Preserved Ratio Impaired Spirometry Findings and Immune Dysfunction Among Adolescents With and Without HIV in Kenya.

Abstract

Background: Chronic lung disease and its association with immune dysfunction are characterized poorly among adolescents with HIV (AWHIVs).

Research question: Is HIV associated with spirometry abnormalities among adolescents, and what role does immune dysfunction play?

Study design and methods: We conducted a cohort study of adolescents (10-19 years of age) with and without HIV in Nairobi, Kenya. We fit adjusted log binomial models using Poisson regression to determine associations between HIV, respiratory symptoms, clinical signs, and, using exploratory factor analysis, biomarkers of immune dysregulation with spirometry abnormalities. We used linear regression to examine similar associations with continuous spirometry variables.

Results: We included 154 AWHIVs (median age, 15 years [interquartile range, 13-18 years]) and 159 adolescents without HIV (AWoHs; median age, 13 years [interquartile range, 11-16 years]). Preserved ratio impaired spirometry (PRISm) findings were the predominant spirometry abnormality (20% in AWHIVs; 12% in AWoHs), followed by a restrictive spirometry pattern (RSP) (18% in AWHIVs; 12% in AWoHs) and obstructive impairments (5% in AWHIVs; 6% in AWoHs). AWHIVs showed a 1.55-fold (95% CI, 1.01-fold to 2.36-fold) increased risk of any spirometry abnormality, a 2.44-fold (95% CI, 1.40-fold to 4.26-fold) increased risk of PRISm findings, and 0.23 SD (95% CI, -0.43 to -0.03 SD) lower mean FVC z score than AWoHs. We detected no associations of respiratory symptoms or clinical signs with any spirometry abnormality among AWHIVs. AWoHs with symptoms and clinical signs were more likely to have any spirometry abnormality than AWoHs without symptoms or signs (aRR, 2.26 [95% CI, 1.23-4.17] and 2.20 [95% CI, 1.22-3.97], respectively). The biomarker factor group reflecting acute inflammation (CRP, SAA) was associated with increased risk of any spirometry abnormality among AWHIVs (aRR, 1.35 [95% CI, 1.06-1.72]) and AWoHs (1.70 [95% CI, 1.34-2.17]). Among AWHIV only, the biomarker factor grouping of endothelial activation (sCD14, soluble intercellular adhesion molecule 1, or soluble vascular cell adhesion molecule 1), lower BMI for age z score, and tobacco smoke exposure were associated with increased risk of any spirometry abnormality (aRR, 1.35 [95% CI, 1.09-1.67], 0.76 [95% CI, 0.62-0.92], and 2.34 [95% CI, 1.28-4.23], respectively) and PRISm findings.

Interpretation: AWHIVs showed an increased risk of any spirometry abnormality, including PRISm findings and RSP, compared with AWoHs. Immune and endothelial activation were associated with spirometry abnormalities among AWHIVs only, suggesting alternative mechanisms of disease in AWHIVs.