Onset Of Asthma Research Articles

Biomarkers Identifying the Effectiveness of Biologic Agents in Moderate to Severe Asthma: A Systematic Review and Meta-Analysis

Introduction: Asthma is a prevalent respiratory condition, and biologic agents have proven effective in managing moderate to severe asthma. However, the role of biomarkers in guiding the use of biologic agents remains unclear. Method: On July 30, 2024, a systematic review and subsequent meta-analysis were conducted by searching three major online databases: PubMed, Web of Science, and Cochrane. Results: The final analysis included 10 studies with a total of 6,709 patients with moderate to severe asthma. The overall pooled effect across all ages demonstrated a rate ratio (RR) reduction of 0.61 (95% CI: 0.46 to 0.80; p < 0.01; I² = 71%). Subgroup analysis revealed an onset or treated age of less than 18 years with RRs of 0.79 (95% CI: 0.62 to 1.02; p = 0.07; I² = 0%) and 0.88 (95% CI: 0.42 to 1.84; p = 0.73; I² = 14%), respectively. Patients with varying blood eosinophil levels showed a pooled RR of 0.51 (95% CI: 0.38 to 0.69; p < 0.01; I² = 82.7%). However, blood eosinophil levels below 150/μL demonstrated a limited effect of biologic agents, with an RR of 0.77 (95% CI: 0.35 to 1.67; p = 0.50; I² = 87%). For patients with all levels of fraction of exhaled nitric oxide (FeNO), the RR was 0.43 (95% CI: 0.30 to 0.62; p < 0.01; I² = 84%). The test for subgroup differences yielded a p-value of < 0.001, indicating that patients with higher FeNO levels experienced a more significant reduction in RR. Conclusion: Patients with asthma onset or treatment before age 18 may benefit less from biologics. Blood eosinophil counts and FeNO levels aid in selecting these therapies.

Comparison of Asthma Phenotypes in Severe Asthma Cohorts (SARP, U-BIOPRED, ProAR and COREA) From 4 Continents.

Asthma is a clinical syndrome with various underlying pathomechanisms and clinical phenotypes. Genetic, ethnic, and geographic factors may influence the differences in clinical presentation, severity, and prognosis. We compared the characteristics of asthma based on the geographical background by analyzing representative cohorts from the United States, Europe, South America, and Asia using the Severe Asthma Research Program (SARP), Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED), Program for Control of Asthma in Bahia (ProAR), and Cohort for Reality and Evolution of Adult Asthma in Korea (COREA), respectively. The clinical characteristics and medications for the SARP (n = 669), U-BIOPRED (n = 509), ProAR (n = 996), and COREA (n = 3,748) were analyzed. Subgroup analysis was performed for severe asthma. The mean age was highest and lowest in the COREA and SARP, respectively. The asthma onset age was lowest in the ProAR. The mean body mass index was highest and lowest in the SARP and COREA, respectively. Baseline pulmonary function was lowest and highest in the U-BIOPRED and COREA, respectively. The number of patients with acute exacerbation in the previous year was highest in U-BIOPRED. The mean blood eosinophil count was highest in COREA. The total immunoglobulin E was highest in the ProAR. The frequency of atopy was highest in the SARP. The principal component analysis plot revealed differences among all cohorts. The cohorts from 4 different continents exhibited different clinical and physiological characteristics, probably resulting from the interplay between genetic susceptibility and geographical factors.

