Current Asthma Research Articles

Fungi in Early-Life House Dust Samples and the Development of Asthma: A Birth Cohort Study.

Rationale: Fungal exposure has been associated with predisposing and protective effects on the development of childhood asthma. Objectives: To study whether early-life house dust mycobiota composition is associated with the development of asthma. Methods: Mycobiota were determined by amplicon sequencing from 382 dust samples collected from living room floors 2 months after birth in homes of the LUKAS cohort. Asthma status by 10.5 years of age was defined from questionnaires and assigned as ever asthma (n = 68) or current asthma (n = 27). Inhalant atopy was clinically determined at the same age. β-composition was analyzed using PERMANOVA-S, and asthma and atopy analyses were performed using discrete time hazard models and logistic regression, respectively. Results: The house dust mycobiota composition based on Bray-Curtis distance was different in the homes of children who later did or did not develop asthma. The first and the fourth axes scores of principal coordinates analysis based on Bray-Curtis were associated with ever asthma. Of the genera with the strongest correlation with these axes, the relative abundance of Boeremia, Cladosporium, Microdochium, Mycosphaerella, and Pyrenochaetopsis showed protective associations with asthma. None of these associations remained significant after mutual adjustment among the five genera or when mutually adjusted for other microbial cell wall markers and previously identified asthma-protective bacterial indices. Neither fungal α-diversity nor load was associated with asthma in the whole population, but higher fungal richness was a risk factor among children on farms. Higher fungal loads (measured via quantitative polymerase chain reaction) in house dust were associated with the risk of inhalant atopy. Conclusions: The results of our analyses from this well-characterized birth cohort suggest that the early-life house dust mycobiota in Finnish homes, characterized via DNA amplicon sequencing, do not have strong predisposing or protective effects on asthma development.

Revisiting asthma pharmacotherapy: where do we stand and where do we want to go?

Several current guidelines/strategies outline a treatment approach to asthma, which primarily consider the goals of improving lung function and quality of life and reducing symptoms and exacerbations. They suggest a strategy of stepping up or down treatment, depending on the patient's overall current asthma symptom control and future risk of exacerbation. While this stepwise approach is undeniably practical for daily practice, it does not always address the underlying mechanisms of this heterogeneous disease. In the last decade, there have been attempts to improve the treatment of severe asthma, such as the addition of a long-acting antimuscarinic agent to the traditional inhaled corticosteroid/long-acting β2-agonist treatment and the introduction of therapies targeting key cytokines. However, despite such strategies several unmet needs in this population remain, motivating research to identify novel targets and develop improved therapeutic and/or preventative asthma treatments. Pending the availability of such therapies, it is essential to re-evaluate the current conventional "one-size-fits-all" approach to a more precise asthma management. Although challenging, identifying "treatable traits" that contribute to respiratory symptoms in individual patients with asthma may allow a more pragmatic approach to establish more personalised therapeutic goals.

Adherence to an Anti-Inflammatory Diet and Atopic Diseases' Prevalence in Adolescence: The Greek Global Asthma Network Study.

Atopic diseases are among the most common morbidities in children and adolescents. The association between adherence to an anti-inflammatory dietary pattern and the prevalence of atopic diseases among adolescents was examined. A total of 1934 adolescents (boys: 47.5%, mean age (standard deviation): 12.7 (0.6) years) were voluntarily enrolled. Participants completed a validated questionnaire on atopic disease status as well as one assessing dietary habits and other sociodemographic and lifestyle characteristics. A special Diet Anti-inflammatory Index (DAI) score was calculated for the evaluation of adherence to an anti-inflammatory dietary pattern. A total of 6.9% of the participants reported current asthma symptoms, while 25.3% reported rhinitis symptoms and 8.9% reported eczema. Adolescents with high adherence to an anti-inflammatory diet were 58% less likely to have asthma symptoms compared with those with low adherence when adjusted for multiple confounders (p < 0.01). No significant associations were observed between the level of adherence to an anti-inflammatory diet and the prevalence of allergic rhinitis and eczema. An anti-inflammatory diet seems to be independently associated with a lower prevalence of asthma in adolescents. Thus, pediatricians and other healthcare providers should promote anti-inflammatory dietary patterns as a preventive measure for atopic diseases from early stages of life.

