Nontypeable Haemophilus influenzae and chronic obstructive pulmonary disease: a review for clinicians

References

• Afonso ET, Minamisava R, Bierrenbach AL, Escalante JJ, Alencar AP, Domingues CM, Morais-Neto OL, Toscano CM, Andrade AL. 2013. Effect of 10-valent pneumococcal vaccine on pneumonia among children, Brazil. Emerg Infect Dis. 19:589–597.
   PubMed Web of Science ®Google Scholar
• Ahrén IL, Janson H, Forsgren A, Riesbeck K. 2001. Protein D expression promotes the adherence and internalization of non-typeable Haemophilus influenzae into human monocytic cells. Microbial Pathogen. 31:151–158.
   PubMed Web of Science ®Google Scholar
• Albert RK, Connett J, Bailey WC, Casaburi R, Cooper JAD, Criner GJ, Curtis JL, Dransfield MT, Han MK, Lazarus SC, et al. 2011. Azithromycin for prevention of exacerbations of COPD. N Engl J Med. 365:689–698.
   PubMed Web of Science ®Google Scholar
• Allison P, Gordon J, Zinnemann K. 1943. The incidence and significance of H. influenzae in chronic bronchiectasis. J Pathol. 55:465–475.
   Google Scholar
• Araki N, Yanagihara K, Morinaga Y, Yamada K, Nakamura S, Yamada Y, Kohno S, Kamihira S. 2010. Azithromycin inhibits nontypeable Haemophilus influenzae-induced MUC5AC expression and secretion via inhibition of activator protein-1 in human airway epithelial cells. Eur J Pharmacol. 644:209–214.
   PubMed Web of Science ®Google Scholar
• Assaad U, El-Masri I, Porhomayon J, El-Solh AA. 2012. Pneumonia immunization in older adults: review of vaccine effectiveness and strategies. Clin Intervent Aging. 7:453–461.
   PubMed Web of Science ®Google Scholar
• Bandi V, Apicella MA, Mason E, Murphy TF, Siddiqi A, Atmar RL, Greenberg SB. 2001. Nontypeable Haemophilus influenzae in the lower respiratory tract of patients with chronic bronchitis. Am J Respir Crit Care Med. 164:2114–2119.
   PubMed Web of Science ®Google Scholar
• Bandi V, Jakubowycz M, Kinyon C, Mason EO, Atmar RL, Greenberg SB, Murphy TF. 2003. Infectious exacerbations of chronic obstructive pulmonary disease associated with respiratory viruses and non-typeable Haemophilus influenzae. FEMS Immunol Med Microbiol. 37:69–75.
   PubMed Web of Science ®Google Scholar
• Banerjee D, Khair OA, Honeybourne D. 2005. The effect of oral clarithromycin on health status and sputum bacteriology in stable COPD. Respir Med. 99:208–215.
   PubMed Web of Science ®Google Scholar
• Barenkamp SJ. 1996. Immunization with high-molecular-weight adhesion proteins of nontypeable Haemophilus influenzae modifies experimental otitis media in chinchillas. Infect Immun 64:1246–1251.
   PubMed Web of Science ®Google Scholar
• Barenkamp SJ. 2013. A new human colonization model for nontypeable Haemophilus influenzae. J Infect Dis. 208:717–719.
   PubMed Web of Science ®Google Scholar
• Beckett EL, Stevens RL, Jarnicki AG, Kim RY, Hanish I, Hansbro NG, Deane A, Keely S, Horvat JC, Yang M, et al. 2013. A short-term model of COPD identifies a role for mast cell tryptase. J Allergy Clin Immunol. 131:752–762.
   PubMed Web of Science ®Google Scholar
• Berenson CS, Garlipp MA, Grove LJ, Maloney J, Sethi S. 2006. Impaired phagocytosis of nontypeable Haemophilus influenzae by human alveolar macrophages in chronic obstructive pulmonary disease. J Infect Dis. 194:1375–1384.
   PubMed Web of Science ®Google Scholar
• Berenson CS, Kruzel RL, Eberhardt E, Dolnick R, Minderman H, Wallace PK, Sethi S. 2014. Impaired innate immune alveolar macrophage response and the predilection for COPD exacerbations. Thorax. 69:811–818.
   PubMed Web of Science ®Google Scholar
• Berglund J, Vink P, Tavares Da Silva F, Lestrate P, Boutriau D. 2014. Safety, immunogenicity, and antibody persistence following an investigational Streptococcus pneumoniae and Haemophilus influenzae triple-protein vaccine in a phase 1 randomized controlled study in healthy adults. Clin Vaccine Immunol. 21:56–65.
   PubMed Web of Science ®Google Scholar
• Berkhof F, Hertog NE, Uil S, Kerstjens H, van den Berg J. 2013. Azithromycin and cough-specific health status in patients with chronic obstructive pulmonary disease and chronic cough: a randomised controlled trial. Respir Res. 14:125.
   PubMed Web of Science ®Google Scholar
• Binks MJ, Temple B, Kirkham L-A, Wiertsema SP, Dunne EM, Richmond PC, Marsh RL, Leach AJ, Smith-Vaughan HC. 2012. Molecular surveillance of true nontypeable Haemophilus influenzae: an evaluation of PCR screening assays. PLoS One. 7:e34083.
   PubMed Web of Science ®Google Scholar
• Blasi F, Bonardi D, Aliberti S, Tarsia P, Confalonieri M, Amir O, Carone M, Di Marco F, Centanni S, Guffanti E. 2010. Long-term azithromycin use in patients with chronic obstructive pulmonary disease and tracheostomy. Pulmon Pharmacol Ther. 23:200–207.
   PubMed Web of Science ®Google Scholar
• Boe DM, Curtis BJ, Chen MM, Ippolito JA, Kovacs EJ. 2015. Extracellular traps and macrophages: new roles for the versatile phagocyte. J Leukocyte Biol. 97:1023–1035.
   PubMed Web of Science ®Google Scholar
• Bosch AA, Biesbroek G, Trzcinski K, Sanders EA, Bogaert D. 2013. Viral and bacterial interactions in the upper respiratory tract. PLoS Pathog. 9:e1003057.
   PubMed Web of Science ®Google Scholar
• Bresser P, Out TA, van Alphen L. k, Jansen HM, Lutter R. 2000. Airway inflammation in nonobstructive and obstructive chronic bronchitis with chronic Haemophilus influenzae airway infection. Am J Respir Crit Care Med. 162:947–952.
   PubMed Web of Science ®Google Scholar
• Butt HL, Clancy RL, Cripps AW, Murree-Allen K, Saunders NA, Sutherland DC, Hensley MJ. 1990. Bacterial colonisation of the respiratory tract in chronic bronchitis. Aust NZ J Med. 20:35–38.
   PubMedGoogle Scholar
• Caramori G, Casolari P, Barczyk A, Durham AL, Di Stefano A, Adcock I. 2016. COPD immunopathology. Semin Immunopathol. 38:497–515.
   PubMed Web of Science ®Google Scholar
• Chambers DC, Gellatly SL, Hugenholtz P, Hansbro PM. 2014. JTD special edition 'hot topics in COPD': the microbiome in COPD. J Thorac Dis. 6:1525–1531.
