Frequency Of Asthma Exacerbations Research Articles

Frequency of Asthma Exacerbations and Upper Respiratory Tract Infections Among Adults With Asthma According to Vaccination Status: Does the annual influenza vaccine have a protective effect?

Annual influenza vaccinations are recommended for asthma patients to prevent seasonal influenza and influenza-triggered asthma exacerbations. However, data on the beneficial effect of this vaccine on the frequency of asthma exacerbations are conflicting. Therefore, this study aimed to assess the effectiveness of the influenza vaccine in terms of reducing the frequency of asthma-related exacerbations and upper respiratory tract infections among adult patients with asthma. This retrospective cohort study was performed from January to December 2018 in Muscat Governorate, Oman. A total of 466 patients attending 9 randomly selected primary health centres in Muscat Governorate were enrolled in the study and followed up for one year post vaccination. Most of the patients were female (70.6%) and had moderate persistent asthma (42.9%). There were 203 patients (43.6%) in the vaccinated group and 263 patients (56.4%) in the non-vaccinated group. A proportion of patients in each group had allergic rhinitis (28.6% and 25.5%, respectively). The frequency of upper respiratory tract infections over the one-year follow-up period was significantly lower in the vaccinated group than in the non-vaccinated group (37.9% versus 73%; relative risk [RR]: 2.299; 95% confidence interval [CI]: 1.834-2.882; P <0.001); however, there was no significant difference in terms of the frequency of asthma exacerbations (41.9% versus 45.2%; RR: 0.925; 95% CI: 0.750-1.141; P >0.050). The influenza vaccine significantly reduces the frequency of upper respiratory tract infections over the following year. However, it does not significantly reduce the frequency of asthma exacerbations among Omani adults with asthma. Further studies are recommended to support the protective effect of the vaccine in this regard.

Direct comparative study of the effectiveness of mepolizumab and dupilumab in patients with severe non-allergic eosinophilic asthma

Introduction. Biologics for severe asthma (SA) treatment are widely used in real clinical practice. But there are very few direct comparative studies at the moment.Aim. To compare mepolizumab and dupilumab effectiveness in patients with non-allergic eosinophilic SA in real clinical practice using regional register of Sverdlovsk region.Materials and methods. The data of patients with non-allergic eosinophilic SA treated with dupilumab (n = 23) and mepolizumab (n = 19) were analyzed. Therapy effectiveness was determined according to BARS and patients’ proportion who achieved asthma remission, dynamics of ACT, AQLQ, FEV1, blood eosinophils, frequency of short-acting bronchodilators use and systemic glucocorticosteroids (SGCS) demand, frequency of asthma exacerbations and hospitalizations.Results. Within 12 months of targeted therapy a good response to biologics according to BARS in 77.8% of patients on dupilumab and in 82.4% of patients on mepolizumab (p = 1.000) was revealed. Remission of SA (without FEV1) was achieved in 62.5% of patients in dupilumab group and in 68.8% of patients in mepolizumab group (p = 1.000). Remission of SA (with FEV1) was achieved in 43.8% of patients on dupilumab and in 56.2% of patients on mepolizumab (p = 0.724). There were statistically significant improvements for all separately analyzed indicators in each observation group. Statistically significant differences after a year of therapy between groups were recorded in terms of eosinophil levels (p &lt; 0.001) and nasal symptoms assessed using the SNOT-22 questionnaire (p = 0.048) in favour of mepolizumab.Conclusions. Patients with non-allergic eosinophilic SA have good response to both dupilumab and mepolizumab. The drugs equally improve disease control, life quality, reduce the need for relievers and SGCS, show a similar safety level.

Exacerbations Among Patients With Asthma Are Largely Dependent on the Presence of Multimorbidity.

