Early life environmental predictors of asthma age-of-onset.

Olivia R Ferry,Manuel A R Ferreira,David L Duffy

doi:10.1002/iid3.27

Olivia R Ferry, Manuel A R Ferreira + Show 1 more

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https://doi.org/10.1002/iid3.27

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Abstract

Prevention strategies that delay the onset of asthma may improve clinical outcomes. To identify early life environmental exposures associated with asthma age-of-onset and potential genetic modifiers of these exposures, we studied 1085 subjects with physician-diagnosed asthma and disease onset at or after age two. Subjects reported retrospectively on their exposure to 17 environmental factors before the age of two. The presence of individual or combinations of these early life exposures was then tested for association with variation in asthma age-of-onset. For exposures significantly associated with age-of-onset, we tested if 26 single nucleotide polymorphisms (SNP) with an established association with allergic disease significantly modified the effect of the exposure. Five environmental exposures were significantly associated with variation in asthma age-of-onset after correction for multiple testing: carpet at home (P = 6 × 10−5), a serious chest illness (P = 10−4), father a cigarette smoker (P = 6 × 10−4) and direct exposure to father's smoking (P = 3 × 10−4). Individuals with early childhood asthma onset, between the ages of two and six, were 1.4-fold (CI 1.1–1.9) more likely to report having lived in a house with carpet and 2.1-fold (CI 1.3–3.5) more likely to report suffering a serious chest illness before the age of two, than asthmatics with later disease onset. We further found these individual risks to increase to 3.2-fold (CI 1.7–6.0) if carpet exposure and suffering a serious chest illness co-occurred before age two. Paternal smoking exposures were less likely to be reported by asthmatics with early when compared to later disease onset (OR 0.5, CI 0.3–0.7). There were no significant SNP interactions with these environmental exposures after correction for multiple testing. Our results suggest that disease onset in individuals at a high-risk of developing asthma can potentially be delayed by avoiding exposure to carpet at home and preventing serious chest illnesses during the first 2 years of life.

Highlights

Asthma is an heterogeneous disease with epidemiological studies suggesting that it can be classified into a number of clinical phenotypes, based on age-of-onset, duration of disease, and clinical characteristics [1,2,3]
Asthma age-of-onset varied between 2 and 72 years, with males reporting an earlier age-of-onset than females
We have identified early life carpet exposure, living in a brick house type and suffering a serious chest illness as environmental predictors of early-onset asthma while paternal smoking exposure was associated with a later onset of asthma

Summary

Introduction

Asthma is an heterogeneous disease with epidemiological studies suggesting that it can be classified into a number of clinical phenotypes, based on age-of-onset, duration of disease, and clinical characteristics [1,2,3]. The clinical phenotype considered most severe is persistent atopic asthma, characterized by an early childhood onset of asthma, before the age of six, worsening lung function over time and no remission of disease in adulthood [3,4,5]. This persistent form of asthma has been linked to reduced asthma control leading to an increased number of emergency care visits [6]. The early life environment is considered to be critical in asthma pathogenesis due to the continued development of the respiratory and immune systems that occurs postnatally [10, 11]. Additional studies have found that the first years of life are a critical period of increased vulnerability of the developing lungs

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