Multimorbidity at sea level and high-altitude urban and rural settings: The CRONICAS Cohort Study.

OBJECTIVE: To characterize the prevalence and clustering of multimorbidity in four diverse geographical settings in Peru. METHODS: Multimorbidity, defined as having ≥2 chronic conditions, was studied in adults aged ≥35 years in four diverse settings in Peru: Lima, Tumbes, and urban and rural Puno. Six of these conditions (alcohol disorder, asthma, chronic obstructive pulmonary disease, depression, diabetes, and hypertension) were cataloged as objectively ascertained chronic conditions and paired in dyads to explore clusters of multimorbidity. RESULTS: We analyzed data from 2890 adults, mean age 55.2 years, 49% males. Overall, 19.1% of participants had multimorbidity, ranging from 14.7% in semi-urban Tumbes to 22.8% in Lima. The dyads with the highest coexistence (approximately 20%) were observed in hypertension and diabetes in Tumbes, whereas the dyads with lowest coexistence (approximately 1%) were those involving asthma in all study sites. In terms of clusters, Tumbes showed a predominance of hypertension and diabetes, urban and rural Puno a predominance of depression and alcohol disorders, and Lima a higher degree of coexistence of all of the six conditions than in the other clusters. CONCLUSION: Multimorbidity is common and the pattern of clusters is highly heterogeneous. The conditions to prioritize will vary in each setting.

Environmental exposures and systemic hypertension are risk factors for decline in lung function.

BACKGROUND: Chronic lung disease is a leading contributor to the global disease burden; however, beyond tobacco smoke, we do not fully understand what risk factors contribute to lung function decline in low-income and middle-income countries. METHODS: We collected sociodemographic and clinical data in a randomly selected, age-stratified, sex-stratified and site-stratified population-based sample of 3048 adults aged ≥35 years from four resource-poor settings in Peru. We assessed baseline and annual pre-bronchodilator and post-bronchodilator lung function over 3 years. We used linear mixed-effects models to assess biological, socioeconomic and environmental risk factors associated with accelerated lung function decline. RESULTS: Mean±SD enrolment age was 55.4±12.5 years, 49.2% were male and mean follow-up time was 2.36 (SD 0.61) years. Mean annual pre-bronchodilator FEV1 decline was 30.3 mL/year (95% CI 28.6 to 32.0) and pre-bronchodilator FVC decline was 32.2 mL/year (30.0 to 34.4). Using multivariable linear mixed-effects regression, we found that urban living, high-altitude dwelling and having hypertension accounted for 25.9% (95% CI 15.7% to 36.1%), 21.3% (11.1% to 31.5%) and 15.7% (3.7% to 26.9%) of the overall mean annual decline in pre-bronchodilator FEV1/height2, respectively. Corresponding estimates for pre-bronchodilator FVC/height2 were 42.1% (95% CI% 29.8% to 54.4%), 36.0% (23.7% to 48.2%) and 15.8% (2.6% to 28.9%) of the overall mean annual decline, respectively. CONCLUSION: Urbanisation, living at high altitude and hypertension were associated with accelerated lung function decline in a population with low daily smoking prevalence.

Patterns of Body Composition Relating to Chronic Respiratory Diseases Among Adults in Four Resource-Poor Settings in Peru.

PURPOSE: Body composition is known to influence the development and progression of chronic respiratory diseases (CRDs). We sought to characterize the unique anthropometric phenotypes that present with asthma, chronic obstructive pulmonary disease (COPD), and chronic bronchitis across four distinct settings in Peru. METHODS: We collected sociodemographic, clinical history, and spirometry data from 2959 participants from Lima, Tumbes, and rural and urban Puno. We compared the prevalence of CRDs among different study sites and described disease phenotypes. We used single and multivariable linear regression to model the influence of CRD status on various descriptors of body composition. RESULTS: Overall prevalence of CRDs varied across sites with the highest prevalence of asthma in Lima (14.5%) and the highest prevalence of COPD in rural Puno (9.9%). Measures of body composition also varied across sites, with highest mean body mass index (BMI) in Lima (28.4 kg/m2) and the lowest mean BMI in rural Puno (25.2 kg/m2). Participants with COPD had the lowest mean fat mass index (FMI) (10.5 kg/m2) and waist circumference (88.3 cm), whereas participants with asthma had the highest mean FMI (14.5 kg/m2), and waist circumference (94.8 cm). In multivariable analysis, participants with COPD had a lower waist circumference (adjusted mean - 2.97 cm, 95% CI 4.62 to - 1.32 cm) when compared to non-CRD participants. CONCLUSIONS: Our findings provide evidence that asthma and chronic bronchitis are more likely to be associated with obesity and higher fat mass, while COPD is associated with being underweight and having less lean mass.