   PubMed Web of Science ®Google Scholar
• Chin CL, Manzel LJ, Lehman EE, Humlicek AL, Shi L, Starner TD, Denning GM, Murphy TF, Sethi S, Look DC. 2005. Haemophilus influenzae from patients with chronic obstructive pulmonary disease exacerbation induce more inflammation than colonizers. Am J Respir Crit Care Med. 172:85–91.
   PubMed Web of Science ®Google Scholar
• Churg A, Zhou S, Wang X, Wang R, Wright JL. 2009. The role of interleukin-1β in murine cigarette smoke: induced emphysema and small airway remodeling. Am J Respir Cell Mol Biol. 40:482–490.
   PubMed Web of Science ®Google Scholar
• Clancy R, Murree-Allen K, Cripps A, Yeung S, Engel M. 1985. Oral immunisation with killed Haemophilus Influenzae for protection against acute bronchitis in chronic obstructive lung disease. The Lancet. 326:1395–1397.
   Google Scholar
• Clancy RL. 2012. Towards a vaccine for chronic obstructive pulmonary disease. Intern Med J. 42:607–613.
   PubMed Web of Science ®Google Scholar
• Clancy RL, Cripps AW, Gebski V. 1990. Protection against recurrent acute bronchitis after oral immunization with killed Haemophilus influenzae. Med J Aust. 152:413–416.
   PubMed Web of Science ®Google Scholar
• Clancy RL, Dunkley M. 2011. Acute exacerbations in COPD and their control with oral immunization with non-typeable Haemophilus Influenzae. Front Immunol. 2:7.
   PubMed Web of Science ®Google Scholar
• Clancy RL, Dunkley M, Sockler LJ, McDonald CF. 2016. Multi-site placebo-controlled randomised clinical trial to assess protection following oral immunisation with inactivated non typeable H. influenzae in COPD. Intern Med J. 46:684–693.
   PubMed Web of Science ®Google Scholar
• Craig JE, Cliffe A, Garnett K, High NJ. 2001. Survival of nontypeable Haemophilus influenzae in macrophages. FEMS Microbiol Lett. 203:55–61.
   PubMed Web of Science ®Google Scholar
• Criner GJ, Bourbeau J, Diekemper RL, Ouellette DR, Goodridge D, Hernandez P, Curren K, Balter MS, Bhutani M, Camp PG, et al. 2015. Executive summary: prevention of acute exacerbation of COPD: American college of Chest Physicians and Canadian Thoracic Society Guideline. Chest. 147:883–893.
   PubMed Web of Science ®Google Scholar
• Curran T, Coyle PV, McManus TE, Kidney J, Coulter WA. 2007. Evaluation of real-time PCR for the detection and quantification of bacteria in chronic obstructive pulmonary disease. FEMS Immunol Med Microbiol. 50:112–118.
   PubMedGoogle Scholar
• Cutter D, Mason KW, Howell AP, Fink DL, Green BA, St. Geme JW. 2002. Immunization with Haemophilus influenzae Hap adhesin protects against nasopharyngeal colonization in experimental mice. J Infect Dis. 186:1115–1121.
   PubMed Web of Science ®Google Scholar
• Decramer M, Janssens W, Miravitlles M. 2012. Chronic obstructive pulmonary disease. Lancet. 379:1341–1351.
   PubMed Web of Science ®Google Scholar
• Denny FW. 1974. Effect of a toxin produced by Haemophilus influenzae on ciliated respiratory epithelium. J Infect Dis. 129:93–100.
   PubMed Web of Science ®Google Scholar
• Desai H, Eschberger K, Wrona C, Grove L, Agrawal A, Grant B, Yin J, Parameswaran GI, Murphy T, Sethi S. 2014. Bacterial colonization increases daily symptoms in patients with chronic obstructive pulmonary disease. Ann ATS. 11:303–309.
   Google Scholar
• Donaldson GC, Seemungal TA, Bhowmik A, Wedzicha JA. 2002. Relationship between exacerbation frequency and lung function decline in chronic obstructive pulmonary disease. Thorax. 57:847–852.
   PubMed Web of Science ®Google Scholar
• Erb-Downward JR, Thompson DL, Han MK, Freeman CM, McCloskey L, Schmidt LA, Young VB, Toews GB, Curtis JL, Sundaram B, et al. 2011. Analysis of the lung microbiome in the ‘healthy’ smoker and in COPD. PLoS One. 6:e16384.
   PubMed Web of Science ®Google Scholar
• Euba B, Moleres J, Viadas C, Barberán M, Caballero L, Grilló M-J, Bengoechea JA, de-Torres JP, Liñares J, Leiva J, Garmendia J. 2015. Relationship between azithromycin susceptibility and administration efficacy for nontypeable Haemophilus influenzae respiratory infection. Antimicrob Agents Chemother. 59:2700–2712.
   PubMed Web of Science ®Google Scholar
• Feenstra TL, van Genugten ML, Hoogenveen RT, Wouters EF, Rutten-van Molken MP. 2001. The impact of aging and smoking on the future burden of chronic obstructive pulmonary disease: a model analysis in the Netherlands. Am J Respir Crit Care Med. 164:590–596.
   PubMed Web of Science ®Google Scholar
• Fernaays MM, Lesse AJ, Sethi S, Cai X, Murphy TF. 2006. Differential genome contents of nontypeable Haemophilus influenzae strains from adults with chronic obstructive pulmonary disease. Infect Immun. 74:3366–3374.
   PubMed Web of Science ®Google Scholar
• Finney L, Ritchie A, Pollar E, Johnston S, Mallia P. 2014. Lower airway colonization and inflammatory response in COPD: a focus on Haemophilus influenzae. Int J COPD. 9:1119–1132.
   Google Scholar
• Forsgren J, Samuelson A, Ahlin A, Jonasson J, Rynnel-Dagoo B, Lindberg A. 1994. Haemophilus influenzae resides and multiplies intracellularly in human adenoid tissue as demonstrated by in situ hybridization and bacterial viability assay. Infect Immun. 62:673–679.
   PubMed Web of Science ®Google Scholar
• Foxwell AR, Kyd JM, Cripps AW. 1998. Nontypeable Haemophilus influenzae: pathogenesis and prevention. Microbiol Mol Biol Rev. 62:294–308.
   PubMed Web of Science ®Google Scholar
• Franklin BS, Bossaller L, De Nardo D, Ratter JM, Stutz A, Engels G, Brenker C, Nordhoff M, Mirandola SR, Al-Amoudi A, et al. 2014. The adaptor ASC has extracellular and 'prionoid' activities that propagate inflammation. Nat Immunol. 15:727–737.
   PubMed Web of Science ®Google Scholar
• Frickmann H, Christner M, Donat M, Berger A, Essig A, Podbielski A, Hagen RM, Poppert S. 2013. Rapid discrimination of Haemophilus influenzae, H. parainfluenzae, and H. haemolyticus by fluorescence in situ hybridization (FISH) and two matrix-assisted laser-desorption-ionization time-of-flight mass spectrometry (MALDI-TOF-MS) platforms. PLoS One. 8:e63222.
