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1.  The 1997–1998 El Niño as an unforgettable phenomenon in northern Peru: a qualitative study 
Disasters  2014;38(2):351-374.
During the 1997–98 El Niño Southern Oscillation (ENSO), Tumbes, Peru received 16 times the annual average rainfall. We explored how Tumbes residents perceived the ENSO’s impact on basic necessities, transport, healthcare, jobs and migration. Forty-five individuals from five rural communities, including those that were isolated and not isolated from the rest of Tumbes during this ENSO, participated in five focus groups and six individuals constructed nutrition diaries. When asked about events in the past twenty years, participants considered the El Niño as a major negative event. Negative effects that were ameliorated quickly were decreased access to transport and healthcare and increased infectious diseases. Residents needed more time to rebuild housing, recover agriculture, livestock and income stability, and return to eating sufficient animal protein. Although large-scale assistance minimized the ENSO’s effects, residents needed more timely support. Residents’ perspectives on their risks to flooding should be considered to generate effective assistance.
doi:10.1111/disa.12046
PMCID: PMC4317261  PMID: 24601921
El Niño Southern Oscillation; Climate change; Floods; Peru; Qualitative
2.  Establishment of a prospective cohort of mechanically ventilated patients in five intensive care units in Lima, Peru: protocol and organisational characteristics of participating centres 
BMJ Open  2015;5(1):e005803.
Introduction
Mechanical ventilation is a cornerstone in the management of critically ill patients worldwide; however, less is known about the clinical management of mechanically ventilated patients in low and middle income countries where limitation of resources including equipment, staff and access to medical information may play an important role in defining patient-centred outcomes. We present the design of a prospective, longitudinal study of mechanically ventilated patients in Peru that aims to describe a large cohort of mechanically ventilated patients and identify practices that, if modified, could result in improved patient-centred outcomes and lower costs.
Methods and analysis
Five Peruvian intensive care units (ICUs) and the Medical ICU at the Johns Hopkins Hospital were selected for this study. Eligible patients were those who underwent at least 24 h of invasive mechanical ventilation within the first 48 h of admission into the ICU. Information on ventilator settings, clinical management and treatment were collected daily for up to 28 days or until the patient was discharged from the unit. Vital status was assessed at 90 days post enrolment. A subset of participants who survived until hospital discharge were asked to participate in an ancillary study to assess vital status, and physical and mental health at 6, 12, 24 and 60 months after hospitalisation, Primary outcomes include 90-day mortality, time on mechanical ventilation, hospital and ICU lengths of stay, and prevalence of acute respiratory distress syndrome. In subsequent analyses, we aim to identify interventions and standardised care strategies that can be tailored to resource-limited settings and that result in improved patient-centred outcomes and lower costs.
Ethics and dissemination
We obtained ethics approval from each of the four participating hospitals in Lima, Peru, and at the Johns Hopkins School of Medicine, Baltimore, USA. Results will be disseminated as several separate publications in different international journals.
doi:10.1136/bmjopen-2014-005803
PMCID: PMC4298097  PMID: 25596196
EPIDEMIOLOGY
3.  Designs of two randomized, community-based trials to assess the impact of alternative cookstove installation on respiratory illness among young children and reproductive outcomes in rural Nepal 
BMC Public Health  2014;14(1):1271.
Background
Acute lower respiratory infections (ALRI) are a leading cause of death among children. Low birthweight is prevalent in South Asia and associated with increased risks of mortality, and morbidity, high levels of indoor household air pollution caused by open burning of biomass fuels are common and associated with high rates of ALRI and low birthweight. Alternative stove designs that burn biomass fuel more efficiently have been proposed as one method for reducing these high exposures and lowering rates of these disorders. We designed two randomized trials to test this hypothesis.
Methods/design
We conducted a pair of community-based, randomized trials of alternative cookstove installation in a rural district in southern Nepal. Phase one was a cluster randomized, modified step-wedge design using an alternative biomass stove with a chimney. A pre-installation period of morbidity assessment and household environmental assessment was conducted for six months in all households. This was followed by a one year step-wedge phase with 12 monthly steps for clusters of households to receive the alternative stove. The timing of alternative stove introduction was randomized. This step-wedge phase was followed in all households by another six month follow-up phase. Eligibility criteria for phase one included household informed consent, the presence of a married woman of reproductive age (15–30 yrs) or a child < 36 months. Children were followed until 36 months of age or the end of the trial. Pregnancies were identified and followed until completion or end of the trial. Phase two was an individually randomized trial of the same alternative biomass stove versus liquid propane gas stove in a subset of households that participated in phase one. Follow-up for phase two was 12 months following stove installation. Eligibility criteria included the same components as phase one except children were only enrolled for morbidity follow-up if they were less than 24 months.
The primary outcomes included: incidence of ALRI in children and birthweight.
Discussion
We presented the design and methods of two randomized trials of alternative cookstoves on rates of ALRI and birthweight.
