Inhaled Corticosteroids in the Long Term Treatment of Asthma and COPD

Abstract Background The first step in SARS-CoV-2 infection is binding of the virus to angiotensin converting enzyme 2 (ACE2) on the airway epithelium. Asthma affects over 300 million people world-wide, many of whom may encounter SARS-CoV-2. Epidemiologic data suggests that asthmatics who get infected may be at increased risk of more severe disease. Our objective was to assess whether maintenance inhaled corticosteroids (ICS), a major treatment for asthma, is associated with airway ACE2 expression in asthmatics. Methods Large airway epithelium (LAE) of asthmatics treated with maintenance ICS (ICS+), asthmatics not treated with ICS (ICS−), and healthy controls (controls) was analyzed for expression of ACE2 and other coronavirus infection-related genes using microarrays. Results As a group, there was no difference in LAE ACE2 expression in all asthmatics vs controls. In contrast, subgroup analysis demonstrated that LAE ACE2 expression was higher in asthmatics ICS+ compared to ICS‾ and ACE2 expression was higher in male ICS+ compared to female ICS+ and ICS‾ of either sex. ACE2 expression did not correlate with serum IgE, absolute eosinophil level, or change in FEV1 in response to bronchodilators in either ICS− or ICS+. Conclusion Airway ACE2 expression is increased in asthmatics on long-term treatment with ICS, an observation that should be taken into consideration when assessing the use of inhaled corticosteroids during the pandemic.

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Airway inflammation in COPD after long-term withdrawal of inhaled corticosteroids

European Respiratory Journal ◽

10.1183/13993003.00839-2016 ◽

2016 ◽

Vol 49 (1) ◽

pp. 1600839 ◽

Cited By ~ 10

Author(s):

Lisette I.Z. Kunz ◽

Nick H.T. ten Hacken ◽

Thérèse S. Lapperre ◽

Wim Timens ◽

Huib A.M. Kerstjens ◽

...

Keyword(s):

Lung Function ◽

Airway Inflammation ◽

Inhaled Corticosteroids ◽

Term Treatment ◽

Chronic Obstructive ◽

Lung Function Decline ◽

Cell Counts ◽

Long Term Treatment ◽

Severe Copd

Long-term treatment with inhaled corticosteroids (ICS) might attenuate lung function decline and decrease airway inflammation in a subset of patients with chronic obstructive pulmonary disease (COPD), and discontinuing ICS treatment could result in further lung function decline. We hypothesised that airway inflammation increases after ICS withdrawal following long-term ICS treatment in COPD.In the GLUCOLD-1 study (GL1), 114 patients with moderate-severe COPD were randomised to 6-month or 30-month treatment with fluticasone propionate (500 µg twice daily), 30-month treatment with fluticasone/salmeterol (500/50 µg twice daily) or placebo. During the 5-year follow-up study (GL2), patients were followed prospectively while being treated by their physician. Bronchial biopsies and induced sputum were collected at baseline, at 30 months (end of GL1) and at 7.5 years (end of GL2) to assess inflammatory cell counts. Data were analysed using linear mixed-effects models.In patients using ICS during GL1 and using ICS 0–50% of the time during GL2 (n=61/85), there were significant increases in GL2 bronchial CD3+ (fold change per year calculated as GL2 minus GL1 2.68, 95% CI 1.87–3.84), CD4+ (1.91, 95% CI 1.33–2.75) and CD8+ cells (1.71, 95% CI 1.15–2.53), and mast cells (1.91, 95% CI 1.36–2.68). The sputum total cell counts increased significantly in GL2 (1.90, 95% CI 1.42–2.54), as did counts of macrophages (2.10, 95% CI 1.55–2.86), neutrophils (1.92, 95% CI 1.39–2.65) and lymphocytes (2.01, 95% CI 1.46–2.78).ICS discontinuation increases airway inflammation in patients with moderate-severe COPD, suggesting that the anti-inflammatory effects of ICS in COPD are not maintained after ICS discontinuation.

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