Karina Romero

Effect of urbanisation on asthma, allergy and airways inflammation in a developing country setting

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/m3) 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 FEV1/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.

Effects of distance from a heavily transited avenue on asthma and atopy in a periurban shantytown in Lima, Peru.

BACKGROUND Proximity to roadways increases the risk of asthma in developed countries; however, relatively little is known about this relationship in developing countries, where rapid and uncontrolled growth of cities has resulted in urban sprawl and heavy traffic volumes. OBJECTIVE We sought to determine the effect of distance from a heavily transited avenue on asthma symptoms and quantitative respiratory outcome measures in a periurban shantytown in Lima, Peru. METHODS We enrolled 725 adolescents aged 13 to 15 years who were administered a survey on asthma symptoms and measured spirometry, response to allergy skin testing, and exhaled nitric oxide (eNO). We calculated distances from the main avenue for all households and measured indoor particulate matter in 100 households. We used multivariable regression to model the risk of asthma symptoms, risk of atopy, eNO levels, and FEV(1)/forced vital capacity ratio as a function of distance. RESULTS Compared against 384 meters, the odds of current asthma symptoms in households living within 100 meters increased by a factor of 2 (P < .05). The odds of atopy increased by a factor of 1.07 for every 100-meter difference in the distance from the avenue (P = .03). We found an inverse relationship in prebronchodilator FEV(1)/forced vital capacity and distance to the avenue in female subjects (P = .01) but not in male subjects. We did not find an association between eNO or household particulate matter levels and distance. CONCLUSION Living in close proximity to a high-traffic-density avenue in a periurban community in Peru was associated with a greater risk of asthma symptoms and atopy. Regulation of mobile-source pollutants in periurban areas of developing countries might help reduce the burden of asthma symptoms and atopy.

The Peru Urban versus Rural Asthma (PURA) Study: methods and baseline quality control data from a cross-sectional investigation into the prevalence, severity, genetics, immunology and environmental factors affecting asthma in adolescence in Peru

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.

Role of exhaled nitric oxide as a predictor of atopy

BackgroundThe 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.MethodsWe 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.ResultsOf 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.ConclusionsFeNO had limited accuracy to identify atopy among the general population; however, it may be a useful indicator of atopic phenotype among asthmatics.

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.

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.

Effect of urbanisation on the relationship between total serum IgE and asthma

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.

Whole Blood Cytokine Response to Local Traffic-Related Particulate Matter in Peruvian Children With and Without Asthma

This study sought to investigate if acute phase immune responses of whole blood from Peruvian children with controlled and uncontrolled asthma differed from children without asthma, following exposure to traffic-related particulate matter (TRPM). TRPM, including particulate matter from diesel combustion, has been shown to stimulate acute airway inflammation in individuals with and without asthma. For this study, a whole blood assay (WBA) was used to test peripheral whole blood samples from 27 children with asthma, and 12 without asthma. Participant blood samples were stimulated, ex vivo, for 24-h with an aqueous extract of TRPM that was collected near study area highways in Lima, Peru. All participant blood samples were tested against the same TRPM extract, in addition to purified bacterial endotoxin and pyrogen-free water, which served as positive and negative WBA controls, respectively. The innate and adaptive cytokine responses were evaluated in cell-free supernatants of the whole blood incubations. Comparatively similar levels were recorded for nine out of the 10 cytokines measured [e.g., – Interleukin (IL)-1β, IL-6, IL-10], regardless of study participant asthma status. However, IL-8 levels in TRPM-stimulated blood from children with uncontrolled asthma were diminished, compared to subjects without asthma (633 pg/ml vs. 1,023 pg/ml, respectively; p < 0.01); IL-8 responses for subjects with controlled asthma were also reduced, but to a lesser degree (799 pg/ml vs. 1,023 pg/ml, respectively; p = 0.10). These relationships were present before, and after, adjusting for age, sex, obesity/overweight status, C-reactive protein levels, and residential proximity to the study area’s major roadway. For tests conducted with endotoxin, there were no discernible differences in cytokine response between groups, for all cytokines measured. The WBA testing conducted for this study highlighted the capacity of the TRPM extract to potently elicit the release of IL-8 from the human whole blood system. Although the small sample size of the study limits the capacity to draw definitive conclusions, the IL-8 responses suggest that that asthma control may be associated with the regulation of a key mediator in neutrophil chemotaxis, at a systemic level, following exposure to PM derived from traffic-related sources.

Exhaled nitric oxide is not a biomarker for pulmonary tuberculosis

Abstract. 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.