Trial registration
Clinicaltrials.gov (NCT00786877, Nov. 5, 2008).
doi:10.1186/1471-2458-14-1271
PMCID: PMC4301623  PMID: 25511324
Pneumonia; ALRI; Birthweight; Biomass fuel; Household air pollution; Improved cookstoves; Randomized trials
4.  CRITICAL CARE TRIAL DESIGN AND INTERPRETATION: A BRIEF PRIMER 
Critical care medicine  2010;38(9):1882-1889.
Objective
Better understanding of the pathophysiology of critical illness has led to an increase in clinical trials designed to improve the clinical care and outcomes of patients with life threatening illness. Knowledge of basic principles of clinical trial design and interpretation will assist the clinician in better applying the results of these studies into clinical practice.
Data Sources
We review selected clinical trials to highlight important design features that will improve understanding of the results of critical care clinical trials.
Main Results
Trial design features such as patient selection, sample size calculation, and primary outcome measure may influence the results of a critical care clinical study. In conjunction with trial design knowledge, understanding the size of the anticipated treatment effect, the importance of any clinical endpoint achieved, and whether patients in the trial are representative of typical patients with the illness will assist the reader in determining whether the results should be applied to usual clinical practice.
Conclusions
Better understanding of important aspects of trial design and interpretation, such as whether patients enrolled in both intervention arms were comparable and whether the primary outcome of the trial is clinically important, will assist the reader in determining whether to apply the findings from the clinical study into clinical practice.
doi:10.1097/CCM.0b013e3181eae226
PMCID: PMC4247355  PMID: 20639755
Clinical Trial; Critical Care; Adult; Outcomes
5.  Critical Illness Outcome Study: An Observational Study on Protocols and Mortality in Intensive Care Units 
Introduction
Many individual Intensive Care Unit (ICU) characteristics have been associated with patient outcomes, including staffing, expertise, continuity and team structure. Separately, many aspects of clinical care in ICUs have been operationalized through the development of complex treatment protocols. The United State Critical Illness and Injury Trials Group-Critical Illness Outcomes Study (USCIITG-CIOS) was designed to determine whether the extent of protocol availability and use in ICUs is associated with hospital survival in a large cohort of United States ICUs. Here, we describe the study protocol and analysis plan approved by the USCIITG-CIOS Steering Committee.
Methods
USCIITG-CIOS is a prospective, observational, ecological multi-centered “cohort” study of mixed ICUs in the U.S. The data collected include organizational information for the ICU (e.g., protocol availability and utilization, multi-disciplinary staffing assessment) and patient level information (e.g. demographics, acute and chronic medical conditions). The primary outcome is all-cause hospital mortality, with the objective being to determine whether there is an association between protocol number and hospital mortality for ICU patients. USCIITG-CIOS is powered to detect a 3% difference in crude hospital mortality between high and low protocol use ICUs, dichotomized according to protocol number at the median. The analysis will utilize regression modeling to adjust for outcome clustering by ICU, with secondary linear analysis of protocol number and mortality and a variety of a priori planned ancillary studies. There are presently 60 ICUs participating in USCIITG-CIOS to enroll approximately 6,000 study subjects.
Conclusions
USCIITG-CIOS is a large multicentric study examining the effect of ICU protocol use on patient outcomes. The primary results of this study will inform our understanding of the relationship between protocol availability, use, and patient outcomes in the ICU. Moreover, given the shortage of intensivists worldwide, the results of USCIITG-CIOS can be used to promote more effective ICU and care team design and will impact the delivery of intensive care services beyond individual practitioners.
Trial Registration
ClinicalTrials.gov Identifier NCT01109719
doi:10.2147/OAJCT.S24223
PMCID: PMC4242589  PMID: 25429244
ICU; Critical Care; Outcomes; Protocols; ICU organization
6.  Diarrhea in Early Childhood: Short-term Association With Weight and Long-term Association With Length 
American Journal of Epidemiology  2013;178(7):1129-1138.
The short-term association between diarrhea and weight is well-accepted, but the long-term association between diarrhea and growth is less clear. Using data from 7 cohort studies (Peru, 1985–1987; Peru, 1989–1991; Peru, 1995–1998; Brazil, 1989–1998; Guinea-Bissau, 1987–1990; Guinea-Bissau, 1996–1997; and Bangladesh, 1993–1996), we evaluated the lagged relationship between diarrhea and growth in the first 2 years of life. Our analysis included 1,007 children with 597,638 child-days of diarrhea surveillance and 15,629 anthropometric measurements. We calculated the associations between varying diarrhea burdens during lagged 30-day periods and length at 24 months of age. The cumulative association between the average diarrhea burden and length at age 24 months was −0.38 cm (95% confidence interval: −0.59, −0.17). Diarrhea during the 30 days prior to anthropometric measurement was consistently associated with lower weight at most ages, but there was little indication of a short-term association with length. Diarrhea was associated with a small but measurable decrease in linear growth over the long term. These findings support a focus on prevention of diarrhea as part of an overall public health strategy for improving child health and nutrition; however, more research is needed to explore catch-up growth and potential confounders.
