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Alterations in gut microbiota in early life have been associated with the development of asthma; however, the role of gut bacteria or the IgA response to gut bacteria in school-aged children with asthma is unclear. To address this question, we profiled the microbial populations in fecal and nasal swab samples by 16S rRNA sequencing from 40 asthma and 40 control children aged 9-17 y from Peru. Clinical history and laboratory evaluation of asthma and allergy were obtained. Fecal samples were analyzed by flow cytometry and sorted into IgA+ and IgA- subsets for 16S rRNA sequencing. We found that the fecal or nasal microbial 16S rRNA diversity and frequency of IgA+ fecal bacteria did not differ between children with or without asthma. However, the α diversity of fecal IgA+ bacteria was decreased in asthma compared with control. Machine learning analysis of fecal bacterial IgA-enrichment data revealed loss of IgA binding to the Blautia, Ruminococcus, and Lachnospiraceae taxa in children with asthma compared with controls. In addition, this loss of IgA binding was associated with worse asthma control (Asthma Control Test) and increased odds of severe as opposed to mild to moderate asthma. Thus, despite little to no change in the microbiota, children with asthma exhibit an altered host IgA response to gut bacteria compared with control participants. Notably, the signature of altered IgA responses is loss of IgA binding, in particular to members of Clostridia spp., which is associated with greater severity of asthma.

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BACKGROUND: Genetic ancestry plays a role in asthma health disparities. OBJECTIVE: Our aim was to evaluate the impact of ancestry on and identify genetic variants associated with asthma, total serum IgE level, and lung function. METHODS: A total of 436 Peruvian children (aged 9-19 years) with asthma and 291 without asthma were genotyped by using the Illumina Multi-Ethnic Global Array. Genome-wide proportions of indigenous ancestry populations from continental America (NAT) and European ancestry from the Iberian populations in Spain (IBS) were estimated by using ADMIXTURE. We assessed the relationship between ancestry and the phenotypes and performed a genome-wide association study. RESULTS: The mean ancestry proportions were 84.7% NAT (case patients, 84.2%; controls, 85.4%) and 15.3% IBS (15.8%; 14.6%). With adjustment for asthma, NAT was associated with higher total serum IgE levels (P < .001) and IBS was associated with lower total serum IgE levels (P < .001). NAT was associated with higher FEV1 percent predicted values (P < .001), whereas IBS was associated with lower FEV1 values in the controls but not in the case patients. The HLA-DR/DQ region on chromosome 6 (Chr6) was strongly associated with total serum IgE (rs3135348; P = 3.438 × 10-10) and was independent of an association with the haplotype HLA-DQA1∼HLA-DQB1:04.01∼04.02 (P = 1.55 × 10-05). For lung function, we identified a locus (rs4410198; P = 5.536 × 10-11) mapping to Chr19, near a cluster of zinc finger interacting genes that colocalizes to the long noncoding RNA CTD-2537I9.5. This novel locus was replicated in an independent sample of pediatric case patients with asthma with similar admixture from Brazil (P = .005). CONCLUSION: This study confirms the role of HLA in atopy, and identifies a novel locus mapping to a long noncoding RNA for lung function that may be specific to children with NAT.

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BACKGROUND: The authors sought to examine physical activity patterns among children with and without asthma in 2 peri-urban communities in Lima, Peru, to identify socioeconomic and demographic risk factors for physical inactivity and examine the relationship between asthma and physical activity. METHODS: The authors measured mean steps per day in 114 children (49 with asthma and 65 without) using pedometers worn over a 1-week period. They also used the 3-day physical activity recall to determine the most common activities carried out by children. RESULTS: The authors found that 84.2% of the children did not meet the daily international physical activity recommendations. Girls took significantly fewer mean steps per day as compared with boys (2258 fewer steps, 95% confidence interval, 1042-3474), but no other factors, including asthma status, showed significant differences in the mean daily steps. Mean daily steps were positively associated with higher socioeconomic status among girls, and current asthma had a larger inverse effect on daily steps in boys when compared with girls. CONCLUSION: Physical activity levels were below recommended guidelines in all children. There is a need for policy and neighborhood-level interventions to address low physical activity levels among Peruvian youth. Special focus should be given to increasing the physical activity levels in girls.

