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Abstract
Background The aetiology of acute exacerbations of COPD (AECOPD) is incompletely understood. Understanding the relationship between chronic bacterial airway infection and viral exposure may explain the incidence and seasonality of these events.
Methods In this prospective, observational cohort study (NCT01360398), patients with COPD aged 40–85 years underwent sputum sampling monthly and at exacerbation for detection of bacteria and viruses. Results are presented for subjects in the full cohort, followed for 1 year. Interactions between exacerbation occurrence and pathogens were investigated by generalised estimating equation and stratified conditional logistic regression analyses.
Findings The mean exacerbation rate per patient-year was 3.04 (95% CI 2.63 to 3.50). At AECOPD, the most common bacterial species were non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis, and the most common virus was rhinovirus. Logistic regression analyses (culture bacterial detection) showed significant OR for AECOPD occurrence when M. catarrhalis was detected regardless of season (5.09 (95% CI 2.76 to 9.41)). When NTHi was detected, the increased risk of exacerbation was greater in high season (October–March, OR 3.04 (1.80 to 5.13)) than low season (OR 1.22 (0.68 to 2.22)). Bacterial and viral coinfection was more frequent at exacerbation (24.9%) than stable state (8.6%). A significant interaction was detected between NTHi and rhinovirus presence and AECOPD risk (OR 5.18 (1.92 to 13.99); p=0.031).
Conclusions AECOPD aetiology varies with season. Rises in incidence in winter may be driven by increased pathogen presence as well as an interaction between NTHi airway infection and effects of viral infection.
Trial registration number Results, NCT01360398.
- COPD Exacerbations
- Respiratory Infection
- Viral infection
- Bacterial Infection
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Footnotes
Collaborators The AERIS Study Group: J Alnajar, R Anderson, E Aris, WR Ballou, A Barton, S Bourne, M Caubet, SC Clarke, D Cleary, C Cohet, N Coombs, K Cox, J-M Devaster, V Devine, N Devos, E Dineen, T Elliott, R Gladstone, S Harden, J Jefferies, V Kim, S Mesia Vela, P Moris, K Ostridge, TG Pascal, M Peeters, S Schoonbroodt, KJ Staples, A Tuck, L Welch, V Weynants, TMA Wilkinson, AP Williams, N Williams, C Woelk, M Wojtas, S Wootton. All members of the AERIS Study Group were involved in the planning, conduct and/or reporting of the work described in the article.
Contributors JM-D, TGP, SB, SW, SS, ACT, SCC, AW and TMAW conceived and designed the study. EA, J-MD, TGP, MP, SS, SB, SW, ACT, NW, KO, KJS, SCC, VK, AW and TMAW collected or generated the data. EA, J-MD, TGP, MP, SB, SW, NW, KO, KJS, SCC, VK, AW and TMAW analysed or interpreted the data. TMAW, EA, SB, SCC, MP and J-MD are members of the core writing team. TMAW, EA, SB, SCC, MP, KJS, AW, SW and J-MD are members of the AERIS publication steering committee. All authors contributed substantially to the development of the manuscript and approved the final version.
Funding The study funder, GlaxoSmithKline Biologicals SA, designed the study in collaboration with the investigators, and coordinated collection, analysis and interpretation of data. The investigators obtained data and cared for the study participants. The authors had full access to all data in the study, contributed to the writing of the report and had final responsibility for the decision to submit for publication.
Competing interests TMAW has received reimbursement for travel and meeting attendance from Boehringer Ingelheim and AstraZeneca, outside of the submitted work. SB received grants and assistance in travel to conferences from GSK outside of the submitted work. SCC received a grant from Pfizer outside of the submitted work. KJS received grants from Asthma UK (08/026) and BMA HC Roscoe Award outside of the submitted work, and he has a patent PCT/GB2010/050821 ‘Ex Vivo Modelling of Therapeutic Interventions’ pending. EA, J-MD, SS and TGP are employees of the GSK group of companies. MP was an employee of the GSK group of companies at the time the study was conducted. EA, J-MD, SS and TGP hold shares/restricted shares in the GSK group of companies. KJS, VK, NW, KO, SW and TMAW received an institutional grant from the GSK group of companies to conduct this study. AW and AT declare no conflicts of interest.
Ethics approval Southampton and South West Hampshire Research Ethics Committee.
Provenance and peer review Not commissioned; externally peer reviewed.