Neighborhood Conditions and Resources in Mid-Childhood and Dampness and Pests at Home in Adolescence

To examine prospectively associations of neighborhood opportunity with the presence of dampness or pests in the home environment during early adolescence. We geocoded residential addresses from 831 children (mean age 7.9years, 2007-2011) in the Project Viva cohort. We linked each address with census tract-level Child Opportunity Index scores, which capture neighborhood conditions and resources influencing child heath including educational, health, environmental, and socioeconomic factors. Our primary outcome was presence of dampness or pests in the home in early adolescence (mean age 13.2years, 2013-2016). Secondary outcomes included current asthma and lung function testing results. Mixed-effects regression models estimated longitudinal associations of Child Opportunity Index scores with outcomes, adjusting for individual and family sociodemographics. Children residing in neighborhoods with greater overall opportunity were less likely to live in homes with dampness or pests approximately 5years later (aOR0.85 per 20-unit increase in Child Opportunity Index percentile rank, 95% CI 0.73-0.998). We observed no significant associations in adjusted models of overall neighborhood opportunity with current asthma or lung function. Lower school poverty or single-parent households and greater access to healthy food or economic resource index were associated with lower odds of a home environment with dampness or pests. More favorable neighborhood conditions in mid-childhood were associated with lower likelihood of living in a home with dampness or pests in the early adolescence.

Standardization of clinical outcomes used in allergen immunotherapy in allergic asthma: An EAACI position paper.

In allergic asthma patients, one of the more common phenotypes might benefit from allergen immunotherapy (AIT) as add-on intervention to pharmacological treatment. AIT is a treatment with disease-modifying modalities, the evidence for efficacy is based on controlled clinical trials following standardized endpoint measures. However, so far there is a lack of a consensus for asthma endpoints in AIT trials. The aim of a task force (TF) of the European Academy of Allergy and Clinical Immunology (EAACI) is evaluating several outcome measures for AIT in allergic asthma. The following domains of outcome measures in asthmatic patients have been evaluated for this position paper (PP): (i) exacerbation rate, (ii) lung function, (iii) ICS withdrawal, (iv) symptoms and rescue medication use, (v) questionnaires (PROMS), (vi) bronchial/nasal provocation, (vii) allergen exposure chambers (AEC) and (viii) biomarkers. Exacerbation rate can be used as a reliable objective primary outcome; however, there is limited evidence due to different definitions of exacerbation. The time after ICS withdrawal to first exacerbation is considered a primary outcome measure. Besides, the advantages and disadvantages and clinical implications of further domains of asthma endpoints in AIT trials are elaborated in this PP. This EAACI-PP aims to highlight important aspects of current asthma measures by critically evaluating their applicability for controlled trials of AIT.

Assessment of asthma mimics among newly diagnosed bronchial asthma patients in Zagazig University Hospitals

BackgroundBronchial asthma may mimic different diseases regarding their similar clinical presentations, so accurate assessment is required to exclude other possible diagnosis before confirming the diagnosis of bronchial asthma. The aim of the study was to identify the percentage of patients in whom the diagnosis of current asthma was confirmed or ruled out after clinical, spirometric assessment, and utilizing all the possible investigations.MethodsA cohort study of newly diagnosed bronchial asthma in adults aged ≥ 18 years were recruited from chest outpatient clinic and chest department. History taking, clinical examination, chest X-ray, and spirometry were done for all patients, while chest high-resolution computed tomography (HRCT), CT pulmonary angiography, or different endoscopies were done when indicated.ResultsTwo hundred recently clinically diagnosed asthmatic patients were recruited with a mean age of 43.2 and 53.4 years in the asthma group and asthma rule out group, respectively. About 55.5% of the studied patients were ruled out to have bronchial asthma after serial assessments of symptoms and spirometric function. There was increased chest wheeze as a respiratory symptom among asthma patients than the other group (p ˂ 0.001), while hemoptysis was significantly a more presenting symptom among patient group whose asthma diagnosis is ruled out (p = 0.009). About 87.6% of asthma confirmed group showed predominant reversible airway obstructive. The sputum cytology analysis of the bronchial asthma group of patients was 42.7% eosinophilic, 24.7% neutrophilic, and 32.6% mixed cellularity. After consuming all the available investigational tools, the most common diseases found among asthma rule out group were cardiac disorders, chronic obstructive pulmonary disease, psychological disorders, rhinitis, and gastro-esophageal reflux disease with percent of 11.5%, 9%, 8.5%, 8%, and 6%, respectively.ConclusionsUtilizing all the available investigational tools in the present study allowed to exclude bronchial asthma and diagnose critical diseases that need specific and urgent therapies as heart diseases, subglottic stenosis, pulmonary hypertension, and interstitial lung diseases.Trial registrationClinicalTrials.gov NCT05776537. Retrospectively registered on 6 March 2023.