   PubMed Web of Science ®Google Scholar
• Garcha DS, Thurston SJ, Patel ARC, Mackay AJ, Goldring JJP, Donaldson GC, McHugh TD, Wedzicha JA. 2012. Changes in prevalence and load of airway bacteria using quantitative PCR in stable and exacerbated COPD. Thorax. 67:1075–1080.
   PubMed Web of Science ®Google Scholar
• Garcia-Nunez M, Millares L, Pomares X, Ferrari R, Perez-Brocal V, Gallego M, Espasa M, Moya A, Monso E. 2014. Severity-related changes of bronchial microbiome in chronic obstructive pulmonary disease. J Clin Microbiol. 52:4217–4223.
   PubMed Web of Science ®Google Scholar
• Gaschler GJ, Zavitz CCJ, Bauer CMT, Stämpfli MR. 2010. Mechanisms of clearance of nontypeable Haemophilus influenzae from cigarette smoke-exposed mouse lungs. Eur Respir J. 36:1131–1142.
   PubMed Web of Science ®Google Scholar
• George SN, Garcha DS, Mackay AJ, Patel ARC, Singh R, Sapsford RJ, Donaldson GC, Wedzicha JA. 2014. Human rhinovirus infection during naturally occurring COPD exacerbations. Eur Respir J. 44:87–96.
   PubMed Web of Science ®Google Scholar
• Gratten M, Gratten H, Poli A, Carrad E, Raymer M, Koki G. 1986. Colonisation of Haemophilus influenzae and Streptococcus pneumoniae in the upper respiratory tract of neonates in Papua New Guinea: primary acquisition, duration of carriage, and relationship to carriage in mothers. Biol Neonate. 50:114–120.
   PubMedGoogle Scholar
• Groenewegen KH, Wouters EFM. 2003. Bacterial infections in patients requiring admission for an acute exacerbation of COPD: a 1-year prospective study. Respir Med. 97:770–777.
   PubMed Web of Science ®Google Scholar
• Gulraiz F, Bellinghausen C, Bruggeman CA, Stassen FR. 2015. Haemophilus influenzae increases the susceptibility and inflammatory response of airway epithelial cells to viral infections. FASEB J. 29:849–858.
   PubMed Web of Science ®Google Scholar
• Guo H, Callaway JB, Ting JPY. 2015. Inflammasomes: mechanism of action, role in disease, and therapeutics. Nat Med. 21:677–687.
   PubMed Web of Science ®Google Scholar
• Haase EM, Yi K, Morse GD, Murphy TF. 1994. Mapping of bactericidal epitopes on the P2 porin protein of nontypeable Haemophilus influenzae. Infect Immun. 62:3712–3722.
   PubMed Web of Science ®Google Scholar
• Hallstrom T, Singh B, Resman F, M. Blom A, Morgelin M, Riesbeck K. 2011. Haemophilus influenzae protein E binds to the extracellular matrix by concurrently interacting with laminin and vitronectin. J Infect Dis. 204:1065–1074.
   PubMed Web of Science ®Google Scholar
• He ZY, Ou LM, Zhang JQ, Bai J, Liu GN, Li MH, Deng JM, MacNee W, Zhong XN. 2010. Effect of 6 months of erythromycin treatment on inflammatory cells in induced sputum and exacerbations in chronic obstructive pulmonary disease. Respiration. 80:445–452.
   PubMed Web of Science ®Google Scholar
• Herath SC, Poole P. 2013. Prophylactic antibiotic therapy for chronic obstructive pulmonary disease (COPD). Cochrane Database Syst Rev. CD009764.
   PubMed Web of Science ®Google Scholar
• Heyl KA, Klassert TE, Heinrich A, Müller MM, Klaile E, Dienemann H, Grünewald C, Bals R, Singer BB, Slevogt H. 2014. Dectin-1 is expressed in human lung and mediates the proinflammatory immune response to nontypeable Haemophilus influenzae. MBIO. 5:01414–e01492.
   Web of Science ®Google Scholar
• Hilty M, Burke C, Pedro H, Cardenas P, Bush A, Bossley C, Davies J, Ervine A, Poulter L, Pachter L, Moffatt MF, Cookson WOC. 2010. Disordered microbial communities in asthmatic airways. PLoS One. 5:e8578.
   PubMed Web of Science ®Google Scholar
• Hogg JC, Timens W. 2009. The pathology of chronic obstructive pulmonary disease. Annu Rev Pathol Mech Dis. 4:435–459.
   PubMed Web of Science ®Google Scholar
• Hong W, Mason K, Jurcisek J, Novotny L, Bakaletz LO, Swords WE. 2007. Phosphorylcholine decreases early inflammation and promotes the establishment of stable biofilm communities of nontypeable Haemophilus influenzae strain 86-028NP in a chinchilla model of otitis media. Infect Immun. 75:958–965.
   PubMed Web of Science ®Google Scholar
• Hotomi M, Ikeda Y, Suzumoto M, Yamauchi K, Green BA, Zlotnick G, Billal DS, Shimada J, Fujihara K, Yamanaka N. 2005. A recombinant P4 protein of Haemophilus influenzae induces specific immune responses biologically active against nasopharyngeal colonization in mice after intranasal immunization. Vaccine. 23:1294–1300.
   PubMed Web of Science ®Google Scholar
• Howard AJ, Dunkin KT, Millar GW. 1988. Nasopharyngeal carriage and antibiotic resistance of Haemophilus influenzae in healthy children. Epidemiol Infect. 100:193–203.
   PubMed Web of Science ®Google Scholar
• Huang YJ, Sethi S, Murphy T, Nariya S, Boushey HA, Lynch SV. 2014. Airway microbiome dynamics in exacerbations of chronic obstructive pulmonary disease. J Clin Microbiol. 52:2813–2823.
   PubMed Web of Science ®Google Scholar
• Hurst JR, Wilkinson TMA, Perera WR, Donaldson GC, Wedzicha JA. 2005. Relationships among bacteria, upper airway, lower airway, and systemic inflammation in COPD*. Chest. 127:1219–1226.
   PubMed Web of Science ®Google Scholar
• Ishinaga H, Jono H, Lim JH, Kweon S-M, Xu H, Ha U-H, Xu H, Koga T, Yan C, Feng X-H, Chen L-F, Li J-D. 2007. TGF-β induces p65 acetylation to enhance bacteria-induced NF-κB activation. EMBO J. 26:1150–1162.
   PubMed Web of Science ®Google Scholar
• Jalalvand F, Littorin N, Su Y-C, Riesbeck K. 2014. Impact of immunization with Protein F on pulmonary clearance of nontypeable Haemophilus influenzae. Vaccine. 32:2261–2264.
   PubMed Web of Science ®Google Scholar
• Jalalvand F, Su YC, Morgelin M, Brant M, Hallgren O, Westergren-Thorsson G, Singh B, Riesbeck K. 2013. Haemophilus influenzae protein F mediates binding to laminin and human pulmonary epithelial cells. J Infect Dis. 207:803–813.
   PubMed Web of Science ®Google Scholar
• Janson H, Ruan M, Forsgren A. 1993. Limited diversity of the protein D gene (hpd) among encapsulated and nonencapsulated Haemophilus influenzae strains. Infect Immun. 61:4546–4552.