Comorbidities can influence asthma control and promote asthma exacerbations (AEs). However, the impact of multimorbidity in AEs, assessed based on long-term follow-up of patients with asthma of different degrees of severity, has received little attention in real-life conditions. To describe the epidemiological and clinical characteristics and predictors of AEs in patients who had presented at least 1 AE in the previous year in the MEchanism of Genesis and Evolution of Asthma (MEGA) cohort. The work-up included a detailed clinical examination, pulmonary function testing, fractional exhaled nitric oxide (FeNO), blood counts, induced sputum, skin prick-tests, asthma questionnaires, and assessment of multimorbidity. The number of moderate-severe AEs in the preceding year was registered for each patient. The study population comprised 486 patients with asthma (23.7% mild, 35% moderate, 41.3% severe). Disease remained uncontrolled in 41.9%, and 47.3% presented ≥1 moderate-severe AE, with a mean (SD) annual exacerbation rate of 0.47 (0.91) vs 2.11 (2.82) in mild and severe asthma, respectively. Comorbidity was detected in 56.4% (66.6% among those with severe asthma). Bronchiectasis, chronic rhinosinusitis with nasal polyps, atopy, psychiatric illnesses, hyperlipidemia, and hypertension were significantly associated with AEs. No associations were found for FeNO, blood eosinophils, or total serum IgE. Sputum eosinophilia and a high-T2 inflammatory pattern were significantly associated with AEs. Multivariable regression analysis showed a significant association with asthma severity, uncontrolled disease, and low prebronchodilator FEV1/FVC. Our study revealed a high frequency of AE in the MEGA cohort. This was strongly associated with multimorbidity, asthma severity, poor asthma control, airflow obstruction, higher sputum eosinophils, and a very high-T2 inflammatory pattern.

Frequency of exacerbation and degree of required asthma medication can characterize childhood longitudinal asthma trajectories

BackgroundTo the best of our knowledge, there have been no investigations of longitudinal asthma trajectories based on asthma exacerbation frequency and medications required for asthma control in children. ObjectiveTo investigate longitudinal asthma trajectories based on the exacerbation frequency throughout childhood and asthma medication ranks. MethodsA total of 531 children aged 7 to 10 years were enrolled from the Korean childhood Asthma Study. Required asthma medications for control of asthma from 6 to 12 years of age and asthma exacerbation frequency from birth to 12 years of age were obtained from the Korean National Health Insurance System database. Longitudinal asthma trajectories were identified on the basis of asthma exacerbation frequency and asthma medication ranks. ResultsFour asthma clusters were identified: lesser exacerbation with low-step treatment (8.1%), lesser exacerbations with middle-step treatment (30.7%), highly frequent exacerbations in early childhood with small-airway dysfunction (5.7%), and frequent exacerbations with high-step treatment (55.6%). The frequent exacerbations with high-step treatment cluster were characterized by a high prevalence of male sex, increased blood eosinophil (counts) with fractional exhaled nitric oxide, and high prevalence of comorbidities. The highly frequent exacerbation in early childhood with small-airway dysfunction cluster was characterized by recurrent wheeze in preschool age, with high prevalence of acute bronchiolitis in infancy and a greater number of family members with small-airway dysfunction at school age. ConclusionThe present study identified 4 longitudinal asthma trajectories on the basis of the frequency of asthma exacerbation and asthma medication ranks. These results would help clarify the heterogeneities and pathophysiologies of childhood asthma.

Oropharyngeal Microbiota Clusters in Children with Asthma or Wheeze Associate with Allergy, Blood Transcriptomic Immune Pathways, and Exacerbation Risk.

