Exhaled nitric oxide is associated with inflammatory biomarkers and risk of acute respiratory exacerbations in children with HIV‐associated chronic lung disease

• Published in: HIV medicine Vol. 25; no. 2; pp. 223 - 232
• Main Authors: Flygel, Trym Thune, Hameiri‐Bowen, Dan, Simms, Victoria, Rowland‐Jones, Sarah, Ferrand, Rashida Abbas, Bandason, Tsitsi, Yindom, Louis‐Marie, Odland, Jon Øyvind, Cavanagh, Jorunn Pauline, Flægstad, Trond, Sovershaeva, Evgeniya
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.02.2024; Wiley
• Subjects: Adolescent; Africa; Azithromycin; Azithromycin - therapeutic use; Biomarkers; Breath Tests; Child; chronic lung disease; exhaled nitric oxide; Generalized linear models; HIV; HIV Infections - complications; HIV Infections - drug therapy; Human immunodeficiency virus; Humans; Inflammation; Lung diseases; Lung Diseases - etiology; Matrix metalloproteinase; Matrix metalloproteinases; Metalloproteinase; Morbidity; Nitric oxide; Nitric Oxide - analysis; Placebos; Regression analysis; Respiratory function; Respiratory tract diseases; Risk factors; Sexually transmitted diseases; Statistical analysis; Statistical models; STD; Young Adult; Zimbabwe; Zimbabwe; exhaled nitric oxide; chronic lung disease; HIV; inflammation; biomarkers; Africa
• ISSN: 1464-2662; 1468-1293; 1468-1293
• DOI: 10.1111/hiv.13565

Objectives Chronic lung disease is a recognized complication in children with HIV. Acute respiratory exacerbations (ARE) are common among this group and cause significant morbidity. Exhaled nitric oxide (eNO) is a known marker of local airway inflammation. We investigated the association between eNO and ARE, biomarkers of systemic inflammation, and the effect of azithromycin on eNO levels. Methods Individuals aged 6–19 years with HIV‐associated chronic lung disease in Harare, Zimbabwe, were enrolled in a placebo‐controlled randomized trial investigating the effect of 48‐week azithromycin treatment on lung function and ARE. eNO levels and biomarkers were measured at inclusion and after treatment in a consecutively enrolled subset of participants. Linear regression and generalized linear models were used to study associations between eNO and ARE, biomarkers, and the effect of azithromycin on eNO levels. Results In total, 172 participants were included in this sub‐study, 86 from the placebo group and 86 from the azithromycin group. Participants experiencing at least one ARE during follow‐up had significantly higher eNO levels at baseline than participants who did not (geometric mean ratio 1.13, 95% confidence interval [CI] 1.03–1.24, p = 0.015), adjusted for trial arm, age, sex and history of tuberculosis. Matrix metalloproteinase (MMP)‐3, ‐7, and ‐10 were significantly associated with higher baseline eNO levels. At 48 weeks, azithromycin treatment did not affect eNO levels (geometric mean ratio 0.86, 95% CI 0.72–1.03, p = 0.103). Conclusion Higher baseline eNO levels were a risk factor for ARE. eNO was associated with proinflammatory biomarkers previously found to contribute to the development of chronic lung disease. The potential use of eNO as a marker of inflammation and risk factor for ARE in HIV‐associated chronic lung disease needs further investigation.