Risk Factors for Physical Inactivity Among Children With and Without Asthma Living in Peri-Urban Communities of Lima, Peru.

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.

Household food insecurity is associated with asthma control in Peruvian children living in a resource-poor setting.

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.

Ambient Air Pollution and Variation in Multiple Domains of Asthma Morbidity among Peruvian Children.

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.

Exhaled Nitric Oxide is Not a Biomarker for Pulmonary Tuberculosis.

To reduce transmission of tuberculosis (TB) in resource-limited countries where TB remains a major cause of mortality, novel diagnostic tools are urgently needed. We evaluated the fractional concentration of exhaled nitric oxide (FeNO) as an easily measured, noninvasive potential biomarker for diagnosis and monitoring of treatment response in participants with pulmonary TB including multidrug resistant-TB in Lima, Peru. In a longitudinal study however, we found no differences in baseline median FeNO levels between 38 TB participants and 93 age-matched controls (13 parts per billion [ppb] [interquartile range (IQR) = 8-26] versus 15 ppb [IQR = 12-24]), and there was no change over 60 days of treatment (15 ppb [IQR = 10-19] at day 60). Taking this and previous evidence together, we conclude FeNO is not of value in either the diagnosis of pulmonary TB or as a marker of treatment response.

Serum folate concentrations, asthma, atopy, and asthma control in Peruvian children.

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.

Low cigarette smoking prevalence in peri-urban Peru: results from a population-based study of tobacco use by self-report and urine cotinine.

BACKGROUND: A recent study found lower self-reported prevalence of tobacco smoking in a peri-urban area of Lima, Peru than previously reported in urban samples. These regions encompass substantial proportions of Peru's population - ones at greater risk of disease due to reduced healthcare access - but have been less often studied. We validate low smoking prevalence with urine cotinine and characterize chronic disease and lung function outcomes between non-, occasional, and daily smokers. METHODS: Data are from the CRONICAS Cohort Study, a population-based longitudinal study in four low-resource Peruvian settings, which began in 2010. Of a baseline cohort of 2978 adults, we prospectively followed 2583 (87%) to determine prevalence of chronic illness. RESULTS: In a baseline sub-sample of 382 participants, median adjusted cotinine was 0.0 mcg/mg (IQR 0-0) for both self-reported non-smokers and occasional smokers compared to 172.3 mcg/mg (IQR 0-709.2) for daily smokers. Creatinine-adjusted cotinine validated daily smoking prevalence of 4.7% at a cutoff of 100 mcg/mg. Kappa statistic for daily smoking and creatinine- adjusted cotinine ≥100 mcg/mg was 0.65 (95% CI 0.47, 0.83), indicating substantial agreement. At baseline, we found 3.3% daily and 8.9% occasional smoking by self-report for the full cohort. Follow-up indicated little difference in chronic disease prevalence between groups. Daily smokers trended toward having a greater decline in FVC (-1%; 95% CI -2.9, 0.8) and FEV1 (-1.3%; 95% CI -3.2, 0.6) over 40 months when compared to non-smokers, whereas the decline in lung function for occasional smokers was similar compared to non-smokers (-0.2% FVC; 95% CI -1.5, 1.0) and (0% FEV1; 95% CI -1.3, 1.3). CONCLUSIONS: Our data places Peru within a previously-described pattern of smoking found in much of Latin America, favoring occasional over daily smoking and low cigarette consumption. We determine that there are not significant differences between smoking groups concerning chronic disease outcomes. We favor distinguishing between daily and occasional smokers in order to accurately characterize these low-use populations.

Identifying biomarkers for asthma diagnosis using targeted metabolomics approaches.

BACKGROUND: The diagnosis of asthma in children is challenging and relies on a combination of clinical factors and biomarkers including methacholine challenge, lung function, bronchodilator responsiveness, and presence of airway inflammation. No single test is diagnostic. We sought to identify a pattern of inflammatory biomarkers that was unique to asthma using a targeted metabolomics approach combined with data science methods. METHODS: We conducted a nested case-control study of 100 children living in a peri-urban community in Lima, Peru. We defined cases as children with current asthma, and controls as children with no prior history of asthma and normal lung function. We further categorized enrollment following a factorial design to enroll equal numbers of children as either overweight or not. We obtained a fasting venous blood sample to characterize a comprehensive panel of targeted markers using a metabolomics approach based on high performance liquid chromatography-mass spectrometry. RESULTS: A statistical comparison of targeted metabolites between children with asthma (n = 50) and healthy controls (n = 49) revealed distinct patterns in relative concentrations of several metabolites: children with asthma had approximately 40-50% lower relative concentrations of ascorbic acid, 2-isopropylmalic acid, shikimate-3-phosphate, and 6-phospho-d-gluconate when compared to children without asthma, and 70% lower relative concentrations of reduced glutathione (all p < 0.001 after Bonferroni correction). Moreover, a combination of 2-isopropylmalic acid and betaine strongly discriminated between children with asthma (2-isopropylmalic acid ≤ 13 077 normalized counts/second) and controls (2-isopropylmalic acid > 13 077 normalized counts/second and betaine ≤ 16 47 121 normalized counts/second). CONCLUSIONS: By using a metabolomics approach applied to serum, we were able to discriminate between children with and without asthma by revealing different metabolic patterns. These results suggest that serum metabolomics may represent a diagnostic tool for asthma and may be helpful for distinguishing asthma phenotypes.

