Diane Gray

Lung Function in African Infants in the Drakenstein Child Health Study: Impact of Lower Respiratory Tract Illness.

Rationale: Lower respiratory tract illness is a major cause of childhood morbidity and mortality. It is unknown whether infants are predisposed to illness because of impaired lung function or whether respiratory illness reduces lung function. Objectives: To investigate the impact of early life exposures, including lower respiratory tract illness, on lung function during infancy. Methods: Infants enrolled in the Drakenstein child health study had lung function at 6 weeks and 1 year. Testing during quiet natural sleep included tidal breathing, exhaled nitric oxide, and multiple breath washout measures. Risk factors for impaired lung health were collected longitudinally. Lower respiratory tract illness surveillance was performed and any episode investigated. Measurements and Main Results: Lung function was tested in 648 children at 1 year. One hundred and fifty (29%) infants had a lower respiratory tract illness during the first year of life. Lower respiratory tract illness was independently associated with increased respiratory rate (4%; 95% confidence interval [CI], 1.01‐1.08; P = 0.02). Repeat episodes further increased respiratory rate (3%; 95% CI, 1.01‐1.05; P = 0.004), decreased tidal volume (−1.7 ml; 95% CI, −3.3 to −0.2; P = 0.03), and increased the lung clearance index (0.13 turnovers; 95% CI, 0.04‐0.22; P = 0.006) compared with infants without illness. Tobacco smoke exposure, lung function at 6 weeks, infant growth, and prematurity were other independent predictors of lung function at 1 year. Conclusions: Early life lower respiratory tract illness impairs lung function at 1 year, independent of baseline lung function. Preventing early life lower respiratory tract illness is important to optimize lung function and promote respiratory health in childhood.

Lung function in African infants: A pilot study

The burden of childhood respiratory illness is large in low and middle income countries (LMICs). Infant lung function (ILF) testing may provide useful information about lung growth and susceptibility to respiratory disease. However, ILF has not been widely available in LMICs settings where the greatest burden of childhood respiratory disease occurs.

Low Rates of Hepatotoxicity in HIV-infected Children on Anti-retroviral Therapy with and without Isoniazid Prophylaxis

This study investigates the incidence of hepatotoxicity in HIV-infected children during anti-retroviral therapy (ART) and the impact of concomitant use of isoniazid preventive therapy. It is a retrospective cohort analysis of HIV-infected children who commenced ART or were followed up between September 1998 and November 2005. Alanine transferase levels were measured at baseline, at 1, 3 and 6 months and then 6 monthly thereafter. Of the 598 children included in the study, 425 were taking ART alone, 73 ART and isoniazid, 39 isoniazid alone and 61 neither isoniazid nor ART. There was no increased risk of hepatotoxicity with ART with or without isoniazid compared to the control group over a 2-year period. Grade 3 or 4 ALT elevations occurred in 19 (3.4%) children, with no cases of fulminant hepatic failure. Severe hepatic events are uncommon in children on ART or isoniazid. There is no increased risk of hepatotoxicity with ART and concurrent isoniazid preventive therapy.

Lung function and exhaled nitric oxide in healthy unsedated African infants

Population‐appropriate lung function reference data are essential to accurately identify respiratory disease and measure response to interventions. There are currently no reference data in African infants. The aim was to describe normal lung function in healthy African infants.

Respiratory impedance in healthy unsedated South African infants: Effects of maternal smoking

Non‐invasive techniques for measuring lung mechanics in infants are needed for a better understanding of lung growth and function, and to study the effects of prenatal factors on subsequent lung growth in healthy infants. The forced oscillation technique requires minimal cooperation from the individual but has rarely been used in infants. The study aims to assess the use of the forced oscillation technique to measure the influence of antenatal exposures on respiratory mechanics in unsedated infants enrolled in a birth cohort study in Cape Town, South Africa.

Management of community- acquired pneumonia in HIV - infected children

Pneumonia is a major cause of childhood mortality and morbidity worldwide, particularly in low-income countries. Often, these are also the countries most affected by the HIV epidemic. Pneumonia is the leading cause of death in HIV-infected children and a major cause of hospitalization and healthcare utilization. A broader spectrum of organisms, such as Pneumocystis jiroveci and Gram-negative bacteria, cause pneumonia in HIV-infected children compared with uninfected children. Etiologic organisms have higher rates of antimicrobial resistance in HIV-infected children. Polymicrobial disease is more common in HIV-infected children and associated with an exponential increase in mortality rate. HIV-infected children develop more severe pneumonia and have a worse outcome than HIV-uninfected children. HIV-exposed but HIV-negative children are also at higher risk of severe pneumonia and death compared with HIV-unexposed children. Although case-management guidelines for childhood pneumonia have led to an overall decrease in global childhood morbidity and mortality, HIV-infected children continue to have unacceptably high treatment failure and case fatality rates despite adherence to these guidelines. Standard guidelines require adaptation for use in high HIV-prevalence areas. Specific preventive interventions, including chemoprophylaxis for P. jiroveci pneumonia or for TB and early initiation of highly active antiretroviral therapy, may significantly reduce the burden of pneumonia in HIV-infected children.