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BACKGROUND: Asthma is one of the conditions that contributes to the global burden of respiratory diseases and has been previously associated with diet intake. The goal of this study was to determine the relationship between diet, assessed by a developed score, and asthma in Peruvian children. METHODS: This study was a cross sectional analysis nested within an unmatched case-control study of children in two peri-urban communities of Lima, Peru. We evaluated 767 children and adolescents (573 with asthma, 194 controls) between 9 and 19 years. Diet was assessed using a food frequency questionnaire (FFQ), with food groups classified as "healthy" or "unhealthy". Asthma control, Lung function and atopy were assessed by Asthma Control Test, Spirometry and InmunoCAP 250 test, respectively. RESULTS: Mean age of participants was 13.8 years (SD 2.6). Mean diet score was 5 (SD 1.23; range 2-8). Healthy Diet Score was associated with asthma status [OR 0.83, 95% CI (0.72, 0.95), p = 0.009] in adjusted analysis. Thus, participants with higher HDS, had lower odds of asthma. In sensitivity analyses, when adjusting for atopy, results did not change significantly. [OR 0.85, 95% CI (0.72, 0.99); p = 0.04]. No association between the HDS and asthma control, FEV1, nor FeNO were observed. Atopy did not modify the association between diet and asthma outcomes. CONCLUSIONS: In our study cohort, better diet quality was associated with lower odds of asthma, but was not associated with asthma control. Diet modification may be a potential intervention to impact the increasing prevalence of this disease.

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Rationale: Prior evidence suggests that there may be an association between asthma and food insecurity. We sought to describe the prevalence of food insecurity access, defined as having sufficient resources for appropriate foods in Lima, Peru, and evaluate its association with asthma status and control.Methods: We analyzed data from 553 children with asthma and 268 healthy controls aged nine to 19 years living in two peri-urban communities in Lima, Peru, in 2013. We used the Household Food Insecurity Access Scale to assess food insecurity. We defined uncontrolled asthma as an asthma control test score ≤19. We used multivariable logistic regressions to determine the relationship between asthma outcomes and food insecurity adjusting for age, sex, socioeconomic status, body mass index, and setting.Results: Average age was 14.2 years (SD 2.7). There was a high prevalence of household food insecurity in our study: 330 participants (40.2%) were food insecure, and average food insecurity access score was 2.7 points (SD 4.2). While being food insecure was not associated with asthma status (OR = 1.23, 95% CI 0.85 to 1.79; p = 0.28), it was associated with a higher odds of having uncontrolled asthma (OR = 2.01, 95% CI 1.13 to 3.59; p = 0.02). Each one-unit increase in food insecurity score (higher scores indicating more insecurity) was associated with 8% higher odds of having uncontrolled asthma (OR = 1.08, 95% CI 1.02 to 1.14; p < 0.01).Conclusions: Worse asthma control was associated with food insecurity. Future studies are needed to better understand the role of food security in determining the success of treatment strategies.

