Small Airway Dysfunction in Cough Variant Asthma: Prevalence, Clinical, and Pathophysiological Features

Introduction: Small airway dysfunction (SAD) commonly presents in patients with classic asthma, which is associated with airway inflammation, disease severity, and asthma control. However, the prevalence of SAD, its relationship with cough severity and airway inflammation, and its development after antiasthmatic treatment in patients with cough variant asthma (CVA) need to be clarified. This study aimed to investigate the prevalence of SAD and its relationship with clinical and pathophysiological characteristics in patients with CVA and the change in small airway function after antiasthmatic treatment.Methods: We retrospectively analyzed 120 corticosteroid-naïve patients with CVA who had finished a standard questionnaire and relevant tests in a specialist cough clinic, such as cough visual analog scale (VAS), differential cells in induced sputum, fractional exhaled nitric oxide (FeNO) measurement, spirometry, and airway hyper-responsiveness. Information of 1-year follow-up was recorded in a part of patients who received complete cough relief after 2 months of treatment. SAD was defined as any two parameters of maximal mid-expiratory flow (MMEF)% pred, forced expiratory flow at 50% of forced vital capacity (FEF50%) pred, and forced expiratory flow at 75% of forced vital capacity (FEF75%) pred measuring <65%.Results: SAD occurred in 73 (60.8%) patients with CVA before treatment. The patients with SAD showed a significantly longer cough duration (24.0 vs. 6.0, p = 0.031), a higher proportion of women (78.1 vs. 59.6%, p = 0.029), older mean age (41.9 vs. 35.4, p = 0.005), and significantly lower forced expiratory volume in 1 s (FEV1%) pred, FEV1/FVC, MMEF% pred, FEF50% pred, FEF75% pred, PEF% pred, and PD20 (all p < 0.01) as compared with patients without SAD. There were no significant differences in cough VAS, sputum eosinophils count, FeNO, and TIgE level between patients with SAD and those without SAD. Among 105 patients who completed 2 months of antiasthmatic treatment and repeatedly experienced spirometry measurement, 57 (54.3%) patients still had SAD, despite a significant improvement in cough VAS, sputum eosinophils, FeNO, FEF50% pred, and PEF% pred (all p < 0.01). As compared with patients without SAD, patients with SAD showed no significant differences in the relapse rate (50.0 vs. 41.9%, p = 0.483) and wheeze development rate (10.4 vs. 0%, p = 0.063) during the follow-up.Conclusions: Small airway dysfunction occurred in over half of patients with CVA and persisted after short-term antiasthmatic treatment, which showed distinctive clinical and pathophysiological features.

Prevalence of COVID-19 in children affected by allergic rhinoconjunctivitis and asthma: results from the second “SIAIP rhinosinusitis and conjunctivitis committee” survey

Background The role of allergic sensitization seems to be protective against SARS CoV2 infection. The aim of this study was to evaluate, using online surveys, the impact of COVID-19 on Italian allergic children, comparing the prevalence of AR and asthma symptoms between the first and second pandemic wave. Methods Both surveys were emailed to Italian pediatricians in April 2020 (first survey) and in March 2021 (second survey). The first one was related to the impact of COVID-19 and the most frequently reported symptoms. The second one was superimposed on the previous one, taking into account some additional aspects in the management of disease. Results A total of 99 pediatricians participated in the first survey and 267 in the second one. The first survey showed that, asthma and allergic rhinoconjunctivitis prevalence was mostly between 0 and 20% throughout the country. The second survey showed a lower prevalence of both diseases nationwide in comparison to the first one. Comparing the two surveys, statistically significant differences were reported only in the distribution of asthma prevalence in Southern Italy while no differences were highlighted in the North and in the Center. Finally regarding allergic rhinoconjunctivitis prevalence, no differences were noticed nationwide. Conclusions Allergic rhinoconjunctivitis and asthma, if under control, did not represent risk factors for the susceptibility to SARS CoV2. Therefore, it is strongly recommended to continue therapies during COVID-19 outbreak, according to the international guidelines. However, being COVID-19 a new disease, actual knowledge will undergo continuous improvements over time.

