Epidemiology and risk factors of asthma-chronic obstructive pulmonary disease overlap in low- and middle-income countries.

BACKGROUND: Asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) represents the confluence of bronchial airway hyperreactivity and chronic airflow limitation and has been described as leading to worse lung function and quality of life than found with either singular disease process. OBJECTIVE: We aimed to describe the prevalence and risk factors for ACO among adults across 6 low- and middle-income countries (LMICs). METHODS: We compiled cross-sectional data for 11,923 participants aged 35 to 92 years from 4 population-based studies in 12 settings. We defined COPD as postbronchodilator FEV1/forced vital capacity ratio below the lower limit of normal, asthma as wheeze or medication use in 12 months or self-reported physician diagnosis, and ACO as having both. RESULTS: The prevalence of ACO was 3.8% (0% in rural Puno, Peru, to 7.8% in Matlab, Bangladesh). The odds of having ACO were higher with household exposure to biomass fuel smoke (odds ratio [OR], 1.48; 95% CI, 0.98-2.23), smoking tobacco (OR, 1.28 per 10 pack-years; 95% CI, 1.22-1.34), and having primary or less education (OR, 1.35; 95% CI, 1.07-1.70) as compared to nonobstructed nonasthma individuals. ACO was associated with severe obstruction (FEV1 %, <50; 31.6% of ACO vs 10.9% of COPD alone) and severe spirometric deficits compared with participants with asthma (-1.61 z scores FEV1; 95% CI, -1.48 to -1.75) or COPD alone (-0.94 z scores; 95% CI, -0.78 to -1.10). CONCLUSIONS: ACO may be as prevalent and more severe in LMICs than has been reported in high-income settings. Exposure to biomass fuel smoke may be an overlooked risk factor, and we favor diagnostic criteria for ACO that include environmental exposures common to LMICs.

Risk factors for the development of acute respiratory distress syndrome in mechanically ventilated adults in Peru: a multicenter observational study.

BACKGROUND: Clinical and epidemiological differences between acute respiratory distress syndrome (ARDS) that presents at the initiation of mechanical ventilation [MV] (ARDS at MV onset) and that which develops during the course of MV (ARDS after MV onset) are not well understood. We conducted an observational study in five Peruvian ICUs to characterize differences between ARDS at MV onset and after MV onset and identify risk factors for the development of ARDS after MV onset. METHODS: We consecutively enrolled critically ill patients with acute respiratory failure requiring at least 24 h of mechanical ventilation and followed them prospectively during the first 28 days and compared baseline characteristics and clinical outcomes by ARDS status. RESULTS: We enrolled 1657 participants on MV (mean age 60.0 years, 55% males) of whom 334 (20.2%) had ARDS at MV onset and 180 (10.9%) developed ARDS after MV onset. Average tidal volume at the initiation of MV was 8.7 mL/kg of predicted body weight (PBW) for participants with ARDS at MV onset, 8.6 mL/kg PBW for those who developed ARDS after MV onset, and 8.5 mL/kg PBW for those who never developed ARDS (p = 0.23). Overall, 90-day mortality was 56% and 55% for ARDS after MV onset and ARDS at MV onset, respectively, as compared to 46% among those who never developed ARDS (p < 0.01). Adults with ARDS had a higher body mass index (BMI) than those without ARDS (27.3 vs 26.5 kg/m2, p < 0.01). Higher peak pressure (adjusted interquartile OR = 1.51, 95% CI 1.21-1.88), higher mean airway pressure (adjusted interquartile OR = 1.41, 95% CI 1.13-1.76), and higher positive end-expiratory pressure (adjusted interquartile OR = 1.29, 95% CI 1.10-1.50) at MV onset were associated with a higher odds of developing ARDS after MV onset. CONCLUSIONS: In this study of mechanically ventilated patients, 31% of study participants had ARDS at some point during their ICU stay. Optimal lung-protective ventilation was not used in a majority of patients. Patients with ARDS after MV onset had a similar 90-day mortality as those with ARDS at MV onset. Higher airway pressures at MV onset, higher PEEP, and higher BMI were associated with the development of ARDS after MV onset.

Lack of an Association Between Household Air Pollution Exposure and Previous Pulmonary Tuberculosis.

CONTEXT: Observational studies investigating household air pollution (HAP) exposure to biomass fuel smoke as a risk factor for pulmonary tuberculosis have reported inconsistent results. OBJECTIVE: To evaluate the association between HAP exposure and the prevalence of self-reported previous pulmonary tuberculosis. DESIGN: We analyzed pooled data including 12,592 individuals from five population-based studies conducted in Latin America, East Africa, and Southeast Asia from 2010 to 2015. We used multivariable logistic regression to model the association between HAP exposure and self-reported previous pulmonary tuberculosis adjusted for age, sex, tobacco smoking, body mass index, secondary education, site and country of residence. RESULTS: Mean age was 54.6 years (range of mean age across settings 43.8-59.6 years) and 48.6% were women (range of % women 38.3-54.5%). The proportion of participants reporting HAP exposure was 38.8% (range in % HAP exposure 0.48-99.4%). Prevalence of previous pulmonary tuberculosis was 2.7% (range of prevalence 0.6-6.9%). While participants with previous pulmonary tuberculosis had a lower pre-bronchodilator FEV1 (mean - 0.7 SDs, 95% CI - 0.92 to - 0.57), FVC (- 0.52 SDs, 95% CI - 0.69 to - 0.33) and FEV1/FVC (- 0.59 SDs, 95% CI - 0.76 to - 0.43) as compared to those who did not, we did not find an association between HAP exposure and previous pulmonary tuberculosis (adjusted odds ratio = 0.86; 95% CI 0.56-1.32). CONCLUSIONS: There was no association between HAP exposure and self-reported previous pulmonary tuberculosis in five population-based studies conducted worldwide.

