer C, Liu X, Kawasaki S, Sharp JG, Rennard SI, Wyatt TA. Long‐term cigarette smoke exposure in a mouse model of ciliated epithelial cell function. Am. J. Respir. Cell Mol. Biol. 2010; 43: 635–40.
    1. Rogers DF. Mucociliary dysfunction in COPD: effect of current pharmacotherapeutic options. Pulm. Pharmacol. Ther. 2005; 18: 1–8.
    1. Sajjan U, Ganesan S, Comstock AT, Shim J, Wang Q, Nagarkar DR, Zhao Y, Goldsmith AM, Sonstein J, Linn MJ et al. Elastase‐ and LPS‐exposed mice display altered responses to rhinovirus infection. Am. J. Physiol. Lung Cell. Mol. Physiol. 2009; 297: L931–44.
    1. De Serres G, Lampron N, La Forge J, Rouleau I, Bourbeau J, Weiss K, Barret B, Boivin G. Importance of viral and bacterial infections in chronic obstructive pulmonary disease exacerbations. J. Clin. Virol. 2009; 46: 129–33.
    1. Sethi S, Evans N, Grant BJ, Murphy TF. New strains of bacteria and exacerbations of chronic obstructive pulmonary disease. N. Engl. J. Med. 2002; 347: 465–71.
    1. Garcha DS, Thurston SJ, Patel AR, Mackay AJ, Goldring JJ, Donaldson GC, McHugh TD, Wedzicha JA. Changes in prevalence and load of airway bacteria using quantitative PCR in stable and exacerbated COPD. Thorax 2012; 67: 1075–80.
    1. Wilkinson TM, Patel IS, Wilks M, Donaldson GC, Wedzicha JA. Airway bacterial load and FEV1 decline in patients with chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 2003; 167: 1090–5.
    1. Marin A, Monso E, Garcia‐Nunez M, Sauleda J, Noguera A, Pons J, Agusti A, Morera J. Variability and effects of bronchial colonisation in patients with moderate COPD. Eur. Respir. J. 2010; 35: 295–302.
    1. Rosell A, Monso E, Soler N, Torres F, Angrill J, Riise G, Zalacain R, Morera J, Torres A. Microbiologic determinants of exacerbation in chronic obstructive pulmonary disease. Arch. Intern. Med. 2005; 165: 891–7.
    1. Patel IS, Seemungal TA, Wilks M, Lloyd‐Owen SJ, Donaldson GC, Wedzicha JA. Relationship between bacterial colonisation and the frequency, character, and severity of COPD exacerbations. Thorax 2002; 57: 759–64.
    1. Monso E, Ruiz J, Rosell A, Manterola J, Fiz J, Morera J, Ausina V. Bacterial infection in chronic obstructive pulmonary disease. A study of stable and exacerbated outpatients using the protected specimen brush. Am. J. Respir. Crit. Care Med. 1995; 152: 1316–20.
    1. Bogaert D, van der Valk P, Ramdin R, Sluijter M, Monninkhof E, Hendrix R, de Groot R, Hermans PW. Host‐pathogen interaction during pneumococcal infection in patients with chronic obstructive pulmonary disease. Infect. Immun. 2004; 72: 818–23.
    1. Domenech A, Puig C, Marti S, Santos S, Fernandez A, Calatayud L, Dorca J, Ardanuy C, Linares J. Infectious etiology of acute exacerbations in severe COPD patients. J. Infect. 2013; 67: 516–23.
    1. Rodrigo‐Troyano A, Suarez‐Cuartin G, Peiro M, Barril S, Castillo D, Sanchez‐Reus F, Plaza V, Restrepo MI, Chalmers JD, Sibila O. Pseudomonas aeruginosa resistance patterns and clinical outcomes in hospitalized exacerbations of COPD. Respirology 2016; 21: 1235–42.
    1. Blasi F, Damato S, Cosentini R, Tarsia P, Raccanelli R, Centanni S, Allegra L; The Chlamydia InterAction with COPD (CIAC) Study Group . Chlamydia pneumoniae and chronic bronchitis: association with severity and bacterial clearance following treatment. Thorax 2002; 57: 672–6.
    1. Hoefsloot W, van Ingen J, Magis‐Escurra C, Reijers MH, van Soolingen D, Dekhuijzen RP, Boeree MJ. Prevalence of nontuberculous mycobacteria in COPD patients with exacerbations. J. Infect. 2013; 66: 542–5.
    1. Zwaans WA, Mallia P, van Winden ME, Rohde GG. The relevance of respiratory viral infections in the exacerbations of chronic obstructive pulmonary disease‐a systematic review. J. Clin. Virol. 2014; 61: 181–8.
    1. Huerta A, Soler N, Esperatti M, Guerrero M, Menendez R, Gimeno A, Zalacain R, Mir N, Aguado JM, Torres A. Importance of Aspergillus spp. isolation in acute exacerbations of severe COPD: prevalence, factors and follow‐up: the FUNGI‐COPD study. Respir. Res. 2014; 15: 17.
    1. Morris A, Sciurba FC, Lebedeva IP, Githaiga A, Elliott WM, Hogg JC, Huang L, Norris KA. Association of chronic obstructive pulmonary disease severity and Pneumocystis colonization. Am. J. Respir. Crit. Care Med. 2004; 170: 408–13.
    1. Calderon EJ, Rivero L, Respaldiza N, Morilla R, Montes‐Cano MA, Friaza V, Munoz‐Lobato F, Varela JM, Medrano FJ, Horra Cde L. Systemic inflammation in patients with chronic obstructive pulmonary disease who are colonized with Pneumocystis jirovecii . Clin. Infect. Dis. 2007; 45: e17–9.
    1. Fitzpatrick ME, Tedrow JR, Hillenbrand ME, Lucht L, Richards T, Norris KA, Zhang Y, Sciurba FC, Kaminski N, Morris A. Pneumocystis jirovecii colonization is associated with enhanced Th1 inflammatory gene expression in lungs of humans with chronic obstructive pulmonary disease. Microbiol. Immunol. 2014; 58: 202–11.
    1. Camargo CA Jr, Ginde AA, Clark S, Cartwright CP, Falsey AR, Niewoehner DE. Viral pathogens in acute exacerbations of chronic obstructive pulmonary disease. Intern. Emerg. Med. 2008; 3: 355–9.
