Details of the RESPIRE and CRECER cohorts have been published elsewhere

Approximately 2.4 billion people worldwide rely on burning biomass fuels, including wood, crop residue, coal, and animal dung for household cooking and heating. These fuels are often burned indoors in simple stoves in often poorly ventilated rooms, emitting substantial amounts of pollutants including particulate matter, carbon monoxide, and polycyclic aromatic hydrocarbons, all components of household air pollution . It is estimated that HAP from biomass fuel is responsible for more than 1.8 million premature deaths and 60.9 million disability-adjusted life-years annually, with the greatest burden experienced in low- and middle-income countries. Women and children have the highest levels of exposure to HAP since they traditionally tend to daily household chores, including cooking and spending time in kitchens. Exposure to biomass smoke during childhood has been shown to impact lung function and increase risk of acute lower respiratory infections. However, less is known about the rates of allergic sensitization and subsequent risk of atopy, which is the tendency to develop allergic diseases such as allergic rhinitis, eczema, and allergic asthma, among children who are exposed to biomass smoke early in childhood. Prior studies focusing on outdoor air pollution suggest that exposure to traffic-related air pollution early in life may enhance the risk of aeroallergen sensitization and increase the risk of developing allergic diseases at older ages. Diesel exhaust, in particular, has been found to enhance risk of aeroallergen sensitization and promote development of allergic asthma. Environmental tobacco smoke exposure early in life has also been associated with the development of allergic sensitization in children. Studies that investigated cooking-related biomass smoke exposure in children have also found it to be associated with elevated risks of asthma, rhinitis,grow drying rack and other respiratory illnesses.

There are, however, limited data regarding the relationship between HAP, aeroallergen sensitization, and atopy in pediatric populations. A cross-sectional study conducted in rural Bavaria in southern Germany in a cohort of school-aged children from 9 to 11 years old found that children living in households using coal or wood for heating were less atopic and less likely to be sensitized towards aeroallergens than children living in households with other forms of heating. In a large study of Finnish children, there was also a negative association between woodstove heating and allergic rhinoconjunctivitis; however, this association disappeared after adjusting for other factors in the residential environment. In another population of children in Spain, the use of a biomass energy source for cooking and indoor heating was not associated with atopic dermatitis. Contrastingly, for children in rural Guatemala, a previous study suggested that the use of an open fire for cooking may be an important risk factor for asthma symptoms and severity later in life. The primary objective of this study is to examine the relationship between early biomass smoke exposure and atopy among a cohort of children enrolled in a HAP-reducing chimney stove intervention trial among a population living in the western highlands of Guatemala. In the study community, women often carry their youngest child on their back during cooking, until the child is approximately 18 months old, exposing the newborn children to high levels of HAP. We hypothesize that the availability of a vented chimney stove would reduce the children’s HAP exposure compared to those who use open fires for cooking and would be associated with risks of allergic sensitization. Participating households and children were recruited from the Randomized Exposure Study of Pollution Indoors and Respiratory Effects cohort and its follow-up study, the Chronic Respiratory Effects of Early Childhood Exposure to Respirable PM study. Briefly, 518 rural Guatemalan women with newborn children who cooked exclusively over an open fire were recruited for the RESPIRE study between October 2002 and December 2004. Households were randomized to either receive a chimney stove , which improves combustion and uses a chimney to vent emissions outdoors, or to continue to cook with their typical open fires until the end of the trial, when they also received the intervention plancha stove. CRECER, the follow up study, took place from 2006 to 2009 and revisited RESPIRE households and recruited 169 new households that were from the same geographical region, exclusively used open fires, had one child in the same age range as the RESPIRE study children and one infant less than 6 months old .

For equity purposes, these new households received a chimney stove at the end of the CRECER study when all exposure and outcome information had already been collected. All households in the study thus received a chimney stove at different time periods: RESPIRE intervention households received the stove when the index children were less than 6 months old; RESPIRE control households received the stove when the index children were approximately 18 months old; new CRECER households received the stove when the index children were approximately 5 years old, and their proxy infant siblings were 18–24 months old. The grouping and study timeline are illustrated in Figure 1. The plancha stoves provided in this study reduced the children’s biomass smoke exposure by improving combustion and venting cooking smoke outdoors. Although this may result in an increase in outdoor exposure, we would expect participants in households with plancha stoves to have lower overall biomass smoke exposure, because the total amount of smoke produced would not increase, and outdoor biomass smoke would affect children for shorter duration and lower intensity. We also hypothesized that group 1 index study children would have the lowest cumulative biomass smoke exposure because they were provided the plancha stoves earliest, followed by groups 2 and 3, respectively. To test these hypotheses, we measured carbon monoxide exposure for the study children. Personal CO exposure was used as a proxy for personal biomass smoke exposure: CO has been shown to correlate well with fine particulate matter exposure in this population, in homes using open fires or chimney stoves. Study participants wore small, passive CO diffusion tubes for 48 h every 3 months during RESPIRE and every 6 months during CRECER. Since group 3 index study children did not have CO measurements obtained when they were <18 months of age, the personal CO exposures of their younger infant siblings were used as a proxy for their early life exposures. Details on exposure assessment methodology, validation, and quality control and assurance have been extensively described elsewhere. We combined data from different measurements, including the aforementioned 48-h samples, to estimate cumulative CO exposure. We used RESPIRE CO tube measurements to estimate cumulative exposure during the first 600 days of life for groups 1 and 2 and used CRECER infant sibling CO tube measurements to estimate cumulative exposure during the first 600 days of life for group 3. Cumulative CO exposure from 600 days old to first allergy questionnaire was estimated based on CRECER CO tube measurements for the study children. We conducted a sensitivity analysis using three alternative calculations for cumulative CO exposure, two of which did not use the 600 days cut point. Details of these calculations can be found in the Table A1.Five rounds of skin prick tests were performed on 539 participants to determine allergic sensitization to six common indoor and outdoor aeroallergens . During each round of SPT, a positive control and a negative control were also performed on each child.