Blockade of MIF biological activity ameliorates house dust mite-induced allergic airway inflammation in humanized MIF mice.

Macrophage migration inhibitory factor (MIF) expression is controlled by a functional promoter polymorphism, where the number of tetranucleotide repeats (CATTn ) corresponds to the level of MIF expression. To examine the role of this polymorphism in a pre-clinical model of allergic asthma, novel humanized MIF mice with increasing CATT repeats (CATT5 and CATT7 ) were used to generate a physiologically relevant scale of airway inflammation following house dust mite (HDM) challenge. CATT7 mice expressing high levels of human MIF developed an aggressive asthma phenotype following HDM challenge with significantly elevated levels of immune cell infiltration, production of inflammatory mediators, goblet cell hyperplasia, subepithelial collagen deposition, and airway resistance compared to wild-type controls. Importantly the potent MIF inhibitor SCD-19 significantly mitigated the pathophysiology observed in CATT7 mice after HDM challenge, demonstrating the fundamental role of endogenous human MIF expression in the severity of airway inflammation in vivo. Up to now, there are limited reproducible in vivo models of asthma airway remodeling. Current asthma medications are focused on reducing the acute inflammatory response but have limited effects on airway remodeling. Here, we present a reproducible pre-clinical model that capitulates asthma airway remodeling and suggests that in addition to having pro-inflammatory effects MIF may play a role in driving airway remodeling.

Urine 2-hydroxyphenanthrene is associated with current asthma: evidence from NHANES 2007-2012.

The current study aims to explore the effects of nine urine monohydroxy PAH metabolites (OHPAH) including 1-hydroxynaphthalene (1-OHNAP), 2-hydroxynaphthalene (2-OHNAP), 3-hydroxyfluorene (3-OHFLU), 9-hydroxyfluorene (9-OHFLU), 1-hydroxyphenanthrene (1-OHPHE), 2-hydroxyphenanthrene (2-OHPHE), 3-hydroxyphenanthrene (3-OHPHE), and 1-hydroxypyrene (1-OHPYR) on current asthma in people in the United States using a variety of statistical techniques. A cross-sectional examination of a subsample of 3804 adults aged ≥20 from the National Health and Nutrition Examination Survey (NHANES) was conducted between 2007 and 2012. To investigate the relationship between urine OHPAHs levels and current asthma, multivariate logistic regression, Bayesian kernel machine regression (BKMR), and quantile g-computation (qgcomp) were utilized. In the multivariate logistic regression model, after controlling for confounders, urine 2-OHPHE was associated with current asthma in both male (AOR = 7.17, 95% CI: 1.28-40.08) and female (AOR = 2.91, 95% CI: 1.06-8.01) smokers. In the qgcomp analysis, 2-OHPHE (39.5%), 1-OHNAP (33.1%), and 2-OHNAP (22.5%) were the major positive contributors to the risk of current asthma (OR = 2.29, 95% CI: 0.99, 5.25), and in female smokers, 9-OHFLU (25.8%), 2-OHFLU (21.5%), and 2-OHPHE (15.1%) were the major positive contributors (OR = 2.19, 95% CI: 1.06, 4.47). The results of the BKMR model basically agreed with qgcomp analysis. Our results demonstrate a strong association of urine 2-OHPHE with current asthma, and further longitudinal studies are needed to understand the precise relationship between PAH exposure and current asthma risk.

The Association of Periconception Asthma Medication Discontinuation with Adverse Obstetric Outcomes.

