Characteristics associated with clinical severity and inflammatory phenotype of naturally occurring virus-induced exacerbations of asthma in adults

Abstract

Background In experimental studies viral infections have been shown to induce type 2 inflammation in asthmatics, but whether this is a feature of naturally occurring virus-induced asthma exacerbations is unknown. Thymic stromal lymphopoietin (TSLP) released from the airway epithelium in response to damage, has been suggested as a link between viral infection and type 2 inflammation, but the role of TSLP in asthma exacerbations is unknown. Objective To assess whether type 2 inflammation, as measured by sputum eosinophils and fractional exhaled nitric oxide (FeNO), is a feature of naturally occurring virus-induced exacerbations of asthma and whether TSLP is associated with this type 2 inflammation. Methods Patients presenting to hospital with acute asthma were examined during the exacerbation, and after 4 weeks recovery. The assessments included spirometry, FeNO and induced sputum for differential counts and TSLP mRNA levels. Nasal swabs were collected for viral detection. Results Sputum eosinophils and FeNO were similar between virus-positive (n=44) and negative patients (n=44). In virus-positive patients, TSLP expression was lower at exacerbation than follow-up (p=0.03). High TSLP at exacerbation was associated with lower sputum eosinophils (p=0.01) and higher FEV1 (p=0.03). In virus-positive patients, %-predicted FEV1 negatively correlated with both FeNO and sputum eosinophils (p=0.02 and p=0.05, respectively). Conclusion Our findings support that type 2 inflammation is present in patients during virus-induced asthma exacerbations, to the same degree as non-viral exacerbations, and correlate negatively with FEV1. However, in virus-positive patients, high TSLP expression during exacerbation was associated with low sputum eosinophils, suggesting that the effect of TSLP in vivo, in the setting of an asthma exacerbation, might be different than the type 2 inducing effects observed in experimental studies.

The Impact of Ambient Environmental Exposures to Microbial Products on Asthma Outcomes from Birth to Childhood

“…The researchers found three variants of the HRV: HRV-A, HRV-B, and HRV-C, with HRV-C being the most virulent for severe asthma exacerbations [15]. Other studies conducted in Japan, France, and Australia have also identified rhinovirus as the most common viral culprit for asthma exacerbations [28,[60][61][62]. White blood cells and neutrophil counts were significantly higher in patients with all HRV variants versus those who were negative for HRV (12.38 ± 5.13 vs. 10.77 ± 4.87 and 64.70 ± 20.27 vs. 56.44 ± 21.95, respectively) [15].…”

“…Zheng et al [15] conducted one of the numerous studies that demonstrated that human rhinovirus (HRV) was the most common viral microbe to induce an asthma exacerbation in children [60][61][62]. Zheng and colleagues collected data from 143 inpatient children with asthma exacerbations, 131 outpatients, including 88 patients with asthma exacerbations, and 43 controls with stable asthma [15].…”

“…Thymic stromal lymphopoietin (TSLP), a cytokine that impacts T cell maturation, also plays a role in asthma severity in patients with viral illnesses. It has been demonstrated to have a positive outcome on patients during viral infections in patients with asthma [60]. Bjerregaard et al [60] performed a study in Australia with 44 virus-positive adolescent and adult patients (including rhinovirus, human coronavirus, parainfluenza virus, and human metapneumovirus) and 44 controls.…”

“…It has been demonstrated to have a positive outcome on patients during viral infections in patients with asthma [60]. Bjerregaard et al [60] performed a study in Australia with 44 virus-positive adolescent and adult patients (including rhinovirus, human coronavirus, parainfluenza virus, and human metapneumovirus) and 44 controls. The researchers found that patients with TSLP expression had lower levels of sputum eosinophils, lower fractional exhaled nitric oxide, higher blood neutrophils, lower asthma control questionnaire scores, and higher FEV 1 in comparison to patients with low TSLP expression levels [60].…”

“…Bjerregaard et al [60] performed a study in Australia with 44 virus-positive adolescent and adult patients (including rhinovirus, human coronavirus, parainfluenza virus, and human metapneumovirus) and 44 controls. The researchers found that patients with TSLP expression had lower levels of sputum eosinophils, lower fractional exhaled nitric oxide, higher blood neutrophils, lower asthma control questionnaire scores, and higher FEV 1 in comparison to patients with low TSLP expression levels [60]. Again, these types of studies are rare for examining variances in lung function and asthma development from birth to childhood.…”