Asthma Events Research Articles

Asthma and the risk of cardiac events among patients with long qt syndrome after age 40

BackgroundLimited data exist on the impact of asthma on long QT syndrome (LQTS) in middle-aged and older adults. ObjectiveThis study aimed to examine the association between asthma, β2-agonist treatment, and cardiac events (CEs) in LQTS patients over 40 years of age. MethodsThe risk of CEs (comprising syncope, aborted cardiac arrest, implantable cardioverter-defibrillator shock, or sudden cardiac death) from age 40 through 75 years, by the presence of asthma with and without treatment with a β2-agonist inhaler, was assessed among 1020 LQTS patients from the Rochester LQTS Registry. ResultsAmong 1020 LQTS patients, 162 (16%) had asthma by age 40 years or subsequent follow-up, with 63% treated with a β2-agonist inhaler. Patients with asthma vs no asthma had a higher cumulative rate of CEs from age 40 through 75 years (44% vs 26%, P < .001). Consistently, multivariate analysis showed that asthma was associated with a 2-fold (hazard ratio 1.97, P = .001) increased risk of CEs. Subgroup analysis showed that the association of asthma with CEs was consistent within risk subsets of LQTS patients, including QTc duration, syncope prior to age 40 years, β-blocker use, sex, and LQTS genotype (all P values for risk subset-by-asthma interaction >.10). Asthma patients with LQTS who were treated with a β2-agonist inhaler did not show an increased risk compared with those who were not treated (hazard ratio 1.02, P = .963). ConclusionThe presence of asthma is associated with increased risk of CEs among middle-aged and older patients with LQTS regardless of baseline risk factors or treatment with a β2-agonist inhaler.

β-Blockers and Asthma: Surprising findings from the FAERS database

Introductionβ-Blockers are essential for cardiovascular disease management but can induce respiratory issues, particularly with non-selective β-blockers. Their safety in asthmatic patients is debated. ObjectiveThis study investigates the link between different classes of β-blockers and the risk of asthma and asthma-like adverse events (AEs) using data from the Food and Drug Administration's Adverse Event Reporting System (FAERS). Methodsβ-Blockers were first reviewed according to European Society of Cardiology classification and then using the Vashistha and Kumar classification. The risk associated with different β-blocker classes was evaluated through disproportionality analysis using the reporting odds ratio (ROR). ResultsAmong 251,145 AEs reported for β-blockers, 4104 were asthma-related. Selective β1-blockers had a higher asthma risk signal (ROR: 1.15) compared to non-selective β-blockers (ROR: 0.90). α- and β-Blockers showed the lowest risk (ROR: 0.51). The Vashistha and Kumar classification detailed risk profiles for various β-blockers, highlighting differences even within the same class. Dual α- and β-blockers, hydrophilic, and lipophilic β-blockers posed lower asthma risks, while selective β1-blockers had higher risks regardless of intrinsic sympathomimetic activity. ConclusionAlthough the signals detected by disproportionality analysis are only candidate risks, the risk stratification resulting from our analysis highlights the need for cautious β-blocker selection in asthmatic patients or those predisposed to asthma. Furthermore, despite the limitations associated with the FAERS data, the study reveals significant variability in risk among different β-blocker classes, crucial for clinical decisions and patient management. Drugs like esmolol, metoprolol, nebivolol, and nadolol may be safer for asthmatic patients, whereas betaxolol, bisoprolol, timolol, and propranolol should be avoided.

Body Mass Index and the Risk of Adult-Onset Asthma: A Prospective Observational Study among 59,668 Middle-Aged Men and Women in Finland.

Introduction: Obesity, in addition to many other negative health consequences, affects pulmonary function and is a potential risk factor for asthma. Methods: We analyzed the association of body mass index (BMI) with incident asthma among 60,639 Finnish men and women aged 25 to 74 years who participated in a population-based chronic disease risk factor survey in 1972, 1977, 1982, 1987, 1992, 1997, 2002, 2007, or 2012. Data on lifestyle factors such as smoking and physical activity, as well as medical history, were obtained, and various physical measurements, including height and weight, were taken at baseline. Incident asthma events were ascertained from the National Social Insurance Institution's register data. The study cohorts were followed-up until the end of 2017 through registers. Results: During the follow-up, 4612 (14%) women and 2578 (9.3%) men developed asthma. The risk of asthma was analyzed in the following three BMI categories: <24.9 (reference category), 25-29.9 (overweight) and ≥30 kg/m2 (obesity). Hazard ratios (95% CI) were 1.34 (1.24-1.43) and 1.57 (1.44-1.71) in women and 1.25 (1.14-1.37) and 1.63 (1.44-1.83) in men. The observed association was independent of smoking, height and leisure-time physical activity. In women, 30.8% (19.2% in men) of the total asthma incidence was attributed to overweight and obesity. Conclusions: Overweight and obesity are important risk factors for asthma.