Prevalence of Asthma and Its Associating Environmental Factors among 6–12-Year-Old Schoolchildren in a Metropolitan Environment—A Cross-Sectional, Questionnaire-Based Study

We aimed to evaluate the prevalence of asthma and its associating environmental factors within a 6–12-year-old population. A cross-sectional, questionnaire-based study was conducted in primary schools located in the capital of Hungary; 3836 eligible parent-reported questionnaires were evaluated. Besides the International Study of Asthma and Allergies in Childhood (ISAAC) phase three core questions for asthma, the survey also assessed various potential risk factors. We introduced the umbrella term cumulative asthma as the union of physician-diagnosed asthma and current wheezing to estimate the lifetime prevalence of asthma. Current wheezing and physician-diagnosed asthma showed a frequency of 9.5% and 6.3%, respectively. They contributed to a cumulative asthma prevalence of 12.6% among the sampled population, with a girl-boy percentage of 37.4% to 62.6%. Air-pollution and weedy areas were associated with greater risk for asthma, while a suburban residence showed lesser odds. Indoor smoking, visible mold, and keeping a dog were defined as risk factors for asthma, while the presence of plants in the bedroom and pet rodents were associated with lower odds ratios. The consumption of fast food, beverages containing additives and margarine were significantly higher in asthmatics, while we found frequent sport activity and cereal intake associated with lower odds ratios for asthma. In this urban environment, we identified an increased asthma prevalence compared to some previously published studies, but the cross-sectional design and the different methodology did not permit us to draw timeframe-dependent conclusions.

Role of Sex Hormones at Different Physiobiological Conditions and Therapeutic Potential in MBD2 Mediated Severe Asthma

Sex hormone has become a “hot topic” to evaluate the hormonal therapeutic potential in severe asthma. Th17 cell is one of the main influencing factors involved in the pathogenesis of severe asthma, hence also called as kernel of severe asthma, and Th17 subtype of non-T2 asthma is less responsive (resistance) to inhaled corticosteroid (ICS), so severe in nature. Methyl-CpG binding domain protein 2 (MBD2) is overexpressed and regulates the Th17 differentiation, showing the possibility of therapeutic target in treating Th17 mediated severe asthma. Sex hormone fluctuates at the different physiobiological conditions of the human body and affects the asthma pathobiology showing its role in asthma prevalence, severity, remission, and therapy. This review briefly overviews the sex hormones, their influence in asthma at the different physiobiological conditions of human body, and MBD2 severe asthma connection with the possible therapeutic potential of sex steroids in MBD2 mediated Th17 predominant severe asthma. Male sex hormone tends to show a beneficial effect and possibly downregulates the expression of Th17 cells via regulating MBD2 through a mechanism distinct from corticosteroid treatment and guides us towards discovery of new therapeutic agent, reduces the asthma-related complications, and promotes long-term survival by lowering the risk of therapy-resistant issues of old age severe asthma.

Socioeconomic status, lifestyle factors and asthma prevalence: results from a population-based study in Sweden

Aim: To examine differences in the prevalence of self-reported diagnosed asthma by socioeconomic status and the contribution of lifestyle factors to these differences. Methods: The study was based on 28,531 persons aged 18 years or older who answered a survey questionnaire sent to a random population sample in mid-Sweden in 2017. The overall response rate was 44%. Socioeconomic status was measured with educational level and economic difficulties, and lifestyle factors with physical activity, smoking, snuff use, risk-drinking of alcohol and obesity. The associations between socioeconomic status and asthma were analysed using multivariate logistic regression. Results: The overall asthma prevalence was 9% among women and 7% in men and decreased with increasing age. Educational level was not independently associated with asthma, but a statistically significant odds ratio (with 95% confidence intervals) for the prevalence of asthma was observed for economic difficulties 1.5 (1.3–1.7). Also, physical inactivity 1.2 (1.1–1.3) and obesity 1.6 (1.4–1.8) were associated with increased asthma prevalence. Smoking and risk-drinking were not statistically significantly associated with asthma whereas snuff users had a higher prevalence of asthma among women. Adjusting for lifestyle factors did not affect the association between socioeconomic status and asthma. Conclusions: In this population-based study, self-reported diagnosed asthma was independently associated with economic difficulties but not with educational level. Lifestyle factors did not explain the association between economic difficulties and asthma prevalence. This applies to both men and women as well as younger and older age groups.