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It is well recognized that exposure to fine particulate matter (PM2.5) affects health adversely, yet few studies from South America have documented such associations due to the sparsity of PM2.5 measurements. Lima's topography and aging vehicular fleet results in severe air pollution with limited amounts of monitors to effectively quantify PM2.5 levels for epidemiologic studies. We developed an advanced machine learning model to estimate daily PM2.5 concentrations at a 1 km2 spatial resolution in Lima, Peru from 2010 to 2016. We combined aerosol optical depth (AOD), meteorological fields from the European Centre for Medium-Range Weather Forecasts (ECMWF), parameters from the Weather Research and Forecasting model coupled with Chemistry (WRF-Chem), and land use variables to fit a random forest model against ground measurements from 16 monitoring stations. Overall cross-validation R2 (and root mean square prediction error, RMSE) for the random forest model was 0.70 (5.97 µg/m3). Mean PM2.5 for ground measurements was 24.7 µg/m3 while mean estimated PM2.5 was 24.9 µg/m3 in the cross-validation dataset. The mean difference between ground and predicted measurements was -0.09 µg/m3 (Std.Dev. = 5.97 µg/m3), with 94.5% of observations falling within 2 standard deviations of the difference indicating good agreement between ground measurements and predicted estimates. Surface downwards solar radiation, temperature, relative humidity, and AOD were the most important predictors, while percent urbanization, albedo, and cloud fraction were the least important predictors. Comparison of monthly mean measurements between ground and predicted PM2.5 shows good precision and accuracy from our model. Furthermore, mean annual maps of PM2.5 show consistent lower concentrations in the coast and higher concentrations in the mountains, resulting from prevailing coastal winds blown from the Pacific Ocean in the west. Our model allows for construction of long-term historical daily PM2.5 measurements at 1 km2 spatial resolution to support future epidemiological studies.

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RATIONALE: A large portion of asthma morbidity occurs in low- and middle-income countries, and Peru suffers particularly high asthma prevalence. Ambient air exposures are also high, and likely play a role. Most studies of environmental exposures focus on understanding contributors to health care utilization or mortality risk; however, less severe outcomes may still impact quality of life (QOL). OBJECTIVES: To study the association between multiple pollutants and several asthma domains in Peruvian children. METHODS: A total of 484 children aged 9-19 years with asthma were followed for 6-9 months, and evaluated for asthma control, asthma-related QOL, missed school days, and health care utilization. We used geographically distributed monitors to estimate air pollutant concentrations and multivariable generalized linear mixed models to model asthma outcomes as a function of pollutants. RESULTS: A total of 67% of children had moderate to severe persistent asthma. In multipollutant models, higher particulate matter less than 2.5 µm in aerodynamic diameter (PM2.5), black carbon, and nitrogen dioxide concentrations were independently associated with worse asthma control. For each interquartile range increase in PM2.5 or nitrogen dioxide concentration, there was a 59% or 34% higher odds of uncontrolled asthma, respectively. If the proportion of PM2.5 that was black carbon increased, there were increased odds of uncontrolled asthma. Similarly, pollutants were independently associated with worse asthma-related QOL, and PM exposure was associated with increased risk of health care utilization. CONCLUSIONS: Our study highlights the importance of pollutant exposures on multiple domains of asthma morbidity among Peruvian children, including not only acute exacerbations, but also on general asthma burden, such as worse asthma symptom control and QOL.

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BACKGROUND: Asthma prevalence continues to increase in low and middle-income countries, presenting challenges in assessing asthma control in resource-poor settings. Previous studies suggest that exhaled carbon monoxide (eCO) is higher with asthma severity and lower with treatment. We hypothesized that eCO levels may be elevated in children with asthma, particularly in children with partially controlled or uncontrolled asthma in a low-resource setting in Lima, Peru. METHODS: We compared average eCO levels between 248 children with asthma and 221 healthy controls as well as the odds of asthma by eCO quartiles (0-1, 2, 3, and ≥4 ppm) using multivariable linear and logistic regression. eCO quartiles were also used to compare the odds of partially controlled or uncontrolled asthma (score ≤19 on the Asthma Control Test) in a multivariable logistic regression model. FINDINGS: Average adjusted eCO level was 0.56 ppm (95% CI 0.07-1.05) higher in children with asthma. The adjusted odds of asthma were 1.22 (95% CI 0.75-1.97), 1.46 (0.81-2.63), and 1.76 (0.96-3.23) in the second, third, and fourth eCO quartiles compared to the first eCO quartile, respectively. Among children with asthma, the adjusted odds of partially controlled or uncontrolled asthma in those in the second, third, and fourth eCO quartiles, compared to the first, were 1.61 (95% CI 0.74-3.48), 3.66 (95% CI 1.51-8.87), and 2.50 (95% CI 1.06-5.90), respectively. INTERPRETATION: eCO may serve as an inexpensive biomarker for asthma control, particularly in low-resource settings.