The Association between GLP-1 Receptor-Based Agonists and the Incidence of Asthma in Patients with Type 2 Diabetes and/or Obesity: A Meta-Analysis

ObjectiveRecent studies have indicated potential anti-inflammatory effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on asthma, which is often comorbid with type 2 diabetes mellitus (T2DM) and obesity. Therefore, we conducted a meta-analysis to assess the association between the administration of glucagon-like peptide-1 (GLP-1) receptor-based agonists and the incidence of asthma in patients with T2DM and/or obesity. MethodsPubMed, Web of Science, Embase, the Cochrane Central Register of Controlled Trials, and Clinicaltrial.gov were systematically searched from inception to July 2023. Randomized controlled trials (RCTs) of GLP-1 receptor-based agonists (GLP-1RA, GLP-1 based dual and triple receptor agonist) with reports of asthma events were included. Outcomes were computed as risk ratios (RR) using a fixedeffects model. ResultsOverall, 39 RCTs with a total of 85,755 participants were included. Compared to non-GLP-1 receptor-based agonist users, a trend of reduced risk of asthma was observed in patients with T2DM or obesity using GLP-1 receptor-based agonist treatments, although the difference was not statistically significant [RR = 0.91, 95% confidence interval (CI): 0.68 to 1.24]. Further Subgroup analyses indicated that the use of light-molecular-weight GLP-1RAs might be associated with a reduced the risk of asthma when compared with non-users (RR = 0.65, 95% CI: 0.43 to 0.99, P = 0.043). We also performed sensitivity analyses for participant characteristics, study design, drug structure, duration of action, and drug subtypes. However, no significant associations were observed. ConclusionCompared with non-users, a modest reduction in the incidence of asthma was observed in patients with T2DM or obesity using GLP-1 receptor-based agonist treatments. Further investigations are warranted to assess the association between GLP-1 receptor-based agonists and the risk of asthma.

Sex and age characteristics of thunderstorm asthma emergency department visits

Severe asthma has been shown to occur in the combined presence of high pollen and thunderstorm conditions, also known as ‘thunderstorm asthma.’ First studied as severe epidemic events, recent longitudinal work studied less dramatic but more frequent occurrences. We explore thunderstorm asthma-related emergency department visits in the Minneapolis-St. Paul metropolitan area and evaluated risk differences by sex and age. We define a thunderstorm asthma exposure event as the daily occurrence of 2 or more lightning strikes during high pollen periods, and use daily counts of asthma-related emergency department visits to estimate relative and absolute risk of severe asthma during thunderstorm asthma events for the full population and for sex and age subgroups. The overall population had a 1.06 (95 % CI: 1.02, 1.09) times higher risk of asthma-related ED visits during thunderstorm asthma events compared to days without thunderstorm asthma events. Children under 18 show no higher risk (RR 1.02; 95 % CI: 0.97 1.08), but adults 18–44 years (RR 1.08; 95 % CI: 1.02, 1.13) and 45 and up (RR 1.08; 95 % CI 1.02, 1.15) show higher relative risk. Absolute risk measures show similar patterns to the age and sex results, but age-sex subgroups show more variation in absolute vs relative risk. Our results support an association between ED visits and thunderstorm asthma and provide evidence of varying risks by sex across the life course. These differences in risk have implications for clinical treatment of this allergic type of asthma and for future research into this poorly recognized environmental exposure.Plain Language Summary: Recent research has highlighted the existence of Thunderstorm asthma events, a phenomenon in which pollen grains rupture in the conditions that occur with a thunderstorm, releasing sub-pollen particles that are capable of triggering severe asthma in susceptible populations. Where severe asthma is a disease that usually impacts children, we find in this study that asthma ED visits associated with thunderstorm asthma events more frequently impact adults, particularly males 18–44 and females 45 and up.

Association of systemic immune-inflammation index with asthma and asthma-related events: a cross-sectional NHANES-based study.