    1. McManus TE, Marley AM, Baxter N, Christie SN, O'Neill HJ, Elborn JS, Coyle PV, Kidney JC. Respiratory viral infection in exacerbations of COPD. Respir. Med. 2008; 102: 1575–80.
    1. Djamin RS, Uzun S, Snelders E, Kluytmans JJ, Hoogsteden HC, Aerts JG, Van Der Eerden MM. Occurrence of virus‐induced COPD exacerbations during four seasons. Infect. Dis. 2015; 47: 96–100.
    1. Hosseini SS, Ghasemian E, Jamaati H, Tabaraie B, Amini Z, Cox K. Association between respiratory viruses and exacerbation of COPD: a case‐control study. Infect. Dis. 2015; 47: 523–9.
    1. Perotin JM, Dury S, Renois F, Deslee G, Wolak A, Duval V, De Champs C, Lebargy F, Andreoletti L. Detection of multiple viral and bacterial infections in acute exacerbation of chronic obstructive pulmonary disease: a pilot prospective study. J. Med. Virol. 2013; 85: 866–73.
    1. Wark PA, Tooze M, Powell H, Parsons K. Viral and bacterial infection in acute asthma and chronic obstructive pulmonary disease increases the risk of readmission. Respirology 2013; 18: 996–1002.
    1. Dai MY, Qiao JP, Xu YH, Fei GH. Respiratory infectious phenotypes in acute exacerbation of COPD: an aid to length of stay and COPD Assessment Test. Int. J. Chron. Obstruct. Pulmon. Dis. 2015; 10: 2257–63.
    1. Mallia P, Message SD, Gielen V, Contoli M, Gray K, Kebadze T, Aniscenko J, Laza‐Stanca V, Edwards MR, Slater L et al. Experimental rhinovirus infection as a human model of chronic obstructive pulmonary disease exacerbation. Am. J. Respir. Crit. Care Med. 2011; 183: 734–42.
    1. Sethi S, Murphy TF. Infection in the pathogenesis and course of chronic obstructive pulmonary disease. N. Engl. J. Med. 2008; 359: 2355–65.
    1. Lapperre TS, Postma DS, Gosman MM, Snoeck‐Stroband JB, ten Hacken NH, Hiemstra PS, Timens W, Sterk PJ, Mauad T. Relation between duration of smoking cessation and bronchial inflammation in COPD. Thorax 2006; 61: 115–21.
    1. Gamble E, Grootendorst DC, Hattotuwa K, O'Shaughnessy T, Ram FS, Qiu Y, Zhu J, Vignola AM, Kroegel C, Morell F et al. Airway mucosal inflammation in COPD is similar in smokers and ex‐smokers: a pooled analysis. Eur. Respir. J. 2007; 30: 467–71.
    1. Hallstrand TS, Hackett TL, Altemeier WA, Matute‐Bello G, Hansbro PM, Knight DA. Airway epithelial regulation of pulmonary immune homeostasis and inflammation. Clin. Immunol. 2014; 151: 1–15.
    1. Sethi S, Maloney J, Grove L, Wrona C, Berenson CS. Airway inflammation and bronchial bacterial colonization in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 2006; 173: 991–8.
    1. Tang FS, Hansbro PM, Burgess JK, Ammit AJ, Baines KJ, Oliver BG. A novel immunomodulatory function of neutrophils on rhinovirus‐activated monocytes in vitro. Thorax 2016; 10: 1039–49.
    1. Hoenderdos K, Condliffe A. The neutrophil in chronic obstructive pulmonary disease. Am. J. Respir. Cell Mol. Biol. 2013; 48: 531–9.
    1. Agusti A, Edwards LD, Rennard SI, MacNee W, Tal‐Singer R, Miller BE, Vestbo J, Lomas DA, Calverley PM, Wouters E et al; Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) Investigators . Persistent systemic inflammation is associated with poor clinical outcomes in COPD: a novel phenotype. PLoS One 2012; 7: e37483.
    1. Desai H, Eschberger K, Wrona C, Grove L, Agrawal A, Grant B, Yin J, Parameswaran GI, Murphy T, Sethi S. Bacterial colonization increases daily symptoms in patients with chronic obstructive pulmonary disease. Ann. Am. Thorac. Soc. 2014; 11: 303–9.
    1. Berenson CS, Kruzel RL, Eberhardt E, Sethi S. Phagocytic dysfunction of human alveolar macrophages and severity of chronic obstructive pulmonary disease. J. Infect. Dis. 2013; 208: 2036–45.
    1. Droemann D, Goldmann T, Tiedje T, Zabel P, Dalhoff K, Schaaf B. Toll‐like receptor 2 expression is decreased on alveolar macrophages in cigarette smokers and COPD patients. Respir. Res. 2005; 6: 68.
    1. Harvey CJ, Thimmulappa RK, Sethi S, Kong X, Yarmus L, Brown RH, Feller‐Kopman D, Wise R, Biswal S. Targeting Nrf2 signaling improves bacterial clearance by alveolar macrophages in patients with COPD and in a mouse model. Sci. Transl. Med. 2011; 3: 78ra32.
    1. Simpson JL, McDonald VM, Baines KJ, Oreo KM, Wang F, Hansbro PM, Gibson PG. Influence of age, past smoking, and disease severity on TLR2, neutrophilic inflammation, and MMP‐9 levels in COPD. Mediators Inflamm. 2013; 2013: 462934.
    1. Murphy TF, Brauer AL, Grant BJ, Sethi S. Moraxella catarrhalis in chronic obstructive pulmonary disease: burden of disease and immune response. Am. J. Respir. Crit. Care Med. 2005; 172: 195–9.
    1. Hogg JC, Chu F, Utokaparch S, Woods R, Elliott WM, Buzatu L, Cherniack RM, Rogers RM, Sciurba FC, Coxson HO et al. The nature of small‐airway obstruction in chronic obstructive pulmonary disease. N. Engl. J. Med. 2004; 350: 2645–53.
    1. Matkovic Z, Miravitlles M. Chronic bronchial infection in COPD. Is there an infective phenotype? Respir. Med. 2013; 107: 10–22.
