Effectiveness of the 10-valent pneumococcal conjugate vaccine on pediatric pneumonia confirmed by ultrasound: a matched case-control study.

BACKGROUND: Bangladesh introduced the 10-valent pneumococcal conjugate vaccine (PCV10) for children aged < 1 year in March 2015. Previous vaccine effectiveness (VE) studies for pneumonia have used invasive pneumococcal disease or chest X-rays. None have used ultrasound. We sought to determine the VE of PCV10 against sonographically-confirmed pneumonia in three subdistrict health complexes in Bangladesh. METHODS: We conducted a matched case-control study between July 2015 and September 2017 in three subdistricts of Sylhet, Bangladesh. Cases were vaccine-eligible children aged 3-35 months with sonographically-confirmed pneumonia, who were matched with two types of controls by age, sex, week of diagnosis, subdistrict health complex (clinic controls) or distance from subdistrict health complex (community controls) and had an illness unlikely due to Streptococcus pneumoniae (clinic controls) or were healthy (community controls). VE was measured using multivariable conditional logistic regression. RESULTS: We evaluated 8926 children (average age 13.3 months, 58% boys) with clinical pneumonia by ultrasound; 2470 had pneumonia with consolidations ≥ 1 cm; 1893 pneumonia cases were matched with 4238 clinic controls; and 1832 were matched with 3636 community controls. VE increased with the threshold used for consolidation size on ultrasound: the adjusted VE of ≥ 2 doses vs. non-recipients of PCV10 against pneumonia increased from 15.8% (95% CI 1.6-28.0%) for consolidations ≥ 1 cm to 29.6% (12.8-43.2%) for consolidations ≥ 1.5 cm using clinic controls and from 2.7% (- 14.2-17.2%) to 23.5% (4.4-38.8%) using community controls, respectively. CONCLUSIONS: PCV10 was effective at reducing sonographically-confirmed pneumonia in children aged 3-35 months of age when compared to unvaccinated children. VE increased with the threshold used for consolidation size on ultrasound in clinic and community controls alike. This study provides evidence that lung ultrasound is a useful alternative to chest X-ray for case-control studies evaluating the effectiveness of vaccines against pneumonia.

Effects of a Household Air Pollution Intervention with Liquefied Petroleum Gas on Cardiopulmonary Outcomes in Peru. A Randomized Controlled Trial.

Rationale: Approximately 40% of people worldwide are exposed to household air pollution (HAP) from the burning of biomass fuels. Previous efforts to document health benefits of HAP mitigation have been stymied by an inability to lower emissions to target levels. Objectives: We sought to determine if a household air pollution intervention with liquefied petroleum gas (LPG) improved cardiopulmonary health outcomes in adult women living in a resource-poor setting in Peru. Methods: We conducted a randomized controlled field trial in 180 women aged 25-64 years living in rural Puno, Peru. Intervention women received an LPG stove, continuous fuel delivery for 1 year, education, and behavioral messaging, whereas control women were asked to continue their usual cooking practices. We assessed for stove use adherence using temperature loggers installed in both LPG and biomass stoves of intervention households. Measurements and Main Results: We measured blood pressure, peak expiratory flow (PEF), and respiratory symptoms using the St. George's Respiratory Questionnaire at baseline and at 3-4 visits after randomization. Intervention women used their LPG stove exclusively for 98% of days. We did not find differences in average postrandomization systolic blood pressure (intervention - control 0.7 mm Hg; 95% confidence interval, -2.1 to 3.4), diastolic blood pressure (0.3 mm Hg; -1.5 to 2.0), prebronchodilator peak expiratory flow/height2 (0.14 L/s/m2; -0.02 to 0.29), postbronchodilator peak expiratory flow/height2 (0.11 L/s/m2; -0.05 to 0.27), or St. George's Respiratory Questionnaire total score (-1.4; -3.9 to 1.2) over 1 year in intention-to-treat analysis. There were no reported harms related to the intervention. Conclusions: We did not find evidence of a difference in blood pressure, lung function, or respiratory symptoms during the year-long intervention with LPG. Clinical trial registered with www.clinicaltrials.gov (NCT02994680).

