Asthma Associated Cytokines Regulate the Expression of SARS-CoV-2 Receptor ACE2 in the Lung Tissue of Asthmatic Patients

It is still controversial whether chronic lung inflammation increases the risk for COVID-19. One of the risk factors for acquiring COVID-19 is the level of expression of SARS-CoV-2 entry receptors, ACE2 and TMPRSS2, in lung tissue. It is, however, not clear how lung tissue inflammation affects expression levels of these receptors. We hence aimed to determine the level of SARS-CoV-2 receptors in lung tissue of asthmatic relative to age, gender, and asthma severity, and to investigate the factors regulating that. Therefore, gene expression data sets of well-known asthmatic cohorts (SARP and U-BIOPRED) were used to evaluate the association of ACE2 and TMPRSS2 with age, gender of the asthmatic patients, and also the type of the underlying lung tissue inflammatory cytokines. Notably, ACE2 and to less extent TMPRSS2 expression were upregulated in the lung tissue of asthmatics compared to healthy controls. Although a differential expression of ACE2, but not TMPRSS2 was observed relative to age within the moderate and severe asthma groups, our data suggest that age may not be a key regulatory factor of its expression. The type of tissue inflammation, however, associated significantly with ACE2 and TMPRSS2 expression levels following adjusting with age, gender and oral corticosteroids use of the patient. Type I cytokine (IFN-γ), IL-8, and IL-19 were associated with increased expression, while Type II cytokines (IL-4 and IL-13) with lower expression of ACE2 in lung tissue (airway epithelium and/or lung biopsies) of moderate and severe asthmatic patients. Of note, IL-19 was associated with ACE2 expression while IL-17 was associated with TMPRSS2 expression in sputum of asthmatic subjects. In vitro treatment of bronchial fibroblasts with IL-17 and IL-19 cytokines confirmed the regulatory effect of these cytokines on SARS-CoV-2 entry receptors. Our results suggest that the type of inflammation may regulate ACE2 and TMPRSS2 expression in the lung tissue of asthmatics and may hence affect susceptibility to SARS-CoV-2 infection.

Ragweed Pollen Concentration Predict Seasonal Oculo-rhinitis and Asthma Severity in Subjects Allergic to Ragweed.

Objectives: 1. To investigate the correlation between ragweed pollen concentration and conjunctival, nasal and asthma symptoms severity in patients allergic to ragweed using ambient pollen exposure in the Milan area during the 2014 ragweed season; 2. to calculate the pollen / symptom thresholds and 3. to assess the effectiveness of ragweed Allergen Immuno Therapy (AIT).Patients: 66 subjects allergic to Amb a 1 enrolled in the study and were divided into two cohorts: AIT treated (24) and non-AIT treated (42).Measurements: Pollen counts and daily symptom/medication patient diaries. Autoregressive Distributed Lag Models were used to develop predictive models of daily symptoms and to evaluate the short-term effects of temporal variations in pollen concentration on the onset of symptoms. Results: We found significant correlations between ragweed pollen load and the intensity of symptoms, for all three symptom categories respectively, both in non-AIT treated (𝛕= 0.341, 0.352, 0.721 and ρ = 0.48, 0.432, 0.881, p-value < 0.001) and in AIT treated patients (O= 0.46, 0.610, 0.66 and ρ = 0.692, 0.805, 0.824; p-value < 0.001). In both cohorts, we observed a positive correlation between the number of symptoms reported and drug use. Mean symptom levels were significantly greater in non-AIT treated than in AIT treated patients (p < 0.001) for all symptom categories. Pollen concentration thresholds for three symptom severity levels were calculated.Conclusions: Ragweed pollen concentration is predictive of symptom severity in ragweed (Amb a 1) allergy patients. AIT treated patients had significantly reduced mean symptom levels compared to non-AIT patients.