    1. Simpson JL, Baines KJ, Horvat JC, Essilfie AT, Brown AC, Tooze M, McDonald VM, Gibson PG, Hansbro PM. COPD is characterized by increased detection of Haemophilus influenzae, Streptococcus pneumoniae and a deficiency of Bacillus species. Respirology 2016; 21: 697–704.
    1. St Geme JW 3rd, Falkow S, Barenkamp SJ. High‐molecular‐weight proteins of nontypeable Haemophilus influenzae mediate attachment to human epithelial cells. Proc. Natl. Acad. Sci. U. S. A. 1993; 90: 2875–9.
    1. Reddy MS, Bernstein JM, Murphy TF, Faden HS. Binding between outer membrane proteins of nontypeable Haemophilus influenzae and human nasopharyngeal mucin. Infect. Immun. 1996; 64: 1477–9.
    1. Sethi S, Murphy TF. Bacterial infection in chronic obstructive pulmonary disease in 2000: a state‐of‐the‐art review. Clin. Microbiol. Rev. 2001; 14: 336–63.
    1. Berenson CS, Murphy TF, Wrona CT, Sethi S. Outer membrane protein P6 of nontypeable Haemophilus influenzae is a potent and selective inducer of human macrophage proinflammatory cytokines. Infect. Immun. 2005; 73: 2728–35.
    1. Essilfie AT, Simpson JL, Dunkley ML, Morgan LC, Oliver BG, Gibson PG, Foster PS, Hansbro PM. Combined Haemophilus influenzae respiratory infection and allergic airways disease drives chronic infection and features of neutrophilic asthma. Thorax 2012; 67: 588–99.
    1. Berenson CS, Wrona CT, Grove LJ, Maloney J, Garlipp MA, Wallace PK, Stewart CC, Sethi S. Impaired alveolar macrophage response to Haemophilus antigens in chronic obstructive lung disease. Am. J. Respir. Crit. Care Med. 2006; 174: 31–40.
    1. Bandi V, Apicella MA, Mason E, Murphy TF, Siddiqi A, Atmar RL, Greenberg SB. Nontypeable Haemophilus influenzae in the lower respiratory tract of patients with chronic bronchitis. Am. J. Respir. Crit. Care Med. 2001; 164: 2114–9.
    1. Murphy TF, Lesse AJ, Kirkham C, Zhong H, Sethi S, Munson RS Jr. A clonal group of nontypeable Haemophilus influenzae with two IgA proteases is adapted to infection in chronic obstructive pulmonary disease. PLoS One 2011; 6: e25923.
    1. Marin A, Garcia‐Aymerich J, Sauleda J, Belda J, Millares L, Garcia‐Nunez M, Serra I, Benet M, Agusti A, Anto JM et al. ; PAC‐COPD Study Group . Effect of bronchial colonisation on airway and systemic inflammation in stable COPD. COPD 2012; 9: 121–30.
    1. Miravitlles M, Espinosa C, Fernández‐Laso E, Martos JA, Maldonado JA, Gallego M. Relationship between bacterial flora in sputum and functional impairment in patients with acute exacerbations of COPD. Chest 1999; 116: 40–6.
    1. Tufvesson E, Bjermer L, Ekberg M. Patients with chronic obstructive pulmonary disease and chronically colonized with Haemophilus influenzae during stable disease phase have increased airway inflammation. Int. J. Chron. Obstruct. Pulmon. Dis. 2015; 10: 881–9.
    1. Parameswaran GI, Wrona CT, Murphy TF, Sethi S. Moraxella catarrhalis acquisition, airway inflammation and protease‐antiprotease balance in chronic obstructive pulmonary disease. BMC Infect. Dis. 2009; 9: 178.
    1. Murphy TF, Brauer AL, Schiffmacher AT, Sethi S. Persistent colonization by Haemophilus influenzae in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 2004; 170: 266–72.
    1. van Alphen L, Jansen HM, Dankert J. Virulence factors in the colonization and persistence of bacteria in the airways. Am. J. Respir. Crit. Care Med. 1995; 151: 2094–9; discussion 2099–100.
    1. Garcia‐Vidal C, Almagro P, Romani V, Rodriguez‐Carballeira M, Cuchi E, Canales L, Blasco D, Heredia JL, Garau J. Pseudomonas aeruginosa in patients hospitalised for COPD exacerbation: a prospective study. Eur. Respir. J. 2009; 34: 1072–8.
    1. Murphy TF, Brauer AL, Eschberger K, Lobbins P, Grove L, Cai X, Sethi S. Pseudomonas aeruginosa in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 2008; 177: 853–60.
    1. Boutou AK, Raste Y, Reid J, Alshafi K, Polkey MI, Hopkinson NS. Does a single Pseudomonas aeruginosa isolation predict COPD mortality? Eur. Respir. J. 2014; 44: 794–7.
    1. Diederen BM, van der Valk PD, Kluytmans JA, Peeters MF, Hendrix R. The role of atypical respiratory pathogens in exacerbations of chronic obstructive pulmonary disease. Eur. Respir. J. 2007; 30: 240–4.
    1. Branden E, Koyi H, Gnarpe J, Gnarpe H, Tornling G. Chronic Chlamydia pneumoniae infection is a risk factor for the development of COPD. Respir. Med. 2005; 99: 20–6.
    1. Seemungal TA, Wedzicha JA, MacCallum PK, Johnston SL, Lambert PA. Chlamydia pneumoniae and COPD exacerbation. Thorax 2002; 57: 1087–8; author reply 1088–9.
    1. Martinez‐Garcia MA, de la Rosa CD, Soler‐Cataluna JJ, Donat‐Sanz Y, Serra PC, Lerma MA, Ballestin J, Sanchez IV, Selma Ferrer MJ, Dalfo AR et al. Prognostic value of bronchiectasis in patients with moderate‐to‐severe chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 2013; 187: 823–31.
    1. Huang CT, Tsai YJ, Wu HD, Wang JY, Yu CJ, Lee LN, Yang PC. Impact of non‐tuberculous mycobacteria on pulmonary function decline in chronic obstructive pulmonary disease. Int. J. Tuberc. Lung Dis. 2012; 16: 539–45.
    1. Char A, Hopkinson NS, Hansell DM, Nicholson AG, Shaw EC, Clark SJ, Sedgwick P, Wilson R, Jordan S, Loebinger MR. Evidence of mycobacterial disease in COPD patients with lung volume reduction surgery; the importance of histological assessment of specimens: a cohort study. BMC Pulm. Med. 2014; 14: 124.