Rationale: Children with preschool wheezing or school-age asthma are reported to have airway microbial imbalances. Objectives: To identify clusters in children with asthma or wheezing using oropharyngeal microbiota profiles. Methods: Oropharyngeal swabs from the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes) pediatric asthma or wheezing cohort were characterized using 16S ribosomal RNA gene sequencing, and unsupervised hierarchical clustering was performed on the Bray-Curtis β-diversity. Enrichment scores of the Molecular Signatures Database hallmark gene sets were computed from the blood transcriptome using gene set variation analysis. Children with severe asthma or severe wheezing were followed up for 12-18 months, with assessment of the frequency of exacerbations. Measurements and Main Results: Oropharyngeal samples from 241 children (age range, 1-17 years; 40% female) revealed four taxa-driven clusters dominated by Streptococcus, Veillonella, Rothia, and Haemophilus. The clusters showed significant differences in atopic dermatitis, grass pollen sensitization, FEV1% predicted after salbutamol, and annual asthma exacerbation frequency during follow-up. The Veillonella cluster was the most allergic and included the highest percentage of children with two or more exacerbations per year during follow-up. The oropharyngeal clusters were different in the enrichment scores of TGF-β (transforming growth factor-β) (highest in the Veillonella cluster) and Wnt/β-catenin signaling (highest in the Haemophilus cluster) transcriptomic pathways in blood (all q values <0.05). Conclusions: Analysis of the oropharyngeal microbiota of children with asthma or wheezing identified four clusters with distinct clinical characteristics (phenotypes) that associate with risk for exacerbation and transcriptomic pathways involved in airway remodeling. This suggests that further exploration of the oropharyngeal microbiota may lead to novel pathophysiologic insights and potentially new treatment approaches.

Endocrine-disrupting chemical exposure augments neutrophilic inflammation in severe asthma through the autophagy pathway.

Corticosteroid resistance, progressive lung function decline, and frequent asthma exacerbations are the hallmarks of neutrophilic asthma (NA). However, the potential contributors and their mechanisms of NA aggravation have not yet been fully clarified. This study was conducted to assess the precise mechanism and inflammatory effects of endocrine-disrupting chemicals using mono-n-butyl phthalate (MnBP) on an NA model. BALB/c mice from normal control and LPS/OVA-induced NA groups were treated with or without MnBP. The effects of MnBP on the airway epithelial cells (AECs), macrophages (Mφ), and neutrophils were investigated in vitro and in vivo. NA mice exposed to MnBP had significantly increased airway hyperresponsiveness, total and neutrophil cell counts in the bronchoalveolar lavage fluid, and the percentage of M1Mφ in the lung tissues compared to those non-exposed to MnBP. In in vitro study, MnBP induced the human neutrophil activation to release neutrophil DNA extracellular traps, Mφ polarizing toward M1Mφ, and AEC damage. Treatment with hydroxychloroquine (an autophagy inhibitor) reduced the effects of MnBP in vivo and in vitro. The results of our study suggest that MnBP exposure may increase the risk of neutrophilic inflammation in severe asthma and autophagy pathway-targeted therapeutics can help control MnBP-induced harmful effects in asthma.

Airway transcriptome networks identify susceptibility to frequent asthma exacerbations in children

Frequent asthma exacerbators, defined as those experiencing more than 1 hospitalization in a year for an asthma exacerbation, represent an important subgroup of individuals with asthma. However, this group remains poorly defined and understudied in children. Our aim was to determine the molecular mechanisms underlying asthma pathogenesis and exacerbation frequency. We performed RNA sequencing of upper airway cells from both frequent and nonfrequent exacerbators enrolled in the Ohio Pediatric Asthma Repository. Through molecular network analysis, we found that nonfrequent exacerbators display an increase in modules enriched for immune system processes, including type 2 inflammation and response to infection. In contrast, frequent exacerbators showed expression of modules enriched for nervous system processes, such as synaptic formation and axonal outgrowth. These data suggest that the upper airway of frequent exacerbators undergoes peripheral nervous system remodeling, representing a novel mechanism underlying pediatric asthma exacerbation.