doi:10.1093/aje/kwt094
PMCID: PMC3783094  PMID: 23966558
child health; diarrhea; malnutrition; stunting; wasting
7.  Behavioral Attitudes and Preferences in Cooking Practices with Traditional Open-Fire Stoves in Peru, Nepal, and Kenya: Implications for Improved Cookstove Interventions 
Global efforts are underway to develop and promote improved cookstoves which may reduce the negative health and environmental effects of burning solid fuels on health and the environment. Behavioral studies have considered cookstove user practices, needs and preferences in the design and implementation of cookstove projects; however, these studies have not examined the implications of the traditional stove use and design across multiple resource-poor settings in the implementation and promotion of improved cookstove projects that utilize a single, standardized stove design. We conducted in-depth interviews and direct observations of meal preparation and traditional, open-fire stove use of 137 women aged 20–49 years in Kenya, Peru and Nepal prior in the four-month period preceding installation of an improved cookstove as part of a field intervention trial. Despite general similarities in cooking practices across sites, we identified locally distinct practices and norms regarding traditional stove use and desired stove improvements. Traditional stoves are designed to accommodate specific cooking styles, types of fuel, and available resources for maintenance and renovation. The tailored stoves allow users to cook and repair their stoves easily. Women in each setting expressed their desire for a new stove, but they articulated distinct specific alterations that would meet their needs and preferences. Improved cookstove designs need to consider the diversity of values and needs held by potential users, presenting a significant challenge in identifying a “one size fits all” improved cookstove design. Our data show that a single stove design for use with locally available biomass fuels will not meet the cooking demands and resources available across the three sites. Moreover, locally produced or adapted improved cookstoves may be needed to meet the cooking needs of diverse populations while addressing health and environmental concerns of traditional stoves.
doi:10.3390/ijerph111010310
PMCID: PMC4210980  PMID: 25286166
cookstove; household air pollution; resource-limited settings; behavior analysis; adoption; qualitative research; formative research; technology
8.  Beyond birth-weight: early growth and adolescent blood pressure in a Peruvian population 
PeerJ  2014;2:e381.
Background. Longitudinal investigations into the origins of adult essential hypertension have found elevated blood pressure in children to accurately track into adulthood, however the direct causes of essential hypertension in adolescence and adulthood remains unclear.
Methods. We revisited 152 Peruvian adolescents from a birth cohort tracked from 0 to 30 months of age, and evaluated growth via monthly anthropometric measurements between 1995 and 1998, and obtained anthropometric and blood pressure measurements 11–14 years later. We used multivariable regression models to study the effects of infantile and childhood growth trends on blood pressure and central obesity in early adolescence.
Results. In regression models adjusted for interim changes in weight and height, each 0.1 SD increase in weight for length from 0 to 5 months of age, and 1 SD increase from 6 to 30 months of age, was associated with decreased adolescent systolic blood pressure by 1.3 mm Hg (95% CI −2.4 to −0.1) and 2.5 mm Hg (95% CI −4.9 to 0.0), and decreased waist circumference by 0.6 (95% CI −1.1 to 0.0) and 1.2 cm (95% CI −2.3 to −0.1), respectively. Growth in infancy and early childhood was not significantly associated with adolescent waist-to-hip ratio.
Conclusions. Rapid compensatory growth in early life has been posited to increase the risk of long-term cardiovascular morbidities such that nutritional interventions may do more harm than good. However, we found increased weight growth during infancy and early childhood to be associated with decreased systolic blood pressure and central adiposity in adolescence.
doi:10.7717/peerj.381
PMCID: PMC4081287  PMID: 25024902
Developmental origins; Lifecourse; Hypertension; Blood pressure; Obesity; Growth and development; Child development; Cohort studies; Peru
9.  Effects of the 1997–1998 El Niño Episode on Community Rates of Diarrhea 
American journal of public health  2012;102(7):e63-e69.
Objectives
To improve our understanding of climate variability and diarrheal disease at the community level and inform predictions for future climate change scenarios, we examined whether the El Niño climate pattern is associated with increased rates of diarrhea among Peruvian children.
Methods
We analyzed daily surveillance data for 367 children aged 0 to 12 years from 2 cohorts in a peri-urban shantytown in Lima, Peru, 1995 through 1998. We stratified diarrheal incidence by 6-month age categories, season, and El Niño, and modeled between-subject heterogeneity with random effects Poisson models.
Results
Spring diarrheal incidence increased by 55% during El Niño compared with before El Niño. This increase was most acute among children older than 60 months, for whom the risk of a diarrheal episode during the El Niño spring was nearly 100% greater (relative risk = 1.96; 95% confidence interval = 1.24, 3.09).
