Acute Exacerbation and Respiratory InfectionS in COPD (AERIS): protocol for a prospective, observational cohort study

Bourne, Simon; Cohet, Catherine; Kim, Viktoriya; Barton, Anna; Tuck, Andy; Aris, Emmanuel; Mesia-Vela, Sonia; Devaster, Jeanne-Marie; Ballou, W Ripley; Clarke, Stuart; Wilkinson, Tom

The co-primary study endpoints are the occurrence of all-cause AECOPD and the occurrence of AECOPD having sputum containing bacterial pathogens as detected by culture (overall and by species). The proportion of subjects at each visit for whom a sputum sample was obtained will be computed; overall and by the method the samples were obtained (spontaneous or induced). The proportion of sputum samples obtained at each visit and positive for specific bacterial pathogens (overall and by bacterial species) will also be calculated. The incidence rate of all-cause AECOPD and of AECOPD having sputum containing bacterial pathogens (overall and by bacterial species) will be calculated, with 95% CI. The 95% CI of the incidence rate will be computed using a model which accounts for repeated events, namely the generalised linear model assuming a negative binomial distribution for the response variable with logarithm as link function, and the logarithm of time for follow-up as an offset variable as a preliminary approach. Other flexible approaches to statistical analysis may also be used. In addition, the same model with covariates (e.g. smoking status at enrolment, number of moderate/severe exacerbations reported in the 12 months prior to enrolment, presence of respiratory pathogenic bacteria detected at the exacerbation visit and at previous visits) will be applied. Incidence rates will also be calculated for moderate AECOPD and for severe AECOPD.