Risk Factors for Poor Asthma Control in an Urban Pediatric Population During the COVID-19 Pandemic

During the COVID-19 pandemic, better asthma control led to the decline in hospital utilization rates for pediatric asthma. However, in Detroit, some children continued to have frequent asthma exacerbations despite a decrease in common triggers. We hypothesized that environmental and socioeconomic factors may be risk factors for asthma exacerbations and poor asthma control

Airway transcriptome networks identify susceptibility to frequent asthma exacerbations in children

Epidemiologic evidence has identified an important, yet understudied, group of pediatric asthmatics comprised of those who experience >1 hospitalization for an exacerbation per year. The goal of this study is to characterize the nasal transcriptomic changes which characterize this important subgroup.

Safety of Live Attenuated Influenza Vaccine in Children With Asthma

Current recommendations caution against the use of live attenuated influenza vaccine (LAIV4) in children ≥5 years of age with asthma. The primary objective was to compare the proportion of participants with asthma exacerbations postimmunization among children with persistent asthma who received LAIV4 versus quadrivalent inactivated influenza vaccine (IIV4).Participants were enrolled over 2 influenza seasons from October 2018 to December 2019 at 3 trial sites (Vanderbilt University Medical Center, Nashville, TN, Duke University Health System, Durham, NC, and Cincinnati Children’s Hospital Medical Center, Cincinnati, OH). Children 5 to 17 years of age with a current diagnosis of persistent asthma (on a daily controller) were considered eligible for the study.Participants were randomly assigned 1:1 to receive IIV4 or LAIV4 and monitored for asthma symptoms, exacerbations, changes in peak expiratory flow rate (PEFR), and changes in the asthma control test for 42 days after vaccination.142 participants were included in the per-protocol analysis. Within 42 days postvaccination, 18 of 142 (13%) experienced an asthma exacerbation: 8 of 74 (11%) in the LAIV4 group versus 10 of 68 (15%) in the IIV4 group (LAIV4-IIV4 = −0.0390 [90% confidence interval −0.1453 to 0.0674]), meeting the bounds for noninferiority. When adjusted for asthma severity, LAIV4 remained noninferior to IIV4. Vaccine reactogenicity was similar between groups.LAIV4 was not associated with increased frequency of asthma exacerbations, an increase in asthma-related symptoms, or a decrease in PEFR compared with IIV4 among children aged 5 to 17 years with asthma.Current Centers for Disease Control and Prevention guidelines advise taking precautions when using the nasal spray flu vaccine in people with asthma 5 years and older. However, this randomized, controlled trial in 5 to 17-year-old children with persistent asthma showed that LAIV4 was no more likely to be associated with asthma exacerbations than IIV4. Historical context also is informative in relatively low enrollment, despite recruitment over 2 flu seasons. There was reduced provider and parental confidence in LAIV4 because of the Centers for Disease Control and Prevention recommendations against use of the nasal spray vaccine for the 2016 to 2017 and 2017 to 2018 seasons because of studies showing that the nasal spray vaccine was less effective than inactivated flu vaccines against the 2009 pandemic H1N1 viruses. LAIV was recommended again in the 2018 to 2019 influenza season, but there have been no effectiveness estimates in the United States. Data from other countries have demonstrated protection from LAIV to be similar to that of the inactivated flu vaccine in children. Nevertheless, these data support reexamining precautions to using LAIV4 in children with asthma, which could be particularly important during influenza pandemics, at times when IIV4 supplies are limited or for children with significant needle aversions.URL: www.pediatrics.org/cgi/doi/10.1542/peds.10.1542/peds.2021-055432