A positive SPT result was indicated by a wheal measurement 3 mm or greater. SPT results were considered invalid if the histamine control was negative or the saline control was positive. Results from children who reported taking antihistamine or cold medications prior to testing were also excluded. Atopic symptoms were assessed via quarterly respiratory questionnaires completed by the study children’s mothers. The QRQs were conducted three times during CRECER to ascertain the occurrence of symptoms associated with asthma,grow glide racks allergic rhinitis, and eczema. The questions were developed based on the International Study of Asthma and Allergies in Childhood questionnaire. All QRQs were conducted by field workers fluent in the participating mothers’ primary language . Details of the questionnaire development and translation processes have been published elsewhere. All questions were close ended and began with “in the last three months”. A child’s final allergic outcome was recorded as positive if the mother reported him/her having positive symptoms in any of the three QRQ rounds. Logistic regression models were used to analyze the relationship between biomass smoke exposure and the risks of developing allergic outcomes. Primary statistical analysis used study group as a categorical exposure variable based on the length of having a chimney stove in the household. Odds ratios and 95% confidence intervals were reported. In this analysis, group 1 is the baseline level, groups 2 and 3 represent intermediate and highest levels of biomass smoke exposure, respectively. Secondary statistical analysis used the estimated cumulative CO exposure as a linear continuous exposure variable. Age, sex, second-hand smoke exposure, the number of children in the family, kitchen structure , child’s average weekly temazcaluse in minutes, number and species of pets and farm animals at home, maternal history of allergic outcomes, parental education, and socioeconomic status were collected from the CRECER baseline questionnaire, and were adjusted for in the logistic regression models. We did not adjust for race because the study population was homogenous, self-identifying as Mam indigenous. Among the 557 households participating in CRECER, 20 lacking valid SPT or QRQ results were excluded. For the two households with twins that both participated in the study, only the first child recorded was kept in the analysis to ensure independence among observations. Respiratory outcomes were available for 537 children, 188 from group 1, 192 from group 2 and 157 from group 3. Valid SPT results were available for 526 children, 184 from group 1, 187 from group 2 and 155 from group 3 . The quality and precision of the five rounds of SPTs during CRECER improved with additional training and more experience of the staff, indicated by the significantly lower number of invalid tests in the later rounds. As such, the results of the last valid round of SPT for each child was recorded as the child’s final allergic sensitization outcome. Among the 526 children with valid SPT results, results for 496 participants were taken from the 5th round of SPT tests. The household-level and child-level demographic characteristics were similar among the three study groups , especially between groups 1 and 2 that were randomized in the RESPIRE study.

Study children were on average 3.6 years old at the first QRQ.Compared with groups 1 and 2, group 3 had higher proportions of maternal history of asthma, rhinitis and eczema, and slightly lower SES. This prospective cohort study followed more than 500 children in rural Guatemala over 7 years and examined associations between cooking-related biomass smoke exposure and childhood atopy outcomes. Children from households that received chimney stoves when the children were approximately 5 years old had higher risks of maternal-reported allergic asthma and rhinitis symptoms compared to children from households that received a chimney stove intervention within the first 6 months of life. A 1 ppm-year higher cumulative CO exposure and its related cumulative biomass smoke exposure was associated with 6–12% higher odds of maternal reported allergic rhinitis and conjunctivitis symptoms. No significant association was found between biomass smoke exposure and eczema or skin prick test outcomes. Notably, the overall prevalence of sensitization to cockroach in this population of rural Guatemalan children was high , which is similar to that reported for inner city children in the U.S. A summary of main results from studies that looked at household biomass smoke exposure and allergic or respiratory outcomes is presented in Table A2. Our finding that higher biomass smoke exposure was associated with maternal-reported respiratory symptoms such as wheezing, sneezing, nasal congestion and rhinorrhea in their children is consistent with other studies that looked at exposure to biomass stove use and self-reported or clinically diagnosed respiratory diseases among children. Prior studies that looked at exposure to cooking and heating-related HAP and atopy outcomes in children residing in high-income countries did not find significant associations after adjusting for lifestyle and socioeconomic factors. In this study, we did not find a significant association between biomass smoke exposure and maternal-reported eczema symptoms. Additionally, there was no significant association between biomass smoke exposure and allergic sensitization as measured by SPT.