Possible aetiologies for COPD exacerbations – more evidence is needed

Under-recognised aetiologies for chronic obstructive pulmonary disease (COPD) exacerbations are especially interesting with regard to exacerbations without inflammatory triggers. They include arrhythmias, diastolic dysfunction, psychological distress, and gastroesophageal reflux disease.

“The majority of COPD exacerbations are due to bacterial or viral infections; some are recognised to be due to environmental pollution and in approximately one-third of cases the aetiology remains unclear,” Prof. Surya P. Bhatt (Birmingham School of Medicine, AL, USA) explained [1]. As the current definition of an acute exacerbation of COPD (AECOPD) is based on acute symptom worsening without mentioning aetiologies, 4 clusters of possible phenotypes were distinguished: bacteria-predominant, eosinophil-predominant, virus-predominant, and pauci-inflammatory [2]. All might require different treatment strategies, and this could play a special role in the pauci-inflammatory group constituting about 20% of AECOPD with no clear identifiable cause [1].

Meta-analyses have established an association between COPD and cardiac disease, especially coronary artery disease and cardiac arrhythmias [1]. It has been hypothesised that AECOPD could be linked to unrecognised arrhythmias, and a small study indeed found that p-wave dispersion, a surrogate for atrial arrhythmia, is greater during exacerbation than during the stable phase, hence possibly predating AECOPD [3]. Furthermore, diastolic dysfunction is a point of discussion: Prof. Bhatt presented unpublished data that found a 3-fold increase of severe exacerbations in patients with diastolic dysfunction and evidence of subclinical pulmonary oedema [1].

“Another comorbidity frequently noted in those with COPD is psychological distress in the form of anxiety or depression, which is present in up to 55% of individuals with COPD,” informed Prof. Bhatt. Depression carries a higher risk for severe exacerbations as well as short- and long-term readmission to hospital [4,5]. However, anxiety is linked to an amplified risk for mild-to-moderate exacerbations, which could be due to augmented awareness of physical symptoms in anxiety patients [1,4].

Gastroesophageal reflux disease: a novel risk factor for AECOPD

An entirely different condition increasing the likelihood of AECOPD is gastroesophageal reflux disease (GERD). A recent meta-analysis identified that the presence of GERD augmented the odds for exacerbated COPD by 5-fold (OR 5.37; 95% CI 2.71–10.64) [6].

Also, vocal cord dysfunction (VCD) and expiratory central airway collapse were among the under-recognised aetiologies. A small study that included patients with COPD or asthma not only detected that VCD was more common in patients with COPD than with asthma, but also that the frequency of VCD was higher in individuals with (very) severe COPD than in the mild/moderate setting [7]. Furthermore, Prof. Bhatt stated, “Another underappreciated source of dyspnoea in individuals with COPD is that of central airway collapse; it is associated with a high risk of moderate as well as severe exacerbations, but whether this is an indicator of risk or it is causal, is not clear at this time.” Prof. Bhatt concluded that even though all these aetiologies are biologically plausible, more data is needed to confirm them.

1. Bhatt SP. Under Recognized Etiologies of Exacerbations. Session B027: Phenotyping acute exacerbations of COPD. ATS 2021 International Conference, 14-19 May.
2. Bafadhel M, et al. Am J Respir Crit Care Med. 2011;184(6):662-71.
3. Chen W, et al. Lancet Respir Med. 2015;3(8):631-9.
4. Laurin C, et al. Am J Respir Crit Care Med. 2012;185(9):918-23.
5. Iyer AS, et al. Ann Am Thorac Soc. 2016;13(2):197-203.
6. Huang C, et al. BMC Pulm Med. 2020;20(1):2.
7. Ruane L, et al. European Respiratory Journal 2019 54 (suppl. 63) OA272.

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Posted on 5 July, 202129 February, 2024