Asthma is associated with persistent airway inflammation, and numerous studies have investigated inflammatory markers causing asthma. However, the systemic immune-inflammation index (SII) is a novel inflammatory marker, with scarce research reporting on the correlation between SII and asthma and asthma-related events. The purpose of this study was to assess the relationship between SII and asthma and asthma-related events (including whether asthma is still present, asthma flare-ups in the past year, and asthma duration) using data from the National Health and Nutrition Examination Survey (NHANES). The study utilized data from NHANES 2009-2018 with asthma and asthma-related events as dependent variables and SII as an independent variable. Multifactor logistic regression was employed to assess the correlation between the independent and dependent variables. Smoothed curve-fitting and threshold effect analyses were also carried out to determine the presence of non-linear relationships. Subgroup analyses were then performed to identify sensitive populations. In this study, we analyzed data from 40,664 participants to elucidate the association between SII and asthma and its related events. The study findings indicated a positive correlation between SII and asthma, with a relative risk increase of 0.03% for asthma incidence per one percentage point increase in SII (OR = 1.0003, 95% CI: 1.0002, 1.0004). For individuals still suffering from asthma, higher SII also indicated a positive correlation with ongoing asthma (OR = 1.0004, 95% CI: 1.0001, 1.0006). However, no statistically significant association was observed between SII and asthma exacerbations within the following year (OR = 1.0001, p > 0.05). When considering the duration of asthma, we observed a slight positive correlation with SII (β = 0.0017, 95% CI: 0.0005, 0.0029). Additionally, a significant non-linear relationship between SII and asthma duration emerged at the threshold of 504.3 (β = 0.0031, 95% CI: 0.0014-0.0048, p = 0.0003). Subgroup analysis revealed a stronger correlation between SII and asthma in male patients (OR = 1.0004, 95% CI: 1.0002-1.0006) and individuals aged 60 and above (OR = 1.0005, 95% CI: 1.0003-1.0007). No gender differences were observed for individuals still suffering from asthma. However, the positive correlation between SII and asthma was more pronounced in participants under 20 years old (OR = 1.0004 in Model 3, 95% CI: 1.0002-1.0006). Specific sensitive subgroups for asthma exacerbation recurrence within the past year were not identified. When considering asthma duration, we observed this association to be significant in male individuals (β = 0.0031 in Model 3, 95% CI: 0.0014-0.0049) as well as individuals aged 20 to 39 (β = 0.0023 in Model 3, 95% CI: 0.0005-0.0040). Our study concludes that SII is positively correlated with the persistence of asthma yet has limited predictive power for asthma recurrence. This highlights SII's potential as a tool for assessing asthma risk and formulating targeted management strategies.

Can glucagon-like peptide-1 receptor agonists induce asthma? An analysis of the FAERS database

Objective Glucagon-like peptide-1 receptor agonists (GLP1RAs), originally developed for the treatment of type 2 diabetes mellitus, have attracted attention for their potential therapeutic benefits in asthma due to their anti-inflammatory properties and effects on airway smooth muscle function. However, concerns have been raised about the possibility of GLP1RAs inducing or exacerbating asthma symptoms. Methods We reviewed data from the US Food and Drug Administration’s (FDA) adverse event (AE) reporting system (FAERS) to examine reports of cases of asthma observed in the real-world during treatment with GLP1RAs. Results Analysis of the FAERS reporting system database has shown that certain GLP1RAs, particularly exenatide, semaglutide and liraglutide, were associated with a higher proportion of respiratory AEs, particularly asthma or asthma-like events. This association was statistically significant at least for semaglutide and liraglutide. Serious asthma-related events and deaths were also reported, with exenatide having the highest proportion of deaths. Conclusions The reasons for the observed differences in the AE profiles of the GLP1RAs remain unclear and may involve various factors such as pharmacological properties, patient characteristics and reporting biases. The complex interplay between the therapeutic benefits of GLP1RAs and the potential respiratory risks requires careful monitoring by clinicians, underpinned by ongoing research efforts to improve patient care and safety.

Garadacimab for hereditary angioedema attack prevention: long-term efficacy, quality of life, and safety data from a phase 2, randomised, open-label extension study