Asthma and risk of adverse pregnancy outcomes: A Mendelian randomization study

BackgroundMultiple empirical investigations have indicated a connection between asthma and adverse pregnancy outcomes (APOs). Nevertheless, the effects of asthma on APOs remain uncertain. MethodsWe performed bi-directional Univariable Mendelian randomization (UVMR) analyses using combined information obtained from genome-wide association studies (GWAS) data that is publicly accessible. The principal approach used to analyze the causal association between asthma or age when diagnosed and APOs was the inverse variance weighted (IVW) method. The two types of data regarding exposure originate from the IEU Open GWAS project, which includes 56,167 and 47,222 European asthma patients, respectively. The data of four APOs were acquired via the GWAS dataset of the FinnGen collaboration. In addition, we implemented multivariable Mendelian randomization (MVMR), controlling for confounding factors such as smoking status, frequent drinking, body mass index (BMI), and live birth quantity. Furthermore, we executed several meticulous sensitivity studies to ascertain the reliability of our MR results. ResultsFollowing the implementation of the Bonferroni adjustment, the UVMR assessment revealed that in the IVW model, asthma was significantly linked to an elevated risk of spontaneous abortion (SA) (odds ratio [OR]: 1.115; 95 % confidence interval [CI]: 1.031–1.206; P = 0.006) and gestational diabetes mellitus (GDM) (OR: 1.125; 95 % CI: 1.037–1.220; P = 0.005). However, there was no causal correlation between asthma and preterm birth (PTB) (OR: 0.979; 95 % CI: 0.897–1.068; P = 0.629) or preeclampsia (PE) (OR: 1.059; 95 % CI: 0.951–1.179; P = 0.297). After adjusting for confounding factors, including smoking status, frequent drinking, BMI, and live birth quantity, the MVMR analysis shows a statistically significant causal relationship between asthma and SA or GDM. Furthermore, our investigation's findings did not reveal a substantial correlation between the age of asthma onset based on genetics and the likelihood of SA or GDM. The inverse MR outcomes indicate a lack of causal connection linking APOs to the incidence of asthma. The validity of these findings were verified by sensitivity analyses. ConclusionsThe evidence provided by this study proves that genetically determined asthma is linked to a higher likelihood of SA and GDM. Further research is required to examine potential pathways. However, no conclusive evidence has been found to support the increased risk of SA and GDM in early asthma diagnosis or the interaction between asthma and PTB or PE, indicating that confounding factors may affect the results of previous observational studies.

Effects of Pregnancy-Onset Asthma on Perinatal Outcomes: A Retrospective Cohort Study

BackgroundIt is unknown whether women with pregnancy-onset asthma are predisposed to worse pregnancy outcomes compared to women with pre-pregnancy asthma. ObjectiveTo explore whether pregnancy-onset asthma leads to worse perinatal outcomes compared with pre-pregnancy asthma. MethodsWomen who were discharged with a diagnosis of asthma and gave birth to a live singleton were included in this retrospective cohort analysis. Women were separated into groups based on whether the asthma was diagnosed during or before pregnancy. Clinical characteristics, perinatal outcomes, and asthma exacerbations (AE) between the two groups were compared. Results335 women were included in this study, of whom 39 (11.6%) had pregnancy-onset asthma and 296 had pre-pregnancy asthma. All the pregnant women in the pregnancy-onset group experienced asthma exacerbations (AE) during pregnancy. The proportion of chronic hypertension, chronic hypertension with superimposed preeclampsia, and spontaneous preterm births in the pregnancy-onset group was significantly higher than that in the pre-pregnancy asthma group. After adjusting for age, BMI, onset of asthma during pregnancy, and severity of AE through multivariate analysis, pregnancy-onset asthma was an independent risk factor for spontaneous preterm birth (aOR 7.71, 95% CI 1.30–46.12), severe AE was an independent risk factor for gestational hypertension and preeclampsia (aOR 3.58, 95% CI 1.30–9.87). ConclusionsDuring pregnancy, pregnancy-onset asthma in women is associated with an exacerbation of the condition. Obstetricians should be vigilant for signs of asthma onset during pregnancy. Other health-care providers should watch out for symptoms of gestational hypertension and preeclampsia in pregnant women with pre-existing or new-onset asthma.

Clinical and allergological characteristics of patients with severe bronchial asthma in the regional registry and phenotyping principles for the targeted therapy choice