   PubMed Web of Science ®Google Scholar
• Juneau RA, Pang B, Weimer KED, Armbruster CE, Swords WE. 2011. Nontypeable Haemophilus influenzae initiates formation of neutrophil extracellular traps. Infect Immun. 79:431–438.
   PubMed Web of Science ®Google Scholar
• Kalathil SG, Lugade AA, Pradhan V, Miller A, Parameswaran GI, Sethi S, Thanavala Y. 2014. T-regulatory cells and programmed death 1(+) T cells contribute to effector T-cell dysfunction in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 190:40–50.
   PubMed Web of Science ®Google Scholar
• Kaplan MJ, Radic M. 2012. Neutrophil extracellular traps (NETs): double-edged swords of innate immunity. J Immunol. 189:2689–2695.
   PubMed Web of Science ®Google Scholar
• Kim RY, Pinkerton JW, Gibson PG, Cooper MA, Horvat JC, Hansbro PM. 2015. Inflammasomes in COPD and neutrophilic asthma. Thorax. 70:1199–1201.
   PubMed Web of Science ®Google Scholar
• King P, Holdsworth S, Freezer N, Holmes P. 2006. Bronchiectasis. Intern Med J. 36:729–737.
   PubMed Web of Science ®Google Scholar
• King PT, Lim S, Pick A, Ngui J, Prodanovic Z, Downey W, Choong C, Kelman A, Baranyai E, Francis M, et al. 2013. Lung T-cell responses to nontypeable Haemophilus influenzae in patients with chronic obstructive pulmonary disease. J Allergy Clin Immunol. 131:1314–1321.
   PubMed Web of Science ®Google Scholar
• King PT, Sharma R. 2015. The lung immune response to nontypeable Haemophilus influenzae (Lung Immunity to NTHi). J Immunol Res. 2015:706376.
   PubMedGoogle Scholar
• King PT, Sharma R, O’Sullivan K, Selemidis S, Lim S, Radhakrishna N, Lo C, Prasad J, Callaghan J, McLaughlin P, et al. 2015. Nontypeable Haemophilus influenzae induces sustained lung oxidative stress and protease expression. PLoS One. 10:e0120371.
   PubMed Web of Science ®Google Scholar
• Ko FWS, Ip M, Chan PKS, Fok JPC, Chan MCH, Ngai JC, Chan DPS, Hui DSC. 2007. A 1-year prospective study of the infectious etiology in patients hospitalized with acute exacerbations of COPD. Chest. 131:44–52.
   PubMed Web of Science ®Google Scholar
• Ko FWS, Ng TKC, Li TST, Fok JPC, Chan MCH, Wu AKL, Hui DSC. 2005. Sputum bacteriology in patients with acute exacerbations of COPD in Hong Kong. Respir Med. 99:454–460.
   PubMed Web of Science ®Google Scholar
• Kristensen M. 1922. Investigations into the occurrence and classification of the haemoglobinophilic bacteria. Copenhagen: Levin & Munksgaard Publishers.
   Google Scholar
• Kurai D, Saraya T, Ishii H, Takizawa H. 2013. Virus-induced exacerbations in asthma and COPD. Front Microbiol. 4:293.
   PubMed Web of Science ®Google Scholar
• Kyd JM, Cripps AW, Novotny LA, Bakaletz LO. 2003. Efficacy of the 26-kilodalton outer membrane protein and two P5 fimbrin-derived immunogens to induce clearance of nontypeable Haemophilus influenzae from the rat middle ear and lungs as well as from the chinchilla middle ear and nasopharynx. Infect Immun. 71:4691–4699.
   PubMed Web of Science ®Google Scholar
• Lambert ND, Ovsyannikova IG, Pankratz VS, Jacobson RM, Poland GA. 2012. Understanding the immune response to seasonal influenza vaccination in older adults: a systems biology approach. Expert Rev Vaccines. 11:985–994.
   PubMed Web of Science ®Google Scholar
• Langereis JD, Hermans PW. 2013. Novel concepts in nontypeable Haemophilus influenzae biofilm formation. FEMS Microbiol Lett. 346:81–89.
   PubMed Web of Science ®Google Scholar
• Leach AJ, Wigger C, Hare K, Hampton V, Beissbarth J, Andrews R, Chatfield M, Smith-Vaughan H, Morris PS. 2015. Reduced middle ear infection with non-typeable Haemophilus influenzae, but not Streptococcus pneumoniae, after transition to 10-valent pneumococcal non-typeable H. influenzae protein D conjugate vaccine. BMC Pediatr. 15:162.
   PubMed Web of Science ®Google Scholar
• Lehmann D, Coakley KJ, Coakley CA, Spooner V, Montgomery JM, Michael A, Riley ID, Smith T, Clancy RL, Cripps AW, Alpers MP. 1991. Reduction in the incidence of acute bronchitis by an oral Haemophilus influenzae vaccine in patients with chronic bronchitis in the highlands of Papua New Guinea. Am Rev Respir Dis. 144:324–330.
   PubMed Web of Science ®Google Scholar
• López-Campos JL, Calero Acuña C. 2013. What is in the guidelines about the pharmacological treatment of chronic obstructive pulmonary disease? Expert Rev Respir Med. 7:43–51.
   PubMed Web of Science ®Google Scholar
• Lugade AA, Bogner PN, Thatcher TH, Sime PJ, Phipps RP, Thanavala Y. 2014. Cigarette Smoke Exposure Exacerbates Lung Inflammation and Compromises Immunity to Bacterial Infection. J Immunol. 192:5226–5235.
   PubMed Web of Science ®Google Scholar
• Mackay AJ, Hurst JR. 2013. COPD exacerbations: causes, prevention, and treatment. Immunol Allergy Clin N Am. 33:95–115.
   PubMed Web of Science ®Google Scholar
• Mallia P, Footitt J, Sotero R, Jepson A, Contoli M, Trujillo-Torralbo M-B, Kebadze T, Aniscenko J, Oleszkiewicz G, Gray K, et al. 2012. Rhinovirus infection induces degradation of antimicrobial peptides and secondary bacterial infection in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 186:1117–1124.
   PubMed Web of Science ®Google Scholar
• Mammen MJ, Sethi S. 2016. COPD and the microbiome. Respirology. 21:590–599.
   PubMed Web of Science ®Google Scholar
• Mannino DM, Buist AS. 2007. Global burden of COPD: risk factors, prevalence, and future trends. The Lancet. 370:765–773.
   PubMed Web of Science ®Google Scholar
• Marin A, Garcia-Aymerich J, Sauleda J, Belda J, Millares L, García-Núñez M, Serra I, Benet M, Agustí A, Antó JM, Monsó E; PAC-COPD Study Group. 2012. Effect of bronchial colonisation on airway and systemic inflammation in stable COPD. COPD. 9:121–130.
   PubMedGoogle Scholar
• Marin A, Monsó E, Garcia-Nuñez M, Sauleda J, Noguera A, Pons J, Agustí A, Morera J. 2010. Variability and effects of bronchial colonisation in patients with moderate COPD. Eur Respir J. 35:295–302.