Garadacimab is a fully human immunoglobulin G4 monoclonal antibody targeting activated factor XII. This study evaluated long-term efficacy, health-related quality of life (HRQoL), and safety data for garadacimab in adults with hereditary angioedema. This global phase 2 study comprised a treatment period 1 (TP1: 12 weeks, double-blind, placebo-controlled) and a treatment period 2 (TP2: ≥44-week open-label extension). Patients aged 18-65 years with clinically confirmed hereditary angioedema were eligible. In TP1, 32 patients were randomly assigned (1:1:1:1) to receive subcutaneous garadacimab (75 mg, 200 mg, or 600 mg) or placebo every 4 weeks (once monthly). Randomisation was done using interactive response technology via block randomisation (block sizes 1-4). Subsequently, six additional patients in TP1 were assigned to open-label garadacimab 400 mg every 2 weeks. At the start of TP2, patients were re-randomised (if receiving placebo, garadacimab 75 mg, or garadacimab 400 mg) or continued to receive garadacimab 200 mg or garadacimab 600 mg once monthly. After a protocol amendment on March 20, 2020, patients originally assigned to the 600 mg dose were down-titrated to 200 mg at their next visit. The primary endpoint (published previously) was monthly attack rate for patients receiving 200 mg or 600 mg garadacimab in TP1 in the intention-to-treat population. Here, we assessed the impact of garadacimab on patient-reported and investigator-reported outcomes and HRQoL as well as long-term efficacy and safety. This trial is registered with ClinicalTrials.gov, NCT03712228, and is completed. Of 54 patients screened between Oct 29, 2018, and Aug 28, 2019, 32 randomised and six open-label patients completed TP1 and entered TP2 (20 in the garadacimab 200 mg group; 18 in the garadacimab 600 mg group; total 38 patients). Median age was 39·0 years (IQR 27·0-53·0), and 21 patients (55%) were female and 17 (45%) were male. In TP2, the median garadacimab exposure was 87·9 weeks (IQR 50·0-106·6) in the garadacimab 200 mg group and 44·1 weeks (24·1-56·1) in the garadacimab 600 mg group. Median monthly attack rates were 0·0 (IQR 0·0-0·1) in the garadacimab 200 mg group and 0·1 (0·0-0·4) in the garadacimb 600 mg group. Median reduction in monthly attack rate versus run-in was 100% (IQR 98-100) with garadacimab 200 mg. HRQoL improvements observed during TP1 with garadacimab were sustained throughout TP2. TP2 safety signals were consistent with TP1. Two patients experienced serious adverse events of diverticular perforation and asthma (not garadacimab-related). Treatment-emergent adverse events were mostly mild or moderate in severity. The most common adverse events were headache (nine of 38, 24%) and abdominal pain (seven of 38, 18%). There were no treatment-related deaths. Once-monthly garadacimab for more than 2 years in patients with hereditary angioedema was well tolerated and efficacious in reducing monthly attack rate and improving HRQoL. These results reveal the potential of long-term prophylactic treatment with 200 mg once-monthly garadacimab towards complete disease control of patients with hereditary angioedema. CSL Behring.

Impact of liquid sublingual immunotherapy on asthma onset and progression in patients with allergic rhinitis: a nationwide population-based study (EfficAPSI study)

BackgroundThe only disease-modifying treatment currently available for allergic rhinitis (AR) is allergen immunotherapy (AIT). The main objective of the EfficAPSI real-world study (RWS) was to evaluate the impact of liquid sublingual immunotherapy (SLIT-liquid) on asthma onset and evolution in AR patients. MethodsAn analysis with propensity score weighting was performed using the EfficAPSI cohort, comparing patients dispensed SLIT-liquid with patients dispensed AR symptomatic medication with no history of AIT (controls). Index date corresponded to the first dispensation of either treatment. The sensitive definition of asthma event considered the first asthma drug dispensation, hospitalisation or long-term disease (LTD) for asthma, the specific one omitted drug dispensation and the combined one considered omalizumab or three ICS+/-LABA dispensation, hospitalisation or LTD. In patients with pre-existing asthma, the GINA treatment step-up evolution was analysed. FindingsIn this cohort including 112 492 SLIT-liquid and 333 082 controls, SLIT-liquid exposure was associated with a significant lower risk of asthma onset versus control, according to all definitions (combined: HR [95%CI]=0·62 [0·60-0·63], sensitive: 0·77 [0·76-0·78], and specific: 0·67 [0·61-0·72]). Exposure to SLIT was associated with a one-third reduction in GINA step-up regardless baseline steps. InterpretationIn this national RWS with the largest number of person-years of follow-up to date in the field of AIT, SLIT-liquid was associated with a significant reduction in the risk of asthma onset or worsening. The use of three definitions (sensitive or specific) and GINA step-up reinforced the rigorous methodology, substantiating SLIT-liquid evidence as a causal treatment option for patients with respiratory allergies. FundingStallergenes Greer

169 Association of Asthma Specialty Care and Adverse Outcomes for Children Enrolled in the Arkansas Medicaid Program

OBJECTIVES/GOALS: Specialty care for asthmatic children should prevent adverse asthma outcomes. This study of children receiving care in the Arkansas Medicaid program used a comparative effectiveness research design to test whether allergy specialty care was associated with reduced adverse asthma outcomes. METHODS/STUDY POPULATION: Using the Arkansas All Payer Claims Database we studied Medicaid-enrolled children with asthma using a propensity score greedy nearest neighbor one-to-one matching algorithm. We matched children with (treatment) and without (comparison) an allergy specialist visit in 2018. The propensity score model included 26 covariates (demographic, clinical, and social determinants of health). Multivariable adjusted logistic regression was used to estimate adverse asthma events (AAE: emergency department visit or inpatient hospitalization with a primary or secondary diagnosis of asthma in 2019). RESULTS/ANTICIPATED RESULTS: We identified 3,031 children with an allergy specialist visit in 2018, and successfully propensity-score matched 2,910 of the treatment group with a non-allergy specialist visit comparison group. The rate of AAEs in 2019 was 9.5% for individuals with an allergy specialist visit versus 10.1% among those without a specialist visit (p=0.450). The adjusted regression analysis showed 20.3% lower rates of AAEs (aOR: 0.797; 95% Confidence Interval: 0.650, 0.977; p=0.029) in 2019 for children with an allergy specialist visit in 2018 compared to those that did not. DISCUSSION/SIGNIFICANCE: Utilizing allergy specialist care was associated with better asthma outcomes in our statewide study of Arkansas Medicaid-enrolled children with asthma. Asthma quality metrics based on guideline-based recommendations for allergy specialist care should be considered in population health management programs.