STIM1 is a core trigger of airway smooth muscle remodeling and hyperresponsiveness in asthma

Airway remodeling and airway hyperresponsiveness are central drivers of asthma severity. Airway remodeling is a structural change involving the dedifferentiation of airway smooth muscle (ASM) cells from a quiescent to a proliferative and secretory phenotype. Here, we show up-regulation of the endoplasmic reticulum Ca2+ sensor stromal-interacting molecule 1 (STIM1) in ASM of asthmatic mice. STIM1 is required for metabolic and transcriptional reprogramming that supports airway remodeling, including ASM proliferation, migration, secretion of cytokines and extracellular matrix, enhanced mitochondrial mass, and increased oxidative phosphorylation and glycolytic flux. Mechanistically, STIM1-mediated Ca2+ influx is critical for the activation of nuclear factor of activated T cells 4 and subsequent interleukin-6 secretion and transcription of pro-remodeling transcription factors, growth factors, surface receptors, and asthma-associated proteins. STIM1 drives airway hyperresponsiveness in asthmatic mice through enhanced frequency and amplitude of ASM cytosolic Ca2+ oscillations. Our data advocates for ASM STIM1 as a target for asthma therapy.

Assessment of Clinical Asthma Score and Asthma Severity Score in Preschool Children with Recurrent Wheezing

Objective: There is no definitive consensus on asthma exacerbation scoring for preschool children with recurrent wheezing. The Clinical Asthma Score (CAS) and Asthma Severity Score (ASS) are two scoring systems that can be used in this population. The aim of this study was to evaluate the relationship between CAS and ASS, acute treatment, and exacerbation outcomes in preschool children with wheezing. Materials and Methods: The study included 70 patients aged 2-5 years who presented to the pediatric emergency department due to an acute wheezing episode. CAS and ASS were evaluated at exacerbation presentation and after initial salbutamol therapy. Results: Presenting scores were significantly higher among patients who had three or more episodes within the last year (p=0.01 for CAS, p=0.019 for ASS). Presenting scores were significantly higher in patients treated with systemic steroid therapy during the episode compared to those who were not (p=0.006 for CAS; p=0.003 for ASS). CAS and ASS predicted the use of acute steroid therapy with a sensitivity of 73.7% and 52.6%, and predicted hospitalization with a sensitivity of 95% and 82.5%, respectively. Conclusion: Our data suggest that these scoring systems can be used to judge the need for systemic steroid therapy and that high scores are associated with greater likelihood of hospital admission. Keywords: Asthma score, children, hospitalization, wheezing, exacerbation

Risks of infection, hospital and ICU admission, and death from COVID-19 in people with asthma: systematic review and meta-analyses

ObjectivesTo determine if and to what degree asthma may predispose to worse COVID-19 outcomes in order to inform treatment and prevention decisions, including shielding and vaccine prioritisation.DesignSystematic review and meta-analysis.SettingElectronic databases were searched (October 2020) for clinical studies reporting at least one of the following stratified by asthma status: risk of infection with SARS-CoV-2; hospitalisation, intensive care unit (ICU) admission or mortality with COVID-19.ParticipantsAdults and children who tested positive for or were suspected to have COVID-19.Main outcome measuresMain outcome measures were the following stratified by asthma status: risk of infection with SARS-CoV-2; hospitalisation, ICU admission or mortality with COVID-19. We pooled odds ratios (ORs) and presented these with 95% confidence intervals (CI). Certainty was assessed using GRADE (Grading of Recommendations, Assessment, Development and Evaluations).Results30 (n=112 420) studies were included (12 judged high quality, 15 medium, 3 low). Few provided indication of asthma severity. Point estimates indicated reduced risks in people with asthma for all outcomes, but in all cases the evidence was judged to be of very low certainty and 95% CIs all included no difference and the possibility of increased risk (death: OR 0.90, 95% CI 0.72 to 1.13, I2=58%; hospitalisation: OR 0.95, 95% CI 0.71 to 1.26; ICU admission: OR 0.96, 95% CI 0.75 to 1.24). Findings on hospitalisation are also limited by substantial unexplained statistical heterogeneity. Within people with asthma, allergic asthma was associated with less COVID-19 risk and concurrent chronic obstructive pulmonary disease was associated with increased risk. In some studies, corticosteroids were associated with increased risk, but this may reflect increased risk in people with more severe asthma.ConclusionsThough absence of evidence of a clear association between asthma and worse outcomes from COVID-19 should not be interpreted as evidence of absence, the data reviewed indicate that risks from COVID-19 in people with asthma, as a whole, may be less than originally anticipated.