    1. Ringshausen FC, Wagner D, de Roux A, Diel R, Hohmann D, Hickstein L, Welte T, Rademacher J. Prevalence of nontuberculous mycobacterial pulmonary disease, Germany, 2009‐2014. Emerg. Infect. Dis. 2016; 22: 1102–5.
    1. Mirsaeidi M, Machado RF, Garcia JG, Schraufnagel DE. Nontuberculous mycobacterial disease mortality in the United States, 1999‐2010: a population‐based comparative study. PLoS One 2014; 9: e91879.
    1. Anno H, Tomashefski JF. Studies on the impairment of respiratory function in pulmonary tuberculosis. Am. Rev. Tuberc. 1955; 71: 333–48.
    1. Chan‐Yeung M, Ho AS, Cheung AH, Liu RW, Yee WK, Sin KM, Wong MM, Lam CW, Chan KS, Lam WK. Determinants of chronic obstructive pulmonary disease in Chinese patients in Hong Kong. Int. J. Tuberc. Lung Dis. 2007; 11: 502–7.
    1. Menezes AM, Hallal PC, Perez‐Padilla R, Jardim JR, Muino A, Lopez MV, Valdivia G, Montes de Oca M, Talamo C, Pertuze J et al. Tuberculosis and airflow obstruction: evidence from the PLATINO study in Latin America. Eur. Respir. J. 2007; 30: 1180–5.
    1. Caballero A, Torres‐Duque CA, Jaramillo C, Bolivar F, Sanabria F, Osorio P, Orduz C, Guevara DP, Maldonado D. Prevalence of COPD in five Colombian cities situated at low, medium, and high altitude (PREPOCOL study). Chest 2008; 133: 343–9.
    1. Lam KB, Jiang CQ, Jordan RE, Miller MR, Zhang WS, Cheng KK, Lam TH, Adab P. Prior TB, smoking, and airflow obstruction: a cross‐sectional analysis of the Guangzhou Biobank Cohort Study. Chest 2010; 137: 593–600.
    1. Lamprecht B, McBurnie MA, Vollmer WM, Gudmundsson G, Welte T, Nizankowska‐Mogilnicka E, Studnicka M, Bateman E, Anto JM, Burney P et al. COPD in never smokers: results from the population‐based Burden of Obstructive Lung Disease study. Chest 2011; 139: 752–63.
    1. Idolor LF, De Guia TS, Francisco NA, Roa CC, Ayuyao FG, Tady CZ, Tan DT, Banal‐Yang S, Balanag VM Jr, Reyes MT et al. Burden of obstructive lung disease in a rural setting in the Philippines. Respirology 2011; 16: 1111–8.
    1. Danielsson P, Olafsdottir IS, Benediktsdottir B, Gislason T, Janson C. The prevalence of chronic obstructive pulmonary disease in Uppsala, Sweden – the Burden of Obstructive Lung Disease (BOLD) study: cross‐sectional population‐based study. Clin. Respir. J. 2012; 6: 120–7.
    1. Govender N, Lalloo UG, Naidoo RN. Occupational exposures and chronic obstructive pulmonary disease: a hospital based case‐control study. Thorax 2011; 66: 597–601.
    1. Lee SW, Kim YS, Kim DS, Oh YM, Lee SD. The risk of obstructive lung disease by previous pulmonary tuberculosis in a country with intermediate burden of tuberculosis. J. Korean Med. Sci. 2011; 26: 268–73.
    1. Hooper R, Burney P, Vollmer WM, McBurnie MA, Gislason T, Tan WC, Jithoo A, Kocabas A, Welte T, Buist AS. Risk factors for COPD spirometrically defined from the lower limit of normal in the BOLD project. Eur. Respir. J. 2012; 39: 1343–53.
    1. Perez‐Padilla R, Fernandez R, Lopez Varela MV, Montes de Oca M, Muino A, Talamo C, Brito Jardim JR, Valdivia G, Baptista Menezes AM. Airflow obstruction in never smokers in five Latin American cities: the PLATINO study. Arch. Med. Res. 2012; 43: 159–65.
    1. Hwang YI, Kim JH, Lee CY, Park S, Park YB, Jang SH, Kim CH, Shin TR, Park SM, Sim YS et al. The association between airflow obstruction and radiologic change by tuberculosis. J. Thorac. Dis. 2014; 6: 471–6.
    1. Smith M, Li L, Augustyn M, Kurmi O, Chen J, Collins R, Guo Y, Han Y, Qin J, Xu G et al. Prevalence and correlates of airflow obstruction in approximately 317,000 never‐smokers in China. Eur. Respir. J. 2014; 44: 66–77.
    1. Amaral AF, Coton S, Kato B, Tan WC, Studnicka M, Janson C, Gislason T, Mannino D, Bateman ED, Buist S et al. Tuberculosis associates with both airflow obstruction and low lung function: BOLD results. Eur. Respir. J. 2015; 46: 1104–12.
    1. Chan TC, Wang HW, Tseng TJ, Chiang PH. Spatial clustering and local risk factors of chronic obstructive pulmonary disease (COPD). Int. J. Environ. Res. Public Health 2015; 12: 15716–27.
    1. Jaganath D, Miranda JJ, Gilman RH, Wise RA, Diette GB, Miele CH, Bernabe‐Ortiz A, Checkley W. Prevalence of chronic obstructive pulmonary disease and variation in risk factors across four geographically diverse resource‐limited settings in Peru. Respir. Res. 2015; 16: 40.
    1. Jo YS, Choi SM, Lee J, Park YS, Lee SM, Yim JJ, Yoo CG, Kim YW, Han SK, Lee CH. The relationship between chronic obstructive pulmonary disease and comorbidities: a cross‐sectional study using data from KNHANES 2010‐2012. Respir. Med. 2015; 109: 96–104.
    1. Lee SJ, Kim SW, Kong KA, Ryu YJ, Lee JH, Chang JH. Risk factors for chronic obstructive pulmonary disease among never‐smokers in Korea. Int. J. Chron. Obstruct. Pulmon. Dis. 2015; 10: 497–506.