Conclusions
El Niño–associated climate variability affects community rates of diarrhea, particularly during the cooler seasons and among older children. Public health officials should develop preventive strategies for future El Niño episodes to mitigate the increased risk of diarrheal disease in vulnerable communities.
doi:10.2105/AJPH.2011.300573
PMCID: PMC3478018  PMID: 22594750
10.  Humidity and Gravimetric Equivalency Adjustments for Nephelometer-Based Particulate Matter Measurements of Emissions from Solid Biomass Fuel Use in Cookstoves 
Great uncertainty exists around indoor biomass burning exposure-disease relationships due to lack of detailed exposure data in large health outcome studies. Passive nephelometers can be used to estimate high particulate matter (PM) concentrations during cooking in low resource environments. Since passive nephelometers do not have a collection filter they are not subject to sampler overload. Nephelometric concentration readings can be biased due to particle growth in high humid environments and differences in compositional and size dependent aerosol characteristics. This paper explores relative humidity (RH) and gravimetric equivalency adjustment approaches to be used for the pDR-1000 used to assess indoor PM concentrations for a cookstove intervention trial in Nepal. Three approaches to humidity adjustment performed equivalently (similar root mean squared error). For gravimetric conversion, the new linear regression equation with log-transformed variables performed better than the traditional linear equation. In addition, gravimetric conversion equations utilizing a spline or quadratic term were examined. We propose a humidity adjustment equation encompassing the entire RH range instead of adjusting for RH above an arbitrary 60% threshold. Furthermore, we propose new integrated RH and gravimetric conversion methods because they have one response variable (gravimetric PM2.5 concentration), do not contain an RH threshold, and is straightforward.
doi:10.3390/ijerph110606400
PMCID: PMC4078586  PMID: 24950062
nephelometer; particulate matter; humidity adjustment; gravimetric equivalent; pDR; low resource environment; biomass burning; cookstove; indoor air quality
11.  Multilevel competing risks in the evaluation of nosocomial infections: time to move on from proportional hazards and even from hazards altogether 
Critical Care  2014;18(3):146.
A competing risk is an event (for example, death in the ICU) that hinders the occurrence of an event of interest (for example, nosocomial infection in the ICU) and it is a common issue in many critical care studies. Not accounting for a competing event may affect how results related to a primary event of interest are interpreted. In the previous issue of Critical Care, Wolkewitz and colleagues extended traditional models for competing risks to include random effects as a means to quantify heterogeneity among ICUs. Reported results from their analyses based on cause-specific hazards and on sub-hazards of the cumulative incidence function were indicative of lack of proportionality of these hazards over time. Here, we argue that proportionality of hazards can be problematic in competing-risk problems and analyses must consider time by covariate interactions as a default. Moreover, since hazards in competing risks make it difficult to disentangle the effects of frequency and timing of the competing events, their interpretation can be murky. Use of mixtures of flexible and succinct parametric time-to-event models for competing risks permits disentanglement of the frequency and timing at the price of requiring stronger data and a higher number of parameters. We used data from a clinical trial on fluid management strategies for patients with acute respiratory distress syndrome to support our recommendations.
doi:10.1186/cc13892
PMCID: PMC4057054  PMID: 25042281
12.  Early anthropometric indices predict short stature and overweight status in a cohort of Peruvians in early adolescence 
While childhood malnutrition is associated with increased morbidity and mortality, less well understood is how early childhood growth influences height and body composition later in life. We revisited 152 Peruvian children who participated in a birth cohort study between 1995 and 1998, and obtained anthropometric and bioimpedance measurements 11 to 14 years later. We used multivariable regression models to study the effects of childhood anthropometric indices on height and body composition in early adolescence. Each standard deviation decrease in length-for-age at birth was associated with a decrease in adolescent height-for-age of 0.7 SD in both boys and girls (all p<0.001) and 9.7 greater odds of stunting (95% CI 3.3 to 28.6). Each SD decrease in length-for-age in the first 30 months of life was associated with a decrease in adolescent height-for-age of 0.4 in boys and 0.6 standard deviation in girls (all p<0.001) and with 5.8 greater odds of stunting (95% CI 2.6 to 13.5). The effect of weight gain during early childhood on weight in early adolescence was more complex to understand. Weight-for-length at birth and rate of change in weight-for-length in early childhood were positively associated with age- and sex-adjusted body mass index and a greater risk of being overweight in early adolescence. Linear growth retardation in early childhood is a strong determinant of adolescent stature, indicating that, in developing countries, growth failure in height during early childhood persists through early adolescence. Interventions addressing linear growth retardation in childhood are likely to improve adolescent stature and related-health outcomes in adulthood.
doi:10.1002/ajpa.22073
PMCID: PMC4013683  PMID: 22552904
Stunting; obesity; development origins
13.  Helicobacter pylori Infection in Infants and Toddlers in South America: Concordance between [13C]Urea Breath Test and Monoclonal H. pylori Stool Antigen Test 
Journal of Clinical Microbiology  2013;51(11):3735-3740.