PM2.5 exposure-induced senescence-associated secretory phenotype in airway smooth muscle cells contributes to airway remodeling

Fine particulate matter (PM2.5) has been linked to increased severity and incidence of airway diseases, especially chronic obstructive pulmonary disease (COPD) and asthma. Airway remodeling is an important event in both COPD and asthma, and airway smooth muscle cells (ASMCs) are key cells which directly involved in airway remodeling. However, it was unclear how PM2.5 affected ASMCs. This study investigates the effects of PM2.5 on airway smooth muscle and its mechanism. We first showed that inhaled particulate matter was distributed in the airway smooth muscle bundle, combined with increased airway smooth muscle bundle and collagen deposition in vivo. Then, we demonstrated that PM2.5 induced up-regulation of collagen-I and alpha-smooth muscle actin (α-SMA) expression in rat and human ASMCs in vitro. Next, we found PM2.5 led to rat and human ASMCs senescence and exhibited senescence-associated secretory phenotype (SASP) by autophagy-induced GATA4/TRAF6/NF-κB signaling, which contributed to collagen-I and α-SMA synthesis as well as airway smooth muscle remodeling. Together, our results provided evidence that SASP induced by PM2.5 in airway smooth muscle cells prompted airway remodeling.

Presence of sputum IgG against eosinophilic inflammatory proteins in asthma.

Sputum immunoglobulin G (Sp-IgG) has been discovered to induce cytolytic extracellular trap cell death in eosinophils, suggesting a potential autoimmune mechanism contributing to asthma. This study aimed to explore the potential origin of Sp-IgG and identify clinically relevant subtypes of Sp-IgG that may indicate autoimmune events in asthma. This study included 165 asthmatic patients and 38 healthy volunteers. We measured Sp-IgG and its five subtypes against eosinophil inflammatory proteins (Sp-IgGEPs), including eosinophil peroxidase, eosinophil major basic protein, eosinophil-derived neurotoxin, eosinophil cationic protein, and Charcot-Leyden Crystal protein in varying asthma severity. Clinical and Mendelian randomization (MR) analyses were conducted. A positive Sp-IgGEPs signature (Sp-IgGEPs+) was defined when any of the five Sp-IgGEPs values exceeded the predefined cutoff thresholds, calculated as the mean values of healthy controls plus twice the standard deviation. The levels of Sp-IgG and Sp-IgGEPs were significantly elevated in moderate/severe asthma than those in mild asthma/healthy groups (all p < 0.05). Sp-IgG levels were positively correlated with airway eosinophil and Sp-IgGEPs. MR analysis showed causality between eosinophil and IgG (OR = 1.02, 95%CI = 1.00-1.04, p = 0.020), and elevated IgG was a risk factor for asthma (OR = 2.05, 95%CI = 1.00-4.17, p = 0.049). Subjects with Sp-IgGEPs+ exhibited worse disease severity and served as an independent risk factor contributing to severe asthma (adjusted-OR = 5.818, adjusted-95% CI = 2.193-15.431, adjusted-p < 0.001). Receiver operating characteristic curve analysis demonstrated that the combination of Sp-IgGEPs+ with non-allergic status, an ACT score < 15, and age ≥ 45 years, effectively predicted severe asthma (AUC = 0.84, sensitivity = 86.20%, specificity = 67.80%). This study identifies a significant association between airway eosinophilic inflammation, Sp-IgG, and asthma severity. The Sp-IgGEPs panel potentially serves as the specific biomarker reflecting airway autoimmune events in asthma.

IPREDICT: proof-of-concept study to develop a predictive model of changes in asthma control.