Introduction. Severe asthma targeted therapy effectiveness depends on precise targeting of the selected drug to the key link in pathogenesis. Therefore, severe asthma phenotyping in real clinical practice is relevant.Aim. To determine main clinical and allergological characteristics of patients with severe asthma and to establish important phenotyping signs determined choice of a targeted drug for severe asthma treatment.Materials and methods. The prospective and retrospective study involved patients (n = 198) of the Sverdlovsk region registry receiving targeted therapy of severe asthma. Considering clinical and allergological picture, allergic, non-allergic eosinophilic and mixed severe asthma phenotypes were identified. Clinical and laboratory characteristics of phenotypes were described. A phenotyping algorithm was developed.Results. In the register of patients (n = 198) with severe asthma, non-allergic eosinophilic asthma was 46.5%, allergic – 34.8%, mixed – 18.7%. Significant signs for phenotyping were identified: age of asthma onset, proven allergy, Phadiatop ImmunoCAP level and blood eosinophils on baseline, concomitant allergic rhinitis, chronic rhinosinusitis with nasal polyps and hyper-sensitivity to NSAIDs. The main signs of allergic severe asthma determined: early onset, proven allergy and a positive result of Phadiatop ImmunoCAP (the probability of allergic phenotype increases with Phadiatop ≥ 1.53 PAU/l). Signs of non-allergic eosinophilic asthma were eosinophilia ≥ 150 cells/µl, absence of allergy, concomitant chronic rhinosinusitis with nasal polyps and hypersensitivity to NSAIDs, late onset (after 30 years). Signs were identified for mixed asthma: presence of proven allergy or latent sensitization in combination with high level of Phadiatop ImmunoCAP, late onset, eosinophilia ≥ 300 cells/µl, chronic rhinosinusitis with nasal polyps, hypersensitivity NSAIDs.Conclusions. The algorithm for severe asthma phenotyping based on the isolation of eosinophilia of allergic and non-allergic origin is proposed. Severe asthma phenotyping, which can be carried out in real clinical practice, should facilitate the selection of an initial targeted drug.

Use of Antibiotics in Infancy and Asthma in Childhood: Confounded or Causal Relationship? A Critical Review of the Literature

Childhood asthma is among the most common chronic lung diseases in the pediatric population, having substantial consequences on the everyday life of children and their caregivers. There remains a lack of a singular, efficacious strategy for averting the inception of childhood asthma. The rate of pediatric antibiotic usage continues to be high, which makes it crucial to understand whether there exists a causal link between the use of antibiotics in infancy and the development of asthma in childhood. In this rostrum, we conduct a critical review of the literature concerning the association of infant antibiotic use and the onset of childhood asthma. Drawing upon the results of 5 meta-analyses addressing this topic and of a recent randomized controlled trial, a notable association emerges between antibiotic exposure in the first year of life and the occurrence of childhood asthma that appears to be beyond potential study limitations (such as reverse causation, confounding by indication, and recall bias). Furthermore, we highlight the need for additional research in this field that could improve our understanding of important aspects of this association and lead to the design of an intervention aimed to deliver antibiotics safely during early life and reduce the burden of childhood asthma.

The Combined Effects of Long Term Mixture Exposure to Temperature and Relative Humidity on Asthma in China

Background: Few previous stud ies ha ve examined the joint effect of long term exposure to temperature and relative humidity ( RH on ast hma This study endeavors t o explore the combined association between long term co exposure to temperature and R H and asthma in China. Methods: The individual data of asthma were collected from the wave 1 to wave 3 (2007 2019) of the Study on global AGEing and adult health in China. M eteorological factors data were obtained from the European Center for Medium range Weather Forecasts Reanalysis 5 (ERA5) and extracted from the corresponding interpolated grid according to individual residential latitude, longi tude and survey time. Individual and joint association of long term exposure to annual mean temperature and RH with asthma were estimated using Cox regression model and Quantile Based g Computation model Q gcomp)gcomp), respectively Then , the joint effects of different temperature RH compound events w ere further estimated Results: We observed negative association between both temperature and RH with asthma. In individual effect analysis, for 1 °C or 1% decrease in 3 year average temperature and RH , asthma increased 4 44 (95% 1 76 7 0 5) and 6 45 (95% 2 79 9 98 respectively. The joint effect of long term exposure to temperature and RH on asthma was also negative . F or each percentile decreasing of both temperature and RH asthma decreased 1.50% (95%CI: 0.85% 2.15%) in total population . People 60 years old and female were more susceptible to mixture exposure to low temperature and low RH. W e also observed a higher risk of asthma in dry cold event ( 2.44 , 95%CI: 1 67 3 55 than wet cold, wet hot and dry hot events Conclusion: Long term exposure to t emperature and RH may jointly associate with asthma , and low RH and cold may have higher risk on asthma onset .

Lack of association of atopic dermatitis severity and morphology with asthma onset and control.