Accurate noninvasive tests for diagnosing Helicobacter pylori infection in very young children are strongly required. We investigated the agreement between the [13C]urea breath test ([13C]UBT) and a monoclonal ELISA (HpSA) for detection of H. pylori antigen in stool. From October 2007 to July 2011, we enrolled 414 infants (123 from Brazil and 291 from Peru) of ages 6 to 30 months. Breath and stool samples were obtained at intervals of at least 3 months from Brazilian (n = 415) and Peruvian (n = 908) infants. [13C]UBT and stool test results concurred with each other in 1,255 (94.86%) cases (kappa coefficient = 0.90; 95% confidence interval [CI] = 0.87 to 0.92). In the H. pylori-positive group, delta-over-baseline (DOB) and optical density (OD) values were positively correlated (r = 0.62; P < 0.001). The positivity of the tests was higher (P < 0.001; odds ratio [OR] = 6.01; 95% CI = 4.50 to 8.04) in Peru (546/878; 62.2%) than in Brazil (81/377; 21.5%) and increased with increasing age in Brazil (P = 0.02), whereas in Peru it decreased with increasing age (P < 0.001). The disagreement between the test results was associated with birth in Brazil and female gender but not with age and diarrhea. Our results suggest that both [13C]UBT and the stool monoclonal test are reliable for diagnosing H. pylori infection in very young children, which will facilitate robust epidemiological studies in infants and toddlers.
doi:10.1128/JCM.01752-13
PMCID: PMC3889760  PMID: 24006009
14.  Lung ultrasound for the diagnosis of pneumonia in adults: a systematic review and meta-analysis 
Respiratory Research  2014;15(1):50.
Background
Guidelines do not currently recommend the use of lung ultrasound (LUS) as an alternative to chest X-ray (CXR) or chest computerized tomography (CT) scan for the diagnosis of pneumonia. We conducted a meta-analysis to summarize existing evidence of the diagnostic accuracy of LUS for pneumonia in adults.
Methods
We conducted a systematic search of published studies comparing the diagnostic accuracy of LUS against a referent CXR or chest CT scan and/or clinical criteria for pneumonia in adults aged ≥18 years. Eligible studies were required to have a CXR and/or chest CT scan at the time of evaluation. We manually extracted descriptive and quantitative information from eligible studies, and calculated pooled sensitivity and specificity using the Mantel-Haenszel method and pooled positive and negative likelihood ratios (LR) using the DerSimonian-Laird method. We assessed for heterogeneity using the Q and I2 statistics.
Results
Our initial search strategy yielded 2726 articles, of which 45 (1.7%) were manually selected for review and 10 (0.4%) were eligible for analyses. These 10 studies provided a combined sample size of 1172 participants. Six studies enrolled adult patients who were either hospitalized or admitted to Emergency Departments with suspicion of pneumonia and 4 studies enrolled critically-ill adult patients. LUS was performed by highly-skilled sonographers in seven studies, by trained physicians in two, and one did not mention level of training. All studies were conducted in high-income settings. LUS took a maximum of 13 minutes to conduct. Nine studies used a 3.5-5 MHz micro-convex transducer and one used a 5–9 MHz convex probe. Pooled sensitivity and specificity for the diagnosis of pneumonia using LUS were 94% (95% CI, 92%-96%) and 96% (94%-97%), respectively; pooled positive and negative LRs were 16.8 (7.7-37.0) and 0.07 (0.05-0.10), respectively; and, the area-under-the-ROC curve was 0.99 (0.98-0.99).
Conclusions
Our meta-analysis supports that LUS, when conducted by highly-skilled sonographers, performs well for the diagnosis of pneumonia. General practitioners and Emergency Medicine physicians should be encouraged to learn LUS since it appears to be an established diagnostic tool in the hands of experienced physicians.
doi:10.1186/1465-9921-15-50
PMCID: PMC4005846  PMID: 24758612
Lung ultrasound; Pneumonia; Meta-analysis
15.  Molecular Determinants of Lung Development 
Development of the pulmonary system is essential for terrestrial life. The molecular pathways that regulate this complex process are beginning to be defined, and such knowledge is critical to our understanding of congenital and acquired lung diseases. A recent workshop was convened by the National Heart, Lung, and Blood Institute to discuss the developmental principles that regulate the formation of the pulmonary system. Emerging evidence suggests that key developmental pathways not only regulate proper formation of the pulmonary system but are also reactivated upon postnatal injury and repair and in the pathogenesis of human lung diseases. Molecular understanding of early lung development has also led to new advances in areas such as generation of lung epithelium from pluripotent stem cells. The workshop was organized into four different topics, including early lung cell fate and morphogenesis, mechanisms of lung cell differentiation, tissue interactions in lung development, and environmental impact on early lung development. Critical points were raised, including the importance of epigenetic regulation of lung gene expression, the dearth of knowledge on important mesenchymal lineages within the lung, and the interaction between the developing pulmonary and cardiovascular system. This manuscript describes the summary of the discussion along with general recommendations to overcome the gaps in knowledge in lung developmental biology.
doi:10.1513/AnnalsATS.201207-036OT
PMCID: PMC3955361  PMID: 23607856
lung development; lung cell fate; lung cell differentiation; tissue interaction; environmental impact
16.  A cross-sectional study of determinants of indoor environmental exposures in households with and without chronic exposure to biomass fuel smoke 
Environmental Health  2014;13:21.