Impact of Mepolizumab on Exacerbations in the US Medicare Population

Asthma is a common chronic respiratory disorder associated with significant disease and economic burden. Mepolizumab is an anti-IL-5 mAb approved for use as an add-on treatment in patients with severe eosinophilic asthma. To assess the impact of mepolizumab initiation on asthma exacerbation frequency, oral corticosteroid (OCS) use, and asthma exacerbation-related costs in a US Medicare population. This was a retrospective cohort study of mepolizumab claims from patients with asthma in the Centers for Medicare and Medicaid Services Medicare database carried out between January 2016 and December 2018. The index date (first claim for mepolizumab) was required to occur between January and December 2017. The baseline and follow-up periods were the 12 months before and 12 months after the index, respectively. Outcomes included changes in the proportion of patients experiencing exacerbations (primary), OCS use (secondary), and asthma exacerbation-related costs during the baseline and follow-up periods. The study identified 1,278 patients (mean age, 67.9 years; 65% female) with one or more prescription or administration claim for mepolizumab who were eligible for study inclusion. There was a significant relative reduction in the proportion of patients with an asthma exacerbation (27%; P < .0001) in the follow-up versus baseline period. Similarly, a lower proportion of patients received OCS for asthma (16% relative reduction; P < .0001), fewer patients were chronic OCS users (5 mg/day or more; 48% relative reduction; P < .0001), and there was a significant decrease in asthma exacerbation-related costs (total reduction, $888; P= .0002) during the follow-up versus the baseline period. Mepolizumab reduced exacerbations, OCS use, and exacerbation-related healthcare costs in a US Medicare population, confirming its benefits in this specific population with severe asthma.

Bronchial asthma: focus on adherence to inhaled therapy

The rising incidence of the disease, severe exacerbations, and risks of death make bronchial asthma an urgent public health problem. Effective control of the disease is recognised as the main goal of modern therapy. Studies conducted in our country and abroad show a low level of bronchial asthma control in most patients. An important condition for achieving control is the patient’s adherence to therapy. Higher adherence rates and, consequently, improved quality of life have been recorded in patients receiving baseline therapy, which involves a single inhalation per day. The long-acting combination powder inhaler fluticasone furoate/ vilanterol is one of the modern drugs with proven efficacy and safety. The drug has been shown to significantly improve lung function and reduce the frequency of asthma exacerbations. Of particular note are the results of a randomised clinical trial carried out in real (everyday) clinical practice. This form of study is non-selective, i.e. it includes a wide group of patients regardless of severity, comorbidities and lifestyle. This approach was used in a study called the Salford Lung Study. It included patients with bronchial asthma who were receiving ongoing maintenance therapy with inhaled glucocorticosteroids or combinations thereof from primary care centres. The study lasted for 52 weeks. The first group consisted of patients treated with the fluticasone furoate/vilanterol combination. Group 2 patients continued to receive baseline therapy. The best response was observed with the fluticasone furoate/vilanterol combination. It was maintained in all subgroups analyzed and was independent of smoking status, baseline control reduction, and number of severe exacerbations in the past year. Adherence to treatment is improved by a single dose and a convenient, intuitive means of delivery. The inhaler requires minimal coordination, is activated with a single movement and has an easy-to-understand dose counter.

Efficacy of omalizumab in the treatment of eosinophilic granulomatous polyangiitis with asthma as the first symptom