   PubMed Web of Science ®Google Scholar
• Martí-Lliteras P, Regueiro V, Morey P, Hood DW, Saus C, Sauleda J, Agustí AGN, Bengoechea JA, Garmendia J. 2009. Nontypeable Haemophilus influenzae clearance by alveolar macrophages is impaired by exposure to cigarette smoke. Infect Immun. 77:4232–4242.
   PubMed Web of Science ®Google Scholar
• Mathers CD, Loncar D. 2006. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med. 3:e442.
   PubMed Web of Science ®Google Scholar
• McCrea KW, Xie J, LaCross N, Patel M, Mukundan D, Murphy TF, Marrs CF, Gilsdorf JR. 2008. Relationships of nontypeable Haemophilus influenzae strains to hemolytic and nonhemolytic haemophilus haemolyticus strains. J Clin Microbiol. 46:406–416.
   PubMed Web of Science ®Google Scholar
• Meshi B, Vitalis TZ, Ionescu D, Elliott WM, Liu C, Wang X-D, Hayashi S, Hogg JC. 2002. Emphysematous lung destruction by cigarette smoke. The effects of latent adenoviral infection on the lung inflammatory response. Am J Respir Cell Mol Biol. 26:52–57.
   PubMed Web of Science ®Google Scholar
• Millares L, Ferrari R, Gallego M, Garcia-Nuñez M, Pérez-Brocal V, Espasa M, Pomares X, Monton C, Moya A, Monsó E. 2014. Bronchial microbiome of severe COPD patients colonised by Pseudomonas aeruginosa. Eur J Clin Microbiol Infect Dis. 33:1101–1111.
   PubMed Web of Science ®Google Scholar
• Millares L, Marin A, Garcia-Aymerich J, Sauleda J, Belda J, Monso E; PAC-COPD Study Group. 2012. Specific IgA and metalloproteinase activity in bronchial secretions from stable chronic obstructive pulmonary disease patients colonized by Haemophilus influenzae. Respir Res. 13:113.
   PubMed Web of Science ®Google Scholar
• Mina MJ, Klugman KP. 2014. The role of influenza in the severity and transmission of respiratory bacterial disease. Lancet Respir Med. 2:750–763.
   PubMed Web of Science ®Google Scholar
• Miyamoto N, Bakaletz LO. 1996. Selective adherence of non-typeable Haemophilus influenzae (NTHi) to mucus or epithelial cells in the chinchilla eustachian tube and middle ear. Microb Pathog. 21:343–356.
   PubMed Web of Science ®Google Scholar
• Moghaddam SJ, Clement CG, De la Garza MM, Zou X, Travis EL, Young HWJ, Evans CM, Tuvim MJ, Dickey BF. 2008. Haemophilus influenzae lysate induces aspects of the chronic obstructive pulmonary disease phenotype. Am J Respir Cell Mol Biol. 38:629–638.
   PubMed Web of Science ®Google Scholar
• Möller LVM, Timens WIM, van der Bij WIM, Kooi KOR, de Wever BOB, Dankert J, van Alphen L. 1998. Haemophilus Influenzae in lung explants of patients with end-stage pulmonary disease. Am J Respir Crit Care Med. 157:950–956.
   PubMed Web of Science ®Google Scholar
• Molyneaux PL, Cox MJ, Willis-Owen SAG, Mallia P, Russell KE, Russell A-M, Murphy E, Johnston SL, Schwartz DA, Wells AU, et al. 2014. The role of bacteria in the pathogenesis and progression of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 190:906–913.
   PubMed Web of Science ®Google Scholar
• Molyneaux PL, Mallia P, Cox MJ, Footitt J, Willis-Owen SAG, Homola D, Trujillo-Torralbo M-B, Elkin S, Kon OM, Cookson WOC, et al. 2013. Outgrowth of the bacterial airway microbiome after rhinovirus exacerbation of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 188:1224–1231.
   PubMed Web of Science ®Google Scholar
• Monso E, Rosell A, Bonet G, Manterola J, Cardona P, Ruiz J, Morera J. 1999. Risk factors for lower airway bacterial colonization in chronic bronchitis. Eur Respir J. 13:338–342.
   PubMed Web of Science ®Google Scholar
• Monsó E, Ruiz J, Rosell A, Manterola J, Fiz J, Morera J, Ausina V. 1995. 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. 152:1316–1320.
   PubMed Web of Science ®Google Scholar
• Murphy TF. 2003. Respiratory infections caused by non-typeable Haemophilus influenzae. Curr Opin Infect Dis. 16:129–134.
   PubMed Web of Science ®Google Scholar
• Murphy TF. 2006. The role of bacteria in airway inflammation in exacerbations of chronic obstructive pulmonary disease. Curr Opin Infect Dis. 19:225–230.
   PubMed Web of Science ®Google Scholar
• Murphy TF. 2015. Vaccines for nontypeable Haemophilus influenzae: the future is now. Clin Vaccine Immunol. 22:459–466.
   PubMed Web of Science ®Google Scholar
• Murphy TF, Bartos LC, Campagnari AA, Nelson MB, Apicella MA. 1986. Antigenic characterization of the P6 protein of nontypable Haemophilus influenzae. Infect Immun. 54:774–779.
   PubMed Web of Science ®Google Scholar
• Murphy TF, Brauer AL, Schiffmacher AT, Sethi S. 2004. Persistent colonization by Haemophilus influenzae in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 170:266–272.
   PubMed Web of Science ®Google Scholar
• Murphy TF, Faden H, Bakaletz LO, Kyd JM, Forsgren A, Campos J, Virji M, Pelton SI. 2009. Nontypeable Haemophilus influenzae as a pathogen in children. Pediatr Infect Dis J. 28:43–48.
   PubMed Web of Science ®Google Scholar
• Murphy TF, Kirkham C, Jones MM, Sethi S, Kong Y, Pettigrew MM. 2015. Expression of IgA proteases by Haemophilus influenzae in the respiratory tract of adults with chronic obstructive pulmonary disease. J Infect Dis. 212:1798–1805.
   PubMed Web of Science ®Google Scholar
• Murphy TF, Sethi S, Klingman KL, Brueggemann AB, Doern GV. 1999. Simultaneous respiratory tract colonization by multiple strains of nontypeable Haemophilus influenzae in chronic obstructive pulmonary disease: implications for antibiotic therapy. J Infect Dis. 180:404–409.
   PubMed Web of Science ®Google Scholar
• Nakamura S, Shchepetov M, Dalia AB, Clark SE, Murphy TF, Sethi S, Gilsdorf JR, Smith AL, Weiser JN. 2011. Molecular basis of increased serum resistance among pulmonary isolates of non-typeable Haemophilus influenzae. PLoS Pathog. 7:e1001247.
   PubMed Web of Science ®Google Scholar
• Nakou A, Papaparaskevas J, Diamantea F, Skarmoutsou N, Polychronopoulos V, Tsakris A. 2014. A prospective study on bacterial and atypical etiology of acute exacerbation in chronic obstructive pulmonary disease. Future Microbiol. 9:1251–1260.