Challenges in the diagnosis of paediatric pneumonia in intervention field trials: recommendations from a pneumonia field trial working group.

Pneumonia is a leading killer of children younger than 5 years despite high vaccination coverage, improved nutrition, and widespread implementation of the Integrated Management of Childhood Illnesses algorithm. Assessing the effect of interventions on childhood pneumonia is challenging because the choice of case definition and surveillance approach can affect the identification of pneumonia substantially. In anticipation of an intervention trial aimed to reduce childhood pneumonia by lowering household air pollution, we created a working group to provide recommendations regarding study design and implementation. We suggest to, first, select a standard case definition that combines acute (≤14 days) respiratory symptoms and signs and general danger signs with ancillary tests (such as chest imaging and pulse oximetry) to improve pneumonia identification; second, to prioritise active hospital-based pneumonia surveillance over passive case finding or home-based surveillance to reduce the risk of non-differential misclassification of pneumonia and, as a result, a reduced effect size in a randomised trial; and, lastly, to consider longitudinal follow-up of children younger than 1 year, as this age group has the highest incidence of severe pneumonia.

Training and standardization of general practitioners in the use of lung ultrasound for the diagnosis of pediatric pneumonia.

BACKGROUND: Pneumonia is a leading cause of death in children of low-resource settings. Barriers to care include an early and accurate diagnosis. Lung ultrasound is a novel tool for the identification of pediatric pneumonia; however, there is currently no standardized approach to train in image acquisition and interpretation of findings in epidemiological studies. We developed a training program for physicians with limited ultrasound experience on how to use ultrasound for the diagnosis of pediatric pneumonia and how to standardize image interpretation using a panel of readers. METHODS: Twenty-five physicians participating in the training program conducted lung ultrasounds in all children with suspected pneumonia, aged 3 to 35 months, presenting to three subdistrict hospitals in Sylhet, Bangladesh, between June 2015 and September 2017. RESULTS: A total of 9051 pediatric lung ultrasound assessments were conducted through 27 months of data collection. Study physicians underwent training and all were successfully standardized, achieving 91% agreement and maintained a sensitivity and specificity of 88% and 92%, respectively, when their diagnosis was compared with experts. Overall kappa between two readers was high (0.86, 95% confidence interval [CI], 0.84-0.87), and remained high when a third expert reader was included (0.80, 95% CI, 0.79-0.81). Agreement and kappa statistics were similarly high when stratified by age, sex, presence of danger signs, or hypoxemia. CONCLUSIONS: Lung ultrasound is a novel tool for the diagnosis of pediatric pneumonia with evidence supporting its validity and feasibility of implementation. Here we introduced a training program that resulted in a high level of inter-sonographer agreement.

Building a Prediction Model for Radiographically Confirmed Pneumonia in Peruvian Children: From Symptoms to Imaging.

BACKGROUND: Community-acquired pneumonia remains the leading cause of death in children worldwide, and current diagnostic guidelines in resource-poor settings are neither sensitive nor specific. We sought to determine the ability to correctly diagnose radiographically confirmed clinical pneumonia when diagnostics tools were added to clinical signs and symptoms in a cohort of children with acute respiratory illnesses in Peru. METHODS: Children < 5 years of age with an acute respiratory illness presenting to a tertiary hospital in Lima, Peru, were enrolled. The ability to predict radiographically confirmed clinical pneumonia was assessed using logistic regression under four additive scenarios: clinical signs and symptoms only, addition of lung auscultation, addition of oxyhemoglobin saturation (Spo2), and addition of lung ultrasound. RESULTS: Of 832 children (mean age, 21.3 months; 59% boys), 453 (54.6%) had clinical pneumonia and 221 (26.6%) were radiographically confirmed. Children with radiographically confirmed clinical pneumonia had lower average Spo2 than those without (95.9% vs 96.6%, respectively; P < .01). The ability to correctly identify radiographically confirmed clinical pneumonia using clinical signs and symptoms was limited (area under the curve [AUC] = 0.62; 95% CI, 0.58-0.67) with a sensitivity of 66% (95% CI, 59%-73%) and specificity of 53% (95% CI, 49%-57%). The addition of lung auscultation improved classification (AUC = 0.73; 95% CI, 0.69-0.77) with a sensitivity of 75% (95% CI, 69%-81%) and specificity of 53% (95% CI, 49%-57%) for the presence of crackles. In contrast, the addition of Spo2 did not improve classification (AUC = 0.73; 95% CI, 0.69-0.77) with a sensitivity of 40% (95% CI, 33%-47%) and specificity of 72% (95% CI, 68%-75%) for an Spo2 ≤ 92%. Adding consolidation on lung ultrasound was associated with the largest improvement in classification (AUC = 0.85; 95% CI, 0.82-0.89) with a sensitivity of 55% (95% CI, 48%-63%) and specificity of 95% (95% CI, 93%-97%). CONCLUSIONS: The addition of lung ultrasound and auscultation to clinical signs and symptoms improved the ability to correctly classify radiographically confirmed clinical pneumonia. Implementation of auscultation- and ultrasound-based diagnostic tools can be considered to improve diagnostic yield of pneumonia in resource-poor settings.