Objective: To investigate the efficacy, and safety of omalizumab in the treatment of eosinophilic granulomatous with polyangiitis (EGPA) with asthma as the first symptom. Method: The clinical characteristics of 22 EGPA patients with asthma as the first symptom treated with omalizumab in the First Affiliated Hospital of Guangzhou Medical University from March 2018 to December 2020 were retrospectively analyzed. The asthma control test (ACT) score, the frequency of asthma exacerbation (AE), the Birmingham Vasculitis Activity Score (BVAS), the variation rate of peak expiratory flow (PEF), the percentage of PEF to predicted value of PEF (PEFpred%), the percentage of forced expiratory volume in first second (FEV1) to predicted value of FEV1 (FEV1pred%), the dosage of oral corticosteroid (OCS) and other clinical data [M(Q1, Q3)] were collected before and after treatment, to observe the efficacy and adverse reactions of omalizumab. Results: There were 22 subjects recruited in this study. The median age was 42 (22-70) years. Eleven of the patients were males. After treated with omalizumab for 4 months, there were 68.2%(15/21) of patients who responded to the treatment. In the response group (n=15), the patients' ACT score increased from 19.0 (16.5, 21.0) to 23.0 (21.5, 24.0) (P=0.001). The frequency of AE decreased from 0.7 (0.3, 1.0) to 0 (0, 0.7) per four mouths (P<0.001). The BVAS decreased from 4.0 (2.0, 6.0) to 2.0 (2.0, 4.0) (P=0.007). The variation rate of PEF decreased from 18.8% (14.0%, 27.7%) to 9.2% (6.8%, 11.9%) (P=0.007). The PEFpred% increased from 80.8% (73.5%, 90.7%) to 100.5% (79.4%, 114.0%) (P=0.005). The maintenance dosage of OCS reduced from 15.0 (10.0, 20.0) mg/d to 8.8 (5.0, 10.0) mg/d (P=0.005). The level of baseline eosinophil in peripheral blood of patients in non-response group was higher than that in response group [11.4% (9.2%, 22.6%) vs 3.4% (1.1%, 6.5%), P<0.05]. A total of 190 injections were performed in 22 patients, and only 4 patients (2.1%) had adverse reactions after a single injection of omalizumab, such as dizziness, swelling of injection site and pruritus. The adverse reactions were tolerable. Conclusions: Omalizumab has certain curative effect on EGPA, can reduce asthmatic symptoms and OCS maintenance dosage, and has a good safety profile. The rate of response to the treatment is higher in patients with mild eosinophilic inflammation.

Exposure to Cigarette Smoke and Daily Physical Activity Associated with Asthma

Background: Asthmatic sufferers complain of sudden relapse when performing daily activities. exposure to cigarette smoke makes asthmatics where the longer the exposure is experienced by the patient, the more frequent asthma exacerbations are experienced. For people with asthma, avoiding excessive physical activity and exposure to cigarette smoke is very necessary to prevent recurrence of symptoms. So it is necessary to control the level of asthma, which is influenced by factors that trigger asthma recurrence. Aim: The purpose of the study was to determine the relationship between daily physical activity and exposure to cigarette smoke on asthma recurrence in asthmatic patients Methods: This type of research uses observational analytic using a cross sectional approach. Sampling in this study using purposive sampling obtained the number of respondents 358 with a vulnerable age of 18-45 years. This research was conducted for 6 months. The measuring instrument for exposure to cigarette smoke uses a questionnaire containing the categories of exposure to cigarette smoke less than 1 hour, exposure to cigarette smoke 1-4 hours and exposure to cigarette smoke more than 4 hours. Physical activity measurement tool using the International Physical Activity Questionnaire (IPAQ). Asthma recurrence was measured by using a questionnaire that refers to the Asthma Control Test (ACT). The research procedure was carried out by researchers by ensuring that respondents were in good health and signed the informed consent provided. Data analysis using Chi-Square test. Result: The results of the Chi Square test with a significance value of = 0.05, p value = 0.000, which means p &lt; then there is a relationship between daily physical activity and exposure to cigarette smoke on asthma recurrence in asthmatic patients. Conclusions: There is a relationship between exposure to cigarette smoke and daily physical activity on asthma relapse in asthmatic patients. It is expected that asthmatics should avoid triggering factors for asthma relapse to achieve controlled asthma levels.

Impact of mepolizumab in patients with high-burden severe asthma within a managed care population