    1. Lee SH, Hwang ED, Lim JE, Moon S, Kang YA, Jung JY, Park MS, Kim SK, Chang J, Kim YS et al. The risk factors and characteristics of COPD among nonsmokers in Korea: an analysis of KNHANES IV and V. Lung 2016; 194: 353–61.
    1. Snider GL, Doctor L, Demas TA, Shaw AR. Obstructive airway disease in patients with treated pulmonary tuberculosis. Am. Rev. Respir. Dis. 1971; 103: 625–40.
    1. Willcox PA, Ferguson AD. Chronic obstructive airways disease following treated pulmonary tuberculosis. Respir. Med. 1989; 83: 195–8.
    1. Plit ML, Anderson R, Van Rensburg CE, Page‐Shipp L, Blott JA, Fresen JL, Feldman C. Influence of antimicrobial chemotherapy on spirometric parameters and pro‐inflammatory indices in severe pulmonary tuberculosis. Eur. Respir. J. 1998; 12: 351–6.
    1. Ramos LM, Sulmonett N, Ferreira CS, Henriques JF, de Miranda SS. Functional profile of patients with tuberculosis sequelae in a university hospital. J. Bras. Pneumol. 2006; 32: 43–7.
    1. Pasipanodya JG, Miller TL, Vecino M, Munguia G, Garmon R, Bae S, Drewyer G, Weis SE. Pulmonary impairment after tuberculosis. Chest 2007; 131: 1817–24.
    1. Girdler‐Brown BV, White NW, Ehrlich RI, Churchyard GJ. The burden of silicosis, pulmonary tuberculosis and COPD among former Basotho goldminers. Am. J. Ind. Med. 2008; 51: 640–7.
    1. Baig IM, Saeed W, Khalil KF. Post‐tuberculous chronic obstructive pulmonary disease. J. Coll. Physicians Surg. Pak. 2010; 20: 542–4.
    1. Rhee CK, Yoo KH, Lee JH, Park MJ, Kim WJ, Park YB, Hwang YI, Kim YS, Jung JY, Moon JY et al. Clinical characteristics of patients with tuberculosis‐destroyed lung. Int. J. Tuberc. Lung Dis. 2013; 17: 67–75.
    1. de la Mora IL, Martinez‐Oceguera D, Laniado‐Laborin R. Chronic airway obstruction after successful treatment of tuberculosis and its impact on quality of life. Int. J. Tuberc. Lung Dis. 2015; 19: 808–10.
    1. Manji M, Shayo G, Mamuya S, Mpembeni R, Jusabani A, Mugusi F. Lung functions among patients with pulmonary tuberculosis in Dar es Salaam ‐ a cross‐sectional study. BMC Pulm. Med. 2016; 16: 58.
    1. Ehrlich RI, Adams S, Baatjies R, Jeebhay MF. Chronic airflow obstruction and respiratory symptoms following tuberculosis: a review of South African studies. Int. J. Tuberc. Lung Dis. 2011; 15: 886–91.
    1. Liaquat A, Iram S, Hussain S, Yusuf NW, Azeem H. Concomitant presence of culture‐proven active pulmonary tuberculosis in patients with chronic obstructive pulmonary disease – a hospital based study. Pak. J. Med. Sci. 2015; 31: 1344–8.
    1. Inghammar M, Ekbom A, Engstrom G, Ljungberg B, Romanus V, Lofdahl CG, Egesten A. COPD and the risk of tuberculosis – a population‐based cohort study. PLoS One 2010; 5: e10138.
    1. Chotirmall SH, Al‐Alawi M, Mirkovic B, Lavelle G, Logan PM, Greene CM, McElvaney NG. Aspergillus‐associated airway disease, inflammation, and the innate immune response. Biomed. Res. Int. 2013; 2013: 723129.
    1. Bafadhel M, McKenna S, Agbetile J, Fairs A, Desai D, Mistry V, Morley JP, Pancholi M, Pavord ID, Wardlaw AJ et al. Aspergillus fumigatus during stable state and exacerbations of COPD. Eur. Respir. J. 2014; 43: 64–71.
    1. Agarwal R, Hazarika B, Gupta D, Aggarwal AN, Chakrabarti A, Jindal SK. Aspergillus hypersensitivity in patients with chronic obstructive pulmonary disease: COPD as a risk factor for ABPA? Med. Mycol. 2010; 48: 988–94.
    1. Jin J, Liu X, Sun Y. The prevalence of increased serum IgE and Aspergillus sensitization in patients with COPD and their association with symptoms and lung function. Respir. Res. 2014; 15: 130.
    1. Guinea J, Torres‐Narbona M, Gijon P, Munoz P, Pozo F, Pelaez T, de Miguel J, Bouza E. Pulmonary aspergillosis in patients with chronic obstructive pulmonary disease: incidence, risk factors, and outcome. Clin. Microbiol. Infect. 2010; 16: 870–7.
    1. Hohl TM, Feldmesser M. Aspergillus fumigatus: principles of pathogenesis and host defense. Eukaryot. Cell 2007; 6: 1953–63.
    1. Bulpa P, Dive A, Sibille Y. Invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary disease. Eur. Respir. J. 2007; 30: 782–800.
    1. Sing ARA, Autenrieth IB, Heesemann J. Pneumocystis carinii carriage in immunocompetent patients with primary pulmonary disorders as detected by single or nested PCR. J. Clin. Microbiol. 1999; 37: 3409–10.
    1. Morris A, Alexander T, Radhi S, Lucht L, Sciurba FC, Kolls JK, Srivastava R, Steele C, Norris KA. Airway obstruction is increased in Pneumocystis‐colonized human immunodeficiency virus‐infected outpatients. J. Clin. Microbiol. 2009; 47: 3773–6.
    1. Matsuse T, Hayashi S, Kuwano K, Keunecke H, Jefferies WA, Hogg JC. Latent adenoviral infection in the pathogenesis of chronic airways obstruction. Am. Rev. Respir. Dis. 1992; 146: 177–84.
    1. Retamales I, Elliott WM, Meshi B, Coxson HO, Pare PD, Sciurba FV, Rogers RM, Hayashi S, Hogg JC. Amplification of inflammation in emphysema and its association with latent adenoviral infection. Am. J. Respir. Crit. Care Med. 2001; 164: 469–73.