Point-of-care gastrointestinal and urinary tract sonography in daily evaluation of gastrointestinal dysfunction in critically ill patients (GUTS Protocol).

There is currently a lack of universally accepted criteria for gastrointestinal (GI) failure or dysfunction in critical care. Moreover, the clinical assessment of intestinal function is notoriously difficult and thus often goes unrecognized, contributing to poor outcomes. A recent grading system has been proposed to define acute gastrointestinal injury (AGI) in conjunction with other organ function scores (e.g., SOFA). Ultrasonography has become widely accepted as a diagnostic tool for GI problems and pathology. We propose a sonographic examination of the abdomen, using the GUTS protocol (gastrointestinal and urinary tract sonography) in critically ill patients as part of the point-of-care ultrasound evaluation in patients with AGI. This article reviews possible applications of ultrasonography that may be relevant to monitor the GI function in critically ill patients. The GI ultrasound protocol (GUTS) focuses on four gastrointestinal endpoints: gastrointestinal diameter, mucosal thickness, peristalsis, and blood flow. Moreover, it is possible to examine the urinary tract and kidney function. Real-time ultrasound with the GUTS protocol is a simple, inexpensive, bedside imaging technique that can provide anatomical and functional information of the GI tract. Further studies are needed to investigate the utility of GUTS with other parameters, such as GI biomarkers, AGI class, and clinical outcomes.

The role of point-of-care ultrasound in intra-abdominal hypertension management.

BACKGROUND: Intra-abdominal hypertension is a common complication in critically ill patients. Recently the Abdominal Compartment Society (WSACS) developed a medical management algorithm with a stepwise approach according to the evolution of the intra-abdominal pressure and aiming to keep IAP ≤ 15 mm Hg. With the increased use of ultrasound as a bedside modality in both emergency and critical care patients, we hypothesized that ultrasound could be used as an adjuvant point-of-care tool during IAH management. This may be particularly relevant to the first and second basic stages of the algorithm. The objective of this paper is to test the use of POCUS as an adjuvant tool in the management of patients with IAH/ACS. METHODS: Seventy-three consecutive adult critically ill patients admitted to the surgical intensive care unit (ICU) of a single urban institution with risk factor for IAH/ACS were enrolled. Those who met the inclusion criteria were allocated to undergo POCUS as an adjuvant tool in their IAH/ACS management. RESULTS: A total of 50 patients met the inclusion criteria and were included in the study. The mean age of study participants was 55 ± 22.6 years, 58% were men, and the most frequent admission diagnosis was post-operative care following abdominal intervention. All admitted patients presented with a degree of IAH during their ICU stay. Following step 1 of the WSACS IAH medical management algorithm, ultrasound was used for NGT placement, confirmation of correct positioning, and evaluation of stomach contents. Ultrasound was comparable to abdominal X-ray, but shown to be superior in determining the gastric content (fluid vs. solid). Furthermore, POCUS allowed faster determination of correct NGT positioning in the stomach (antrum), avoiding bedside radiation exposure. Ultrasound also proved useful in: 1) evaluation of bowel activity; 2) identification of large bowel contents; 3) identification of patients that would benefit from bowel evacuation (enema) as an adjuvant to lower IAP; 4) and in the diagnosis of moderate to large amounts of free intra-abdominal fluid. CONCLUSION: POCUS is a powerful systematic ultrasound technique that can be used as an adjuvant in intra-abdominal hypertension management. It has the potential to be used in both diagnosis and treatment during the course of IAH.

Increased Cardiometabolic Risk and Worsening Hypoxemia at High Altitude.