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.

Pneumococcal Conjugate Vaccine impact assessment in Bangladesh.

The study examines the impact of the introduction of 10-valent Pneumococcal Conjugate Vaccine (PCV10) into Bangladesh's national vaccine program. PCV10 is administered to children under 1 year-old; the scheduled ages of administration are at 6, 10, and 18 weeks. The study is conducted in ~770,000 population containing ~90,000 <5 children in Sylhet, Bangladesh and has five objectives: 1) To collect data on community-based pre-PCV incidence rates of invasive pneumococcal diseases (IPD) in 0-59 month-old children in Sylhet, Bangladesh; 2) To evaluate the effectiveness of PCV10 introduction on Vaccine Type (VT) IPD in 3-59 month-old children using an incident case-control study design. Secondary aims include measuring the effects of PCV10 introduction on all IPD in 3-59 month-old children using case-control study design, and quantifying the emergence of Non Vaccine Type IPD; 3) To evaluate the effectiveness of PCV10 introduction on chest radiograph-confirmed pneumonia in children 3-35 months old using incident case-control study design. We will estimate the incidence trend of clinical and radiologically-confirmed pneumonia in 3-35 month-old children in the study area before and after introduction of PCV10; 4) To determine the feasibility and utility of lung ultrasound for the diagnosis of pediatric pneumonia in a large sample of children in a resource-limited setting. We will also evaluate the effectiveness of PCV10 introduction on ultrasound-confirmed pneumonia in 3-35 month-old children using an incident case-control design and to examine the incidence trend of ultrasound-confirmed pneumonia in 3-35 month-old children in the study area before and after PCV10 introduction; and 5) To determine the direct and indirect effects of vaccination status on nasopharyngeal colonization on VT pneumococci among children with pneumonia .  This paper presents the methodology. The study will allow us to conduct a comprehensive and robust assessment of the impact of national introduction of PCV10 on pneumococcal disease in Bangladesh.

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.

Effects of a liquefied petroleum gas stove intervention on pollutant exposure and adult cardiopulmonary outcomes (CHAP): study protocol for a randomized controlled trial.