Asthma is one of the most well-recognized comorbidities of atopic dermatitis (AD). However, the relationship of AD severity and morphology with asthma characteristics in adults is not well defined. To understand associations of AD severity and morphology with comorbid asthma age-of-onset and control in adults with AD. A cross-sectional, dermatology practice-based study was performed in adults (≥ 18years) with AD and history of asthma (N = 252). Self-administered electronic questionnaires were completed by patients, including demographics, patient-reported outcomes measures of AD severity, history of asthma, age-of-onset, and Asthma Control Test (ACT). Multivariable logistic regression models were constructed to examine relationships between AD severity and morphology with asthma age-of-onset and control. The mean ± standard deviation ACT score was 21.7 ± 4.3 (range 5-25), with 55 (21.8%) having ACT scores ≤ 19 indicating poorly controlled asthma. AD severity and morphology were not associated with adult-onset asthma or poor asthma control. AD severity and morphology were not consistently associated with comorbid asthma age-of-onset or control in adults with AD.

The New Paradigm: The Role of Proteins and Triggers in the Evolution of Allergic Asthma.

Epithelial barrier damage plays a central role in the development and maintenance of allergic inflammation. Rises in the epithelial barrier permeability of airways alter tissue homeostasis and allow the penetration of allergens and other external agents. Different factors contribute to barrier impairment, such as eosinophilic infiltration and allergen protease action-eosinophilic cationic proteins' effects and allergens' proteolytic activity both contribute significantly to epithelial damage. In the airways, allergen proteases degrade the epithelial junctional proteins, allowing allergen penetration and its uptake by dendritic cells. This increase in allergen-immune system interaction induces the release of alarmins and the activation of type 2 inflammatory pathways, causing or worsening the main symptoms at the skin, bowel, and respiratory levels. We aim to highlight the molecular mechanisms underlying allergenic protease-induced epithelial barrier damage and the role of immune response in allergic asthma onset, maintenance, and progression. Moreover, we will explore potential clinical and radiological biomarkers of airway remodeling in allergic asthma patients.

Adopting electric school buses in the United States: Health and climate benefits

Electric school buses have been proposed as an alternative to reduce the health and climate impacts of the current U.S. school bus fleet, of which a substantial share are highly polluting old diesel vehicles. However, the climate and health benefits of electric school buses are not well known. As they are substantially more costly than diesel buses, assessing their benefits is needed to inform policy decisions. We assess the health benefits of electric school buses in the United States from reduced adult mortality and childhood asthma onset risks due to exposure to ambient fine particulate matter (PM2.5). We also evaluate climate benefits from reduced greenhouse-gas emissions. We find that replacing the average diesel bus in the U.S. fleet in 2017 with an electric bus yields $84,200 in total benefits. Climate benefits amount to $40,400/bus, whereas health benefits amount to $43,800/bus due to 4.42*10-3 fewer PM2.5-attributable deaths ($40,000 of total) and 7.42*10-3 fewer PM2.5-attributable new childhood asthma cases ($3,700 of total). However, health benefits of electric buses vary substantially by driving location and model year (MY) of the diesel buses they replace. Replacing old, MY 2005 diesel buses in large cities yields $207,200/bus in health benefits and is likely cost-beneficial, although other policies that accelerate fleet turnover in these areas deserve consideration. Electric school buses driven in rural areas achieve small health benefits from reduced exposure to ambient PM2.5. Further research assessing benefits of reduced exposure to in-cabin air pollution among children riding buses would be valuable to inform policy decisions.

Ultra-Processed Foods Consumption and Asthma in the Western Diet

Obesity is considered an important risk factor for the onset of asthma, playing a key role in enhancing the disease’s severity. However, there is increasing evidence linking not only obesity but also overweight with a higher risk of asthma. Although the correlation between obesity and asthma has already been reported, several aspects are still not fully elucidated, mainly about the inflammatory processes underlying both diseases. It is well known that Western-type calorically rich diets and overfeeding can act as triggers of chronic metabolic inflammation, but few studies have examined associations between ultra-processed foods (UPFs) intake, despite its positive correlation with obesity, and biomarkers of inflammation. In addition to their nutrient composition, UPF may have chemical additives and contaminants from packaging, whose effects on health and food addiction are still under research. In this review, we provide an overview of the current data that identify the associations between the obese asthma phenotype and UPF consumption, highlighting the potential central role played by the intestinal microbiota.

Allergen skin test responses in broad U.S. asthma population in those with and without rhinitis.