Miele, Catherine H., Alan R. Schwartz, Robert H. Gilman, Luu Pham, Robert A. Wise, Victor G. Davila-Roman, Jonathan C. Jun, Vsevolod Y. Polotsky, J. Jaime Miranda, Fabiola Leon-Velarde, and William Checkley. Increased cardiometabolic risk and worsening hypoxemia at high altitude. High Alt Med Biol. 17:93-100, 2016.-Metabolic syndrome, insulin resistance, diabetes, and dyslipidemia are associated with an increased risk of cardiovascular disease. While excessive erythrocytosis is associated with cardiovascular complications, it is unclear how worsening hypoxemia of any degree affects cardiometabolic risk factors in high-altitude populations. We studied the relationship between daytime resting oxyhemoglobin saturation and cardiometabolic risk factors in adult participants living in Puno, Peru (3825 m above sea level). We used multivariable logistic regression models to study the relationship between having a lower oxyhemoglobin saturation and markers of cardiometabolic risk. Nine hundred and fifty-four participants (mean age 55 years, 52% male) had information available on pulse oximetry and markers of cardiometabolic risk. Average oxyhemoglobin saturation was 90% (interquartile range 88%-92%) and 43 (4.5%) had excessive erythrocytosis. Older age, decreased height-adjusted lung function, and higher body mass index (BMI) were associated with having an oxyhemoglobin saturation ≤85%. When adjusting for age, sex, socioeconomic status, having excessive erythrocytosis, and site, we found that each 5% decrease in oxyhemoglobin saturation was associated with a higher adjusted odds of metabolic syndrome (OR = 1.35, 95% CI: 1.07-1.72, p < 0.04), insulin resistance as defined by homeostasis model assessment-insulin resistance (HOMA-IR) >2 mass units (OR = 1.29, 95% CI: 1.00-1.67, p < 0.05), hemoglobin A1c ≥6.5% (OR = 1.66, 95% CI: 1.09-2.51, p < 0.04), and high sensitivity C-reactive protein (hs-CRP) ≥3 mg/L (OR = 1.46, 95% CI: 1.09-1.96, p < 0.01). In high-altitude populations in Puno, Peru, a higher BMI and lower pulmonary function were associated with lower resting daytime oxyhemoglobin saturation. Lower resting oxyhemoglobin saturation, in turn, was associated with higher odds of having multiple unfavorable cardiometabolic factors. Worsening hypoxia of any degree in high-altitude dwellers may be an independent risk factor for cardiovascular disease.

Urbanization and Daily Exposure to Biomass Fuel Smoke Both Contribute to Chronic Bronchitis Risk in a Population with Low Prevalence of Daily Tobacco Smoking.

OBJECTIVE: Risk factors beyond tobacco smoking associated with chronic bronchitis are not well understood. We sought to describe the prevalence and risk factors of chronic bronchitis across four distinct settings in Peru with overall low prevalence of tobacco smoking yet varying degrees of urbanization, daily exposure to biomass fuel smoke and living at high altitude. METHODS: We analyzed data of 2,947 participants from rural and urban Puno, Lima and Tumbes including spirometry, blood samples, anthropometry and administered questionnaires about respiratory symptoms. We used multivariable Poisson regression to assess biologic, socioeconomic and environmental risk factors associated with chronic bronchitis. RESULTS: Overall prevalence of chronic bronchitis was 5.9% (95%CI 5.1%-6.9%) with variation by setting: prevalence was lower in semi-urban Tumbes (1.3%) vs. highly urbanized Lima (8.9%), urban Puno (7.0%) and rural Puno (7.8%; p < 0.001). Chronic bronchitis was more common among participants with vs. without COPD based on FEV1/FVC< LLN (12.1% vs 5.6%, p < 0.01) and it was associated with increased reporting of dyspnea on exertion (p < 0.001), hospitalization (p = 0.003) and workdays missed due to respiratory symptoms (p < 0.001). Older age (Prevalence ratio [PR] = 1.23 for each 10-years of age, 95%CI 1.09-1.40) past history of asthma (PR = 2.87, 95%CI 1.80-4.56), urbanization (PR = 3.34, 95%CI 2.18-5.11) and daily exposure to biomass fuel smoke (PR = 2.00, 95%CI 1.30-3.07) were all associated with chronic bronchitis. CONCLUSIONS: We found important variations in the prevalence of chronic bronchitis across settings. Prevalence increased with both urbanization and with daily exposure to biomass fuel smoke. Having chronic bronchitis was also associated with worse patient-centered outcomes including dyspnea, hospitalization and missed workdays.

Urbanisation but not biomass fuel smoke exposure is associated with asthma prevalence in four resource-limited settings.