    1. Meshi B, Vitalis TZ, Ionescu D, Elliott WM, Liu C, Wang XD, Hayashi S, Hogg JC. Emphysematous lung destruction by cigarette smoke the effects of latent adenoviral infection on the lung inflammatory response. Am. J. Respir. Cell Mol. Biol. 2002; 26: 52–7.
    1. Keicho N, Elliott WM, Hogg JC, Hayashi S. Adenovirus E1A upregulates interleukin‐8 expression induced by endotoxin in pulmonary epithelial cells. Am. J. Physiol. 1997; 272: L1046–52.
    1. Keicho N, Elliott WM, Hogg JC, Hayashi S. Adenovirus E1A gene dysregulates ICAM‐1 expression in transformed pulmonary epithelial cells. Am. J. Respir. Cell Mol. Biol. 1997; 16: 23–30.
    1. Seemungal T, Harper‐Owen R, Bhowmik A, Moric I, Sanderson G, Message S, Mac Callum P, Meade TW, Jeffries DJ, Johnston SL et al. Respiratory viruses, symptoms, and inflammatory markers in acute exacerbations and stable chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 2001; 164: 1618–23.
    1. Wilkinson TM, Donaldson GC, Johnston SL, Openshaw PJ, Wedzicha JA. Respiratory syncytial virus, airway inflammation, and FEV1 decline in patients with chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 2006; 173: 871–6.
    1. Falsey AR, Formica MA, Hennessey PA, Criddle MM, Sullender WM, Walsh EE. Detection of respiratory syncytial virus in adults with chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 2006; 173: 639–43.
    1. Budden KF, Gellatly SL, Wood DL, Cooper MA, Morrison M, Hugenholtz P, Hansbro PM. Emerging pathogenic links between microbiota and the gut‐lung axis. Nat. Rev. Microbiol. 2017; 15: 55–63.
    1. Chotirmall SH, Gellatly SL, Budden KF, Mac Aogain M, Shukla SD, Wood DL, Hugenholtz P, Pethe K, Hansbro PM. Microbiomes in respiratory health and disease: an Asia‐Pacific perspective. Respirology 2017; 22: 240–50.
    1. Mammen MJ, Sethi S. COPD and the microbiome. Respirology 2016; 21: 590–9.
    1. Sze MA, Dimitriu PA, Hayashi S, Elliott WM, McDonough JE, Gosselink JV, Cooper J, Sin DD, Mohn WW, Hogg JC. The lung tissue microbiome in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 2012; 185: 1073–80.
    1. Pragman A, Kim H, Reilly C, Wendt C, Isaacson R. The lung microbiome in moderate and severe chronic obstructive pulmonary disease. PLoS One 2012; 7: e47305.
    1. Morris A, Beck J, Schloss P, Campbell T, Crothers K, Curtis J, Flores S, Fontenot A, Ghedin E, Huang L et al. Comparison of the respiratory microbiome in healthy nonsmokers and smokers. Am. J. Respir. Crit. Care Med. 2013; 187: 1067–75.
    1. Garcia‐Nunez M, Millares L, Pomares X, Ferrari R, Perez‐Brocal V, Gallego M, Espasa M, Moya A, Monso E. Severity‐related changes of bronchial microbiome in chronic obstructive pulmonary disease. J. Clin. Microbiol. 2014; 52: 4217–23.
    1. Sze MA, Dimitriu PA, Suzuki M, McDonough JE, Campbell JD, Brothers JF, Erb‐Downward JR, Huffnagle GB, Hayashi S, Elliott WM et al. Host response to the lung microbiome in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 2015; 192: 438–45.
    1. Huang YJ, Sethi S, Murphy T, Nariya S, Boushey HA, Lynch SV. Airway microbiome dynamics in exacerbations of chronic obstructive pulmonary disease. J. Clin. Microbiol. 2014; 52: 2813–23.
    1. Young JC, Chehoud C, Bittinger K, Bailey A, Diamond JM, Cantu E, Haas AR, Abbas A, Frye L, Christie JD et al. Viral metagenomics reveal blooms of anelloviruses in the respiratory tract of lung transplant recipients. Am. J. Transplant. 2015; 15: 200–9.
    1. Fischer N, Indenbirken D, Meyer T, Lutgehetmann M, Lellek H, Spohn M, Aepfelbacher M, Alawi M, Grundhoff A. Evaluation of unbiased next‐generation sequencing of RNA (RNA‐seq) as a diagnostic method in influenza virus‐positive respiratory samples. J. Clin. Microbiol. 2015; 53: 2238–50.
    1. Willner D, Furlan M, Haynes M, Schmieder R, Angly FE, Silva J, Tammadoni S, Nosrat B, Conrad D, Rohwer F. Metagenomic analysis of respiratory tract DNA viral communities in cystic fibrosis and non‐cystic fibrosis individuals. PLoS One 2009; 4: e7370.
    1. Mitchell AB, Oliver BG, Glanville AR. Translational aspects of the human respiratory virome. Am. J. Respir. Crit. Care Med. 2016; 194: 1458–64.
    1. McManus TE, Marley AM, Baxter N, Christie SN, Elborn JS, O'Neill HJ, Coyle PV, Kidney JC. High levels of Epstein‐Barr virus in COPD. Eur. Respir. J. 2008; 31: 1221–6.
    1. Tan DB, Amran FS, Teo TH, Price P, Moodley YP. Levels of CMV‐reactive antibodies correlate with the induction of CD28(null) T cells and systemic inflammation in chronic obstructive pulmonary disease (COPD). Cell. Mol. Immunol. 2016; 13: 551–3.
    1. Utokaparch S, Sze MA, Gosselink JV, McDonough JE, Elliott WM, Hogg JC, Hegele RG. Respiratory viral detection and small airway inflammation in lung tissue of patients with stable, mild COPD. COPD 2014; 11: 197–203.
    1. Singh M, Lee SH, Porter P, Xu C, Ohno A, Atmar RL, Greenberg SB, Bandi V, Gern J, Amineva S et al. Human rhinovirus proteinase 2A induces TH1 and TH2 immunity in patients with chronic obstructive pulmonary disease. J. Allergy Clin. Immunol. 2010; 125: 1369–78.e2.
    1. Molyneaux PL, Mallia P, Cox MJ, Footitt J, Willis‐Owen SA, Homola D, Trujillo‐Torralbo MB, Elkin S, Kon OM, Cookson WO et al. Outgrowth of the bacterial airway microbiome after rhinovirus exacerbation of chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 2013; 188: 1224–31.