Background: Asthma and allergic rhinitis are pathologically interlinked conditions. Despite skin testing (ST) being pivotal for evaluating allergic sensitization, U.S. data that date back to 1960s on ST reactivity patterns in subjects with asthma remain sparse. Objective: The purpose of this study was to elucidate seasonal, perennial ST responses, and their relationship with asthma severity, early versus late onset disease, and immunoglobulin E (IgE) levels. Methods: Five hundred patients with asthma were randomly selected from the National Jewish Health electronic medical record over a 3-year span. Demographic, clinical, and allergen ST reactivity data for a battery of seasonal and perennial allergens were procured, including total IgE levels, asthma onset, and severity, by using t-tests, χ² tests, and Analysis of Variance (ANOVA), patterns of reactivity were assessed for overall, seasonal, and perennial allergens in relation to IgE levels, asthma onset, and severity. Results: Of the 500 patients, 398 were analyzed. 63.3% were women, 50.1% had adult-onset asthma, and 86.1% had rhinitis; 75.3% tested positive to one or more allergens, with men demonstrating higher overall (p = 0.039) and perennial (p = 0.035) sensitization. ST reactivity varied based on the presence of rhinitis for seasonal (p = 0.028) but not perennial (p = 0.733) allergens. Asthma severity was not significantly associated with ST reactivity (p > 0.10). ST positivity for perennial (p < 0.001) but not seasonal (p = 0.128) allergens was higher in childhood-onset asthma versus adult-onset asthma despite both groups having a large percentage of reactors. Elevated IgE levels correlated with ST reactivity (p < 0.01). Conclusion: Our study represents a unique comprehensive evaluation of ST reactivity in a U.S. asthma population, which is lacking in the literature, when factoring in asthma onset, severity, and IgE levels. Our findings underscore the importance of allergen sensitization in asthma, regardless of severity, concurrent rhinitis symptoms, or asthma onset, which challenge some of the prevailing assumptions about the relationship between allergen sensitization and asthma onset.

Use of Electronic Nicotine Delivery Systems and Age of Asthma Onset Among US Adults and Youths.

The association of use of electronic nicotine delivery systems (ENDS) with the age of asthma onset is unknown. To explore the association of past 30-day ENDS use with the age of asthma onset in adults and youths who did not have asthma or chronic obstructive pulmonary disease and never used cigarettes. This cohort study was a secondary analysis of waves 1 to 6 of the US nationally representative Population of Tobacco and Health Study (2013-2021). Eligible participants included adults (≥18 years) and youths (12-17 years) who did not have asthma or chronic obstructive pulmonary disease at the first wave of participation. Data analysis was conducted from September 2022 to April 2024. Past 30-day ENDS use at the first wave of participation in the study preceding the onset of asthma. Lower and upper age limits were estimated using the age reported at the first wave of participation and the number of weeks between follow-up waves until asthma was first reported or censored. The association of past 30-day ENDS use with the age of asthma onset was estimated using weighted interval-censoring Cox regression. The cumulative hazard function for the age of asthma onset was estimated using interval-censoring survival analysis. A total of 24 789 participants were included, with 7766 adults (4461 female [weighted percentage, 59.11%] and 3305 male [weighted percentage, 40.89%]), representing 80.0 million adults, and 17 023 youths (8514 female [weighted percentage, 50.60%] and 8496 male [weighted percentage 49.32%]), representing 33.9 million youths. By age 27 years, 6.2 per 1000 adults reported asthma incidence (hazard ratio [HR], 0.62%; 95% CI, 0.46%-0.75%). While controlling for covariates, there was a 252% increased risk of the onset of asthma at earlier ages for adults who used ENDS in the past 30 days vs adults who did not (adjusted HR, 3.52; 95% CI, 1.24-10.02). For youths, there was no association of ENDS use in the past 30 days with age of asthma onset (adjusted HR, 1.79; 95% CI, 0.67-4.77), which could be due to a lack of statistical power. In this cohort study, past 30-day ENDS use among adults was associated with earlier ages of asthma onset. These findings suggest that prevention and cessation programs directed to adults who use ENDS are needed to educate the public, protect public health, prevent adverse health outcomes, and motivate users to stop. Furthermore, modifying symptom-screening asthma guidelines, resulting in earlier asthma detection and treatment, may reduce morbidity and mortality due to asthma.