Lung function abnormalities in HIV-infected adults and children

Despite the advent of antiretroviral therapy (ART), the human immunodeficiency virus (HIV) epidemic remains a global health crisis with a high burden of respiratory disease among infected persons. While the early complications of the epidemic were dominated by opportunistic infections, improved survival has led to the emergence of non‐infectious conditions that are associated with chronic respiratory symptoms and pulmonary disability. Obstructive ventilatory defects and reduced diffusing capacity are common findings in adults, and the association between HIV and chronic obstructive pulmonary disease is increasingly recognized. There is synergism between viral factors, opportunistic infections, conventional influences like tobacco smoke and biomass fuel exposure, and potentially, the immunological effects of ART on the development of HIV‐associated chronic obstructive lung disease. Pulmonary function data for HIV‐infected infants and children are scarce, but shows that bronchiectasis and obliterative bronchiolitis with severe airflow limitation are major problems, particularly in the developing world. However, studies from these regions are sorely lacking. There is thus a major unmet need to understand the influences of chronic HIV infection on the lung in both adults and children, and to devise strategies to manage and prevent these diseases in HIV‐infected individuals. It is important for clinicians working with HIV‐infected individuals to have an appreciation of their effects on measurements of lung function.

Determinants of early-life lung function in African infants.

Background Low lung function in early life is associated with later respiratory illness. There is limited data on lung function in African infants despite a high prevalence of respiratory disease. Aim To assess the determinants of early lung function in African infants. Method Infants enrolled in a South African birth cohort, the Drakenstein child health study, had lung function measured at 6–10 weeks of age. Measurements, made with the infant breathing via a facemask during natural sleep, included tidal breathing, sulfur hexafluoride multiple breath washout and the forced oscillation technique. Information on antenatal and early postnatal exposures was collected using questionnaires and urine cotinine. Household benzene exposure was measured antenatally. Results Successful tests were obtained in 645/675 (95%) infants, median (IQR) age of 51 (46–58) days. Infant size, age and male gender were associated with larger tidal volume. Infants whose mothers smoked had lower tidal volumes (−1.6 mL (95% CI −3.0 to −0.1), p=0.04) and higher lung clearance index (0.1 turnovers (95% CI 0.01 to 0.3), p=0.03) compared with infants unexposed to tobacco smoke. Infants exposed to alcohol in utero or household benzene had lower time to peak tidal expiratory flow over total expiratory time ratios, 10% (95% CI −15.4% to −3.7%), p=0.002) and 3.0% (95% CI −5.2% to −0.7%, p=0.01) lower respectively compared with unexposed infants. HIV-exposed infants had higher tidal volumes (1.7 mL (95% CI 0.06 to 3.3) p=0.04) compared with infants whose mothers were HIV negative. Conclusion We identified several factors including infant size, sex, maternal smoking, maternal alcohol, maternal HIV and household benzene associated with altered early lung function, many of which are factors amenable to public health interventions. Long-term study of lung function and respiratory disease in these children is a priority to develop strategies to strengthen child health.

Lung Function in South African Adolescents Infected Perinatally with HIV and Treated Long-Term with Antiretroviral Therapy

Rationale: Lung disease is a common cause of mortality and morbidity in HIV‐infected adolescents, but there is limited information on the spectrum of lung function impairment in adolescents on antiretroviral therapy. Objectives: To investigate lung function in HIV‐infected adolescents on antiretroviral therapy in the Cape Town Adolescent Antiretroviral Cohort (Cape Town, South Africa). Methods: A total of 515 South African adolescents, aged 9‐14 years, stable on antiretroviral therapy for at least 6 months, underwent baseline lung function testing. Measures included spirometry, nitrogen multiple‐breath washout, forced oscillation technique, 6‐minute walk test, single‐breath carbon monoxide diffusion testing, and bronchodilator response testing. A comparator group of 110 age‐ and ethnicity‐matched HIV‐uninfected adolescents was also tested. Results: For the HIV‐infected adolescents (mean [SD] age 12 [1.6] years, 52% male), the median (interquartile range) duration of antiretroviral therapy was 7.6 (4.6‐9.2) years. The median (interquartile range) nadir CD4 was 510.5 (274‐903) cells/mm3. HIV‐infected adolescents had significantly lower FEV1, FVC, FEV1/FVC, diffusing capacity of carbon monoxide, respiratory system compliance, and functional residual capacity than HIV‐uninfected adolescents (P < 0.05 for all associations). HIV‐infected adolescents had higher airway resistance and lung clearance index than HIV‐uninfected adolescents (P < 0.05 for all associations). Although generally small in magnitude, these differences remained significant after adjusting for age, sex, and height. In addition, age, sex, height, and history of past lower respiratory tract infection or pulmonary tuberculosis were associated with reduced lung function. Conclusions: Perinatally infected South African HIV‐infected adolescents on antiretroviral therapy have lower lung function than uninfected adolescents. Prior lower respiratory tract infection or pulmonary tuberculosis is associated with lower lung function.

Isoniazid preventive therapy in HIV-infected children on antiretroviral therapy: a pilot study.

SETTING Tuberculosis (TB) is a common cause of mortality and morbidity in children infected with the human immunodeficiency virus (HIV). Data on isoniazid preventive therapy (IPT) efficacy in HIV-infected children receiving antiretroviral therapy (ART) are inconclusive. OBJECTIVE To assess the efficacy, tolerability and safety of isoniazid (INH) in HIV-infected children on ART. DESIGN A pilot randomised controlled study of INH was undertaken in HIV-infected children on ART. The primary outcome measure was TB disease or death. RESULTS A total of 167 children were randomised to receive INH (n = 85) or placebo (n = 82), and followed for a median of 34 months (interquartile range [IQR] 24-52). The median age was 35 months (IQR 15-65). There was one death in a child on INH and none in the placebo group. Eleven (6.6%) cases of TB occurred, 4 (5%) in the INH and 7 (9%) in the placebo group. Among the TB cases, 5 were culture confirmed-2 in the INH group and 3 in the placebo group, all susceptible to INH. Severe adverse events occurred rarely (n = 6; 2%). CONCLUSION IPT is safe and well tolerated in HIV-infected children on concomitant ART. This study supports the need for a larger study to assess efficacy in HIV-infected children living in TB-endemic areas.