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BACKGROUND: Air pollution exposure may contribute to rhinoconjunctivitis morbidity in children with underlying airways disease. Prior studies have not assessed rhinoconjunctivitis-related quality of life (QOL) in children with asthma chronically exposed to air pollution. METHODS: Children ages 9-19 years with asthma from peri-urban Peru, self-reporting rhinoconjunctivitis symptoms (n = 484), were administered the Rhinoconjunctivitis QOL Questionnaire (RQLQ) at repeated intervals over one year, with scores dichotomized into bothered (>0) and not bothered (= 0). Individual weekly exposures to particulate matter<2.5µm (PM2.5) and its black carbon (BC) component were estimated by inverse distance weighted methods. Generalized estimating equations, adjusting for covariates, estimated associations of PM2.5 and BC with QOL. RESULTS: Participants were on average 13 years old, 55% female, and majority were atopic (77%). Mean (SD) PM2.5 and BC concentrations were 21(3.2) µg/m3 and 4.4(1.5) µg/m3, respectively. In adjusted multi-pollutant models, each 10µg/m3 increase in PM2.5 was associated with increased odds of worse rhinoconjunctivitis QOL (OR;[95% CI]: 1.83;[1.33,2.52]). A 10% increase in the BC proportion was associated with higher rhinitis burden (OR;[95% CI]: 1.80;[1.22,2.66]), while increases in the non-BC component of PM did not significantly impact rhinoconjunctivitis QOL. Associations were similar regardless of atopy. CONCLUSION: Higher PM2.5 and BC exposure is associated with worse rhinitis QOL among asthmatic children.

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BACKGROUND: The relationship between folate status and asthma-related outcomes has not been carefully examined in low- and middle-income countries where folate deficiency is common. METHODS: Ancillary analysis of an unmatched case-control study in which we analyzed serum folate concentrations in 412 children with asthma and 342 controls living in peri-urban communities in Lima, Peru. We examined baseline associations between folate and asthma, atopy, total serum IgE, pulmonary function, and fractional exhaled nitric oxide. We then followed children with asthma longitudinally for 6-9 months and assessed associations between folate and odds of uncontrolled asthma (defined as Asthma Control Test score ≤ 19) and of ≥1 emergency visits during follow-up. RESULTS: A 10 ng/mL decrease in serum folate was associated with 45% higher adjusted odds of asthma (OR = 1.45, 95% CI 1.05-2.02). The folate-asthma relationship differed by atopic status: a 10 ng/mL decrease in serum folate was associated with a 2.4-fold higher odds of asthma among children without atopy (2.38, 1.20-4.72) and 23% higher odds of asthma in children with atopy (1.23, 0.85-1.80). Among children with asthma, a 10 ng/mL decrease in serum folate was associated with 62% higher odds of uncontrolled asthma (1.62, 1.02-2.56) and 73% higher odds of ≥1 emergency visits during follow-up (1.73, 1.05-2.85). CONCLUSIONS: Serum folate concentrations were inversely associated with asthma, but this effect was stronger in children without atopy. Among children with asthma, lower serum folate concentrations were associated with higher risk of uncontrolled asthma.