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.

Noninvasive Assessment of Excessive Erythrocytosis as a Screening Method for Chronic Mountain Sickness at High Altitude.

Vyas, Kaetan J., David Danz, Robert H. Gilman, Robert A. Wise, Fabiola León-Velarde, J. Jaime Miranda, and William Checkley. Noninvasive assessment of excessive erythrocytosis as a screening method for chronic mountain sickness at high altitude. High Alt Med Biol 16:162-168, 2015.--Globally, over 140 million people are at risk of developing chronic mountain sickness, a common maladaptation to life at high altitude (>2500 meters above sea level). The diagnosis is contingent upon the identification of excessive erythrocytosis (EE). Current best practices to identify EE require a venous blood draw, which is cumbersome for large-scale surveillance. We evaluated two point-of-care biomarkers to screen for EE: noninvasive spot-check tests of total hemoglobin and oxyhemoglobin saturation (Pronto-7, Masimo Corporation). We conducted paired evaluations of total serum hemoglobin from a venous blood draw and noninvasive, spot-check testing of total hemoglobin and oxyhemoglobin saturation with the Pronto-7 in 382 adults aged ≥35 years living in Puno, Peru (3825 meters above sea level). We used the Bland-Altman method to measure agreement between the noninvasive hemoglobin assessment and the gold standard lab hemoglobin analyzer. Mean age was 58.8 years and 47% were male. The Pronto-7 test was unsuccessful in 21 (5%) participants. Limits of agreement between total hemoglobin measured via venous blood draw and the noninvasive, spot-check test ranged from -2.8 g/dL (95% CI -3.0 to -2.5) to 2.5 g/dL (95% CI 2.2 to 2.7), with a bias of -0.2 g/dL (95% CI -0.3 to -0.02) for the difference between total hemoglobin and noninvasive hemoglobin concentrations. Overall, the noninvasive spot-check test of total hemoglobin had a better area under the receiver operating characteristic curve compared to oxyhemoglobin saturation for the identification of EE as measured by a gold standard laboratory hemoglobin analyzer (0.96 vs. 0.82; p<0.001). Best cut-off values to screen for EE with the Pronto 7 were ≥19.9 g/dL in males and ≥17.5 g/dL in females. At these cut-points, sensitivity and specificity were both 92% and 89% for males and females, respectively. A noninvasive, spot-check test of total hemoglobin had low bias and high discrimination for the detection of EE in high altitude Peru, and may be a useful point-of-care tool for large-scale surveillance in high-altitude settings.

Prevalence of chronic obstructive pulmonary disease and variation in risk factors across four geographically diverse resource-limited settings in Peru.

BACKGROUND: It is unclear how geographic and social diversity affects the prevalence of chronic obstructive pulmonary disease (COPD). We sought to characterize the prevalence of COPD and identify risk factors across four settings in Peru with varying degrees of urbanization, altitude, and biomass fuel use. METHODS: We collected sociodemographics, clinical history, and post-bronchodilator spirometry in a randomly selected, age-, sex- and site-stratified, population-based sample of 2,957 adults aged ≥35 years (median age was 54.8 years and 49.3% were men) from four resource-poor settings: Lima, Tumbes, urban and rural Puno. We defined COPD as a post-bronchodilator FEV1/FVC < 70%. RESULTS: Overall prevalence of COPD was 6.0% (95% CI 5.1%-6.8%) but with marked variation across sites: 3.6% in semi-urban Tumbes, 6.1% in urban Puno, 6.2% in Lima, and 9.9% in rural Puno (p < 0.001). Population attributable risks (PARs) of COPD due to smoking ≥10 pack-years were less than 10% for all sites, consistent with a low prevalence of daily smoking (3.3%). Rather, we found that PARs of COPD varied by setting. In Lima, for example, the highest PARs were attributed to post-treatment tuberculosis (16% and 22% for men and women, respectively). In rural Puno, daily biomass fuel for cooking among women was associated with COPD (prevalence ratio 2.22, 95% CI 1.02-4.81) and the PAR of COPD due to daily exposure to biomass fuel smoke was 55%. CONCLUSIONS: The burden of COPD in Peru was not uniform and, unlike other settings, was not predominantly explained by tobacco smoking. This study emphasizes the role of biomass fuel use, and highlights pulmonary tuberculosis as an often neglected risk factor in endemic areas.