   PubMed Web of Science ®Google Scholar
• Novotny LA, Jurcisek JA, Godfroid F, Poolman JT, Denoël PA, Bakaletz LO. 2006. Passive immunization with human anti-protein D antibodies induced by polysaccharide protein D conjugates protects chinchillas against otitis media after intranasal challenge with Haemophilus influenzae. Vaccine. 24:4804–4811.
   PubMed Web of Science ®Google Scholar
• O'Grady K, Grimwood A, Cripps K, Mulholland H, Smith-Vaughan M, Danchin N, Wood A, Wilson R, Thornton P, Torzillo P, et al. 2016. Potential clinical efficacy of the 10-valent pneumococcal-Protein D conjugate vaccine in children with chronic suppurative lung diseases: a double-blind randomised controlled trial. Poster presented at: 10th International Symposium on Pneumococci & Pneumococcal Diseases; Glasgow, Scotland.
   Google Scholar
• O’Grady K-AF, Grimwood K, Cripps A, Mulholland EK, Morris P, Torzillo PJ, Wood N, Smith-Vaughan H, Revell A, Wilson A, et al. 2013. Does a 10-valent pneumococcal-Haemophilus influenzae protein D conjugate vaccine prevent respiratory exacerbations in children with recurrent protracted bacterial bronchitis, chronic suppurative lung disease and bronchiectasis: protocol for a randomised controlled trial. Trials. 14:282–282.
   PubMed Web of Science ®Google Scholar
• Otczyk D, Cripps A. 2010. Mucosal immunization: a realistic alternative. Hum Vaccines. 6:29–21.
   Google Scholar
• Otczyk DC, Clancy RL, Cripps AW. 2011. Haemophilus influenzae and smoking-related obstructive airways disease. Int J Chronic Obstruct Pulmonary Dis. 6:345–351.
   PubMed Web of Science ®Google Scholar
• Palmu AA, Jokinen J, Nieminen H, Syrjanen R, Ruokokoski E, Puumalainen T, Moreira M, Schuerman L, Borys D, Kilpi TM. 2014. Vaccine effectiveness of the pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10) against clinically suspected invasive pneumococcal disease: a cluster-randomised trial. Lancet Respir Med. 2:717–727.
   PubMed Web of Science ®Google Scholar
• Papi A, Bellettato CM, Braccioni F, Romagnoli M, Casolari P, Caramori G, Fabbri LM, Johnston SL. 2006. Infections and airway inflammation in chronic obstructive pulmonary disease severe exacerbations. Am J Respir Crit Care Med. 173:1114–1121.
   PubMed Web of Science ®Google Scholar
• Parnham MJ, Haber VE, Giamarellos-Bourboulis EJ, Perletti G, Verleden GM, Vos R. 2014. Azithromycin: mechanisms of action and their relevance for clinical applications. Pharmacol Therapeutics. 143:225–245.
   PubMed Web of Science ®Google Scholar
• Patel IS, Seemungal TAR, Wilks M, Lloyd-Owen SJ, Donaldson GC, Wedzicha JA. 2002. Relationship between bacterial colonisation and the frequency, character, and severity of COPD exacerbations. Thorax. 57:759–764.
   PubMed Web of Science ®Google Scholar
• Pfeiffer R, Beck M. 1892. I.-Preliminary communication on the exciting causes of influenza. Br Med J. 1:128.
   PubMedGoogle Scholar
• Pfeiffer RFJ. 1892. Weitere mittheilungen über den Influenza-Erreger. Dtsch med Wochenschr. 18:28.
   Google Scholar
• Pfeiffer RFJ. 1893. Die Aetiologie der Influenza. Zeitschr f Hygiene. 13:357–386.
   Google Scholar
• Pickering J, Richmond PC, Kirkham L-AS. 2014. Molecular tools for differentiation of nontypeable Haemophilus influenzae from Haemophilus haemolyticus. Front Microbiol. 5:664.
   PubMed Web of Science ®Google Scholar
• Pickering J, Smith-Vaughan H, Beissbarth J, Bowman JM, Wiertsema S, Riley TV, Leach AJ, Richmond P, Lehmann D, Kirkham L-A. 2014. Diversity of nontypeable Haemophilus influenzae strains colonizing Australian aboriginal and non-aboriginal children. J Clin Microbiol. 52:1352–1357.
   PubMed Web of Science ®Google Scholar
• Pittman M. 1931. Variation and type specificity in the bacterial species Hemophilus influenzae. J Exp Med. 53:471–492.
   PubMedGoogle Scholar
• Pizzutto SJ, Yerkovich ST, Upham JW, Hales BJ, Thomas WR, Chang AB. 2014. Children with chronic suppurative lung disease have a reduced capacity to synthesize interferon-gamma in vitro in response to non-typeable Haemophilus influenzae. PLoS One. 9:e104236.
   PubMed Web of Science ®Google Scholar
• Pizzutto SJ, Yerkovich ST, Upham JW, Hales BJ, Thomas WR, Chang AB. 2015. Improving immunity to Haemophilus influenzae in children with chronic suppurative lung disease. Vaccine. 33:321–326.
   PubMed Web of Science ®Google Scholar
• Poolman JT, Bakaletz L, Cripps A, Denoel PA, Forsgren A, Kyd J, Lobet Y. 2000. Developing a nontypeable Haemophilus influenzae (NTHi) vaccine. Vaccine. 19(Suppl 1):S108–S115.
   PubMed Web of Science ®Google Scholar
• Pragman AA, Kim HB, Reilly CS, Wendt C, Isaacson RE. 2012. The lung microbiome in moderate and severe chronic obstructive pulmonary disease. PLoS One. 7:e47305.
   PubMed Web of Science ®Google Scholar
• Prymula R, Peeters P, Chrobok V, Kriz P, Novakova E, Kaliskova E, Kohl I, Lommel P, Poolman J, Prieels J-P, Schuerman L. 2006. Pneumococcal capsular polysaccharides conjugated to protein D for prevention of acute otitis media caused by both Streptococcus pneumoniae and non-typable Haemophilus influenzae: a randomised double-blind efficacy study. The Lancet. 367:740–748.
   PubMed Web of Science ®Google Scholar
• Rosadini CV, Ram S, Akerley BJ. 2014. Outer membrane protein P5 is required for resistance of nontypeable Haemophilus influenzae to both the classical and alternative complement pathways. Infect Immun. 82:640–649.
   PubMed Web of Science ®Google Scholar
• Rosell A, Monso E, Soler N, Torres F, Angrill J, Riise G, Zalacain R, Morera J, Torres A. 2005. Microbiologic determinants of exacerbation in chronic obstructive pulmonary disease. Arch Intern Med. 165:891–897.
   PubMed Web of Science ®Google Scholar
• Rotta detto Loria J, Rohmann K, Droemann D, Kujath P, Rupp J, Goldmann T, Dalhoff K. 2013. Nontypeable Haemophilus Influenzae infection upregulates the NLRP3 inflammasome and leads to caspase-1-dependent secretion of interleukin-1β: a possible pathway of exacerbations in COPD. PLoS One. 8:e66818.