Objective To evaluate the real-world impact of mepolizumab on the incidence of asthma exacerbations, oral corticosteroid (OCS) use and asthma exacerbation-related costs in patients with high-burden severe asthma. Methods This was a retrospective study of the MarketScan Commercial and Medicare Databases in patients with high-burden severe asthma (≥80th percentile of total healthcare expenditure and/or significant comorbidity burden). Patients were ≥12 years of age upon mepolizumab initiation (index date November 1, 2015–December 31, 2018) and had ≥2 mepolizumab administrations during the 6 months post-index. Asthma exacerbation frequency (primary outcome), use of OCS (secondary outcome), and asthma exacerbation-related costs (exploratory outcome) were assessed during the 12 months pre-index (baseline) and post-index (follow-up). Results In total, 281 patients were analyzed. Mepolizumab significantly reduced the proportion of patients with any asthma exacerbation (P < 0.001) or exacerbations requiring hospitalization (P = 0.004) in the follow-up versus baseline period. The mean number of exacerbations decreased from 2.5 to 1.5 events/patient/year (relative reduction: 40.0%; P < 0.001). The proportion of patients with ≥1 OCS claim also decreased significantly from 94.0% to 81.9% (relative reduction: 12.9%; P < 0.001), corresponding to a decrease from 6.6 to 4.7 claims/person/year (P < 0.001). Of the 264 patients with ≥1 OCS claim during baseline, 191 (72.3%) showed a decrease in mean daily OCS use by ≥50% in 117 patients (61.3%). Total asthma exacerbation-related costs were significantly lower after mepolizumab was initiated (P < 0.001). Conclusions Mepolizumab reduced exacerbation frequency, OCS use and asthma exacerbation-related costs in patients with high-cost severe asthma. Mepolizumab provides real-world benefits to patients, healthcare systems and payers.

Determinants of asthma control and exacerbations in moderate to severe asthma

Determinants of asthma control and exacerbations in moderate to severe asthma

A genome-wide association study on frequent exacerbation of asthma depending on smoking status

PurposeExacerbation of asthma is affected by genetic and environmental factors, but little is known about genetic differences according to smoking status. We evaluated genetic factors associated with asthma exacerbations in smokers and non-smokers, and identified the underlying mechanisms via a genome-wide association study (GWAS) and gene-level analyses according to smoking status. MethodsA GWAS on the annual frequency of asthma exacerbations was performed in 420 non-smoking and 188 smoking patients with asthma. Gene-wise associations were analyzed by Multi-marker Analysis of GenoMic Annotation (MAGMA); Gene Ontology analysis was also performed. ResultsIn the non-smoker group, 189 genes showed significant associations with the annual frequency of exacerbations (permutated P < 0.001). The top 10 genes were F5, KLRC1, TAFA2, AIRE, IER3IP1, CHMP2A, IL31RA, ZNF497, DNMT3L, and MYT1L (permutated P = 1.0 × 10−4 – 1.7 × 10−4). In smoking asthmatics, 140 genes—including KANK1, ZMYND12, ZNF34, ANXA11, VAV2, CCDC150, CCDC30, CATSPER3, ARMH2, and MPRIP (permutated P = 9.23 × 10−5 – 5.50 × 10−4)—were associated with asthma exacerbations. Genes participating in the innate immune response in non-smokers and the regulation of cell fate (including apoptosis) in smokers were the major causal genes of asthma exacerbation (FDR q < 0.05). ConclusionsOur findings not only suggest novel genetic candidates for predicting asthma exacerbations, but also that asthma treatment strategies should take into account smoking behavior.

Treatment Resistance in Severe Asthma Patients With a Combination of High Fraction of Exhaled Nitric Oxide and Low Blood Eosinophil Counts.