The individualized PREdiction of DIsease Control using digital sensor Technology (iPREDICT) program was developed for asthma management using digital technology. Devices were integrated into daily lives of patients to establish a predictive model of asthma control by measuring changes from baseline health status with minimal device burden. To establish baseline disease characteristics of the study participants, detect changes from baseline associated with asthma events, and evaluate algorithms capable of identifying triggers and predicting asthma control changes from baseline data. Patient experience and compliance with the devices were also explored. This was a multicenter, observational, 24-week, proof-of-concept study conducted in the United States. Patients (⩾12 years) with severe, uncontrolled asthma engaged with a spirometer, vital sign monitor, sleep monitor, connected inhaler devices, and two mobile applications with embedded patient-reported outcome (PRO) questionnaires. Prospective data were linked to data from electronic health records and transmitted to a secure platform to develop predictive algorithms. The primary endpoint was an asthma event: symptom worsening logged by patients (PRO); peak expiratory flow (PEF) < 65% or forced expiratory volume in 1 s < 80%; increased short-acting β2-agonist (SABA) use (>8 puffs/24 h or >4 puffs/day/48 h). For each endpoint, predictive models were constructed at population, subgroup, and individual levels. Overall, 108 patients were selected: 66 (61.1%) completed and 42 (38.9%) were excluded for failure to respond/missing data. Predictive accuracy depended on endpoint selection. Population-level models achieved low accuracy in predicting endpoints such as PEF < 65%. Subgroups related to specific allergies, asthma triggers, asthma types, and exacerbation treatments demonstrated high accuracy, with the most accurate, predictive endpoint being >4 SABA puffs/day/48 h. Individual models, constructed for patients with high endpoint overlap, exhibited significant predictive accuracy, especially for PEF < 65% and >4 SABA puffs/day/48 h. This multidimensional dataset enabled population-, subgroup-, and individual-level analyses, providing proof-of-concept evidence for development of predictive models of fluctuating asthma control.

Free fatty acid 3 receptor agonist AR420626 reduces allergic responses in asthma and eczema in mice

Free fatty acid 3 receptor (FFA3; previously GPR41) is a G protein-coupled receptor that senses short-chain fatty acids and dietary metabolites produced by the gut microbiota. FFA3 deficiency reportedly exacerbates inflammatory events in asthma. Herein, we aimed to determine the therapeutic potential of FFA3 agonists in treating inflammatory diseases. We investigated the effects of N-(2,5-dichlorophenyl)-4-(furan-2-yl)-2-methyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxamide (AR420626), an FFA3 agonist, in in vivo models of chemically induced allergic asthma and eczema in BALB/c mice. Administration of AR420626 decreased the number of immune cells in the bronchoalveolar lavage fluid and skin. AR420626 suppressed inflammatory cytokine expression in the lung and skin tissues. Histological examination revealed that AR420626 suppressed inflammation in the lungs and skin. Treatment with AR420626 significantly suppressed the enhanced lymph node size and inflammatory cytokine levels. Overall, FFA3 agonist AR420626 could suppress allergic asthma and eczema, implying that activation of FFA3 might be a therapeutic target for allergic diseases.

Efficacy and safety of sublingual versus subcutaneous immunotherapy in children with allergic rhinitis: a systematic review and meta-analysis.

To systematically compare the efficacy and safety of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) in children with allergic rhinitis (AR). PubMed, Embase, Cochrane Library, and Web of Science were searched from inception to March 2, 2023. Outcomes included symptom scores (SSs), medication scores (MSs), symptom and medication scores (SMSs), new sensitizations, development of asthma, improvement, and treatment-related adverse events (TRAEs). The quality of the included studies was assessed by the modified Jadad scale and Newcastle-Ottawa scale (NOS). Meta-regression was carried out to explore the source of heterogeneity. Subgroup analysis was further conducted in terms of study design [randomized controlled trials (RCTs), cohort studies], allergen [house dust mites (HDMs), grass pollen], treatment duration (≥ 24, 12-23 or < 12 months), allergen immunotherapy (AIT) modality (drops or tablets), and AIT protocol [continuous, pre-seasonal, co-seasonal, or after the grass pollen season (GPS)]. Sensitivity analysis was conducted for all outcomes. A Bayesian framework and a Monte Carlo Markov Chain (MCMC) model were developed for indirect comparison. Totally 50 studies with 10813 AR children were included, with 4122 treated with SLIT, 1852 treated with SCIT, and 4839 treated with non-SLIT or non-SCIT therapy. For direct comparison, the SLIT group had a similar SS to the SCIT group [pooled standardized mean difference (SMD): 0.41, 95% confidence interval (CI): -0.46, 1.28, P = 0.353]. Comparable MSs were observed in the SLIT and SCIT groups (pooled SMD: 0.82, 95%CI: -0.88, 2.53, P = 0.344). For indirect comparison, no significant differences were found in SSs (pooled SMD: 1.20, 95% credibility interval (CrI): -1.70, 4.10), MSs (pooled SMD: 0.57, 95%CrI: -1.20, 2.30), SMSs (pooled SMD: 1.80, 95%CrI: -0.005, 3.60), new sensitizations [pooled relative risk (RR): 0.34, 95%CrI: 0.03, 3.58], and development of asthma (pooled RR: 0.68, 95%CrI: 0.01, 26.33) between the SLIT and SCIT groups; the SLIT group illustrated a significantly lower incidence of TRAEs than the SCIT group (pooled RR: 0.17, 95%CrI: 0.11, 0.26). Considering both efficacy and safety, SLIT might be a more favorable AIT than SCIT in the treatment of pediatric AR, which may serve as a decision-making reference for clinicians. PROSPERO (CRD42023460693).