Association between Household Air Pollution Exposure and Chronic Obstructive Pulmonary Disease Outcomes in 13 Low- and Middle-Income Country Settings.

RATIONALE: Forty percent of households worldwide burn biomass fuels for energy, which may be the most important contributor to household air pollution. OBJECTIVES: To examine the association between household air pollution exposure and chronic obstructive pulmonary disease (COPD) outcomes in 13 resource-poor settings. METHODS: We analyzed data from 12,396 adult participants living in 13 resource-poor, population-based settings. Household air pollution exposure was defined as using biomass materials as the primary fuel source in the home. We used multivariable regressions to assess the relationship between household air pollution exposure and COPD outcomes, evaluated for interactions, and conducted sensitivity analyses to test the robustness of our findings. MEASUREMENTS AND MAIN RESULTS: Average age was 54.9 years (44.2-59.6 yr across settings), 48.5% were women (38.3-54.5%), prevalence of household air pollution exposure was 38% (0.5-99.6%), and 8.8% (1.7-15.5%) had COPD. Participants with household air pollution exposure were 41% more likely to have COPD (adjusted odds ratio, 1.41; 95% confidence interval, 1.18-1.68) than those without the exposure, and 13.5% (6.4-20.6%) of COPD prevalence may be caused by household air pollution exposure, compared with 12.4% caused by cigarette smoking. The association between household air pollution exposure and COPD was stronger in women (1.70; 1.24-2.32) than in men (1.21; 0.92-1.58). CONCLUSIONS: Household air pollution exposure was associated with a higher prevalence of COPD, particularly among women, and it is likely a leading population-attributable risk factor for COPD in resource-poor settings.

Low Body Mass Index Is Associated with Higher Odds of COPD and Lower Lung Function in Low- and Middle-Income Countries.

The relationship of body mass index (BMI) with lung function and COPD has been previously described in several high-income settings. However, few studies have examined this relationship in resource-limited settings where being underweight is more common. We evaluated the association between BMI and lung function outcomes across 14 diverse low- and middle-income countries. We included data from 12,396 participants aged 35-95 years and used multivariable regressions to assess the relationship between BMI with either COPD and lung function while adjusting for known risk factors. An inflection point was observed at a BMI of 19.8 kg/m2. Participants with BMI < 19.8 kg/m2 had a 2.28 greater odds (95% CI 1.83-2.86) of having COPD and had a 0.21 (0.13-0.30) lower FEV1 and 0.34 (0.27-0.41) lower FEV1/FVC z-score compared to those with BMI ≥ 19.8 kg/m2. The association with lung function remained even after excluding participants with COPD. Individuals with lower BMI were more likely to have COPD and had lower lung function compared to those in higher BMI. The association with lung function remained positive even after excluding participants with COPD, suggesting that being underweight may also play a role in having worse lung function.

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.

Novel metrics for growth model selection.

BACKGROUND: Literature surrounding the statistical modeling of childhood growth data involves a diverse set of potential models from which investigators can choose. However, the lack of a comprehensive framework for comparing non-nested models leads to difficulty in assessing model performance. This paper proposes a framework for comparing non-nested growth models using novel metrics of predictive accuracy based on modifications of the mean squared error criteria. METHODS: Three metrics were created: normalized, age-adjusted, and weighted mean squared error (MSE). Predictive performance metrics were used to compare linear mixed effects models and functional regression models. Prediction accuracy was assessed by partitioning the observed data into training and test datasets. This partitioning was constructed to assess prediction accuracy for backward (i.e., early growth), forward (i.e., late growth), in-range, and on new-individuals. Analyses were done with height measurements from 215 Peruvian children with data spanning from near birth to 2 years of age. RESULTS: Functional models outperformed linear mixed effects models in all scenarios tested. In particular, prediction errors for functional concurrent regression (FCR) and functional principal component analysis models were approximately 6% lower when compared to linear mixed effects models. When we weighted subject-specific MSEs according to subject-specific growth rates during infancy, we found that FCR was the best performer in all scenarios. CONCLUSION: With this novel approach, we can quantitatively compare non-nested models and weight subgroups of interest to select the best performing growth model for a particular application or problem at hand.

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.

Factors associated with head circumference and indices of cognitive development in early childhood.