BACKGROUND: Biomass fuel smoke is a leading risk factor for the burden of disease worldwide. International campaigns are promoting the widespread adoption of liquefied petroleum gas (LPG) in resource-limited settings. However, it is unclear if the introduction and use of LPG stoves, in settings where biomass fuels are used daily, reduces pollution concentration exposure, improves health outcomes, or how cultural and social barriers influence the exclusive adoption of LPG stoves. METHODS: We will conduct a randomized controlled, field intervention trial of LPG stoves and fuel distribution in rural Puno, Peru, in which we will enroll 180 female participants aged 25-64 years and follow them for 2 years. After enrollment, we will collect information on sociodemographic characteristics, household characteristics, and cooking practices. During the first year of the study, LPG stoves and fuel tanks will be delivered to the homes of 90 intervention participants. During the second year, participants in the intervention arm will keep their LPG stoves, but the gas supply will stop. Control participants will receive LPG stoves and vouchers to obtain free fuel from distributors at the beginning of the second year, but gas will not be delivered. Starting at baseline, we will collect longitudinal measurements of respiratory symptoms, pulmonary function, blood pressure, endothelial function, carotid artery intima-media thickness, 24-h dietary recalls, exhaled carbon monoxide, quality-of-life indicators, and stove-use behaviors. Environmental exposure assessments will occur six times over the 2-year follow-up period, consisting of 48-h personal exposure and kitchen concentration measurements of fine particulate matter and carbon monoxide, and 48-h kitchen concentrations of nitrogen dioxide for a subset of 100 participants. DISCUSSION: Findings from this study will allow us to better understand behavioral patterns, environmental exposures, and cardiovascular and pulmonary outcomes resulting from the adoption of LPG stoves. If this trial indicates that LPG stoves are a feasible and effective way to reduce household air pollution and improve health, it will provide important information to support widespread adoption of LPG fuel as a strategy to reduce the global burden of disease. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02994680 , Cardiopulmonary Outcomes and Household Air Pollution (CHAP) Trial. Registered on 28 November 2016.

Disparities in dietary intake and physical activity patterns across the urbanization divide in the Peruvian Andes.

BACKGROUND: Diet and activity are thought to worsen with urbanization, thereby increasing risk of obesity and chronic diseases. A better understanding of dietary and activity patterns across the urbanization divide may help identify pathways, and therefore intervention targets, leading to the epidemic of overweight seen in low- and middle-income populations. Therefore, we sought to characterize diet and activity in a population-based study of urban and rural residents in Puno, Peru. METHODS: We compared diet and activity in 1005 (503 urban, 502 rural) participants via a lifestyle questionnaire. We then recruited an age- and sex-stratified random sample of 50 (25 urban, 25 rural) participants to further characterize diet and activity. Among these participants, diet composition and macronutrient intake was assessed by three non-consecutive 24-h dietary recalls and physical activity was assessed using Omron JH-720itc pedometers. RESULTS: Among 1005 participants, we found that urban residents consumed protein-rich foods, refined grains, sugary items, and fresh produce more frequently than rural residents. Among the 50 subsample participants, urban dwellers consumed more protein (47 vs. 39 g; p = 0.05), more carbohydrates (280 vs. 220 g; p = 0.03), more sugary foods (98 vs. 48 g, p = 0.02) and had greater dietary diversity (6.4 vs 5.8; p = 0.04). Rural subsample participants consumed more added salt (3.1 vs 1.7 g, p = 0.006) and tended to consume more vegetable oil. As estimated by pedometers, urban subsample participants burned fewer calories per day (191 vs 270 kcal, p = 0.03). CONCLUSIONS: Although urbanization is typically thought to increase consumption of fat, sugar and salt, our 24-h recall results were mixed and showed lower levels of obesity in rural Puno were not necessarily indicative of nutritionally-balanced diets. All subsample participants had relatively traditional lifestyles (low fat intake, limited consumption of processed foods and frequent walking) that may play a role in chronic disease outcomes in this region.

Cardiometabolic correlates of sleep disordered breathing in Andean highlanders.

Associations between sleep disordered breathing (SDB) and cardiometabolic outcomes have not been examined in highlanders.We performed nocturnal polygraphy in Peruvian highlanders (3825 m). Multivariable linear regression models examined associations between SDB metrics and haemoglobin, glucose tolerance (haemoglobin A1c (HbA1c)), fasting glucose, homeostatic model-based assessments of insulin resistance and ß-cell function (HOMA-IR and HOMA-ß, respectively), blood pressure, and lipids, while adjusting for age, sex, body mass index (BMI) and wake oxygenation.Participants (n=187; 91 men) were (median (interquartile range)) 52 (45-62) years old, and had a BMI of 27.0 (24.3-29.5) kg·m-2 and 87% (85-88%) oxyhaemoglobin (arterial oxygen) saturation during wakefulness. In fully adjusted models, worsening nocturnal hypoxaemia was associated with haemoglobin elevations in men (p=0.03), independent of wake oxygenation and apnoea-hypopnoea index (AHI), whereas worsening wake oxygenation was associated with haemoglobin elevations in older women (p=0.02). In contrast, AHI was independently associated with HbA1c elevations (p<0.05). In single-variable models, nocturnal hypoxaemia was associated with higher HbA1c, HOMA-IR and HOMA-ß (p<0.001, p=0.02 and p=0.04, respectively), whereas AHI was associated with HOMA-IR, systolic blood pressure and triglyceride elevations (p=0.02, p=0.01 and p<0.01, respectively). These associations were not significant in fully adjusted models.In highlanders, nocturnal hypoxaemia and sleep apnoea were associated with distinct cardiometabolic outcomes, conferring differential risk for excessive erythrocytosis and glucose intolerance, respectively.