Association of Roadway Proximity with Indoor Air Pollution in a Peri-Urban Community in Lima, Peru.

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.

Association Between Adherence to the Mediterranean Diet and Asthma in Peruvian Children.

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.

Relationship between daily exposure to biomass fuel smoke and blood pressure in high-altitude Peru.

Household air pollution from biomass fuel use affects 3 billion people worldwide; however, few studies have examined the relationship between biomass fuel use and blood pressure. We sought to determine if daily biomass fuel use was associated with elevated blood pressure in high altitude Peru and if this relationship was affected by lung function. We analyzed baseline information from a population-based cohort study of adults aged ≥ 35 years in Puno, Peru. Daily biomass fuel use was self-reported. We used multivariable regression models to examine the relationship between daily exposure to biomass fuel smoke and blood pressure outcomes. Interactions with sex and quartiles of forced vital capacity were conducted to evaluate for effect modification. Data from 1004 individuals (mean age, 55.3 years; 51.7% women) were included. We found an association between biomass fuel use with both prehypertension (adjusted relative risk ratio, 5.0; 95% confidence interval, 2.6-9.9) and hypertension (adjusted relative risk ratio, 3.5; 95% confidence interval, 1.7-7.0). Biomass fuel users had a higher systolic blood pressure (7.0 mm Hg; 95% confidence interval, 4.4-9.6) and a higher diastolic blood pressure (5.9 mm Hg; 95% confidence interval, 4.2-7.6) when compared with nonusers. We did not find interaction effects between daily biomass fuel use and sex or percent predicted forced vital capacity for either systolic blood pressure or diastolic blood pressure. Biomass fuel use was associated with a higher likelihood of having hypertension and higher blood pressure in Peru. Reducing exposure to household air pollution from biomass fuel use represents an opportunity for cardiovascular prevention.

Association Between Serum 25-Hydroxy Vitamin D Levels and Blood Pressure Among Adolescents in Two Resource-Limited Settings in Peru.

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.

Longitudinal assessment of high versus low levels of fractional exhaled nitric oxide among children with asthma and atopy.

PURPOSE: Fractional exhaled nitric oxide (FeNO) has emerged as an important biomarker in asthma. Increasing evidence points to atopy as a confounding factor in the interpretation of elevated FeNO. We conducted a longitudinal study to understand the clinical significance of FeNO as an inflammatory biomarker. METHODS: We identified 19 children aged 13-15 years at baseline with a significant elevation in FeNO ≥ 80 parts per billion (ppb) and randomly selected a group of children of similar age with a moderate elevation (40-79 ppb) and normal-to-low FeNO (<40 ppb). Between November 2010 and July 2011, three additional study visits were conducted. RESULTS: Ninety-three children participated in the study. There were 16, 24, and 53 participants in the high, mid, and low FeNO groups. During 1.5 years of follow-up, mean FeNO levels were 82.6 ppb (standard deviation [SD] = 65.9) for atopic asthmatics, 50.6 ppb (SD = 42.6) for nonasthmatic atopics, 17.0 ppb (SD = 10.8) for nonatopic asthmatics, and 17.8 ppb (SD = 13.9) for nonatopic nonasthmatics (p < 0.001). FeNO levels remained stable: 63 % of the high FeNO group had a FeNO ≥ 80 across all 4 measurements and 87 % of the normal-to-low FeNO group had a FeNO of <40 across all 4 measurements. The high FeNO group also was found to have an elevation in IL-5 (p = 0.04), IL-6 (p = 0.003), IL-10 (p = 0.002), and total serum IgE (p < 0.001), after adjustment by age, sex, height, body mass index, and atopy and asthma status. CONCLUSIONS: An elevation of FeNO appears to indicate an atopic phenotype regardless of an asthma diagnosis, clinical symptoms, or corticosteroid use. An elevation of FeNO also is associated with a systemic elevation in inflammatory cytokines.

Role of exhaled nitric oxide as a predictor of atopy.

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.