   PubMed Web of Science ®Google Scholar
• Sajjan US, Jia Y, Newcomb DC, Bentley JK, Lukacs NW, LiPuma JJ, Hershenson MB. 2006. H. influenzae potentiates airway epithelial cell responses to rhinovirus by increasing ICAM-1 and TLR3 expression. FASEB J. 20:2121–2123.
   PubMed Web of Science ®Google Scholar
• Salvi SS, Barnes PJ. 2009. Chronic obstructive pulmonary disease in non-smokers. Lancet. 374:733–743.
   PubMed Web of Science ®Google Scholar
• Schuerman L, Borys D, Hoet B, Forsgren A, Prymula R. 2009. Prevention of otitis media: now a reality? Vaccine. 27:5748–5754.
   PubMed Web of Science ®Google Scholar
• Schuliga M. 2015. NF-kappaB signaling in chronic inflammatory airway disease. Biomolecules. 5:1266–1283.
   PubMed Web of Science ®Google Scholar
• Seemungal TAR, Wilkinson TMA, Hurst JR, Perera WR, Sapsford RJ, Wedzicha JA. 2008. Long-term erythromycin therapy is associated with decreased chronic obstructive pulmonary disease exacerbations. Am J Respir Crit Care Med. 178:1139–1147.
   PubMed Web of Science ®Google Scholar
• Segal LN, Rom WN, Weiden MD. 2014. Lung microbiome for clinicians. New discoveries about bugs in healthy and diseased lungs. Ann ATS. 11:108–116.
   Google Scholar
• Sethi S, Evans N, Grant BJB, Murphy TF. 2002. New strains of bacteria and exacerbations of chronic obstructive pulmonary disease. N Engl J Med. 347:465–471.
   PubMed Web of Science ®Google Scholar
• Sethi S, Jones P, Theron M, Miravitlles M, Rubinstein E, Wedzicha J, Wilson R; PULSE Study Group. 2010. Pulsed moxifloxacin for the prevention of exacerbations of chronic obstructive pulmonary disease: a randomized controlled trial. Respir Res. 11:10.
   PubMed Web of Science ®Google Scholar
• Sethi S, Murphy TF. 2001. Bacterial infection in chronic obstructive pulmonary disease in 2000: a state-of-the-art review. Clin Microbiol Rev. 14:336–363.
   PubMed Web of Science ®Google Scholar
• Sethi S, Murphy TF. 2008. Infection in the pathogenesis and course of chronic obstructive pulmonary disease. N Engl J Med. 359:2355–2365.
   PubMed Web of Science ®Google Scholar
• Sethi S, Sethi R, Eschberger K, Lobbins P, Cai X, Grant BJB, Murphy TF. 2007. Airway bacterial concentrations and exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 176:356–361.
   PubMed Web of Science ®Google Scholar
• Shimizu T, Shimizu S. 2012. Azithromycin inhibits mucus hypersecretion from airway epithelial cells. Mediat Inflamm. 6:265714.
   Google Scholar
• Shurin PA, Pelton SI, Tager IB, Kasper DL. 1980. Bactericidal antibody and susceptibility to otitis media caused by nontypable strains of Haemophilus influenzae. J Pediatr. 97:364–369.
   PubMed Web of Science ®Google Scholar
• Simpson JL, Powell H, Baines KJ, Milne D, Coxson HO, Hansbro PM, Gibson PG. 2014. The effect of azithromycin in adults with stable neutrophilic COPD: a double blind randomised, placebo controlled trial. PLoS One. 9:e105609.
   PubMed Web of Science ®Google Scholar
• Singh R, Mackay A, Patel A, Garcha D, Kowlessar B, Brill S, Donnelly L, Barnes P, Donaldson G, Wedzicha J. 2014. Inflammatory thresholds and the species-specific effects of colonising bacteria in stable chronic obstructive pulmonary disease. Respir Res. 15:114.
   PubMed Web of Science ®Google Scholar
• Slevogt H, Schmeck B, Jonatat C, Zahlten J, Beermann W, van Laak V, Opitz B, Dietel S, N'Guessan PD, Hippenstiel S, et al. 2006. Moraxella catarrhalis induces inflammatory response of bronchial epithelial cells via MAPK and NF-κB activation and histone deacetylase activity reduction. Am J Physiol. 290:L818–L826.
   Google Scholar
• Slinger R, Chan F, Ferris W, Yeung S-W, St. Denis M, Gaboury I, Aaron SD. 2006. Multiple combination antibiotic susceptibility testing of nontypeable Haemophilus influenzae biofilms. Diagn Microbiol Infect Dis. 56:247–253.
   PubMed Web of Science ®Google Scholar
• Smith W, Andrewes C, Laidlaw P. 1933. A virus obtained from influenza patients. Lancet. 2:66–68.
   Google Scholar
• Soler N, Torres A, Ewig S, Gonzalez J, Celis R, El-Ebiary M, Hernandez C, Rodriguez-Roisin R. 1998. Bronchial microbial patterns in severe exacerbations of chronic obstructive pulmonary disease (COPD) requiring mechanical ventilation. Am J Respir Crit Care Med. 157:1498–1505.
   PubMed Web of Science ®Google Scholar
• Song XM, Forsgren A, Janson H. 1995. The gene encoding protein D (hpd) is highly conserved among Haemophilus influenzae type b and nontypeable strains. Infect Immun. 63:696–699.
   PubMed Web of Science ®Google Scholar
• Spagnolo P, Fabbri LM, Bush A. 2013. Long-term macrolide treatment for chronic respiratory disease. Eur Respir J. 42:239–251.
   PubMed Web of Science ®Google Scholar
• St Geme JW, Falkow S, Barenkamp SJ. 1993. High-molecular-weight proteins of nontypable Haemophilus influenzae mediate attachment to human epithelial cells. Proc Natl Acad Sci USA. 90:2875–2879.
   PubMed Web of Science ®Google Scholar
• Stampfli MR, Anderson GP. 2009. How cigarette smoke skews immune responses to promote infection, lung disease and cancer. Nat Rev Immunol. 9:377–384.
   PubMed Web of Science ®Google Scholar
• Starner TD, Shrout JD, Parsek MR, Appelbaum PC, Kim G. 2008. Subinhibitory concentrations of azithromycin decrease nontypeable Haemophilus influenzae biofilm formation and diminish established biofilms. Antimicrob Agents Chemother. 52:137–145.
   PubMed Web of Science ®Google Scholar
• Swords WE. 2012. Nontypeable Haemophilus influenzae biofilms: role in chronic airway infections. Front Cell Inf Microbio. 2:97.
   PubMed Web of Science ®Google Scholar
• Sze MA, Dimitriu PA, Hayashi S, Elliott WM, McDonough JE, Gosselink JV, Cooper J, Sin DD, Mohn WW, Hogg JC. 2012. The lung tissue microbiome in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 185:1073–1080.
   PubMed Web of Science ®Google Scholar
• Tandon M, Gebski V. 1991. A controlled trial of a killed Haemophilus influenzae vaccine for prevention of acute exacerbations of chronic bronchitis. Aust NZ J Med. 21:428–432.