Cross-Sectional Comparison of Sleep-Disordered Breathing in Native Peruvian Highlanders and Lowlanders.

Pham, Luu V., Christopher Meinzen, Rafael S. Arias, Noah G. Schwartz, Adi Rattner, Catherine H. Miele, Philip L. Smith, Hartmut Schneider, J. Jaime Miranda, Robert H. Gilman, Vsevolod Y. Polotsky, William Checkley, and Alan R. Schwartz. Cross-sectional comparison of sleep-disordered breathing in native Peruvian highlanders and lowlanders. High Alt Med Biol. 18:11-19, 2017. BACKGROUND: Altitude can accentuate sleep disordered breathing (SDB), which has been linked to cardiovascular and metabolic diseases. SDB in highlanders has not been characterized in large controlled studies. The purpose of this study was to compare SDB prevalence and severity in highlanders and lowlanders. METHODS: 170 age-, body-mass-index- (BMI), and sex-matched pairs (age 58.2 ± 12.4 years, BMI 27.2 ± 3.5 kg/m2, and 86 men and 84 women) of the CRONICAS Cohort Study were recruited at a sea-level (Lima) and a high-altitude (Puno, 3825 m) setting in Peru. Participants underwent simultaneous nocturnal polygraphy and actigraphy to characterize breathing patterns, movement arousals, and sleep/wake state. We compared SDB prevalence, type, and severity between highlanders and lowlanders as measured by apnea-hypopnea index (AHI) and pulse oximetry (SPO2) during sleep. RESULTS: Sleep apnea prevalence was greater in highlanders than in lowlanders (77% vs. 54%, p < 0.001). Compared with lowlanders, highlanders had twofold elevations in AHI due to increases in central rather than obstructive apneas. In highlanders compared with lowlanders, SPO2 was lower during wakefulness and decreased further during sleep (p < 0.001). Hypoxemia during wakefulness predicted sleep apnea in highlanders, and it appears to mediate the effects of altitude on sleep apnea prevalence. Surprisingly, hypoxemia was also quite prevalent in lowlanders, and it was also associated with increased odds of sleep apnea. CONCLUSIONS: High altitude and hypoxemia at both high and low altitude were associated with increased SDB prevalence and severity. Our findings suggest that a large proportion of highlanders remain at risk for SDB sequelae.

Perceptions of Improved Biomass and Liquefied Petroleum Gas Stoves in Puno, Peru: Implications for Promoting Sustained and Exclusive Adoption of Clean Cooking Technologies.

Many households in low- and middle-income countries cook with inefficient biomass-burning stoves, which cause high levels of household air pollution and threaten long-term health. Although clean stoves and fuels are available, uptake and consistent use has been low. Using observations and in-depth interviews, we assessed the attitudes, preferences, and beliefs about traditional versus liquefied petroleum gas (LPG) stoves in rural Puno, Peru. A total of 31 in-depth interviews were conducted with primary cooks and their families, health workers, community leaders, and improved stove contractors. Six in-home observations of meal preparation were also conducted. Six major barriers to consistent use of clean stoves were identified: (1) perceived differences in food taste and nutrition by stove type; (2) cooking niches filled by different stoves; (3) social norms related to cooking practices; (4) safety concerns; (5) comparative costs of using different stoves; and (6) lack of awareness and concern about long-term health risks. These findings suggest that to successfully reduce household air pollution, clean cooking programs and policies must consider the many factors influencing adoption beyond health, such as cost, taste, fears, and cultural traditions. These factors could be incorporated into community-based and national efforts to scale-up sustained and exclusive adoption of clean cooking.