Background
Burning biomass fuels indoors for cooking is associated with high concentrations of particulate matter (PM) and carbon monoxide (CO). More efficient biomass-burning stoves and chimneys for ventilation have been proposed as solutions to reduce indoor pollution. We sought to quantify indoor PM and CO exposures in urban and rural households and determine factors associated with higher exposures. A secondary objective was to identify chronic vs. acute changes in cardiopulmonary biomarkers associated with exposure to biomass smoke.
Methods
We conducted a census survey followed by a cross-sectional study of indoor environmental exposures and cardiopulmonary biomarkers in the main household cook in Puno, Peru. We measured 24-hour indoor PM and CO concentrations in 86 households. We also measured PM2.5 and PM10 concentrations gravimetrically for 24 hours in urban households and during cook times in rural households, and generated a calibration equation using PM2.5 measurements.
Results
In a census of 4903 households, 93% vs. 16% of rural vs. urban households used an open-fire stove; 22% of rural households had a homemade chimney; and <3% of rural households participated in a national program encouraging installation of a chimney. Median 24-hour indoor PM2.5 and CO concentrations were 130 vs. 22 μg/m3 and 5.8 vs. 0.4 ppm (all p<0.001) in rural vs. urban households. Having a chimney did not significantly reduce median concentrations in 24-hour indoor PM2.5 (119 vs. 137 μg/m3; p=0.40) or CO (4.6 vs. 7.2 ppm; p=0.23) among rural households with and without chimneys. Having a chimney did not significantly reduce median cook-time PM2.5 (360 vs. 298 μg/m3, p=0.45) or cook-time CO concentrations (15.2 vs. 9.4 ppm, p=0.23). Having a thatched roof (p=0.007) and hours spent cooking (p=0.02) were associated with higher 24-hour average PM concentrations. Rural participants had higher median exhaled CO (10 vs. 6 ppm; p=0.01) and exhaled carboxyhemoglobin (1.6% vs. 1.0%; p=0.04) than urban participants.
Conclusions
Indoor air concentrations associated with biomass smoke were six-fold greater in rural vs. urban households. Having a homemade chimney did not reduce environmental exposures significantly. Measures of exhaled CO provide useful cardiopulmonary biomarkers for chronic exposure to biomass smoke.
doi:10.1186/1476-069X-13-21
PMCID: PMC3978088  PMID: 24655424
Biomass smoke; Biomass fuel; Cookstoves; Biomarkers; Exhaled carbon monoxide; Environmental exposure
17.  Measuring socioeconomic status in multicountry studies: results from the eight-country MAL-ED study 
Background
There is no standardized approach to comparing socioeconomic status (SES) across multiple sites in epidemiological studies. This is particularly problematic when cross-country comparisons are of interest. We sought to develop a simple measure of SES that would perform well across diverse, resource-limited settings.
Methods
A cross-sectional study was conducted with 800 children aged 24 to 60 months across eight resource-limited settings. Parents were asked to respond to a household SES questionnaire, and the height of each child was measured. A statistical analysis was done in two phases. First, the best approach for selecting and weighting household assets as a proxy for wealth was identified. We compared four approaches to measuring wealth: maternal education, principal components analysis, Multidimensional Poverty Index, and a novel variable selection approach based on the use of random forests. Second, the selected wealth measure was combined with other relevant variables to form a more complete measure of household SES. We used child height-for-age Z-score (HAZ) as the outcome of interest.
Results
Mean age of study children was 41 months, 52% were boys, and 42% were stunted. Using cross-validation, we found that random forests yielded the lowest prediction error when selecting assets as a measure of household wealth. The final SES index included access to improved water and sanitation, eight selected assets, maternal education, and household income (the WAMI index). A 25% difference in the WAMI index was positively associated with a difference of 0.38 standard deviations in HAZ (95% CI 0.22 to 0.55).
Conclusions
Statistical learning methods such as random forests provide an alternative to principal components analysis in the development of SES scores. Results from this multicountry study demonstrate the validity of a simplified SES index. With further validation, this simplified index may provide a standard approach for SES adjustment across resource-limited settings.
doi:10.1186/1478-7954-12-8
PMCID: PMC4234146  PMID: 24656134
Socioeconomic status; Child growth; Classification; Measurement
18.  Molecular Determinants of Lung Development 
Development of the pulmonary system is essential for terrestrial life. The molecular pathways that regulate this complex process are beginning to be defined, and such knowledge is critical to our understanding of congenital and acquired lung diseases. A recent workshop was convened by the National Heart, Lung, and Blood Institute to discuss the developmental principles that regulate the formation of the pulmonary system. Emerging evidence suggests that key developmental pathways not only regulate proper formation of the pulmonary system but are also reactivated upon postnatal injury and repair and in the pathogenesis of human lung diseases. Molecular understanding of early lung development has also led to new advances in areas such as generation of lung epithelium from pluripotent stem cells. The workshop was organized into four different topics, including early lung cell fate and morphogenesis, mechanisms of lung cell differentiation, tissue interactions in lung development, and environmental impact on early lung development. Critical points were raised, including the importance of epigenetic regulation of lung gene expression, the dearth of knowledge on important mesenchymal lineages within the lung, and the interaction between the developing pulmonary and cardiovascular system. This manuscript describes the summary of the discussion along with general recommendations to overcome the gaps in knowledge in lung developmental biology.
doi:10.1513/AnnalsATS.201207-036OT
PMCID: PMC3955361  PMID: 23607856
lung development; lung cell fate; lung cell differentiation; tissue interaction; environmental impact
19.  A cross-sectional study of differences in 6-min walk distance in healthy adults residing at high altitude versus sea level 
Background
We sought to determine if adult residents living at high altitude have developed sufficient adaptation to a hypoxic environment to match the functional capacity of a similar population at sea level. To test this hypothesis, we compared the 6-min walk test distance (6MWD) in 334 residents living at sea level vs. at high altitude.