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.

Prevalence, clinical profile, iron status, and subject-specific traits for excessive erythrocytosis in andean adults living permanently at 3,825 meters above sea level.

BACKGROUND: Excessive erythrocytosis (EE) is a prevalent condition in populations living at high altitudes (> 2,500 m above sea level). Few large population-based studies have explored the association between EE and multiple subject-specific traits including oxygen saturation, iron status indicators, and pulmonary function. METHODS: We enrolled a sex-stratified and age-stratified sample of 1,065 high-altitude residents aged ≥ 35 years from Puno, Peru (3,825 m above sea level) and conducted a standardized questionnaire and physical examination that included spirometry, pulse oximetry, and a blood sample for multiple clinical markers. Our primary objectives were to estimate the prevalence of EE, characterize the clinical profile and iron status indicators of subjects with EE, and describe subject-specific traits associated with EE. RESULTS: Overall prevalence of EE was 4.5% (95% CI, 3.3%-6.0%). Oxygen saturation was significantly lower among EE than non-EE group subjects (85.3% vs 90.1%, P < .001) but no difference was found in iron status indicators between both groups (P > .09 for all values). In multivariable logistic regression, we found that age ≥ 65 years (OR = 2.45, 95% CI, 1.16-5.09), male sex (3.86, 1.78-9.08), having metabolic syndrome (2.66, 1.27-5.75) or being overweight (5.20, 1.95-16.77), pulse oximetry < 85% (14.90, 6.43-34.90), and % predicted FVC < 80% (13.62, 4.40-41.80) were strongly associated with EE. Attributable fractions for EE were greatest for being overweight (26.7%), followed by male sex (21.5%), pulse oximetry < 85% (16.4%), having metabolic syndrome (14.4%), and % predicted FVC < 80% (9.3%). CONCLUSIONS: We found a lower prevalence of EE than in previous reports in the Peruvian Andes. Although the presence of hypoxemia and decreased vital capacity were strongly associated with excessive erythrocytosis, being overweight or having metabolic syndrome were associated with an important fraction of cases in our study population.

Association of CYP2C19 polymorphisms and lansoprazole-associated respiratory adverse effects in children.

OBJECTIVE: To determine whether cytochrome P450 (CYP)2C19 haplotype associates with lansoprazole-associated adverse event frequency. STUDY DESIGN: Respiratory adverse events from a clinical trial of lansoprazole in children with asthma were analyzed for associations with extensive or poor metabolizer (PM) phenotype based on CYP2C19 haplotypes. Carriers of CYP2C19*2, *3, *8, or *9 alleles were PMs; carriers of 2 wild-type alleles were extensive metabolizers (EMs). Plasma concentrations of lansoprazole were determined in PM and EM phenotypes. RESULTS: The frequency of upper respiratory infection among PMs (n = 45) was higher than that among EMs (n = 91), which in turn was higher than that in placebo subjects (n = 135; P = .0039). The frequency of sore throat (ST) was similarly distributed among EMs and PMs (P = .0015). The OR (95% CI) for upper respiratory infections in PMs was 2.46 (1.02-5.96) (P = .046); for EMs, the OR (95% CI) was 1.55 (0.86-2.79). The OR (95% CI) for ST in EMs and PMs was 2.94 (1.23-7.05, P = .016) vs 1.97 (1.09-3.55, P = .024), respectively. Mean ± SD plasma concentrations of lansoprazole were higher in PMs than in EMs: 207 ± 179 ng/mL vs 132 ± 141 ng/mL (P = .04). CONCLUSIONS: Lansoprazole-associated upper respiratory infections and ST in children are related in part to CYP2C19 haplotype. Our data suggest that lansoprazole-associated adverse events in children may be mitigated by adjusting the conventional dose in PMs. Additional studies are required to replicate our findings.

Chronic exposure to biomass fuel is associated with increased carotid artery intima-media thickness and a higher prevalence of atherosclerotic plaque.