Trend of asthma prevalence among children based on regional urbanization level in Japan; 2006–2019

Although it has been known that the prevalence of asthma tends to be higher among children in the metropolitan areas of Japan, trends of the prevalence with respect to the regional urbanization level has not been investigated in recent years. We investigated trends in the prevalence of asthma among children and air pollutant concentrations by regional urbanization levels using data from the School Health Statistics Survey in Japan from 2006 to 2019. We calculated the age-standardized prevalence of asthma for each year, gender, regional urbanization level, and annual percent change (APC). In addition, the slope index of inequality (SII) and relative index of inequality (RII) were calculated for evaluating disparity in age-standardized asthma prevalence depending on regional urbanization levels. Moreover, we calculated the mean of the annual average values by regional urbanization levels for sulfur dioxide (SO2), nitrogen dioxide (NO2), suspended particulate matter (SPM), carbon monoxide (CO), and photochemical oxidant (Ox) from 2006 to 2018. We found that the age-standardized prevalence significantly decreased in the periods in the metropolis for males and females, and the degree of the decrease was largest in the metropolis. Conversely, the age-standardized prevalence increased in towns and villages, and the APC was greater than zero. In addition, both the SII and RII showed significant decreasing trends in the study period, and the regional disparity shrank over the years. Moreover, concentrations of the air pollutants were highest in the metropolis throughout the years except for Ox, whereas the difference in the concentrations of NO2, SPM, and CO decreased between the metropolis and the other areas over the years. In conclusion, disparity in asthma prevalence depending on regional urbanization level decreased from 2006 to 2019, and there is a possibility that regional difference in trend of the air pollutants is related to the result.

Targeted analysis of genomic regions enriched in African ancestry reveals novel classical HLA alleles associated with asthma in Southwestern Europeans

Despite asthma has a considerable genetic component, an important proportion of genetic risks remain unknown, especially for non-European populations. Canary Islanders have the largest African genetic ancestry observed among Southwestern Europeans and the highest asthma prevalence in Spain. Here we examined broad chromosomal regions previously associated with an excess of African genetic ancestry in Canary Islanders, with the aim of identifying novel risk variants associated with asthma susceptibility. In a two-stage cases-control study, we revealed a variant within HLA-DQB1 significantly associated with asthma risk (rs1049213, meta-analysis p = 1.30 × 10–7, OR [95% CI] = 1.74 [1.41–2.13]) previously associated with asthma and broad allergic phenotype. Subsequent fine-mapping analyses of classical HLA alleles revealed a novel allele significantly associated with asthma protection (HLA-DQA1*01:02, meta-analysis p = 3.98 × 10–4, OR [95% CI] = 0.64 [0.50–0.82]) that had been linked to infectious and autoimmune diseases, and peanut allergy. HLA haplotype analyses revealed a novel haplotype DQA1*01:02-DQB1*06:04 conferring asthma protection (meta-analysis p = 4.71 × 10–4, OR [95% CI] = 0.47 [0.29– 0.73]).

BCG Vaccination in Early Childhood and Risk of Atopic Disease: A Systematic Review and Meta-Analysis

Background. Several large-scale studies suggest that Bacille Calmette–Guerin (BCG) vaccination in early childhood may reduce the risk of atopic diseases, but the findings remain controversial. Here, we aimed to investigate the potential correlation between early childhood BCG vaccination and the risk of developing atopic diseases. Methods. Eligible studies published on PubMed, EMBASE, and Cochrane CENTRAL were systematically sourced from 1950 to July 2021. Studies with over 100 participants and focusing on the association between BCG vaccine and atopic diseases including eczema, asthma, and rhinitis were included. Preliminary assessment of methods, interventions, outcomes, and study quality was performed by two independent investigators. Odds ratio (OR) with 95% confidence interval (CI) was calculated. Random effects of the meta-analysis were performed to define pooled estimates of the effects. Results. Twenty studies with a total of 222,928 participants were selected. The quantitative analysis revealed that administering BCG vaccine in early childhood reduced the risk of developing asthma significantly (OR 0.77, 95% CI 0.63 to 0.93), indicating a protective efficacy of 23% against asthma development among vaccinated children. However, early administration of BCG vaccine did not significantly reduce the risk of developing eczema (OR 0.94, 95% CI 0.76 to 1.16) and rhinitis (OR 0.99, 95% CI 0.81 to 1.21). Further analysis revealed that the effect of BCG vaccination on asthma prevalence was significant especially in developed countries (OR 0.73, 95% CI 0.58 to 0.92). Conclusion. BCG vaccination in early childhood is associated with reduced risk of atopic disease, especially in developed countries.