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

Chronic obstructive pulmonary disease (COPD) is an inflammatory disease of the lung, characterised by progressive airflow limitation that is not fully reversible. 1 COPD is the most common chronic respiratory illness in older adults, affecting an estimated 210 million people worldwide. 2 This condition has a substantial impact on quality-of-life. 2 The Global Burden of Disease Study found COPD to be the third leading cause of death globally and the ninth leading cause of years of life lost due to premature mortality in 2010, 3 accounting for 3.7% of years lived with disability and 3.1% of disability-adjusted life years worldwide. 4, 5 COPD also imposes a substantial socioeconomic burden. In 2001, the total cost of COPD in Europe was reported to be €38.7 billion. 6 Considerable progress has been made concerning the epidemiology, pathophysiology and clinical management of COPD in recent years. However, significant challenges remain. Improved understanding of acute exacerbations of COPD (AECOPD) is a key research priority. AECOPD are highly relevant clinically, being a major cause of COPD-related morbidity and mortality, 7-11 as well as accounting for a substantial proportion of the significant social, healthcare and economic burden of COPD. 6 It has been estimated that AECOPD account for approximately 70% of total healthcare costs associated with COPD. 12 Patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage II or more disease experience 1 or 2 exacerbations annually. Exacerbation varies from patient to patient with severity of disease. 13 Various triggers for AECOPD have been identified; 1 however, up to 75% of all exacerbations are associated with the detection of bacterial and/or viral respiratory pathogens. 14, 15 Exacerbations associated with detectable respiratory pathogens have been shown to have a more marked impact on 14 With the introduction of new molecular sequencing techniques, the traditional belief that healthy lungs are sterile has been refuted. There is increasing evidence that the lower respiratory tract contains a diverse microbial flora that differs between health and disease. [16] [17] [18] [19] [20] The presence of potentially pathogenic microorganisms in the inflamed airways of patients with COPD is well-documented, with up to 50% of patients with stable COPD showing evidence of lower airway bacterial colonisation using traditional culture techniques. 15, 21, 22 In patients with COPD, bacterial detection in lower airway derived samples is associated with increased airway inflammation, reduced lung function and more frequent exacerbations. [23] [24] [25] Acquisition of new pathogen strains also appears to be associated with an increased risk of AECOPD. 15, 21, 26 Estimates of the relative contribution of different pathogens to AECOPD vary. However, non-typeable Haemophilus influenzae appears to be the major bacterial pathogen associated with AECOPD, followed by Streptococcus pneumoniae, Moraxella catarrhalis and Pseudomonas aeruginosa. 14, 15 Respiratory viruses commonly associated with AECOPD include human rhinoviruses, influenza and parainfluenza viruses, respiratory syncytial virus, coronavirus and adenovirus. 15 Improved understanding of the role of infectious pathogens in AECOPD may lead to the development of more targeted strategies for treatment and prevention. This