Airway expression of SARS-CoV-2 receptor, ACE2, and proteases, TMPRSS2 and furin, in severe asthma

BackgroundPatients with severe asthma may have a greater risk of dying from COVID-19 disease caused by SARS-CoV-2 virus. Angiotensin converting enzyme 2 (ACE2) receptor and enzyme proteases, transmembrane protease, serine 2 (TMPRSS2) and furin are needed for the attachment and invasion of the virus into host cells. We determined whether their expression in the airways of severe asthma patients is increased. MethodWe examined the microarray mRNA expression of ACE2, TMPRSS2 and furin in the sputum, bronchial brush and bronchial biopsies of participants in the European U-BIOPRED cohort. ResultsACE2 and furin sputum gene expression was significantly increased in severe non-smoking asthma compared to mild-moderate asthma and healthy volunteers. By contrast, TMPRSS2 expression in bronchial biopsy and bronchial brushings was increased in severe smoking and ex-smoking asthmatics, and so was furin expression in bronchial brushings. Several clinical parameters including male gender, oral steroid use and nasal polyps were positively associated with ACE2, TMPRSS2 and furin expression levels. There was a higher expression of ACE2 and furin in the sputum neutrophilic molecular phenotype with inflammasome activation compared to the eosinophilic Type2-high or paucigranulocytic phenotypes. The enrichment score of the IL-13-Type2 gene signature was positively correlated with ACE2, TMPRSS2 and furin levels. ConclusionThese key determinants of virus entry into the lungs may contribute to the poorer outcomes from COVID-19 disease in patients with severe asthma. "take home" messageIn severe asthma, gene expression of ACE, TMPRSS2 and furin are elevated compared to mild-moderate asthma and healthy volunteers, particularly in neutrophilic asthma. This might explain the increased risk of death in severe asthma afflicted with COVID19.

Future Risks in Patients With Severe Asthma

A major burden of severe asthma is the future risk of adverse health outcomes. Patients with severe asthma are prone to serious exacerbation and deterioration of lung function and may experience side effects of medications such as oral corticosteroids (OCSs). However, such future risk is not easily measurable in daily clinical practice. In particular, currently available tools to measure asthma control and asthma-related quality of life incompletely predict the future risk of medication-related morbidity. This is a significant issue in asthma management. This review summarizes the current evidence of future risk in patients with severe asthma. As future risk is poorly perceived by controlled asthmatics, our review focuses on the risk in patients with ‘controlled’ severe asthma. Of note, it is likely that long-term OCS therapy may not prevent future asthma progression, including lung function decline. In addition, the risk of drug side effects increases even during low-dose OCS therapy. Thus, novel treatments are highly desirable for reducing future risks without any loss of asthma control.

Age and Sex Distribution of Chinese Chronic Cough Patients and Their Relationship With Capsaicin Cough Sensitivity

PURPOSE: An older female predominance has been reported among chronic cough patients in Western countries, which is considered to be associated with a higher cough sensitivity in females. However, the characteristics of Chinese chronic cough patients remain unclear. This study aimed to explore the age and sex distribution as well as their relationship with cough reflex sensitivity to capsaicin in Chinese chronic cough patients. METHODS: We analyzed the demographic features of 1,882 consecutive chronic cough patients who attended our cough clinic in Guangzhou, China. Cough sensitivity to capsaicin, which was defined as the lowest concentration of capsaicin causing 5 coughs or more (C5), was measured in 539 of the 1,882 patients and 68 healthy volunteers. RESULTS: The mean age of the patients was 43.0 ± 13.7 years and patients aged <50 years accounted for more than two-thirds of the study population. Around 87% of the patients were never-smokers. The proportion of females (51.5%) was almost equal to that of males (48.5%). The pattern of the age and sex distribution was consistently reflected within most common causes of chronic cough, while a female predominance was shown in patients with cough-variant asthma and patients aged ≥50 years. Female patients had higher cough sensitivity to capsaicin than male patients (log C5: 1.58 ± 0.84 vs. 2.04 ± 0.84 μmol/L, P = 0.001), and patients aged ≥50 years had higher cough sensitivity to capsaicin than patients aged <50 years. CONCLUSIONS: In China, patients with chronic cough have a roughly equal sex distribution and a middle-aged predominance, irrespective of a higher cough sensitivity to capsaicin in females and older patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02591550

Physician-prescribed Asthma Treatment Regimen does not differ Between Smoking and Non-smoking Patients With Asthma in Seoul and Gyunggi province of Korea

PURPOSE: Smoking has detrimental effects on asthma symptom control and response to treatment and is prevalent among asthma patients in South Korea. The aim of this study is to determine the prevalence of smoking among asthma patients in South Korea and to compare the medication regimens of asthma patients who do and do not smoke. METHODS: A cross-sectional survey was conducted from August 2010 to January 2011. Participating physicians (N=25) recorded demographic and clinical data on all asthma patients presenting during the study period (N=2,032), and then recruited a subset of patients (N=500) for the survey such that half were self-reported current smokers. Recruited patients were between the ages of 18 and 60. RESULTS: Among presenting asthma patients, 17.3% were current smokers, 19.2% were former smokers, and 63.5% had never smoked. Within the analyzable study population (N=471), 212 patients reported smoking currently, 79 smoking formerly, and 180 never smoking. Among current and former smokers, 79.7% and 81.0%, respectively, were men, while women represented 80.5% of patients who had never smoked. Agreement was strong between physician-determined smoking status and patient-reported smoking status (kappa=0.82; P<0.001). However, asthma medication regimens examined according to GINA treatment steps did not differ by smoking status. In addition, mean quality of life scores and level of asthma control did not differ by smoking status. CONCLUSIONS: In South Korea, physicians are well aware of the smoking status of their patients. However, smoking status did not affect the prescribed medication regimens of this population of asthma patients.