Andrew Higham

Small airways disease (SAD) is a cardinal feature of chronic obstructive pulmonary disease (COPD) first recognized in the nineteenth century. The diverse histopathological features associated with SAD underpin the heterogeneous nature of COPD. Our understanding of the key molecular mechanisms which drive the pathological changes are not complete. In this article we will provide a historical overview of key histopathological studies which have helped shape our understanding of SAD and discuss the hallmark features of airway remodelling, mucous plugging and inflammation. We focus on the relationship between SAD and emphysema, SAD in the early stages of COPD, and the mechanisms which cause SAD progression, including bacterial colonization and exacerbations. We discuss the need to specifically target SAD to attenuate the progression of COPD.

BACKGROUND: The use of electronic cigarettes (e-cigs) is increasing and there is widespread perception that e-cigs are safe. E-cigs contain harmful chemicals; more research is needed to evaluate the safety of e-cig use. Our aim was to investigate the effects of e-cigs on the inflammatory response of human neutrophils. METHODS: Neutrophils were exposed to e-cig vapour extract (ECVE) and the expression of CD11b and CD66b was measured by flow cytometry and MMP-9 and CXCL8 by ELISA. We also measured the activity of neutrophil elastase (NE) and MMP-9, along with the activation of inflammatory signalling pathways. Finally we analysed the biochemical composition of ECVE by ultra-high performance liquid chromatography mass spectrometry. RESULTS: ECVE caused an increase in the expression of CD11b and CD66b, and increased the release of MMP-9 and CXCL8. Furthermore, there was an increase in NE and MMP-9 activity and an increase in p38 MAPK activation. We also identified several harmful chemicals in ECVE, including known carcinogens. CONCLUSIONS: ECVE causes a pro-inflammatory response from human neutrophils. This raises concerns over the safety of e-cig use.

The 2019 coronavirus disease (COVID-19) pandemic is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Clinical outcomes, including mortality, are worse in males, older individuals and patients with comorbidities. COPD patients are included in shielding strategies due to their susceptibility to virus-induced exacerbations, compromised pulmonary function and high prevalence of associated comorbidities. Using evidence from basic science and cohort studies, this review addresses key questions concerning COVID-19 and COPD. First, are there mechanisms by which COPD patients are more susceptible to SARS-CoV-2 infection? Secondly, do inhaled corticosteroids offer protection against COVID-19? And, thirdly, what is the evidence regarding clinical outcomes from COVID-19 in COPD patients? This up-to-date review tackles some of the key issues which have significant impact on the long-term outlook for COPD patients in the context of COVID-19.

PURPOSE OF REVIEW: Chronic obstructive pulmonary disease (COPD) and COVID-19 have many potentially negative interrelationships, which may influence the course of infection and clinical outcomes. The aim of this review is to provide clinicians with an up-to-date perspective of the complex interactions between COPD and COVID-19. RECENT FINDINGS: We consider mechanisms that could increase SARS-CoV-2 infection susceptibility in COPD, including increased ACE2 expression, reduced antiviral defence and dysfunctional immunity. We review evidence that COPD is associated with worse clinical outcomes from COVID-19 in analyses that have adjusted for confounding factors, and describe the mechanisms responsible. We discuss the use of inhaled corticosteroids in the context of susceptibility to COVID-19, and consider the impact of COVID-19 on the usual care of COPD patients. SUMMARY: The current review highlights the evidence that COPD patients have worse outcomes from COVID-19, and the multiple mechanisms responsible.

Objective Mortality from coronavirus disease 2019 (COVID‐19) is increased in patients with chronic obstructive pulmonary disease (COPD). Furthermore, higher BMI is related to severe disease. Severe acute respiratory syndrome coronavirus 2 utilizes angiotensin converting enzyme 2 (ACE2) to gain cellular entry. Methods Whether ACE2 bronchial epithelial expression is increased in COPD patients who have overweight compared with those who do not was investigated by RNA sequencing. Results Increased ACE2 expression was observed in patients with COPD with overweight (mean BMI, 29 kg/m 2 ) compared with those without overweight (mean BMI, 21 kg/m 2 ) ( P = 0.004). Conclusions Increased ACE2 expression may cause increased severe acute respiratory syndrome coronavirus 2 infection of the respiratory tract. Overweight COPD patients may be at greater risk for developing severe COVID‐19.