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

Identifying ALOX15-initiated lipid peroxidation increases susceptibility to ferroptosis in asthma epithelial cells

Ferroptosis is a programmed form of cell death regulated by iron and has been linked to the development of asthma. However, the precise mechanisms driving ferroptosis in asthma remain elusive. To gain deeper insights, we conducted an analysis of nasal epithelial and sputum samples from the GEO database using three machine learning methods. Our investigation identified a pivotal gene, Arachidonate 15-lipoxygenase (ALOX15), associated with ferroptosis in asthma. Through both in vitro and in vivo experiments, we further confirmed the significant role of ALOX15 in ferroptosis in asthma. Our results demonstrate that ferroptosis manifests in an HDM/LPS-induced allergic airway inflammation (AAI) mouse model, mimicking human asthma, and in HDM/LPS-stimulated 16HBE cells. Moreover, we observed an up-regulation of ALOX15 expression in HDM/LPS-induced mice and cells. Notably, silencing ALOX15 markedly decreased HDM/LPS-induced ferroptosis in 16HBE cells. These findings indicate that ferroptosis may be implicated in the onset and progression of asthma, with ALOX15-induced lipid peroxidation raising the susceptibility to ferroptosis in asthmatic epithelial cells.

COVID-19 and Asthma Onset in Children.

Respiratory viral infections increase risk of asthma in infants and children. Infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus can cause severe lung inflammation and prolonged respiratory symptoms. We sought to determine whether SARS-CoV-2 infection modified pediatric incident asthma risk. This retrospective cohort study examined children ages 1 to 16 within the Children's Hospital of Philadelphia Care Network who received polymerase chain reaction (PCR) testing for SARS-CoV-2 between March 1, 2020 and February 28, 2021. Multivariable Cox regression models assessed the hazard ratio of new asthma diagnosis between SARS-CoV-2 PCR positive and SARS-CoV-2 PCR negative groups within an 18-month observation window. Models were adjusted for demographic characteristics, socioeconomic variables, and atopic comorbidities. There were 27 423 subjects included in the study. In adjusted analyses, SARS-CoV-2 PCR positivity had no significant effect on the hazard of new asthma diagnosis (hazard ratio [HR]: 0.96; P = .79). Black race (HR: 1.49; P = .004), food allergies (HR: 1.26; P = .025), and allergic rhinitis (HR: 2.30; P < .001) significantly increased the hazard of new asthma diagnosis. Preterm birth (HR: 1.48; P = .005) and BMI (HR: 1.13; P < .001) significantly increased the hazard of new asthma diagnosis for children <5 years old. SARS-CoV-2 PCR positivity was not associated with new asthma diagnosis in children within the observation period, although known risk factors for pediatric asthma were confirmed. This study informs the prognosis and care of children with a history of SARS-CoV-2 infection.

Effects of COVID-19 pandemic–associated reduction in respiratory infections on infantile asthma development

BackgroundIt is speculated that the COVID-19 pandemic associated reduction in the prevalence of respiratory tract infections has influenced on the incidence of asthma in infants. ObjectivesWe investigated an association between the reduction in viral infections and the reduction in asthma in infants. MethodsThe subjects were infants born in the early stages of the COVID-19 pandemic in Japan, which began in February 2020. A questionnaire survey related to asthma and allergy was conducted at 18 months and 3 years old. These results were compared to those of age-matched infants during the non-pandemic period. ResultsThere were no epidemics of viral infectious diseases until the target child was 18 months old. At 18 months, the incidence of asthma/asthmatic bronchitis diagnosed by physicians in pandemic infants was significantly lower than that in non-pandemic infants. In 3-year-old infants, no marked difference was observed between non-pandemic infants and pandemic infants, except for an increase in RSV infection in pandemic infants. In a comparative study of the same infants at 18 months and 3 years old, an increased prevalence of asthma/asthmatic bronchitis was observed in pandemic infants. Furthermore, the incidence of asthma after RSV infection in pandemic infants was significantly lower than that in non-pandemic infants. ConclusionThe COVID-19 pandemic-associated reduction in respiratory tract infections may have reduced the incidence of asthma in infancy, and RSV infection after 18 months old had little effect on the onset of asthma. These results indicate the importance of preventing respiratory tract infections in early infancy.

