Clinical Characteristics and Lung Function in Older Children Vertically Infected With Human Immunodeficiency Virus in Malawi

Abstract

Background: Antiretroviral therapy (ART) has led to increased survival of children with vertically acquired human immunodeficiency virus infection. Significant morbidity arises from respiratory symptoms, but aetiology and pulmonary function abnormalities have not been systematically studied.

Methods: Human immunodeficiency virus-positive children aged 8-16 years were systematically recruited within clinics in Blantyre, Malawi. Clinical review, quality of life assessment, spirometry, and chest radiography were performed.

Results: One hundred sixty participants had a mean of age 11.1 (range, 8-16) years and 50.0% were female. Cough was present in 60 (37.5%) participants, and 55 (34.4%) had moderate or severe dyspnoea. Thirty-four (22.1%) participants had digital clubbing. Thirty-three (20.6%) participants were hypoxic at rest. One hundred eighteen (73.8%) of the children were receiving ART; median CD4 count was 698 cells/µL in these compared with 406 cells/µL in ART-naive individuals (P < .001). From 145 spirometry traces (90.6%), mean forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were 1.06 and 0.89 standard deviations below predicted mean, respectively. Twenty-one (14.5%) traces demonstrated obstructive defects and 26 (17.9%) reduced FVC. Lung function abnormality was not associated with any clinical findings. Of the 51 individuals with abnormal lung function, the mean increase in FEV1 after salbutamol was 3.8% (95% confidence interval, 0.02-7.53). "Tramlines" and ring shadows were seen on chest radiographs in over half of cases.

Conclusions: Symptoms of chronic lung disease were highly prevalent with 2 main clinical phenotypes: "cough" and "hypoxia". Lung function abnormalities are common, poorly responsive to bronchodilators, and apparent throughout the age range of our cohort. Pathological causes remain to be elucidated. Cough and hypoxic phenotypes could be a useful part of diagnostic algorithms if further validated.

Keywords: HIV; case definition; chronic lung disease; infectious disease transmission; respiratory function tests; vertical.

Figure 1.

Study flowchart. Flow diagram illustrates participant retention and quality of spirometry throughout the study. CXR, chest x-ray.

Figure 2.

Spirometry results overview. Graphs illustrating the degree and distribution of spirometric abnormality. (A) Boxes represent 25th and 75th percentiles, whiskers represent 10th and 90th percentiles, with outliers shown as individual dots. Upper limit of normal (ULN) and lower limit of normal (LLN) drawn by dashed line at +1.64 standard deviation (SD) and −1.64 SD from the mean, respectively. (B) Forced expiratory volume (FEV₁) z-score for all participants as a function of age. Linear regression model is shown as a solid line. There is a nonsignificant tendency to reducing FEV₁ with increasing age in this cohort (r² = 0.026; P = .054). Similar results for forced vital capacity obtained (results not shown).

Figure 3.

Proposed CLD phenotypes. Proportional areas diagram illustrating the proposed CLD phenotypes, “cough” and “hypoxia”, and their overlap with individuals with abnormal spirometry. Percentages indicate the proportion of the entire study population for which spirometry data were available.