This study aimed to investigate asthma medication reduction in the periconceptional period as it relates to asthma status and adverse outcomes in pregnancy. In a prospective cohort study, self-reported current and past asthma medications were collected and analyzes compared measures of asthma status in women who discontinued asthma medication in the 6 months prior to enrollment ("step-down") versus those who did not ("no change"). Evaluation of asthma was done at three study visits (one per trimester) and by daily diaries, including measures of lung function (percent predicted forced expiratory volume in 1 and 6 s [%FEV1, %FEV6], peak expiratory flow [%PEF], forced vital capacity [%FVC], FEV1 to FVC ratio [FEV1/FVC]), lung inflammation (fractional exhaled nitric oxide [FeNO], ppb), rate of asthma symptoms (activity limitation, night symptoms, rescue inhaler use, wheeze, shortness of breath, cough, chest tightness, chest pain), and rate of asthma exacerbations. Adverse pregnancy outcomes were also evaluated. Adjusted regression analyses examined whether adverse outcomes differed by periconceptional asthma medication changes. Of 279 participants included in analyses, 135 (48.4%) did not change asthma medication in the periconceptional period, whereas 144 (51.6%) reported a step down in medication. Those in the step-down group were more likely to have milder disease (88 [61.1%] in the step-down vs. 74 [54.8%] in the no change group), exhibited less activity limitation (rate ratio [RR]: 0.68, 95% confidence interval [CI]: 0.47-0.98), and experienced fewer asthma attacks (RR: 0.53, 95% CI: 0.34-0.84) during pregnancy. The step-down group had a nonsignificant increase in overall odds of experiencing an adverse pregnancy outcome (odds ratio: 1.62, 95% CI: 0.97-2.72). Over half of women with asthma reduce asthma medication in the periconceptional period. Although these women typically have milder disease, a step down in medication may be associated with an increased risk of adverse pregnancy outcomes. · Many women reduce their asthma medication in pregnancy.. · Reduction is more common among those with mild disease.. · Medication reduction may lead to adverse pregnancy outcomes..

Asthma disparities among U.S. children and adults

Objective To assess factors that are associated with asthma prevalence and asthma attacks among children (0–17 years) and adults (18 years and over) in the United States of America. Methods The 2019–2021 National Health Interview Survey data were analyzed using multivariable logistic regression models to determine associations between health outcomes (i.e. current asthma and asthma attacks) and demographic and socioeconomic factors. Each health outcome was regressed over each characteristic variable, adjusting for age, sex, and race/ethnicity for adults and sex and race/ethnicity for children. Results Asthma was more common among children who were male, blacks, parental education less than bachelor’s, or had public health insurance, and among adults who had less than a bachelor’s degree, do not own a home, or not in the workforce. Persons in families facing difficulty paying medical bills were more likely to have current asthma (children: aPR = 1.62[1.40–1.88]; adults: aPR = 1.67[1.55–1.81]) and asthma attacks (children: aPR = 1.34[1.15–1.56]; adults: aPR = 1.31[1.20–1.43]). Persons with family income <100% federal poverty threshold (FPT) (children: aPR = 1.39[1.17–1.64]; adults: aPR = 1.64[1.50–1.80]) or adults 100–199% FPT (aPR = 1.28[1.19–1.39]) were more likely to have current asthma. Children and adults with family income <100% FPT and adults 100–199% FPT were also more likely to have asthma attacks. Having asthma attacks was common among adults not in the workforce as well (aPR = 1.17[1.07–1.27]). Conclusions Asthma affects certain groups disproportionately. The findings of this paper suggesting asthma disparities continue to persist may increase public health programs awareness to better deliver effective and evidence-based interventions.

Macrophages Orchestrate Airway Inflammation, Remodeling, and Resolution in Asthma.

Asthma is a heterogenous chronic inflammatory lung disease with endotypes that manifest different immune system profiles, severity, and responses to current therapies. Regardless of endotype, asthma features increased immune cell infiltration, inflammatory cytokine release, and airway remodeling. Lung macrophages are also heterogenous in that there are separate subsets and, depending on the environment, different effector functions. Lung macrophages are important in recruitment of immune cells such as eosinophils, neutrophils, and monocytes that enhance allergic inflammation and initiate T helper cell responses. Persistent lung remodeling including mucus hypersecretion, increased airway smooth muscle mass, and airway fibrosis contributes to progressive lung function decline that is insensitive to current asthma treatments. Macrophages secrete inflammatory mediators that induce airway inflammation and remodeling. Additionally, lung macrophages are instrumental in protecting against pathogens and play a critical role in resolution of inflammation and return to homeostasis. This review summarizes current literature detailing the roles and existing knowledge gaps for macrophages as key inflammatory orchestrators in asthma pathogenesis. We also raise the idea that modulating inflammatory responses in lung macrophages is important for alleviating asthma.