Timing of complementary feeding for early childhood allergy prevention: An overview of systematic reviews.

To summarise and critically appraise systematic review (SR) evidence on the effects of timing of complementary feeding (CF) on the occurrence of allergic sensitisation and disease. Overview of SRs. AMSTAR-2 and ROBIS were used to assess methodological quality and risk of bias (RoB) of SRs. RoB 2 Tool was used to assess RoB of primary randomised controlled trials (RCTs) (or extracted). The certainty of evidence (CoE) was assessed using GRADE. Findings were synthesised narratively. MEDLINE (via PubMed and Ovid), the Cochrane Library and Web of Science Core Collection (2010 to 27 February 2023). SRs investigating the effects of timing of CF in infants or young children (0-3 years) on risk of developing food allergy (FA), allergic sensitisation, asthma, allergic rhinitis, atopic eczema and adverse events based on RCT evidence. Eleven SRs were included. Only two SRs had low RoB; common issues were failure to report on funding of primary studies and failure to provide a list of excluded trials. Common limitations of included trials were lack of blinding of outcome assessment or detailed trial preregistration, and inadequate handling of high loss to follow up. Primary study overlap was very high for specific FA and slight to moderate for FA in general and other primary outcomes. Introducing specific foods (peanut, cooked egg) early probably reduces the risk of specific FA. Evidence forother allergic outcomes was mostly very uncertain and based on few primary studies. Trials varied regarding timing of CF, nature of complementary foods and population risk, which limited comparability between SRs. For developing guidelines to support decision-making on the timing of CF as a preventive strategy, early introduction of specific foods (i.e. egg and peanut) seems promising and safe, whereas more extensive research is required regarding other allergic outcomes and potential adverse events.

Development of an Asthma Exacerbation Risk Prediction Model for Conversational Use by Adults in England.

Improving accurate risk assessment of asthma exacerbations, and reduction via relevant behaviour change among people with asthma could save lives and reduce health care costs. We developed a simple personalised risk prediction model for asthma exacerbations using factors collected in routine healthcare data for use in a risk modelling feature for automated conversational systems. We used pseudonymised primary care electronic healthcare records from the Clinical Practice Research Datalink (CPRD) Aurum database in England. We combined variables for prediction of asthma exacerbations using logistic regression including age, gender, ethnicity, Index of Multiple Deprivation, geographical region and clinical variables related to asthma events. We included 1,203,741 patients divided into three cohorts to implement temporal validation: 898,763 (74.7%) in the training sample, 226,754 (18.8%) in the testing sample and 78,224 (6.5%) in the validation sample. The Area under the ROC curve (AUC) for the full model was 0.72 and for the restricted model was 0.71. Using a cut-off point of 0.1, approximately 27 asthma reviews by clinicians per 100 patients would be prevented compared with a strategy that all patients are regarded as high risk. Compared with patients without an exacerbation, patients who exacerbated were older, more likely to be female, prescribed more SABA and ICS in the preceding 12 months, have history of GORD, COPD, anxiety, depression, live in very deprived areas and have more severe disease. Using information available from routinely collected electronic healthcare record data, we developed a model that has moderate ability to separate patients who had an asthma exacerbation within 3 months from their index date from patients who did not. When comparing this model with a simplified model with variables that can easily be self-reported through a WhatsApp chatbot, we have shown that the predictive performance of the model is not substantially different.

Improvement of quality of life in a family of a child with asthma after using the Written Asthma Action Plan (WAAP)

