Rationale There is growing concern that post–tuberculosis disease (TB) sequelae and morbidity are substantial, but no studies have controlled for preexisting factors before disease. Whether children have post-TB morbidity is not well characterized. Objectives To assess the effect of a TB diagnosis on wheezing episodes, lung function, and anthropometric measurements among children enrolled in a prospective birth cohort study in South Africa. Methods We prospectively followed children from birth through 5 years for TB using diagnostic tests including chest radiography and repeated induced sputum sample testing with Xpert MTB/RIF and liquid culture. We longitudinally measured health outcomes including growth, wheezing, and lung function up to 5 years. Mixed-effects linear regression models were used to assess growth and lung function after TB. Poisson regression was used to assess risk of subsequent wheezing. Measurements and Main Results Among 1,068 participants, 96 TB cases occurred (1,228 cases per 100,000 person-years [95% confidence interval (CI), 1,006–1,500]) occurred over 7,815 child-years of follow-up. TB was associated with lower length-for-age (−0.40 [95% CI, −0.68 to −0.11]), weight-for-age (−0.30 [95% CI, −0.59 to −0.01]), and body mass index (−0.54 [95% CI, −0.83 to −0.25]) z -scores at 5 years. Children developing TB were consistently more likely to wheeze regardless of the timing of TB. Children with diagnoses of TB between 0 and 1 year of age had reduced time to peak tidal expiratory flow over total expiratory time (−2.35% [95% CI, −4.86% to −0.17%]) and higher fractional exhaled nitric oxide (2.88 ppb [95% CI, 0.57–5.19 ppb]) at 5 years. Children with diagnoses of TB between 1 and 4 years of age had impaired V t (−9.32 ml [95% CI, −14.89 to −3.75 ml]) and time to peak tidal expiratory flow over total expiratory time (−2.73% [95% CI, −5.45% to −0.01%]) at 5 years. Conclusions Prevention of TB disease in the first few years of life may have substantial long-term benefits through childhood.

Objective: To assess the impact of HIV and antiretroviral exposure without infection on lung growth and function over the first 2 years of life. Design: Prospective observational study of an African birth cohort, Drakenstein Child Health Study. Method: Infants enrolled antenatally had lung function measured at 6 weeks, 1 and 2 years. HIV-infected women received antiretroviral therapy (ART) as per local guidelines. The association between HIV and antiretroviral exposure with lung function was assessed using mixed effects modelling. Results: Of 1143 infants born, two HIV-infected infants were excluded from analysis; 909 (80%) infants had lung function collected at 6 weeks [190 (21%) were HIV-exposed uninfected (HEU)]; 782 (69%) at 1 year and 741 (65%) at 2 years. At 6 weeks HEU infants had larger tidal volume compared with HIV-unexposed infants (1.13 ml, confidence interval: 0.02-2.23, P ¼ 0.045). High maternal viral load was associated with a 17% lower expiratory flow over 2 years (0.17, confidence interval 0.00-0.34, P ¼ 0.046). First-line ART initiated during pregnancy was associated with lower infant tidal volume at 6 weeks compared with those who initiated ART before pregnancy (À2.7 ml, À5.31 to À0.10, P ¼ 0.042), and low maternal CD4 þ cell counts associated with lower infant tidal over 2 years (À11.1 ml, À18.58-3.58, P ¼ 0.004). Conclusion: HIV exposure is associated with altered lung function in early life, with a vulnerable HEU subgroup based on maternal disease severity, immunological compromise and ART exposure. These data highlight the importance of ongoing surveillance of respiratory health in HEU children.

Obesity, a complex metabolic disorder, is characterized by mitochondrial dysfunction and oxidative stress. Increased expression of uncoupling protein 2 (UCP2) during obesity is an adaptive response to suppress the production of reactive oxygen species. The aims of this study were to compare the expression of UCP2 in diet-induced obese Wistar rats that differed according to age and their severity of obesity, and to compare UCP2 expression in the liver and muscle of these rats. UCP2 messenger RNA and protein expression was increased 4.6-fold (p < 0.0001) and 3.0-fold (p < 0.05), respectively, in the liver of the older and heavier rats. In contrast, UCP2 expression was decreased twofold (p < 0.005) in the muscle of these rats, while UCP3 messenger RNA (mRNA) was increased twofold (p < 0.01). Peroxisome proliferator-activated receptor alpha (PPARα) was similarly increased (3.0-fold, p < 0.05) in the liver of the older and more severe obese rats. Total protein content was increased (2.3-fold, p < 0.0001), while 5' adenosine monophosphate-activated protein kinase (AMPK) activity was decreased (1.3-fold, p = 0.05) in the liver of the older, heavier rats. No difference in total protein content and AMPK expression was observed in the muscle of these rats. This study showed that the expression of UCP2 varies according to age and the severity of obesity and supports the widely held notion that increased UCP2 expression is an adaptive response to increased fatty acid β-oxidation and reactive oxygen species production that occurs during obesity. An understanding of metabolic adaptation is imperative to gain insight into the underlying causes of disease, thus facilitating intervention strategies to combat disease progression.