Methods
We enrolled 168 healthy adults aged ≥35 years residing at sea level in Lima and 166 individuals residing at 3,825 m above sea level in Puno, Peru. Participants completed a 6-min walk test, answered a sociodemographics and clinical questionnaire, underwent spirometry, and a blood test.
Results
Average age was 54.0 vs. 53.8 years, 48% vs. 43% were male, average height was 155 vs. 158 cm, average blood oxygen saturation was 98% vs. 90%, and average resting heart rate was 67 vs. 72 beats/min in Lima vs. Puno. In multivariable regression, participants in Puno walked 47.6 m less (95% CI -81.7 to -13.6 m; p < 0.01) than those in Lima. Other variables besides age and height that were associated with 6MWD include change in heart rate (4.0 m per beats/min increase above resting heart rate; p < 0.001) and percent body fat (-1.4 m per % increase; p = 0.02).
Conclusions
The 6-min walk test predicted a lowered functional capacity among Andean high altitude vs. sea level natives at their altitude of residence, which could be explained by an incomplete adaptation or a protective mechanism favoring neuro- and cardioprotection over psychomotor activity.
doi:10.1186/2046-7648-3-3
PMCID: PMC3909455  PMID: 24484777
Six-minute walk test; High altitude adaptation; Hypoxia; Functional capacity
20.  Multiple Norovirus Infections in a Birth Cohort in a Peruvian Periurban Community 
Serial norovirus infections with multiple genotypes were found among a Peruvian birth cohort early in infancy. Protection against the subsequent infection was genotype specific, suggesting that norovirus vaccines may need to target multiple genotypes.
Background. Human noroviruses are among the most common enteropathogens globally, and are a leading cause of infant diarrhea in developing countries. However, data measuring the impact of norovirus at the community level are sparse.
Methods. We followed a birth cohort of children to estimate norovirus infection and diarrhea incidence in a Peruvian community. Stool samples from diarrheal episodes and randomly selected nondiarrheal samples were tested by polymerase chain reaction for norovirus genogroup and genotype. Excretion duration and rotavirus coinfection were evaluated in a subset of episodes.
Results. Two hundred twenty and 189 children were followed to 1 and 2 years of age, respectively. By 1 year, 80% (95% confidence interval [CI], 75%–85%) experienced at least 1 norovirus infection and by 2 years, 71% (95% CI, 65%–77%) had at least 1 episode of norovirus-associated diarrhea. Genogroup II (GII) infections were 3 times more frequent than genogroup 1 (GI) infections. Eighteen genotypes were found; GII genotype 4 accounted for 41%. Median excretion duration was 34.5 days for GII vs 8.5 days for GI infection (P = .0006). Repeat infections by the same genogroup were common, but repeat infections by the same genotype were rare. Mean length-for-age z score at 12 months was lower among children with prior norovirus infection compared to uninfected children (coefficient: −0.33 [95% CI, −.65 to −.01]; P = .04); the effect persisted at 24 months.
Conclusions. Norovirus infection occurs early in life and children experience serial infections with multiple genotypes, suggesting genotype-specific immunity. An effective vaccine would have a substantial impact on morbidity, but may need to target multiple genotypes.
doi:10.1093/cid/cit763
PMCID: PMC3905757  PMID: 24300042
norovirus; infant diarrhea; gastroenteritis; birth cohort; natural infection
21.  Feasibility intervention trial of two types of improved cookstoves in three resource-limited settings: study protocol for a randomized controlled trial 
Trials  2013;14:327.
Background
Exposure to biomass fuel smoke is one of the leading risk factors for disease burden worldwide. International campaigns are currently promoting the widespread adoption of improved cookstoves in resource-limited settings, yet little is known about the cultural and social barriers to successful improved cookstove adoption and how these barriers affect environmental exposures and health outcomes.
Design
We plan to conduct a one-year crossover, feasibility intervention trial in three resource-limited settings (Kenya, Nepal and Peru). We will enroll 40 to 46 female primary cooks aged 20 to 49 years in each site (total 120 to 138).