Respiratory and population effects of e-cigarettes: A Chinese perspective.

Respiratory and population effects of e-cigarettes: A Chinese perspective.

Impact of asthma on working life: an analysis of the French CONSTANCES cohort

ObjectivesAsthma has significant occupational consequences. The objective of our study was to investigate the links between asthma and the career path, taking into account gender and age at asthma onset.MethodsUsing...

Lung function at 16-19 years in males and females born very prematurely.

To determine if there were differences in lung function at 16-19 years of age between males and females born very prematurely. Females compared with males would have superior lung function and exercise capacity. Cohort study. Those born at less than 29 weeks of gestational age. Lung function testing (spirometry, oscillometry, diffusion capacity, lung clearance index, and plethysmography), a shuttle sprint test for exercise capacity, and a respiratory symptoms questionnaire. Amongst 150 participants, males had poorer lung function compared with females with mean z score differences (95% CI [confidence interval]) after adjustment: forced expiratory flow at 75% (FEF75 ) (-0.60 [-0.97,-0.24]), forced expiratory flow at 50% (FEF50 ) (-0.39 [-0.72,-0.07]), forced expiratory flow at 25%-75% (FEF25-75 ) (-0.62 [-0.98,-0.26]), the ratio of the forced expiratory volume in the first one second to the forced vital capacity of the lungs (FEV1 :FVC ratio) (-0.71 [-1.09,-0.34]), diffusing capacity of the lungs for carbon monoxide (DLCO) (-0.41 [-0.78,-0.03]), diffusing capacity of the lung for carbon monoxide divided by alveolar volume (DLCO/VA) (-0.57 [-0.86,-0.28]). Exercise capacity and self-reported exercise were both significantly better in males than females (46% males achieving between 1250 and 1500 m shuttle sprint distance vs. 4.8% females) and 74% males versus 67% females undertaking some exercise. There were no significant differences by sex in the prevalence of either wheeze or current asthma. Males had poorer lung function than females at age 16-19 years, but their exercise capacity was superior to females.

Prevalence, severity and risk factors for asthma in school-going adolescents in KwaZulu Natal, South Africa

BackgroundAsthma remains highly prevalent, with more severe symptoms in low-income to middle-income countries (LMICs) compared with high-income countries. Identifying risk factors for severe asthma symptoms can assist with improving outcomes....

Adult asthma prevalence and trend analysis by urban-rural status across sociodemographic characteristics-United States, 2012-20.

Asthma prevalence estimates among adults are limited for urban-rural classification across sociodemographic characteristics. This study examined current asthma prevalence and annual trends by 6-level urban-rural categories across sociodemographic characteristics among US adults. Asthma prevalence for 2020 and annual trends for 2012-20 were estimated using Behavioral Risk Factor Surveillance System data. The 2013 National Center for Health Statistics urban and rural categories were used to define urban-rural status. Current asthma prevalence was higher in medium (9.7%; prevalence ratio 1.103 [95% CI 1.037, 1.174]) and small (9.9%; 1.111 [1.031, 1.197]) metro than in large fringe metropolitan (8.6%), was higher in micropolitan (10.2%) than in both large fringe (8.6%; 1.115 [1.042, 1.194]) and large central metropolitan (8.8%; 1.080 [1.001, 1.066]) areas. Prevalence by sociodemographic characteristics varied between urban-rural scheme; the prevalence was significantly higher among adults aged 55-64 years in micropolitan (11.9%), women in small metro (12.8%), and other race non-Hispanic in noncore (most rural) (13.6%) areas, adults without a high school diploma in micropolitan areas (13.8%), household income <100% of federal poverty level in micropolitan areas (15.7%), and adults with insurance coverage in micropolitan areas (10.3%) compared to the corresponding populations in other urban-rural categories. During 2012-20, an increasing trend in prevalence was observed only in medium metro areas, with an annual percentage change of 0.81. Asthma prevalence differed by 6-level urban-rural categories. These findings might be helpful in establishing effective asthma control programs and targeting resource allocation at the local level.

