Current indoor allergen levels of fungi and cats, but not house dust mites, influence allergy and asthma in adults with high dust mite exposure

C1 - Journal Articles Referee

Outdoor fungal spores and acute respiratory effects in vulnerable individuals

Background Many outdoor fungal spores are ubiquitous, respirable and possibly allergenic. They may contribute to asthma symptoms; however, little is known about their effects on respiratory function. Objective To investigate if outdoor fungal spore levels were associated with lung function or airway inflammation, and whether fungal sensitization or current asthma modified any associations. Methods Cross-sectional associations between same day (Lag0) and cumulative 3-day lagged (Lag0-3) counts of 12 outdoor fungal spore taxa and pre-bronchodilator spirometry (FEV1, FVC, FEF25%–75%), bronchodilator response (BDR) and airway inflammation (fractional exhaled nitric oxide (FeNO) and exhaled breath condensate (EBC) nitrogen oxides (NOx) and pH were investigated in 936 Melbourne Atopy Cohort Study participants during September 2009 to December 2011. Generalized linear models were used to quantify associations with lung function, FeNO and EBC pH; generalized estimating equations for BDR; and ordinal logistic regression for EBC NOx. Models were adjusted for age, sex, height, temperature, relative humidity, grass pollen and sample storage time. Potential effect modification by fungal sensitization and current asthma were examined using interaction terms. Results Mixed associations were found. Higher levels of Ustilago/smuts were associated with lower lung function at Lag0 (FEV1: 21ml [95%CI -36, −7]; FEF25%–75%: 39ml [-65, −13]) and Lag0-3 (FEV1: 9ml [-14, −4]; FEF25%–75% −18ml [-27, −9]). Positive BDR was associated with Ustilago/smuts (Lag0 OR = 1.1 [1.04, 1.2]; Lag0-3 OR = 1.04 [1.02, 1.07]), Alternaria (Lag0 OR = 1.3 [1.0, 1.6]) and Drechslera (Lag0 OR = 1.1 [1.03, 1.2]). Higher EBC NOx was associated with Cladosporium (Lag0-3 OR = 1.1 [1.0, 1.2]), Alternaria (Lag0-3 OR = 1.1 [1.0, 1.3]). No associations were found with higher FeNO. In those with fungal sensitization, Ustilago/smuts and Drechslera were associated with lower FEV1 and FVC; Cladosporium was associated with increased FEV1, FVC and FEF25%–75% but also with higher FeNO and lower EBC pH. In those with current asthma, Alternaria, Ustilago/smuts and Drechslera were associated with lower FEV1, FVC, FEF25–75% and EBC pH. Conclusion Exposure to outdoor fungal spores may be associated with lower lung function and increased airway inflammation, particularly in those with fungal sensitization and/or current asthma

Early life exposure to coal mine fire smoke emissions and altered lung function in young children

Background and objective Long‐term respiratory risks following exposure to relatively short periods of poor air quality early in life are unknown. We aimed to evaluate the association between exposure to a 6‐week episode of air pollution from a coal mine fire in children aged <2 years, and their lung function 3 years after the fire. Methods We conducted a prospective cohort study. Individual exposure to 24‐h average and peak concentrations of particulate matter with an aerodynamic diameter <2.5 μm in diameter (PM2.5) during the fire were estimated using dispersion and chemical transport modelling. Lung function was measured using the forced oscillation technique (FOT), generating standardized Z‐scores for resistance and reactance at a frequency of 5 Hz (Rrs5 and Xrs5), and area under the reactance curve (AX). We used linear regression models to assess the associations between PM2.5 exposure and lung function, adjusted for potential confounders. Results Of the 203 infants originally recruited, 84 aged 4.3 ± 0.5 years completed FOT testing. Median (interquartile range, IQR) for average and peak PM2.5 were 7.9 (6.8–16.8) and 103.4 (60.6–150.7) μg/m3, respectively. The mean ± SD Z‐scores for Rrs5, Xrs5 and AX were 0.56 ± 0.80, –0.76 ± 0.88 and 0.72 ± 0.92, respectively. After adjustment for potential confounders including maternal smoking during pregnancy, a 10 μg/m3 increase in average PM2.5 was significantly associated with worsening AX (β‐coefficient: 0.260; 95% CI: 0.019, 0.502), while the association between a 100‐μg/m3 increase in peak PM2.5 and AX was borderline (0.166; 95% CI: −0.002, 0.334). Conclusion Infant exposure to coal mine fire emissions could be associated with long‐term impairment of lung reactance

The Exposome Approach in Allergies and Lung Diseases: Is It Time to Define a Preconception Exposome?

Emerging research suggests environmental exposures before conception may adversely affect allergies and lung diseases in future generations. Most studies are limited as they have focused on single exposures, not considering that these diseases have a multifactorial origin in which environmental and lifestyle factors are likely to interact. Traditional exposure assessment methods fail to capture the interactions among environmental exposures and their impact on fundamental biological processes, as well as individual and temporal factors. A valid estimation of exposure preconception is difficult since the human reproductive cycle spans decades and the access to germ cells is limited. The exposome is defined as the cumulative measure of external exposures on an organism (external exposome), and the associated biological responses (endogenous exposome) throughout the lifespan, from conception and onwards. An exposome approach implies a targeted or agnostic analysis of the concurrent and temporal multiple exposures, and may, together with recent technological advances, improve the assessment of the environmental contributors to health and disease. This review describes the current knowledge on preconception environmental exposures as related to respiratory health outcomes in offspring. We discuss the usefulness and feasibility of using an exposome approach in this research, advocating for the preconception exposure window to become included in the exposome concept

Age-of-onset information helps identify 76 genetic variants associated with allergic disease

Risk factors that contribute to inter-individual differences in the age-of-onset of allergic diseases are poorly understood. The aim of this study was to identify genetic risk variants associated with the age at which symptoms of allergic disease first develop, considering information from asthma, hay fever and eczema. Self-reported age-of-onset information was available for 117,130 genotyped individuals of European ancestry from the UK Biobank study. For each individual, we identified the earliest age at which asthma, hay fever and/or eczema was first diagnosed and performed a genome-wide association study (GWAS) of this combined age-of-onset phenotype. We identified 50 variants with a significant independent association (P<3x10-8) with age-of-onset. Forty-five variants had comparable effects on the onset of the three individual diseases and 38 were also associated with allergic disease case-control status in an independent study (n = 222,484). We observed a strong negative genetic correlation between age-of-onset and case-control status of allergic disease (rg = -0.63, P = 4.5x10-61), indicating that cases with early disease onset have a greater burden of allergy risk alleles than those with late disease onset. Subsequently, a multivariate GWAS of age-of-onset and case-control status identified a further 26 associations that were missed by the univariate analyses of age-of-onset or case-control status only. Collectively, of the 76 variants identified, 18 represent novel associations for allergic disease. We identified 81 likely target genes of the 76 associated variants based on information from expression quantitative trait loci (eQTL) and non-synonymous variants, of which we highlight ADAM15, FOSL2, TRIM8, BMPR2, CD200R1, PRKCQ, NOD2, SMAD4, ABCA7 and UBE2L3. Our results support the notion that early and late onset allergic disease have partly distinct genetic architectures, potentially explaining known differences in pathophysiology between individuals