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BACKGROUND: Evidence suggests free mono-hydroxyvitamin D (25[OH]D) concentrations are more strongly linked to certain outcomes than total concentrations; however, no studies have examined the relation between free 25(OH)D and respiratory or allergic disease. OBJECTIVE: To examine associations between total and free 25(OH)D concentrations and asthma outcomes. METHODS: We quantified total and free 25(OH)D concentrations in 137 Peruvian children with asthma and 152 children without asthma and examined associations with asthma outcomes. RESULTS: Mean age ± SD was 13 ± 2.5 years, and 50.2% were boys. Mean total and measured free 25(OH)D concentrations were 29 ± 9.5 ng/mL and 5.0 ± 1.3 pg/mL, respectively. Lower free but not total 25(OH)D concentrations were significantly associated with atopy in all children (total, odds ratio [OR] 1.3 per 10-ng/mL decrease, 95% confidence interval [CI] 0.95-1.7, P = .12; vs free, OR 1.3 per 1-pg/mL decrease, 95% CI 1.0-1.6, P = .02) and children with asthma (total, OR 1.1 per 10-ng/mL decrease, 95% CI 0.75-1.7, P = .57; vs free, OR 1.6 per 1-pg/mL decrease, 95% CI 1.0-2.5, P = .04). Free but not total 25(OH)D levels were significantly associated with pre-bronchodilator forced expiratory volume in 1 second (total, 0.11 L, -0.12 to 0.34, P = .34; vs free, 0.20 L, 0.021-0.39, P = .03) and forced vital capacity (total, 0.13 L, -0.12 to 0.37, P = .31; vs free, 0.22 L, 0.026-0.42, P = .03) Z-scores in children with asthma. CONCLUSION: Atopy, forced expiratory volume in 1 second, and forced vital capacity were more strongly linked to free than to total 25(OH)D concentrations, suggesting the free form might be more relevant in modulating allergic disease risk and pulmonary function in children with asthma.

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BACKGROUND: Urbanisation is an important contributor to the prevalence of asthma worldwide, and the burden of this effect in low-income and middle-income countries undergoing rapid industrialisation appears to be growing. We sought to characterise adult asthma prevalence across four geographically diverse settings in Peru and identify both individual and environmental risk factors associated with adult asthma. METHODS: We collected sociodemographics, clinical history and spirometry in adults aged ≥35 years. We defined asthma as meeting one of the three criteria: physician diagnosis, self-report of wheezing attack or use of asthma medications. We used multivariable logistic regression to assess individual and environmental factors associated with adult asthma. RESULTS: We analysed data from 2953 participants (mean age 55 years; 49% male). Overall asthma prevalence was 7.1%, which varied with urbanisation: highest in Lima (14.5%), followed by urban Puno (4.0%), semiurban Tumbes (3.8%) and rural Puno (1.8%). In multivariable analysis, being male (OR=0.60, 95% CI 0.39 to 0.93) and living at high altitude (OR=0.26, 95% CI 0.16 to 0.42) were associated with lower odds of having asthma, whereas living in an urban setting (OR=4.72, 95% CI 3.15 to 7.23) and family history of asthma (OR=1.83, 95% CI 1.19 to 2.73) were associated with higher odds. Current daily exposure to biomass fuel smoke (OR=1.18, 95% CI 0.70 to 1.91) and smoking (OR=0.99, 95% CI 0.73 to 1.22) were not associated with asthma. CONCLUSIONS: These findings confirm that urbanisation is an environmental risk factor of asthma, questions biomass fuel smoke exposure as an important risk factor and proposes high altitude as possibly protective against the development of asthma.

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The influence of traffic-related air pollution on indoor residential exposure is not well characterized in homes with high natural ventilation in low-income countries. Additionally, domestic allergen exposure is unknown in such populations. We conducted a pilot study of 25 homes in peri-urban Lima, Peru to estimate the effects of roadway proximity and season on residential concentrations. Indoor and outdoor concentrations of particulate matter (PM2.5), nitrogen dioxide (NO2), and black carbon (BC) were measured during two seasons, and allergens were measured in bedroom dust. Allergen levels were highest for dust mite and mouse allergens, with concentrations above clinically relevant thresholds in over a quarter and half of all homes, respectively. Mean indoor and outdoor pollutant concentrations were similar (PM2.5: 20.0 vs. 16.9 µg/m³, BC: 7.6 vs. 8.1 µg/m³, NO2: 7.3 vs. 7.5 ppb), and tended to be higher in the summer compared to the winter. Road proximity was significantly correlated with overall concentrations of outdoor PM2.5 (rs = -0.42, p = 0.01) and NO2 (rs = -0.36, p = 0.03), and outdoor BC concentrations in the winter (rs = -0.51, p = 0.03). Our results suggest that outdoor-sourced pollutants significantly influence indoor air quality in peri-urban Peruvian communities, and homes closer to roadways are particularly vulnerable.