Allergic Comorbidity Is a Risk Factor for Not Attending Scheduled Outpatient Visits in Children with Asthma

Asthma is one of the most common chronic diseases in children globally. Previous studies have shown that not attending asthma primary care consultations is associated with poorer treatment adherence and increased risk of loss of asthma control on a short-term basis. Here, we investigated long-term patterns and predictors of not attending scheduled asthma outpatient visits during 5-years of follow-up in 146 children with asthma. Of the 146 children, 67 (46%) did not attend at least one scheduled appointment, amounting to a total of 122 (10.8%) missed of 1133 scheduled appointments. In a multivariate analysis adjusting for total scheduled visits in the 5-year period any allergic sensitization was a significant risk factor for not attending ≥1 scheduled appointment (aOR = 6.6 (95% CI, 1.3–39.7), p = 0.03), which was not the case for asthma treatment step or lung function. Furthermore, atopic predisposition decreased the risk of non-attendance (aOR = 0.36 (0.13–0.92), p = 0.04). We found no association between non-attendance, treatment adherence or loss of asthma control. This study highlights that allergic comorbidity, but not degree of asthma severity, identifies a group of children with asthma who are prone to not attend scheduled outpatient appointments.

Unraveling the Relationship of Asthma and COVID-19

Viral infections are one of the main causes of asthma exacerbations. During the COVID-19 era, concerns regarding the relationship of SARS-CoV2 with asthma have been raised. The concerns are both for COVID severity and asthma exacerbations. Many studies on COVID-19 epidemiology and comorbidities have assessed whether asthma represents a risk factor for SARS-CoV2 infection and/or more severe course of the disease. This review covers the current evidence on the prevalence of asthma in COVID-19 and its association with susceptibility to and severity of SARS-CoV2 infection. It will examine the possible role of underlying asthma severity in COVID-19 related outcomes as well as the molecular mechanisms involved in the co-existence of these entities. The possible role of asthma inflammatory phenotypes will also be evaluated. Finally, the impact of asthma comorbidities and the implications of asthma medication on COVID-19 will be addressed.

Clinical Characteristics and Economic Burden of Asthma in China: A Multicenter Retrospective Study

Background: Asthma is a common chronic airway inflammation that produces a healthcare burden on the economy.Objective: To obtain a better understanding of the clinical status and disease burden of patients with asthma in China. Methods: A retrospective study based on the computerized medical records in the Jinan Health Medical Big Data Platform between 2011 and 2019 (n = 31,082) was carried out. The asthma severity of each patient was assessed retrospectively and categorized as mild, moderate, or severe according to GINA 2018. Results: The results revealed that the majority (75.0%) of patients suffered from mild asthma. Patients treated with ICS/LABA at emergency department visits had lower frequencies of exacerbations in the following year compared with non-ICS/LABA treated patients.The incidence rates for 1 exacerbation are 14.49% vs 15.01 for the patients treated with ICS/LABA and without. The rates are 11.94% and 19.12% for 2 exacerbations above. The numbers are 6.51% vs 12.92% for 3 exacerbations above. The rates are 4.10% vs 9.35% for 4 exacerbations above. Also the difference got the statistical significance (p <0.001), COPD and GRED, two comorbidities related to asthma, were risk factors for asthma exacerbation. Finally, patients who suffered from exacerbations produced a heavier economic burden compared to the patients who never suffered exacerbations(mean costs are ￥3,339.67 vs ￥968.45 separately). Conclusions: These results provide a reference for clinicians and patients to obtain a better treatment and therapy strategy management for asthma sufferers.

Social Determinants of Emergency Department Visits in Mild Compared To Moderate and Severe Asthma

Social determinants of health (SDH) influence emergency department (ED) use among children with asthma. We aimed to examine if SDH were more strongly associated with ED use among children with moderate/severe compared to mild asthma. This study utilized the 2016-2019 data from the National Survey of Children’s Health. Children with asthma ages 0-17 years (N=9,937) were included in the analysis. Asthma severity and all-cause ED use in the past year were reported by caregivers. The association between patient factors and ED visits was evaluated using ordinal logistic regression. Based on the study sample, 29% of children with asthma had moderate/severe asthma. In the mild group, 30% visited the ED at least once in the past 12 months, compared to 49% in the moderate/severe group. SDH associated with ED visits included race/ethnicity, insurance coverage, and parental educational attainment, but the strength of these associations did not vary according to asthma severity. In a nationally-representative data set, SDH were equally predictive of ED use regardless of children’s asthma severity. Interventions to reduce ED use among children with asthma should be considered for children with any severity of asthma, especially children in socially disadvantaged groups at higher risk of ED utilization.