Associations between serum per- and polyfluoroalkyl substances and asthma morbidity in the National Health and Nutrition Examination Survey (2003-18).

Per- and polyfluoroalkyl substances (PFAS) are a class of chemicals widely used in manufacturing and are highly resistant to degradation, so they accumulate in the environment. Serum concentrations of these so-called forever chemicals have been associated with impairment of innate and adaptive immune responses. The relationship between serum PFAS levels and asthma morbidity has not been studied. We tested the association between serum PFAS concentration and asthma exacerbations. We performed secondary analysis of data from the National Health and Nutrition Examination Survey (NHANES, 2003-18). We fit multivariable logistic regression models to estimate odds ratios and 95% CIs for asthma exacerbation in the prior 12 months, given serum concentrations of PFAS. Models were adjusted for relevant covariates. Of 1101 participants with self-reported current asthma and available serum PFAS data, we observed that higher serum perfluorooctanoic and perfluorodecanoic acids were associated with greater odds of asthma attacks in the previous 12 months (respectively, adjusted odds ratio 1.16, 95% CI 1.01, 1.33; and adjusted odds ratio 1.21, 95% CI 1.03, 1.43). After stratification by age, the association between perfluorooctanoic acid and asthma attacks was significant in the 12-18-year-old group only (adjusted odds ratio 1.56, 95% CI 1.06, 2.31). No significant relationships were observed between PFAS and asthma-related emergency department visits. After correction for multiple comparison testing, none of the associations reached the threshold of significance. The role of these bioaccumulative forever chemicals in susceptibility to asthma attacks warrants further examination in longitudinal studies. (J Allergy Clin Immunol Global 2023;2:100078.).

Vitamin D mediated mitigation of fibrotic remodeling in asthma is associated with metabolic reprogramming

Vitamin D mediated mitigation of fibrotic remodeling in asthma is associated with metabolic reprogramming Rakhee K. Ramakrishnan1, Zaina Kalaji1, Khuloud Bajbouj1, Rabih Halwani1,2, Qutayba Hamid1,3 1 Sharjah Institute for Medical Research – College of Medicine, University of Sharjah, Sharjah, United Arab Emirates 2 Immunology Research Lab, College of Medicine, King Saud University, Riyadh, Saudi Arabia 3 Meakins-Christie Laboratories, McGill University, Montreal, Quebec, CanadaAsthma is a heterogeneous disorder that is associated with chronic airway inflammation and remodeling of the airways. While vitamin D deficiency has shown correlations with various clinical features of asthma, the mechanisms responsible for this action is poorly understood. This study therefore explored the molecular mechanisms associated with the anti-remodeling potential of vitamin D. We hypothesized that vitamin D induced metabolic reprogramming contributes to its anti-fibrotic activity. To this end, primary lung fibroblasts from asthmatic and non-asthmatic individuals were stimulated with TGF-β1 alone or in combination with the biologically active form of vitamin D, calcitriol. The expression of various fibrotic and metabolic markers was assessed both at the transcript and protein level. While vitamin D receptor (VDR) was constitutively expressed in human lung fibroblasts, calcitriol treatment induced a robust VDR response in asthmatic fibroblasts indicating increased VDR functionality in these cells when compared to normal. TGF-β1 stimulation led to an increase in the expression of several fibrotic markers, including COL1A1, COL3A1, COL5A1, FN1 and ACTA2, which was reversed after calcitriol treatment. These anti-fibrotic effects of calcitriol were associated with dysregulated AMPK signaling and an inhibition of TGF-β1-induced mitochondrial ROS release. Our findings thus, highlight the ability of vitamin D in regulating the cellular mitochondrial metabolism induced by TGF-β1 in lung fibroblasts, suggesting a possible mechanism associated with its anti-fibrotic activity. Since current asthma therapeutics do not effectively target the airway structural changes that are increasingly associated with asthma severity, vitamin D supplementation presents an attractive therapeutic avenue to attenuate subepithelial fibrosis and airway remodeling in asthmatic airways. We would like to acknowledge the funding received from University of Sharjah targeted research grant (ID 2101090295) in conducting this study. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Respiratory syncytial virus infection during infancy and asthma during childhood in the USA (INSPIRE): a population-based, prospective birth cohort study