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PURPOSE: Adherence to a Mediterranean diet pattern may be associated with lower asthma prevalence in children. We sought to corroborate these findings in Peruvian children. METHODS: This case-control study included children of ages 9-19 years living in Lima, Peru. A food frequency questionnaire (FFQ) was completed and diet pattern was analyzed using a modified Mediterranean diet score (MDS). Primary analysis investigated the relationship between MDS and asthma status. Maternal education, age, sex, and body mass index category were included in multivariate model. Secondary outcomes included asthma control, forced expiratory volume in 1 s (FEV1), allergic rhinitis, and atopic status. RESULTS: 287 participants with asthma and 96 controls without asthma completed a FFQ. Mean age was 13.5 years. According to the asthma control test (ACT), 86 % of those with asthma were controlled (score >19). MDS scores ranged 6-18 (median 15). In adjusted analysis, being above the median MDS scores was associated with decreased odds of asthma [OR = 0.55, 95 % CI (0.33, 0.92), p = 0.02]. Among children whose mothers completed secondary education, being above the median MDS significantly decreased the odds of asthma [OR = 0.31, 95 % CI (0.14, 0.71), p < 0.01], whereas among those whose mothers did not complete secondary education there was no protective effect [OR = 0.86, 95 % CI (0.43, 1.7), p = 0.66]. There was no association between MDS scores and asthma control, FEV1, allergic rhinitis, or atopic status. CONCLUSION: Adherence to the Mediterranean diet was inversely associated with having asthma among children in Lima, Peru. This effect was strongest among children with better educated mothers.

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INTRODUCTION: Serum 25-hydroxyvitamin D (25OHD) deficiency (<50 nmol/l or 20 ng/ml) has been associated with increased blood pressure (BP) in observational studies. A paucity of data on this relationship is available in Latin American or child populations. This study investigates the association between 25OHD levels and BP in adolescents at risk for vitamin D deficiency in 2 Peruvian settings. METHODS: In a population-based study of 1,441 Peruvian adolescents aged 13-15 years, 1,074 (75%) provided a serum blood sample for 25OHD analysis and BP measurements. Relationships between 25OHD and BP metrics were assessed using multiple linear regressions, adjusted for anthropometrics and sociodemographic factors. RESULTS: 25OHD deficiency was associated with an elevated diastolic BP (DBP) (1.09 mm Hg increase, 95% confidence interval: 0.04 to 2.14; P = 0.04) compared to nondeficient adolescents. Systolic BP (SBP) trended to increase with vitamin D deficiency (1.30 mm Hg increase, 95% confidence interval: -0.13 to 2.72; P = 0.08). Mean arterial pressure (MAP) was also greater in adolescents with 25OHD (1.16 mm Hg increase, 95% confidence interval: 0.10 to 2.22; P = 0.03). SBP was found to demonstrate a U-shaped relationship with 25OHD, while DBP and MAP demonstrated inverse J-shaped relationships with serum 25OHD status. The association between 25OHD deficiency and BP was not different across study sites (all P ≥ 0.19). DISCUSSION: Adolescents deficient in 25OHD demonstrated increased DBP and MAP and a trend toward increased SBP, when compared to nondeficient subjects. 25OHD deficiency early in life was associated with elevated BP metrics, which may predispose risk of hypertension later in adulthood.