BACKGROUND: Biomass fuels are used for cooking in the majority of rural households worldwide. While their use is associated with an increased risk of lung diseases and all-cause mortality, the effects on cardiovascular disease (CVD) are not well characterised. Exposure to biomass fuel smoke has been associated with lung-mediated inflammation and oxidative stress, which may increase the risk of atherosclerosis as evaluated by carotid intima-media thickness (CIMT), carotid atherosclerotic plaque prevalence and blood pressure. METHODS: A cross-sectional study was performed in 266 adults aged ≥35 years in Puno, Peru (3825 m above sea level). We stratified participants by their long-term history of exposure to clean fuel (n=112) or biomass fuel (n=154) and measured 24 h indoor particulate matter (PM2.5) in a random subset (n=84). Participants completed questionnaires and underwent a clinical assessment, laboratory analyses and carotid artery ultrasound. The main outcome measures were CIMT, carotid plaque and blood pressure. RESULTS: The groups were similar in age and gender. The biomass fuel group had greater unadjusted mean CIMT (0.66 vs 0.60 mm; p<0.001), carotid plaque prevalence (26% vs 14%; p=0.03), systolic blood pressure (118 vs 111 mm Hg; p<0.001) and median household PM2.5 (280 vs 14 µg/m(3); p<0.001). In multivariable regression, the biomass fuel group had greater mean CIMT (mean difference=0.03 mm, 95% CI 0.01 to 0.06; p=0.02), a higher prevalence of carotid plaques (OR=2.6, 95% CI 1.1 to 6.0; p=0.03) and higher systolic blood pressure (mean difference=9.2 mm Hg, 95% CI 5.4 to 13.0; p<0.001). CONCLUSIONS: Chronic exposure to biomass fuel was associated with increased CIMT, increased prevalence of atherosclerotic plaques and higher blood pressure. These findings identify biomass fuel use as a risk factor for CVD, which may have important global health implications.

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.

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.

Optimizing the 6-min walk test as a measure of exercise capacity in COPD.

BACKGROUND: It is uncertain whether the effort and expense of performing a second walk for the 6-min walk test improves test performance. Hence, we attempted to quantify the improvement in 6-min walk distance if an additional walk were to be performed. METHODS: We studied patients consecutively enrolled into the National Emphysema Treatment Trial who prior to randomization and after 6 to 10 weeks of pulmonary rehabilitation performed two 6-min walks on consecutive days (N = 396). Patients also performed two 6-min walks at 6-month follow-up after randomization to lung volume reduction surgery (n = 74) or optimal medical therapy (n = 64). We compared change in the first walk distance to change in the second, average-of-two, and best-of-two walk distances. RESULTS: Compared with the change in the first walk distance, change in the average-of-two and best-of-two walk distances had better validity and precision. Specifically, 6 months after randomization to lung volume reduction surgery, changes in the average-of-two (r = 0.66 vs r = 0.58, P = .01) and best-of-two walk distances (r = 0.67 vs r = 0.58, P = .04) better correlated with the change in maximal exercise capacity (ie, better validity). Additionally, the variance of change was 14% to 25% less for the average-of-two walk distances and 14% to 33% less for the best-of-two walk distances than the variance of change in the single walk distance, indicating better precision. CONCLUSIONS: Adding a second walk to the 6-min walk test significantly improves its performance in measuring response to a therapeutic intervention, improves the validity of COPD clinical trials, and would result in a 14% to 33% reduction in sample size requirements. Hence, it should be strongly considered by clinicians and researchers as an outcome measure for therapeutic interventions in patients with COPD.

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/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.

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.

Transient bulging fontanelle after vaccination: case report and review of the vaccine adverse event reporting system.

OBJECTIVE: To describe the features of transient bulging fontanelle (TBF) after vaccination. STUDY DESIGN: We searched the Vaccine Adverse Event Reporting System database for reports describing bulging fontanelle. We defined a definite TBF case as a patient with a bulging fontanelle, normal neuroimaging and cerebrospinal fluid analysis, and absence of a depressed level of consciousness, focal neurologic findings, or identified cause. Follow-up had to reveal normal development. Probable cases lacked either lumbar puncture or neuroimaging or both but met all other criteria. RESULTS: We identified 18 patients with definite or probable TBF. The median age at presentation was 4.5 months, interval from vaccination to symptom onset was 18 hours, and time to resolution was 3 days. Fifteen children were febrile. CONCLUSIONS: We cannot conclude that vaccines cause TBF. Further controlled studies are necessary. Even if further research verifies TBF as a rare side effect, immunization benefits would still vastly outweigh this hypothetical risk. However, confirmation of a vaccine association could modify the management of infants who develop TBF after immunizations.