Methods
At baseline, we will collect information on sociodemographic characteristics and cooking practices, and measure respiratory health and blood pressure for all participating women. An initial observational period of four months while households use their traditional, open-fire design cookstoves will take place prior to randomization. All participants will then be randomized to receive one of two types of improved, ventilated cookstoves with a chimney: a commercially-constructed cookstove (Envirofit G3300/G3355) or a locally-constructed cookstove. After four months of observation, participants will crossover and receive the other improved cookstove design and be followed for another four months. During each of the three four-month study periods, we will collect monthly information on self-reported respiratory symptoms, cooking practices, compliance with cookstove use (intervention periods only), and measure peak expiratory flow, forced expiratory volume at 1 second, exhaled carbon monoxide and blood pressure. We will also measure pulmonary function testing in the women participants and 24-hour kitchen particulate matter and carbon monoxide levels at least once per period.
Discussion
Findings from this study will help us better understand the behavioral, biological, and environmental changes that occur with a cookstove intervention. If this trial indicates that reducing indoor air pollution is feasible and effective in resource-limited settings like Peru, Kenya and Nepal, trials and programs to modify the open burning of biomass fuels by installation of low-cost ventilated cookstoves could significantly reduce the burden of illness and death worldwide.
Trial registration
ClinicalTrials.gov NCT01686867
doi:10.1186/1745-6215-14-327
PMCID: PMC3852602  PMID: 24112419
Improved cookstove; Ventilated cookstove; Behavior change; Adoption; Indoor air pollution; DLCO; Spirometry; Biomass fuel
22.  OBSTRUCTIVE LUNG DISEASE AND EXPOSURE TO BURNING BIOMASS FUEL IN THE INDOOR ENVIRONMENT 
Global heart  2012;7(3):265-270.
It is estimated that up to half of the world’s population burns biomass fuel (wood, crop residues, animal dung and coal) for indoor uses such as cooking, lighting and heating. As a result, a large proportion of women and children are exposed to high levels of household air pollution (HAP). The short and long term effects of these exposures on the respiratory health of this population are not clearly understood. On May 9–11, 2011 NIH held an international workshop on the "Health Burden of Indoor Air Pollution on Women and Children," in Arlington, VA. To gather information on the knowledge base on this topic and identify research gaps, ahead of the meeting we conducted a literature search using PubMed to identify publications that related to HAP, asthma, and chronic obstructive pulmonary disease (COPD). Abstracts were all analyzed and we report on those considered by the respiratory sub study group at the meeting to be most relevant to the field. Many of the studies published are symptom-based studies (as opposed to objective measures of lung function or clinical examination etc.) and measurement of HAP was not done. Many found some association between indoor exposures to biomass smoke as assessed by stove type (e.g., open fire vs. liquid propane gas) and respiratory symptoms such as wheeze and cough. Among the studies that examined objective measures (e.g. spirometry) as a health outcome, the data supporting an association between biomass smoke exposure and COPD in adult women are fairly robust, but the findings for asthma are mixed. If an association was observed between the exposures and lung function, most data seemed to demonstrate mild to moderate reductions in lung function, the pathophysiological mechanisms of which need to be investigated. In the end, the group identified a series of scientific gaps and opportunities for research that need to be addressed to better understand the respiratory effects of exposure to indoor burning of the different forms of biomass fuels.
doi:10.1016/j.gheart.2012.06.016
PMCID: PMC3489498  PMID: 23139916
Biomass smoke; cooking fuel smoke; Indoor air pollution; COPD; asthma
23.  Mortality and Denial of Admission to an Intensive Care Unit 
doi:10.1164/rccm.201202-0343ED
PMCID: PMC3359892  PMID: 22589309
24.  Role of exhaled nitric oxide as a predictor of atopy 
Respiratory Research  2013;14(1):48.
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.
doi:10.1186/1465-9921-14-48
PMCID: PMC3654880  PMID: 23639047
Allergic sensitization; Asthma; Exhaled nitric; Allergic rhinitis
25.  Revisiting the Relationship of Weight and Height in Early Childhood12 
Advances in Nutrition  2012;3(2):250-254.
Ponderal and linear growth of children has been widely studied; however, epidemiologic evidence of a relationship between the two is inconsistent. Child undernutrition in the form of low height for age and low weight for height continues to burden the developing world. A downward shift in the distribution of height for age in the first 2 y of life is commonly observed in many developing countries and is usually summarized as the percentage stunted (height for age Z-score <−2). Similar shifts are seen in weight for height; however, weight-for-height shifts are often less extreme, perhaps because weight for height is more tightly biologically controlled. Low height for age and low weight for height in childhood share some common factors, including food insecurity, infectious diseases, and inappropriate feeding practices. Reductions in weight for height, generally seen as a short-term response to inadequate dietary intake or utilization, are thought to precede decreases in height for age; however, given an adequate diet and no further insults, catch-up linear growth can occur. Serial instances of decreased weight for height, however, are thought to limit the degree of catch-up growth attained, contributing to linear growth retardation. Additional research is needed to identify the factors associated with recovery of linear growth after a child experiences decreased weight for height. Although the direct relationship between weight for height and height for age is likely limited, each of these measurements indicates important information about the general health of children and their risk of the development of illness or dying; therefore, eliminating the downward shift of height for age and weight for height in developing countries should be prioritized as a public policy.
doi:10.3945/an.111.001099
PMCID: PMC3648729  PMID: 22516736

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