ABSTRACT Background: Asthma is a common childhood disease that leads to impairment of quality of life (QOL) of both the children affected by the disease and their caregivers. Management of asthma includes pharmacotherapy along with education about asthma and its self-management, which is most often given verbally. There is limited evidence regarding the benefits of using a written asthma action plan (WAAP) that has been improved using pictorial representation. Objective: The study aimed to assess the effectiveness of a WAAP in improving the QOL of children with bronchial asthma and also of their caregivers. It also educates the patients and families about various triggers and danger signs of an acute attack of asthma. Methods: This was an interventional study with the aim of improving the quality of asthma management. Children of age group 7–17 years in whom the diagnosis of asthma was made and those parents and children who could read and answer the questionnaire (mini-PAQLQ and PACQLQ) were included in the study. Subjects were randomized into Case and Control groups. The intervention was to give the randomly selected patients (Case group) an individualized WAAP along with standard asthma care to both groups. Both groups were followed up to assess and record variations in the quality of life. Results: The P value was highly significant in the following parameters post-intervention: missed doses of controller medication (P value = 0.001), need for rescue medication (&lt;0.001), ACT score (0.001), total PAQLQ (&lt;0.001), and PACQLQ (&lt;0.001) score. Though statistical significance was not established, improvement was also observed in the number of unscheduled OPD visits (P value = 0.082) and hospitalization events (P value = 0.554). Conclusion: On being provided with the WAAP, the frequency of acute asthma events, treatment compliance, and QOL improved. There was a significant increase in the primary outcomes-PAQLQ and PACQLQ scores. Significant improvement in the secondary outcomes-number of missed school days, missed doses of controller medication, need for rescue medication, and ACT score was also observed.

Extreme weather and asthma: a systematic review and meta-analysis.

Climate change's influence on extreme weather events poses a significant threat to the morbidity and mortality of asthma patients. The aim of this study was to examine associations between extreme weather events and asthma-related outcomes. A systematic literature search for relevant studies was performed using the PubMed, EMBASE, Web of Science and ProQuest databases. Fixed-effects and random-effects models were applied to estimate the effects of extreme weather events on asthma-related outcomes. We observed that extreme weather events were associated with increasing risks of general asthma outcomes with relative risks of 1.18-fold for asthma events (95% CI 1.13-1.24), 1.10-fold for asthma symptoms (95% CI 1.03-1.18) and 1.09-fold for asthma diagnoses (95% CI 1.00-1.19). Extreme weather events were associated with increased risks of acute asthma exacerbation with risk ratios of asthma emergency department visits of 1.25-fold (95% CI 1.14-1.37), of asthma hospital admissions of 1.10-fold (95% CI 1.04-1.17), of asthma outpatient visits of 1.19-fold (95% CI 1.06-1.34) and of asthma mortality of 2.10-fold (95% CI 1.35-3.27). Additionally, an increase in extreme weather events increased risk ratios of asthma events by 1.19-fold in children and 1.29-fold in females (95% CI 1.08-1.32 and 95% CI 0.98-1.69, respectively). Thunderstorms increased the risk ratio of asthma events by 1.24-fold (95% CI 1.13-1.36). Our study showed that extreme weather events more prominently increased the risk of asthma morbidity and mortality in children and females. Climate change is a critical concern for asthma control.

Mechanical forces suppress antiviral innate immune responses from asthmatic airway epithelial cells following rhinovirus infection.

Bronchoconstriction is the main physiological event in asthma, which leads to worsened clinical symptoms and generates mechanical stress within the airways. Virus infection is the primary cause of exacerbations in people with asthma, however, the impact that bronchoconstriction itself on host antiviral responses and viral replication is currently not well understood. Here we demonstrate how mechanical forces generated during bronchoconstriction may suppress antiviral responses at the airway epithelium without any difference in viral replication. Primary bronchial epithelial cells from donors with asthma were differentiated at the air-liquid interface. Differentiated cells were apically compressed (30 cmH2O) for 10 min every hour for 4 days to mimic bronchoconstriction. Two asthma disease models were developed with the application of compression, either before ("poor asthma control model," n = 7) or following ("exacerbation model," n = 4) rhinovirus (RV) infection. Samples were collected at 0, 24, 48, 72, and 96 h postinfection (hpi). Viral RNA, interferon (IFN)-β, IFN-λ, and host defense antiviral peptide gene expressions were measured along with IFN-β, IFN-λ, TGF-β2, interleukin-6 (IL-6), and IL-8 protein expression. Apical compression significantly suppressed RV-induced IFN-β protein from 48 hpi and IFN-λ from 72 hpi in the poor asthma control model. There was a nonsignificant reduction of both IFN-β and IFN-λ proteins from 48 hpi in the exacerbation model. Despite reductions in antiviral proteins, there was no significant change in viral replication in either model. Compressive stress mimicking bronchoconstriction inhibits antiviral innate immune responses from asthmatic airway epithelial cells when applied before RV infection.NEW & NOTEWORTHY Bronchoconstriction is the main physiological event in asthma, which leads to worsened clinical symptoms and generates mechanical stress within the airways. Virus infection is the primary cause of exacerbations in people with asthma, however, the impact of bronchoconstriction on host antiviral responses and viral replication is unknown. We developed two disease models, in vitro, and found suppressed IFN response from cells following the application of compression and RV-A1 infection. This explains why people with asthma have deficient IFN response.