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BACKGROUND: Genome-wide association studies have yet to identify the majority of genetic variants involved in asthma. We hypothesized that expression quantitative trait locus (eQTL) mapping can identify novel asthma genes by enabling prioritization of putative functional variants for association testing. OBJECTIVE: We evaluated 6706 cis-acting expression-associated variants (eSNPs) identified through a genome-wide eQTL survey of CD4(+) lymphocytes for association with asthma. METHODS: eSNPs were tested for association with asthma in 359 asthmatic patients and 846 control subjects from the Childhood Asthma Management Program, with verification by using family-based testing. Significant associations were tested for replication in 579 parent-child trios with asthma from Costa Rica. Further functional validation was performed by using formaldehyde-assisted isolation of regulatory elements (FAIRE) quantitative PCR and chromatin immunoprecipitation PCR in lung-derived epithelial cell lines (Beas-2B and A549) and Jurkat cells, a leukemia cell line derived from T lymphocytes. RESULTS: Cis-acting eSNPs demonstrated associations with asthma in both cohorts. We confirmed the previously reported association of ORMDL3/GSDMB variants with asthma (combined P = 2.9 × 10(-8)). Reproducible associations were also observed for eSNPs in 3 additional genes: fatty acid desaturase 2 (FADS2; P = .002), N-acetyl-α-D-galactosaminidase (NAGA; P = .0002), and Factor XIII, A1 (F13A1; P = .0001). Subsequently, we demonstrated that FADS2 mRNA is increased in CD4(+) lymphocytes in asthmatic patients and that the associated eSNPs reside within DNA segments with histone modifications that denote open chromatin status and confer enhancer activity. CONCLUSIONS: Our results demonstrate the utility of eQTL mapping in the identification of novel asthma genes and provide evidence for the importance of FADS2, NAGA, and F13A1 in the pathogenesis of asthma.

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BACKGROUND: The fractional exhaled nitric oxide (FeNO) is a quantitative, noninvasive and safe measure of airways inflammation that may complement the assessment of asthma. Elevations of FeNO have recently been found to correlate with allergic sensitization. Therefore, FeNO may be a useful predictor of atopy in the general population. We sought to determine the diagnostic accuracy of FeNO in predicting atopy in a population-based study. METHODS: We conducted a cross-sectional study in an age- and sex- stratified random sample of 13 to 15 year-olds in two communities in Peru. We asked participants about asthma symptoms, environmental exposures and sociodemographics, and underwent spirometry, assessment of FeNO and an allergy skin test. We used multivariable logistic regression to model the odds of atopy as a function of FeNO, and calculated area-under-the-curves (AUC) to determine the diagnostic accuracy of FeNO as a predictor of atopy. RESULTS: Of 1441 recruited participants, 1119 (83%) completed all evaluations. Mean FeNO was 17.6 ppb (SD=0.6) in atopics and 11.6 ppb (SD=0.8) in non-atopics (p<0.001). In multivariable analyses, a FeNO>20 ppb was associated with an increase in the odds of atopy in non-asthmatics (OR=5.3, 95% CI 3.3 to 8.5) and asthmatics (OR=16.2, 95% CI 3.4 to 77.5). A FeNO>20 ppb was the best predictor for atopy with an AUC of 68% (95% CI 64% to 69%). Stratified by asthma, the AUC was 65% (95% CI 61% to 69%) in non-asthmatics and 82% (95% CI 71% to 91%) in asthmatics. CONCLUSIONS: FeNO had limited accuracy to identify atopy among the general population; however, it may be a useful indicator of atopic phenotype among asthmatics.

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It is unclear if the relationship of total serum IgE with asthma varies with degree of urbanisation. We hypothesised that the relationship of total serum IgE to asthma is more pronounced in an urban versus a rural environment. We enrolled 1441 children aged 13-15 years in a peri-urban shanty town in Lima, Peru (n=725) and 23 villages in rural Tumbes, Peru (n=716). We asked participants about asthma and allergy symptoms, environmental exposures and sociodemographics; and performed spirometry, and exhaled nitric oxide and allergy skin testing. We obtained blood for total serum IgE in 1143 (79%) participants. Geometric means for total serum IgE were higher in Lima versus Tumbes (262 versus 192 kU·L(-1); p<0.001). The odds of asthma increased by factors of 1.6 (95% CI 1.3-2.0) versus 1.4 (95% CI 0.9-2.1) per log unit increase in total serum IgE in Lima versus Tumbes, respectively. Atopy was an effect modifier of the relationship of total serum IgE on asthma. Among atopics and non-atopics, the odds of asthma increased by a factor of 2.0 (95% CI 1.5-2.7) and 1.0 (95% CI 0.7-1.4) per log unit increase in total serum IgE, respectively. Total serum IgE was associated with atopic asthma but not with non-atopic asthma. Urbanisation did not appear to be an effect modifier of this relationship.

