Introduction
Asthma is the most common chronic disease of childhood in high-income countries and is estimated to affect 358 millions worldwide.1 Asthma is increasing in prevalence in many low and middle-income countries (LMICs).2 Temporal trends of increasing asthma prevalence in LMICs are considered to be related to urbanization and loss of protective exposures associated with rural residence.3
Recent years have seen increasing urbanization in LMICs, accompanied by reductions in poverty, improved access to basic services, and transformation of the living environment.3 Under such circumstances, the intensity of microbial exposures in early childhood is likely to have declined, affecting the maturation and regulation of the immune system and risk of inflammatory diseases including asthma.4,5
Geohelminths (caused by Ascaris lumbricoides , Trichuris truchiura , and hookworm) infect over 1 billion humans worldwide6 and are most prevalent among children living in conditions of poverty in tropical regions of LMICs. Geohelminths cause chronic infections that are associated with modulation of host Th2 inflammatory mechanisms.7 The tight regulation of Th2 inflammatory responses may modulate inflammation associated with allergy and asthma. It has been suggested that the lower prevalence of asthma symptoms observed in rural compared to urban populations in tropical regions of LMICs3 is explained by the immune modulatory effects of endemic geohelminth infections.5
Epidemiological studies of the relationship between geohelminths and allergic inflammation (measured by atopy) or asthma have shown conflicting findings in cross-sectional analyses and intervention studies done largely in schoolchildren.8-14 We hypothesized that in utero or early childhood exposures to geohelminths protect against the development of atopy and asthma in later childhood. To test this hypothesis, we followed an Ecuadorian cohort from birth to 8 years of age in an area of high endemicity. Previous analyses from the cohort showed a protective effect of maternal geohelminths on atopy to mite allergens at 3 years.15At 5 years, we observed that maternal infections increased the risk of wheeze while childhood infections protected against wheeze and atopy to perennial aeroallergens, and raised the possibility that childhood infections might modulate wheeze through non-allergic mechanisms.16
To understand better the effects of early childhood geohelminth exposures on wheeze, asthma and atopy, and whether the previously observed effects persist, we report findings at 8 years including novel measurements of airways inflammation and reactivity to provide further insights on effects of geohelminths on non-atopic wheezing illness and asthma.