    1. Nguyen LD, Viscogliosi E, Delhaes L. The lung mycobiome: an emerging field of the human respiratory microbiome. Front. Microbiol. 2015; 6: 89.
    1. Cui L, Lucht L, Tipton L, Rogers MB, Fitch A, Kessinger C, Camp D, Kingsley L, Leo N, Greenblatt RM et al. Topographic diversity of the respiratory tract mycobiome and alteration in HIV and lung disease. Am. J. Respir. Crit. Care Med. 2015; 191: 932–42.
    1. Christensen PJ, Preston AM, Ling T, Du M, Fields WB, Curtis JL, Beck JM. Pneumocystis murina infection and cigarette smoke exposure interact to cause increased organism burden, development of airspace enlargement, and pulmonary inflammation in mice. Infect. Immun. 2008; 76: 3481–90.
    1. Shipley TW, Kling HM, Morris A, Patil S, Kristoff J, Guyach SE, Murphy JE, Shao X, Sciurba FC, Rogers RM et al. Persistent Pneumocystis colonization leads to the development of chronic obstructive pulmonary disease in a nonhuman primate model of AIDS. J. Infect. Dis. 2010; 202: 302–12.
    1. Muzurovic S, Hukic M, Babajic E, Smajic R. The relationship between cigarette smoking and oral colonization with Candida species in healthy adult subjects. Med. Glas. (Zenica) 2013; 10: 397–9.
    1. Alanazi H, Semlali A, Perraud L, Chmielewski W, Zakrzewski A, Rouabhia M. Cigarette smoke‐exposed Candida albicans increased chitin production and modulated human fibroblast cell responses. Biomed. Res. Int. 2014; 2014: 963156.
    1. Letuve S, Kozhich A, Arouche N, Grandsaigne M, Reed J, Dombret MC, Kiener PA, Aubier M, Coyle AJ, Pretolani M. YKL‐40 is elevated in patients with chronic obstructive pulmonary disease and activates alveolar macrophages. J. Immunol. 2008; 181: 5167–73.
    1. Seibold MA, Donnelly S, Solon M, Innes A, Woodruff PG, Boot RG, Burchard EG, Fahy JV. Chitotriosidase is the primary active chitinase in the human lung and is modulated by genotype and smoking habit. J. Allergy Clin. Immunol. 2008; 122: 944–50.e3.
    1. James AJ, Reinius LE, Verhoek M, Gomes A, Kupczyk M, Hammar U, Ono J, Ohta S, Izuhara K, Bel E et al; BIOAIR (Longitudinal Assessment of Clinical Course and Biomarkers in Severe Chronic Airway Disease) Consortium . Increased YKL‐40 and chitotriosidase in asthma and chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med 2016; 193: 131–42.
    1. Anthonisen NR, Manfreda J, Warren CP, Hershfield ES, Harding GK, Nelson NA. Antibiotic therapy in exacerbations of chronic obstructive pulmonary disease. Ann. Intern. Med. 1987; 106: 196–204.
    1. Daniels JM, Snijders D, de Graaff CS, Vlaspolder F, Jansen HM, Boersma WG. Antibiotics in addition to systemic corticosteroids for acute exacerbations of chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 2010; 181: 150–7.
    1. Llor C, Moragas A, Hernandez S, Bayona C, Miravitlles M. Efficacy of antibiotic therapy for acute exacerbations of mild to moderate chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 2012; 186: 716–23.
    1. Stefan MS, Rothberg MB, Shieh MS, Pekow PS, Lindenauer PK. Association between antibiotic treatment and outcomes in patients hospitalized with acute exacerbation of COPD treated with systemic steroids. Chest 2013; 143: 82–90.
    1. Verduri A, Luppi F, D'Amico R, Balduzzi S, Vicini R, Liverani A, Ruggieri V, Plebani M, Barbaro MP, Spanevello A et al. Antibiotic treatment of severe exacerbations of chronic obstructive pulmonary disease with procalcitonin: a randomized noninferiority trial. PLoS One 2015; 10: e0118241.
    1. Wang JX, Zhang SM, Li XH, Zhang Y, Xu ZY, Cao B. Acute exacerbations of chronic obstructive pulmonary disease with low serum procalcitonin values do not benefit from antibiotic treatment: a prospective randomized controlled trial. Int. J. Infect. Dis. 2016; 48: 40–5.
    1. van de Geijn GM, Denker S, Meuleman‐van Waning V, Koeleman HG, Birnie E, Braunstahl GJ, Njo TL. Evaluation of new laboratory tests to discriminate bacterial from nonbacterial chronic obstructive pulmonary disease exacerbations. Int. J. Lab. Hematol. 2016; 38: 616–28.
    1. Qian W, Huang GZ. Neutrophil CD64 as a marker of bacterial infection in acute exacerbations of chronic obstructive pulmonary disease. Immunol. Invest. 2016; 45: 490–503.
    1. Marjanovic N, Bosnar M, Michielin F, Wille DR, Anic‐Milic T, Culic O, Popovic‐Grle S, Bogdan M, Parnham MJ, Erakovic Haber V. Macrolide antibiotics broadly and distinctively inhibit cytokine and chemokine production by COPD sputum cells in vitro. Pharmacol. Res. 2011; 63: 389–97.
    1. Menzel M, Akbarshahi H, Bjermer L, Uller L. Azithromycin induces anti‐viral effects in cultured bronchial epithelial cells from COPD patients. Sci. Rep. 2016; 6: 28698.
    1. Simpson JL, Powell H, Baines KJ, Milne D, Coxson HO, Hansbro PM, Gibson PG. The effect of azithromycin in adults with stable neutrophilic COPD: a double blind randomised, placebo controlled trial. PLoS One 2014; 9: e105609.
    1. Albert RK, Connett J, Bailey WC, Casaburi R, Cooper JA Jr, Criner GJ, Curtis JL, Dransfield MT, Han MK, Lazarus SC et al. Azithromycin for prevention of exacerbations of COPD. N. Engl. J. Med. 2011; 365: 689–98.
