Contents lists available at ScienceDirect Respiratory Physiology & Neurobiology journal homepage: www.elsevier.com/locate/resphysiol Is cough important in acute exacerbations of COPD? Michael G. Crooks ⁎ , Timothy Brown, Alyn H. Morice Department of Respiratory Medicine, Institute of Clinical and Applied Health Research, Hull York Medical School, United Kingdom ARTICLE INFO Keywords: Chronic obstructive pulmonary disease Cough Exacerbation Reflux Telehealth ABSTRACT Chronic obstructive pulmonary disease is predicted to become the 4th leading cause of death worldwide by 2030. The natural history of the disease includes progressive symptoms punctuated by acute exacerbations during which symptoms rapidly deteriorate. The resulting disability places significant burden on health and social care systems. Cough is the second most common symptom reported by COPD patients, is a source of significant distress and is associated with adverse outcomes. We discuss the importance of cough in COPD, its mechanism and the relationship between cough and COPD exacerbations. We review the literature and present original data relating to the investigation of cough during COPD exacerbation, its associations and potential benefits of cough monitoring. 1. Introduction Chronic Obstructive Pulmonary Disease (COPD) is a preventable and treatable chronic respiratory disease. In the developed world, it is largely caused by cigarette smoking in susceptible individuals and it is associated with significant morbidity and mortality. COPD was re- sponsible for 3 million deaths worldwide in 2010 and is predicted to become the 4th leading cause of death by 2030 (Lozano et al., 2012; Mathers and Loncar, 2006). Breathlessness, cough, sputum production and wheeze are frequently experienced by people with COPD. Although symptom burden increases with disease severity, it is recognised that individuals experience significant symptom variability with periods of rapid worsening termed acute exacerbations (AECOPD). The combina- tion of disability resulting from progressive symptoms and the tendency to exacerbations places a significant burden on health and social care services. As such, there is an urgent need to optimise COPD manage- ment to minimise patients’ symptoms, reduce exacerbations and iden- tify and treat them early when they occur. After breathlessness, cough is the second most commonly experienced symptom in COPD patients and it frequently worsens during exacerbation (Calverley et al., 2005). We discuss cough in COPD before focussing on potential ways that mon- itoring a patient’s cough can be used to improve their management. 2. Cough in COPD Cough is a common symptom in COPD with 60–80% of patients reporting having had a cough within the past 7 days (de Oliveira et al., 2013; Kessler et al., 2011). There is a diurnal variation with half of COPD patients reporting their cough to be most troublesome on waking in the morning (Kessler et al., 2011). Indeed, coughing at night is re- latively rare, possibly due to increased vagal tone either diminishing cough reflex sensitivity or closure of the oesophageal sphincter (Fig. 1) (Crooks et al., 2016; Lee and Birring, 2010). A chronic bronchitis phenotype is characterised by a cough with sputum production, occurring most days for three months for 2 con- secutive years. Originally chronic bronchitis was claimed to have no adverse effects on COPD (Fletcher and Peto, 1977). However, later observational studies have demonstrated that cough with sputum pro- duction is associated with adverse outcomes including more frequent exacerbations (Burgel et al., 2009), accelerated lung function decline (Vestbo et al., 1996) and increased risk of mortality (Ekberg-Aronsson et al., 2005; Lahousse et al., 2017). The cause of cough in COPD is likely to be multifactorial and vary significantly between individuals. Environmental exposures, altered respiratory mechanics due to hyperinflation, airway inflammation with mucus hypersecretion, and comorbidities all potentially impact cough in COPD patients. A study by Sumner et al. utilised objective cough monitoring in 68 subjects with COPD and demonstrated cough frequency to be related to smoking history, current cigarette consumption and reported sputum production (Sumner et al., 2013). Only a weak correlation was observed with cough reflex sensitivity to capsaicin, however this is also true of other respiratory diseases associated with cough. In the 39 subjects that were able to provide a sputum sample for differential cell count, a trend towards a positive correlation between day time cough frequency and sputum eosinophils and neutrophils was observed. Multivariate analysis https://doi.org/10.1016/j.resp.2018.02.005 Received 14 November 2017; Received in revised form 31 January 2018; Accepted 8 February 2018 ⁎ Corresponding author at: Department of Respiratory Medicine, Institute of Clinical and Applied Health Research, Hull York Medical School, Castle Hill Hospital, Cottingham, HU16 5JQ, United Kingdom. E-mail address: Michael.crooks@nhs.net (M.G. Crooks). Respiratory Physiology & Neurobiology xxx (xxxx) xxx–xxx 1569-9048/ © 2018 Published by Elsevier B.V. Please cite this article as: Crooks, M.G., Respiratory Physiology & Neurobiology (2018), https://doi.org/10.1016/j.resp.2018.02.005