BACKGROUND: While head circumference (HC) has been related to intracranial volume and brain size, its association with cognitive function remains unclear. We sought to understand the relationship among various biological and socioeconomic risk factors, HC and cognitive development. METHODS: We analysed data across resource-poor settings in Bangladesh, India, Nepal, Peru, South Africa and Tanzania from the Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development longitudinal birth cohort study. Participating children were enrolled and followed up between 2009 and 2014. A final sample of 1210 children aged 0-24 months were included in the analyses. The main outcomes were HC for age Z-score and cognitive, gross motor and language scores from Bayley Scales of Infant Development-III tests. Length, weight and HC were measured monthly, and cognitive tests were administered at 6, 15 and 24 months of age. To disentangle the associations between risk factors and HC from linear growth and to distinguish the direct and indirect effects of these risk factors on cognitive function, we conducted mediation analysis using longitudinal models to account for all data measured during follow-up. RESULTS: Average HC-for-age Z-score (HCAZ) was -0.54 (95% CI -0.47 to -0.62) near birth and -1.01 (95% CI -0.94 to -1.08) at 24 months. Children with higher enrolment weight (p<0.0001), higher socioeconomic score (p=0.00037) and taller mothers (p=0.00084) had higher HCAZ at all ages, while enteropathogen infection (p=0.013) and more febrile episodes (p=0.013) were associated with lower HCAZ. The associations between HCAZ and enrolment weight-for-age, maternal height, socioeconomic status or pathogen burden were partly mediated through their associations with length-for-age. HCAZ showed no association with cognitive, gross motor or language skills at 6, 15 and 24 months of age. CONCLUSIONS: The main risk factors associated with HC are similar to those associated with body length, and HC is not related to cognitive function.

Validation of the Saint George's Respiratory Questionnaire in Uganda.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) will soon be the third leading global cause of death and is increasing rapidly in low/middle-income countries. There is a need for local validation of the Saint George's Respiratory Questionnaire (SGRQ), which can be used to identify those experiencing lifestyle impairment due to their breathing. METHODS: The SGRQ was professionally translated into Luganda and reviewed by our field staff and a local pulmonologist. Participants included a COPD-confirmed clinic sample and COPD-positive and negative members of the community who were enrolled in the Lung Function in Nakaseke and Kampala (LiNK) Study. SGRQs were assembled from all participants, while demographic and spirometry data were additionally collected from LiNK participants. RESULTS: In total, 103 questionnaires were included in analysis: 49 with COPD from clinic, 34 community COPD-negative and 20 community COPD-positive. SGRQ score varied by group: 53.5 for clinic, 34.4 for community COPD-positive and 4.1 for community COPD-negative (p<0.001). The cross-validated c statistic for SGRQ total score predicting COPD was 0.87 (95% CI 0.75 to 1.00). SGRQ total score was associated with COPD severity (forced expiratory volume in 1 s per cent of predicted), with an r coefficient of -0.60 (-0.75, -0.39). SGRQ score was associated with dyspnoea (OR 1.05/point; 1.01, 1.09) and cough (1.07; 1.03, 1.11). CONCLUSION: Our Luganda language SGRQ accurately distinguishes between COPD-positive and negative community members in rural Uganda. Scores were correlated with COPD severity and were associated with odds of dyspnoea and cough. We find that it can be successfully used as a respiratory questionnaire for obstructed adults in Uganda.

Asthma and Allergic Disorders in Uganda: A Population-Based Study Across Urban and Rural Settings.

BACKGROUND: Allergic diseases are increasing in sub-Saharan Africa, but few studies have characterized the burden among adults. OBJECTIVE: We conducted a study to evaluate the prevalence and risk factors of allergic disorders in urban and rural Uganda. METHODS: We present a cross-sectional analysis of enrollment data from a population-based cohort study of adults aged ≥35 years in urban and rural Uganda. Sociodemographic and both lifetime and 12-month respiratory symptoms data were collected and spirometry was conducted following standard guidelines. RESULTS: In 1,308 adults (median age 43.8 years and 52.3% female), we found an age-adjusted prevalence of 6.8% for asthma (9.8% urban, 4.3% rural; P < .001), 11.9% for allergic rhinitis (16.4% urban, 7.8% rural; P < .001), and 8.2% for eczema (9.9% urban, 7.8% rural; P = .15). Urbanization was the primary driver of asthma, accounting for 61.4% of cases (95% confidence interval [CI] 22.0% to 83.4%), and was the strongest risk factor for any allergic illness (odds ratio [OR] = 1.87, 95% CI 1.39-2.51). Parental asthma was not associated with allergic illness. Asthma was associated with a lower forced expiratory volume in 1 second (FEV1) by 0.56 z scores (95% CI 0.33-0.80). We found a dose-response association between lower quintiles of the FEV1/forced vital capacity ratio and both hospitalization (OR = 1.77, 95% CI 1.21-2.59) and impairment in daily activities (1.65, 1.20-2.27). CONCLUSIONS: Asthma and allergic rhinitis were twice as prevalent in urban settings. Asthma was associated with greater impairment and worse lung function outcomes. We identified a high prevalence of allergic disorders in Uganda, which can be expected to increase due to urbanization and resultant exposures throughout early development.