    1. Han MK, Tayob N, Murray S, Dransfield MT, Washko G, Scanlon PD, Criner GJ, Casaburi R, Connett J, Lazarus SC et al. Predictors of chronic obstructive pulmonary disease exacerbation reduction in response to daily azithromycin therapy. Am. J. Respir. Crit. Care Med. 2014; 189: 1503–8.
    1. Segal LN, Clemente JC, Wu BG, Wikoff WR, Gao Z, Li Y, Ko JP, Rom WN, Blaser MJ, Weiden MD. Randomised, double‐blind, placebo‐controlled trial with azithromycin selects for anti‐inflammatory microbial metabolites in the emphysematous lung. Thorax 2017; 72: 13–22.
    1. Calverley PM, Anderson JA, Celli B, Ferguson GT, Jenkins C, Jones PW, Yates JC, Vestbo J. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N. Engl. J. Med. 2007; 356: 775–89.
    1. Sin DD, Tashkin D, Zhang X, Radner F, Sjobring U, Thoren A, Calverley PM, Rennard SI. Budesonide and the risk of pneumonia: a meta‐analysis of individual patient data. Lancet 2009; 374: 712–9.
    1. Janson C, Larsson K, Lisspers KH, Stallberg B, Stratelis G, Goike H, Jorgensen L, Johansson G. Pneumonia and pneumonia related mortality in patients with COPD treated with fixed combinations of inhaled corticosteroid and long acting beta2 agonist: observational matched cohort study (PATHOS). BMJ 2013; 346: f3306.
    1. Suissa S, Patenaude V, Lapi F, Ernst P. Inhaled corticosteroids in COPD and the risk of serious pneumonia. Thorax 2013; 68: 1029–36.
    1. Dransfield MT, Bourbeau J, Jones PW, Hanania NA, Mahler DA, Vestbo J, Wachtel A, Martinez FJ, Barnhart F, Sanford L et al. Once‐daily inhaled fluticasone furoate and vilanterol versus vilanterol only for prevention of exacerbations of COPD: two replicate double‐blind, parallel‐group, randomised controlled trials. Lancet Respir. Med. 2013; 1: 210–23.
    1. O'Toole RF, Shukla SD, Walters EH. TB meets COPD: an emerging global co‐morbidity in human lung disease. Tuberculosis (Edinb.) 2015; 95: 659–63.
    1. Yamaya M, Azuma A, Takizawa H, Kadota J, Tamaoki J, Kudoh S. Macrolide effects on the prevention of COPD exacerbations. Eur. Respir. J. 2012; 40: 485–94.
    1. Gan WQ, Man SF, Senthilselvan A, Sin DD. Association between chronic obstructive pulmonary disease and systemic inflammation: a systematic review and a meta‐analysis. Thorax 2004; 59: 574–80.
    1. Kang CI, Song JH. Antimicrobial resistance in Asia: current epidemiology and clinical implications. Infect. Chemother. 2013; 45: 22–31.
    1. Hui DS, Ip M, Ling T, Chang SC, Liao CH, Yoo CG, Kim DK, Yoon HI, Udompanich V, Mogmeud S et al. A multicentre surveillance study on the characteristics, bacterial aetiologies and in vitro antibiotic susceptibilities in patients with acute exacerbations of chronic bronchitis. Respirology 2011; 16: 532–9.
    1. Pettigrew MM, Tsuji BT, Gent JF, Kong Y, Holden PN, Sethi S, Murphy TF. Effect of fluoroquinolones and macrolides on eradication and resistance of Haemophilus influenzae in chronic obstructive pulmonary disease. Antimicrob. Agents Chemother. 2016; 60: 4151–8.
    1. Nightingale CH. Pharmacokinetics and pharmacodynamics of newer macrolides. Pediatr. Infect. Dis. J. 1997; 16: 438–43.
    1. Desai H, Richter S, Doern G, Heilmann K, Dohrn C, Johnson A, Brauer A, Murphy T, Sethi S. Antibiotic resistance in sputum isolates of Streptococcus pneumoniae in chronic obstructive pulmonary disease is related to antibiotic exposure. COPD 2010; 7: 337–44.
    1. Montero M, Dominguez M, Orozco‐Levi M, Salvado M, Knobel H. Mortality of COPD patients infected with multi‐resistant Pseudomonas aeruginosa: a case and control study. Infection 2009; 37: 16–9.
    1. Kyd JM, McGrath J, Krishnamurthy A. Mechanisms of bacterial resistance to antibiotics in infections of COPD patients. Curr. Drug Targets 2011; 12: 521–30.
    1. Stolz D, Christ‐Crain M, Bingisser R, Leuppi J, Miedinger D, Muller C, Huber P, Muller B, Tamm M. Antibiotic treatment of exacerbations of COPD: a randomized, controlled trial comparing procalcitonin‐guidance with standard therapy. Chest 2007; 131: 9–19.
    1. Wang W, Li JJ, Foster PS, Hansbro PM, Yang M. Potential therapeutic targets for steroid‐resistant asthma. Curr. Drug Targets 2010; 11: 957–70.
    1. Fricker M, Deane A, Hansbro PM. Animal models of chronic obstructive pulmonary disease. Expert Opin. Drug Discov. 2014; 9: 629–45.
    1. Jones B, Donovan C, Liu G, Harrison C, Gomez HM, Wiegman CH, Adcock IM, Knight DA, Hirota JA, Hansbro PM. Animal models of COPD: what do they tell us? . Respirology 2017; 22: 21–32.
    1. Bourke JE, Bai Y, Donovan C, Esposito JG, Tan X, Sanderson MJ. Novel small airway bronchodilator responses to rosiglitazone in mouse lung slices. Am. J. Respir. Cell Mol. Biol. 2014; 50: 748–56.
    1. Donovan C, Seow HJ, Royce SG, Bourke JE, Vlahos R. Alteration of airway reactivity and reduction of ryanodine receptor expression by cigarette smoke in mice. Am. J. Respir. Cell Mol. Biol. 2015; 53: 471–8.
    1. Sturton RG, Trifilieff A, Nicholson AG, Barnes PJ. Pharmacological characterization of indacaterol, a novel once daily inhaled 2 adrenoceptor agonist, on small airways in human and rat precision‐cut lung slices. J. Pharmacol. Exp. Ther. 2008; 324: 270–5.

Source: PubMed

Sponsors et collaborateurs

Les conditions médicales

Interventions en matière de drogue

3
S'abonner