Early-life severe respiratory syncytial virus (RSV) infection has been associated with the onset of childhood wheezing illnesses. However, the relationship between RSV infection during infancy and the development of childhood asthma is unclear. We aimed to assess the association between RSV infection during infancy and childhood asthma. INSPIRE is a large, population-based, birth cohort of healthy infants with non-low birthweight born at term between June and December, 2012, or between June and December, 2013. Infants were recruited from 11 paediatric practices across middle Tennessee, USA. We ascertained RSV infection status (no infection vs infection) in the first year of life using a combination of passive and active surveillance with viral identification through molecular and serological techniques. Children were then followed up prospectively for the primary outcome of 5-year current asthma, which we analysed in all participants who completed 5-year follow-up. Statistical models, which were done for children with available data, were adjusted for child's sex, race and ethnicity, any breastfeeding, day-care attendance during infancy, exposure to second-hand smoke in utero or during early infancy, and maternal asthma. Of 1946 eligible children who were enrolled in the study, 1741 (89%) had available data to assess RSV infection status in the first year of life. The proportion of children with RSV infection during infancy was 944 (54%; 95% CI 52-57) of 1741 children. The proportion of children with 5-year current asthma was lower among those without RSV infection during infancy (91 [16%] of 587) than those with RSV infection during infancy (139 [21%] of 670; p=0·016). Not being infected with RSV during infancy was associated with a 26% lower risk of 5-year current asthma than being infected with RSV during infancy (adjusted RR 0·74, 95% CI 0·58-0·94, p=0·014). The estimated proportion of 5-year current asthma cases that could be prevented by avoiding RSV infection during infancy was 15% (95% CI 2·2-26·8). Among healthy children born at term, not being infected with RSV in the first year of life was associated with a substantially reduced risk of developing childhood asthma. Our findings show an age-dependent association between RSV infection during infancy and childhood asthma. However, to definitively establish causality, the effect of interventions that prevent, delay, or decrease the severity of the initial RSV infection on childhood asthma will need to be studied. US National Institutes of Health.

Association between maternal occupational exposure to cleaning chemicals during pregnancy and childhood wheeze and asthma.

Asthma is a leading cause of childhood morbidity in the U.S. and a significant public health concern. The prenatal period is a critical window during which environmental influences, including maternal occupational exposures, can shape child respiratory health. Cleaning chemicals are commonly encountered in occupational settings, yet few studies have examined the potential link between prenatal occupational exposures to cleaning chemicals and risk of childhood wheeze and asthma. We evaluated the potential influence of maternal occupational exposure to cleaning chemicals during pregnancy on pediatric asthma and wheeze at child age 4-6 years in 453 mother-child pairs from two longitudinal pregnancy cohorts, TIDES and GAPPS, part of the ECHO prenatal and early childhood pathways to health (ECHO-PATHWAYS) consortium. Maternal occupational exposure to cleaning chemicals was defined based on reported occupation and frequency of occupational use of chemicals during pregnancy. Child current wheeze and asthma outcomes were defined by parental responses to a widely-used, standardized respiratory outcomes questionnaire administered at child age 4-6 years. Multivariable Poisson regression with robust standard errors was used to estimate relative risk (RR) of asthma in models adjusted for confounding. Effect modification by child sex was assessed using product interaction terms. Overall, 116 mothers (25.6%) reported occupational exposure to cleaning chemicals during pregnancy, 11.7% of children had current wheeze, and 10.2% had current asthma. We did not identify associations between prenatal exposure to cleaning chemicals and current wheeze [RRadjusted 1.03, 95% confidence interval (CI): 0.56, 1.90] or current asthma (RRadjusted 0.89, CI: 0.46, 1.74) in the overall sample. Analyses of effect modification suggested an adverse association among females for current wheeze (RR 1.82, CI: 0.76, 4.37), compared to males (RR 0.68, CI: 0.29, 1.58), though the interaction p-value was >0.05. We did not observe evidence of associations between maternal prenatal occupational exposure to cleaning chemicals and childhood wheeze or asthma in the multi-site ECHO-PATHWAYS consortium. We leveraged longitudinal U.S. pregnancy cohorts with rich data characterization to expand on limited and mixed literature. Ongoing research is needed to more precisely characterize maternal occupational chemical exposures and impacts on child health in larger studies.