Geographical variation in the progression of type 2 diabetes in Peru: The CRONICAS Cohort Study.

BACKGROUND: The study aims were to estimate the incidence and risk factors for T2D in four settings with different degree of urbanization and altitude in Peru. METHODS: Prospective cohort study conducted in urban, semi-urban, and rural areas in Peru. An age- and sex-stratified random sample of participants was taken from the most updated census. T2D was defined as fasting blood glucose ⩾7.0mmol/L or taking anti-diabetes medication. Exposures were divided into two groups: geographical variables (urbanization and altitude), and modifiable risk factors. Incidence, relative risks (RR), 95% confidence intervals (95%CI), and population attributable fractions (PAF) were estimated. RESULTS: Data from 3135 participants, 48.8% males, mean age 55.6years, was analyzed. Overall baseline prevalence of T2D was 7.1% (95%CI 6.2-8.0%). At follow-up, including 6207 person-years of follow-up, a total of 121 new T2D cases were accrued, equating to an incidence of 1.95 (95%CI 1.63-2.33) per 100 person-years. There was no urban to rural gradient in the T2D incidence; however, compared to sea level sites, participants living in high altitude had a higher incidence of diabetes (RR=1.58; 95%CI 1.01-2.48). Obesity had the highest attributable risk for developing T2D, although results varied by setting, ranging from 14% to 80% depending on urbanization and altitude. CONCLUSIONS: Our results suggest that the incidence of T2D was greater in high altitude sites. New cases of diabetes were largely attributed to obesity, but with substantial variation in the contribution of obesity depending on the environment. These findings can inform appropriate context-specific strategies to reduce the incidence of diabetes.

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.

Lung Transplant Outcomes in Systemic Sclerosis with Significant Esophageal Dysfunction. A Comprehensive Single-Center Experience.

RATIONALE: Consideration of lung transplantation in patients with systemic sclerosis (SSc) remains guarded, often due to the concern for esophageal dysfunction and the associated potential for allograft injury and suboptimal post-lung transplantation outcomes. OBJECTIVES: The purpose of this study was to systematically report our single-center experience regarding lung transplantation in the setting of SSc, with a particular focus on esophageal dysfunction. METHODS: We retrospectively reviewed all lung transplants at our center from January 1, 2000 through August 31, 2012 (n = 562), comparing the SSc group (n = 35) to the following lung transplant diagnostic subsets: all non-SSc (n = 527), non-SSc diffuse fibrotic lung disease (n = 264), and a non-SSc matched group (n = 109). We evaluated post-lung transplant outcomes, including survival, primary graft dysfunction, acute rejection, bronchiolitis obliterans syndrome, and microbiology of respiratory isolates. In addition, we defined severe esophageal dysfunction using esophageal manometry and esophageal morphometry criteria on the basis of chest computed tomography images. For patients with SSc referred for lung transplant but subsequently denied (n = 36), we queried the reason(s) for denial with respect to the concern for esophageal dysfunction. MEASUREMENTS AND MAIN RESULTS: The 1-, 3-, and 5-year post-lung transplant survival for SSc was 94, 77, and 70%, respectively, and similar to the other groups. The remaining post-lung transplant outcomes evaluated were also similar between SSc and the other groups. Approximately 60% of the SSc group had severe esophageal dysfunction. Pre-lung transplant chest computed tomography imaging demonstrated significantly abnormal esophageal morphometry for SSc when compared with the matched group. Importantly, esophageal dysfunction was the sole reason for lung transplant denial in a single case. CONCLUSIONS: Relative to other lung transplant indications, our SSc group experienced comparable survival, primary graft dysfunction, acute rejection, bronchiolitis obliterans syndrome, and microbiology of respiratory isolates, despite the high prevalence of severe esophageal dysfunction. Esophageal dysfunction rarely precluded active listing for lung transplantation.

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.