Background: Combining a fraction of exhaled nitric oxide (FeNO) and blood eosinophil count (B-EOS) may be a useful strategy for administration of biologics such as anti-IgE or anti-IL-5 to patients with type 2 inflammatory-predominant severe asthma and is important to be elucidated considering the increasing use of biologics. Methods: This cross-sectional study analyzed the clinical data from 114 adult patients with severe asthma, who were treated at Saitama Medical University Hospital. The eligible patients were stratified into four subgroups defined by thresholds of FeNO and blood eosinophil (B-EOS) counts to detect sputum eosinophilia, using the receiver operating characteristic curve analysis. A total of 75 patients with optimal samples were stratified into four subtypes defined by thresholds of sputum eosinophilia and neutrophilia. Clinical characteristics, pattern of biologics, and distribution of sputum subtypes were analyzed in the stratified subclasses according to the FeNO and B-EOS thresholds. The asthma exacerbation (AE)-free time of the FeNO/B-EOS subgroups and any biologics treatment including anti-IgE or anti-IL-5 use were examined using the Kaplan–Meier method. The hazard ratios (HRs) for AE-free time were examined using the Cox proportional hazard model. Results: The optimal cutoff values for prediction of sputum eosinophilia were defined as ≥2.7% wherein for FeNO as ≥27 ppb and B-EOS as ≥265/µL were considered. The high-FeNO subgroups showed significant high total IgE, compared with the low FeNO. The high-FeNO/high-B-EOS and the high-FeNO/low-B-EOS subgroups showed the largest prevalence of mepolizumab and benralizumab use among the other FeNO/B-EOS, respectively. The high-FeNO/low-B-EOS showed the largest frequency of AEs, high HR, and the shortest AE-free time, among the other FeNO/B-EOS. The sputum eosinophil-predominant subtype was the great majority in the high FeNO/high B-EOS. A diverse distribution of sputum leukocyte-predominant subtype was observed in the other FeNO/B-EOS. The subsequent AE-free time and its HR were comparable among the biologics use groups. Conclusion: The strategy of classifying severe asthma based on the combination of FeNO and B-EOS proposes particular refractory type 2 severe asthma and underlying airway inflammation as a feasible trait for optimal biologics use.

Blood miRNAs Are Linked to Frequent Asthma Exacerbations in Childhood Asthma and Adult COPD.

: RationaleMicroRNAs have been independently associated with asthma and COPD; however, it is unclear if microRNA associations will overlap when evaluating retrospective acute exacerbations. Objective: We hypothesized that peripheral blood microRNAs would be associated with retrospective acute asthma exacerbations in a pediatric asthma cohort and that such associations may also be relevant to acute COPD exacerbations. Methods: We conducted small-RNA sequencing on 374 whole-blood samples from children with asthma ages 6–14 years who participated in the Genetics of Asthma in Costa Rica Study (GACRS) and 450 current and former adult smokers with and without COPD who participated in the COPDGene study. Measurements and Main Results: After QC, we had 351 samples and 649 microRNAs for Differential Expression (DE) analysis between the frequent (n = 183) and no or infrequent exacerbation (n = 168) groups in GACRS. Fifteen upregulated miRs had odds ratios (OR) between 1.22 and 1.59 for a doubling of miR counts, while five downregulated miRs had ORs between 0.57 and 0.8. These were assessed for generalization in COPDGene, where three of the upregulated miRs (miR-532-3p, miR-296-5p, and miR-766-3p) and two of the downregulated miRs (miR-7-5p and miR-451b) replicated. Pathway enrichment analysis showed MAPK and PI3K-Akt signaling pathways were strongly enriched for target genes of DE miRNAs and miRNAs generalizing to COPD exacerbations, as well as infection response pathways to various pathogens. Conclusion: miRs (451b; 7-5p; 532-3p; 296-5p and 766-3p) associated with both childhood asthma and adult COPD exacerbations may play a vital role in airflow obstruction and exacerbations and point to shared genomic regulatory machinery underlying exacerbations in both diseases.

DO FAST/JUNK FOODS HAVE AN EFFECT ON ASTHMA IN CHILDREN

Certain types of food may increase or decrease the frequency of asthma exacerbations. The study is aimed at determining whether there is an association between consuming fast/junk foods and asthma. A well-adjusted, standardized questionnaire was used for the collection of information. This study is focused on finding a relationship between fast food intake and frequency and severity of asthma exacerbation rather than a causative relationship. This is a cross-sectional study done in the southern part of India in the state of Kerala. The correlation between fast food and asthma is established through a detailed analysis of the results. After adjusting for confounding variables like Environmental Tobacco Smoke (ETS) and allergens at home we were able to indicate that fast/junk food consumption is a risk factor for asthma symptom exacerbation in children.