Tuberculous pericarditis is associated with high morbidity and mortality even if antituberculosis therapy is administered. We evaluated the effects of adjunctive glucocorticoid therapy and Mycobacterium indicus pranii immunotherapy in patients with tuberculous pericarditis. Using a 2-by-2 factorial design, we randomly assigned 1400 adults with definite or probable tuberculous pericarditis to either prednisolone or placebo for 6 weeks and to either M. indicus pranii or placebo, administered in five injections over the course of 3 months. Two thirds of the participants had concomitant human immunodeficiency virus (HIV) infection. The primary efficacy outcome was a composite of death, cardiac tamponade requiring pericardiocentesis, or constrictive pericarditis. There was no significant difference in the primary outcome between patients who received prednisolone and those who received placebo (23.8% and 24.5%, respectively; hazard ratio, 0.95; 95% confidence interval [CI], 0.77 to 1.18; P=0.66) or between those who received M. indicus pranii immunotherapy and those who received placebo (25.0% and 24.3%, respectively; hazard ratio, 1.03; 95% CI, 0.82 to 1.29; P=0.81). Prednisolone therapy, as compared with placebo, was associated with significant reductions in the incidence of constrictive pericarditis (4.4% vs. 7.8%; hazard ratio, 0.56; 95% CI, 0.36 to 0.87; P=0.009) and hospitalization (20.7% vs. 25.2%; hazard ratio, 0.79; 95% CI, 0.63 to 0.99; P=0.04). Both prednisolone and M. indicus pranii, each as compared with placebo, were associated with a significant increase in the incidence of cancer (1.8% vs. 0.6%; hazard ratio, 3.27; 95% CI, 1.07 to 10.03; P=0.03, and 1.8% vs. 0.5%; hazard ratio, 3.69; 95% CI, 1.03 to 13.24; P=0.03, respectively), owing mainly to an increase in HIV-associated cancer. In patients with tuberculous pericarditis, neither prednisolone nor M. indicus pranii had a significant effect on the composite of death, cardiac tamponade requiring pericardiocentesis, or constrictive pericarditis. (Funded by the Canadian Institutes of Health Research and others; IMPI ClinicalTrials.gov number, NCT00810849.)

In sub-Saharan Africa, little is known about the damage to respiratory health caused by biomass smoke and tobacco smoke. We assessed the prevalence of chronic obstructive pulmonary disease (COPD) and related risk factors in a rural region of Uganda. We did this prospective observational cross-sectional study in rural Masindi, Uganda. We randomly selected people above the age of 30 years from 30 villages. Trained local health-care workers asked validated questionnaires and administered spirometry to participants. We defined COPD as FEV1:FVC less than the lower limit of normal. We calculated prevalence of COPD and tested its association with risk factors. Between April 13, and Aug 14, 2012, we invited 620 people to participate, of whom 588 provided acceptable spirometry and were analysed. Mean age was 45 years (SD 13·7); 297 (51%) were women. 546 (93%) were exposed to biomass smoke. The prevalence of COPD was 16·2% (15·4% in men, 16·8% in women). Prevalence was highest in people aged 30-39 years (17 [38%] of 45 men, 20 [40%] of 50 women). 20 (44%) of 45 men with COPD were current smokers (mean age 40 years, SD 7·5), 11 (24%) were former smokers (mean age 49 years, SD 11·0); four [8%] of 50 women were current smokers (mean age 52 years, SD 18·1), nine (18%) were former smokers (mean age 64 years, SD 16·2). Mean Clinical COPD Questionnaire score was 0·81 (SD 0·78), mean Medical Research Council dyspnoea score was 1·33 (SD 0·65); 28 (30%) of 95 patients had had one or more exacerbations past 12 months. COPD was associated with wheeze (odds ratio 2·17, 95% CI 1·09-4·34; p=0·028) and being a former smoker (1·96, 1·07-3·59; p=0·029). In this rural district of Uganda, COPD starts early in life. Major risk factors were biomass smoke for both sexes and tobacco smoke for men. In addition to high smoking prevalence in men, biomass smoke could be a major health threat to men and women in rural areas of Uganda. International Primary Care Respiratory Group.

Rationale: Mycobacterium tuberculosis is transmitted by infectious aerosols, but assessing infectiousness currently relies on sputum microscopy that does not accurately predict the variability in transmission. Objectives: To evaluate the feasibility of collecting cough aerosols and the risk factors for infectious aerosol production from patients with pulmonary tuberculosis (TB) in a resource-limited setting. Methods: We enrolled subjects with suspected TB in Kampala, Uganda and collected clinical, radiographic, and microbiological data in addition to cough aerosol cultures. A subset of 38 subjects was studied on 2 or 3 consecutive days to assess reproducibility. Measurements and Main Results: M. tuberculosis was cultured from cough aerosols of 28 of 101 (27.7%; 95% confidence interval [CI], 19.9–37.1%) subjects with culture-confirmed TB, with a median 16 aerosol cfu (range, 1–701) in 10 minutes of coughing. Nearly all (96.4%) cultivable particles were 0.65 to 4.7 μm in size. Positive aerosol cultures were associated with higher Karnofsky performance scores (P = 0.016), higher sputum acid-fast bacilli smear microscopy grades (P = 0.007), lower days to positive in liquid culture (P = 0.004), stronger cough (P = 0.016), and fewer days on TB treatment (P = 0.047). In multivariable analyses, cough aerosol cultures were associated with a salivary/mucosalivary (compared with purulent/mucopurulent) appearance of sputum (odds ratio, 4.42; 95% CI, 1.23–21.43) and low days to positive (per 1-d decrease; odds ratio, 1.17; 95% CI, 1.07–1.33). The within-test (kappa, 0.81; 95% CI, 0.68–0.94) and interday test (kappa, 0.62; 95% CI, 0.43–0.82) reproducibility were high. Conclusions: A minority of patients with TB (28%) produced culturable cough aerosols. Collection of cough aerosol cultures is feasible and reproducible in a resource-limited setting.

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.

Asthma, rhinitis, and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of “one‐airway‐one‐disease,” coined over 20 years ago, is a simplistic approach of the links between upper‐ and lower‐airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitization and multimorbidity, (iii) advances in mHealth for novel phenotype definitions, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches, and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper‐ and lower‐airway allergic diseases with skin, gut, and neuropsychiatric multimorbidities, is the “Epithelial Barrier Hypothesis.” This review determined that the “one‐airway‐one‐disease” concept does not always hold true and that several phenotypes of disease can be defined. These phenotypes include an extreme “allergic” (asthma) phenotype combining asthma, rhinitis, and conjunctivitis. Rhinitis alone and rhinitis and asthma multimorbidity represent two distinct diseases with the following differences: (i) genomic and transcriptomic background (Toll‐Like Receptors and IL‐17 for rhinitis alone as a local disease; IL‐33 and IL‐5 for allergic and non‐allergic multimorbidity as a systemic disease), (ii) allergen sensitization patterns (mono‐ or pauci‐sensitization versus polysensitization), (iii) severity of symptoms, and (iv) treatment response. In conclusion, rhinitis alone (local disease) and rhinitis with asthma multimorbidity (systemic disease) should be considered as two distinct diseases, possibly modulated by the microbiome, and may be a model for understanding the epidemics of chronic and autoimmune diseases.