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OBJECTIVES: According to a large-scale international survey, Peru has one of the highest prevalences of asthma worldwide; however, data from this survey were limited to participants from urban Lima. The authors sought to characterise the epidemiology of asthma in Peru in two regions with disparate degrees of urbanisation. In this manuscript, the authors summarise the study design and implementation. DESIGN: A cross-sectional study. PARTICIPANTS: Using census data of 13-15-year-old adolescents from two communities in Peru, the authors invited a random sample of participants in Lima (n=725) and all adolescents in Tumbes (n=716) to participate in our study. PRIMARY AND SECONDARY OUTCOME MEASURES: The authors asked participants to complete a questionnaire on asthma symptoms, environmental exposures and socio-demographics and to undergo spirometry before and after bronchodilator, skin allergy testing and exhaled nitric oxide testing. The authors obtained blood samples for haematocrit, total IgE levels, vitamin D levels and DNA in all participants and measured indoor particulate matter concentrations for 48 h in a random subset of 70-100 households at each site. RESULTS: Of 1851 eligible participants, 1441 (78%) were enrolled and 1159 (80% of enrolled) completed all physical tests. 1283 (89%) performed spirometry according to standard guidelines, of which 86% of prebronchodilator tests and 92% of postbronchodilator tests were acceptable and reproducible. 92% of allergy skin tests had an adequate negative control. The authors collected blood from 1146 participants (79%) and saliva samples from 148 participants (9%). Overall amounts of DNA obtained from blood or saliva were 25.8 µg, with a 260/280 ratio of 1.86. CONCLUSIONS: This study will contribute to the characterisation of a variety of risk factors for asthma, including urbanisation, total IgE levels, vitamin D levels and candidate genes, in a resource-poor setting. The authors present data to support high quality of survey, allergic, spirometric and genetic data collected in our study.

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BACKGROUND: Asthma is a growing public health problem in developing countries. However, few studies have studied the role of urbanisation in this phenomenon. It was hypothesised that children living in a peri-urban setting in Peru have higher rates of asthma and allergy than rural counterparts. METHODS: 1441 adolescents aged 13-15 years were enrolled from two settings: a peri-urban shanty town in Lima (n = 725) and 23 rural villages in Tumbes (n = 716). Participants filled in questionnaires on asthma and allergy symptoms, environmental exposures and sociodemographics, and underwent spirometry, and exhaled nitric oxide (eNO) and allergy skin testing. Indoor particulate matter (PM) concentrations were measured in 170 households. RESULTS: Lima adolescents had higher rates of lifetime wheezing (22% vs 10%), current asthma symptoms (12% vs 3%) and physician-diagnosed asthma (13% vs 2%; all p <0.001). Current rhinitis (23% vs 12%), eczema (12% vs 0.4%), atopy (56% vs 38%), personal history of cigarette smoking (7.4% vs 1.3%) and mean indoor PM (31 vs 13 µg/m(3)) were also higher in Lima (all p < 0.001). The peri-urban environment of Lima was associated with a 2.6-fold greater odds (95% CI 1.3 to 5.3) of asthma in multivariable regression. Forced expiratory volumes were higher and FEV(1)/FVC (forced expiratory volume in 1 s/forced vital capacity) ratios were lower in Lima (all p < 0.001). Higher eNO values in Lima (p < 0.001) were attributable to higher rates of asthma and atopy. CONCLUSIONS: Peri-urban adolescents had more asthma, atopy and airways inflammation and were exposed to more indoor pollution. The findings provide evidence of the risks posed to lung health by peri-urban environments in developing countries.

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