Characterization of PDGF-Induced Subcellular Calcium Regulation through Calcium Channels in Airway Smooth Muscle Cells by FRET Biosensors

The homeostasis of cellular calcium is fundamental for many physiological processes, while the calcium levels remain inhomogeneous within cells. During the onset of asthma, epithelial and inflammatory cells secrete platelet-derived growth factor (PDGF), inducing the proliferation and migration of airway smooth muscle (ASM) to the epidermal layer, narrowing the airway. The regulation of ASM cells by PDGF is closely related to the conduction of calcium signals. In this work, we generated subcellular-targeted FRET biosensors to investigate calcium regulation in the different compartments of ASM cells. A PDGF-induced cytoplasmic calcium [Ca2+]C increase was attributed to both extracellular calcium influx and endoplasmic reticulum (ER) calcium [Ca2+]ER release, which was partially regulated by the PLC-IP3R pathway. Interestingly, the removal of the extracellular calcium influx led to inhibited ER calcium release, likely through inhibitory effects on the calcium-dependent activation of the ER ryanodine receptor. The inhibition of the L-type calcium channel on the plasma membrane or the SERCA pump on the ER resulted in both reduced [Ca2+]C and [Ca2+]ER from PDGF stimulation, while IP3R channel inhibition led to reduced [Ca2+]C only. The inhibited SERCA pump caused an immediate [Ca2+]C increase and [Ca2+]ER decrease, indicating active calcium exchange between the cytosol and ER storage in resting cells. PDGF-induced calcium at the outer mitochondrial membrane sub-region showed a similar regulatory response to cytosolic calcium, not influenced by the inhibition of the mitochondrial calcium uniporter channel. Therefore, our work identifies calcium flow pathways among the extracellular medium, cell cytosol, and ER via regulatory calcium channels. Specifically, extracellular calcium flow has an essential function in fully activating ER calcium release.

Respiratory Diseases Associated With Wildfire Exposure in Outdoor Workers

Wildfires, including forest fires, bushfires, and landscape fires, have become increasingly prevalent, fueled by climate change and environmental factors, posing significant challenges to both ecosystems and public health. This review article examines the relationship between wildfires and respiratory diseases in outdoor workers, with a main focus on airway disease. In addition to the expected effects of direct thermal respiratory injuries, and possible carbon monoxide poisoning, there are associations between wildfires and upper and lower respiratory effects including infections, as well as exacerbations of asthma and COPD. A few studies have also shown an increased risk of new onset asthma among wildfire firefighters. Outdoor workers are likely to have greater exposure to wildfire smoke with associated increased risks of adverse effects. As wildfires become increasingly prevalent globally, it is crucial to understand the various dimensions of this association. Furthermore, this review addresses preventive measures and potential interventions to alleviate the airway burden on individuals during and after work with wildfires events.

Residential greenness during pregnancy and early life and development of asthma up to 27 years of age: The Espoo Cohort Study

Previous studies have suggested that living close to green spaces has protective health effects, but potential effects on asthma are contradictory. We investigated the association between the amount of greenness in the residential area during pregnancy and early life and development of asthma in the first 27 years of life. The study population included all 2568 members of the Espoo Cohort Study, Finland. We calculated individual-level exposure to green space measured as cumulative Normalized Difference Vegetation Index (cumNDVI in unit-months) within 300 m of the participant's residence during pregnancy and the first two years of life in both spring and summer seasons. The onset of asthma was assessed using information from the baseline and follow-up surveys. Exposure to residential greenness in the spring season during pregnancy was associated with an increased risk of asthma up to 6 years of age, with an adjusted hazard ratio (aHR) of 3.72 (95% confidence interval (CI): 1.11, 12.47) per 1 unit increase in cumNDVI. Increased greenness in the summer during pregnancy associated with asthma up to 6 years, with an aHR of 1.41 (95% CI: 0.85, 2.32). The effect was found to be related to increased greenness particularly during the third trimester of pregnancy, with an aHR of 2.37 (95% CI: 1.36, 4.14) per 1 unit increase of cumNDVI. These associations were weaker at the ages of 12 and 27 years. No association was found between NDVI in the first two years of life and the development of asthma. Our findings provide novel evidence that exposure to greenness during pregnancy increases the risk of developing asthma. The adverse effects were strongest for the prenatal greenness in the spring season and in the third trimester of pregnancy. Both the season and trimester of exposure to greenness are critical in the development of asthma.