   Google Scholar
• Teo E, House H, Lockhart K, Purchuri Sai N, Pushparajah J, Cripps Allan W, van Driel Mieke L. 2014. Haemophilus influenzae oral vaccination for preventing acute exacerbations of chronic bronchitis and chronic obstructive pulmonary disease. Cochrane Database Syst Rev. CD010010.
   PubMed Web of Science ®Google Scholar
• Tregnaghi MW, Saez-Llorens X, Lopez P, Abate H, Smith E, Posleman A, Calvo A, Wong D, Cortes-Barbosa C, Ceballos A, et al. 2014. Efficacy of pneumococcal nontypable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in young Latin American children: a double-blind randomized controlled trial. PLoS Med. 11:e1001657.
   PubMed Web of Science ®Google Scholar
• Tufvesson E, Bjermer L, Ekberg M. 2015. Patients with chronic obstructive pulmonary disease and chronically colonized with Haemophilus influenzae during stable disease phase have increased airway inflammation. Int J COPD. 10:881–889.
   Google Scholar
• Turnbaugh PJ, Ley RE, Hamady M, Fraser-Liggett C, Knight R, Gordon JI. 2007. The human microbiome project: exploring the microbial part of ourselves in a changing world. Nature. 449:804–810.
   PubMed Web of Science ®Google Scholar
• Unger BL, Faris A, Ganesan NS, Comstock AT, Hershenson MB, Sajjan US. 2012. Rhinovirus attenuates non-typeable Hemophilus influenzae-stimulated IL-8 responses via TLR2-dependent degradation of IRAK-1. PLoS Pathog. 8:e1002969.
   PubMed Web of Science ®Google Scholar
• Ursell LK, Metcalf JL, Parfrey LW, Knight R. 2012. Defining the human microbiome. Nutrit Rev. 70:S38–S44.
   PubMed Web of Science ®Google Scholar
• Uzun S, Djamin RS, Kluytmans JAJW, Mulder PGH, van't Veer NE, Ermens AAM, Pelle AJ, Hoogsteden HC, Aerts JGJV, van der Eerden MM. 2014. Azithromycin maintenance treatment in patients with frequent exacerbations of chronic obstructive pulmonary disease (COLUMBUS): a randomised, double-blind, placebo-controlled trial. Lancet Respir Med. 2:361–368.
   PubMed Web of Science ®Google Scholar
• van den Bergh MR, Spijkerman J, Swinnen KM, Francois NA, Pascal TG, Borys D, Schuerman L, Ijzerman EP, Bruin JP, van der Ende A, et al. 2013. Effects of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D-conjugate vaccine on nasopharyngeal bacterial colonization in young children: a randomized controlled trial. Clin Infect Dis. 56:e30–e39.
   PubMed Web of Science ®Google Scholar
• Van Eldere J, Slack MPE, Ladhani S, Cripps AW. 2014. Non-typeable Haemophilus influenzae, an under-recognised pathogen. Lancet Infect Dis. 14:1281–1292.
   PubMed Web of Science ®Google Scholar
• Vestbo J, Hurd SS, Agusti AG, Jones PW, Vogelmeier C, Anzueto A, Barnes PJ, Fabbri LM, Martinez FJ, Nishimura M, et al. 2013. Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease, GOLD executive summary. Am J Respir Crit Care Med. 187:347–365.
   PubMed Web of Science ®Google Scholar
• Vogelmeier CF, Criner GJ, Martinez FJ, Anzueto A, Barnes PJ, Bourbeau J, Celli BR, Chen R, Decramer M, Fabbri LM, et al. 2017. Global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease 2017 report. GOLD executive summary. Am J Respir Crit Care Med. 195:557–582.
   PubMed Web of Science ®Google Scholar
• Wang JH, Kwon HJ, Jang YJ. 2009. Rhinovirus enhances various bacterial adhesions to nasal epithelial cells simultaneously. The Laryngoscope. 119:1406–1411.
   PubMed Web of Science ®Google Scholar
• Watson K, Carville K, Bowman J, Jacoby P, Riley TV, Leach AJ, Lehmann D; Kalgoorlie Otitis Media Research Project Team. 2006. Upper respiratory tract bacterial carriage in aboriginal and non-aboriginal children in a semi-arid area of Western Australia. Pediatr Infect Dis J. 25:782–790.
   PubMed Web of Science ®Google Scholar
• Wedzicha JA, Singh R, Mackay AJ. 2014. Acute COPD Exacerbations. Clin Chest Med. 35:157–163.
   PubMed Web of Science ®Google Scholar
• Wilkinson TMA, Hurst JR, Perera WR, Wilks M, Donaldson GC, Wedzicha JA. 2006. Effect of interactions between lower airway bacterial and rhinoviral infection in exacerbations of COPD. Chest 129:317–324.
   PubMed Web of Science ®Google Scholar
• Wilkinson TMA, Patel IS, Wilks M, Donaldson GC, Wedzicha JA. 2003. Airway bacterial load and FEV1 decline in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 167:1090–1095.
   PubMed Web of Science ®Google Scholar
• Wilson R, Sethi S, Anzueto A, Miravitlles M. 2013. Antibiotics for treatment and prevention of exacerbations of chronic obstructive pulmonary disease J Infect. 67:497–515.
   PubMed Web of Science ®Google Scholar
• Winokur PL, Chaloner K, Doern GV, Ferreira J, Apicella MA. 2013. Safety and Immunological Outcomes Following Human Inoculation With Nontypeable Haemophilus influenzae. J Infect Dis. 208:728–738.
   PubMed Web of Science ®Google Scholar
• Xu X, Steere RR, Fedorchuk CA, Pang J, Lee J-Y, Lim JH, Xu H, Pan ZK, Maggirwar SB, Li J-D. 2011. Activation of epidermal growth factor receptor is required for NTHi-induced NF-κB-dependent inflammation. PLoS One. 6:e28216.
   PubMed Web of Science ®Google Scholar
• Zakharkina T, Heinzel E, Koczulla RA, Greulich T, Rentz K, Pauling JK, Baumbach J, Herrmann M, Grünewald C, Dienemann H, et al. 2013. Analysis of the airway microbiota of healthy individuals and patients with chronic obstructive pulmonary disease by T-RFLP and clone sequencing. PLoS One. 8:e68302.
   PubMed Web of Science ®Google Scholar
• Zalacain R, Sobradillo V, Amilibia J, Barron J, Achotegui V, Pijoan J, Llorente J. 1999. Predisposing factors to bacterial colonization in chronic obstructive pulmonary disease. Eur Respir J. 13:343–348.
   PubMed Web of Science ®Google Scholar
• Zhu B, Xiao D, Zhang H, Zhang Y, Gao Y, Xu L, Lv J, Wang Y, Zhang J, Shao Z. 2013. MALDI-TOF MS distinctly differentiates nontypable Haemophilus influenzae from Haemophilus haemolyticus. PLoS One. 8:e56139.
   PubMed Web of Science ®Google Scholar
• Zwaans WAR, Mallia P, van Winden MEC, Rohde GGU. 2014. The relevance of respiratory viral infections in the exacerbations of chronic obstructive pulmonary disease: a systematic review. J Clin Virol. 61:181–188.
   PubMed Web of Science ®Google Scholar