Flygel, Trym ThuneHameiri-Bowen, DanSimms, VictoriaRowland-Jones, SarahFerrand, Rashida AbbasBandason, TsitsiYindom, Louis-MarieOdland, Jon OyvindCavanagh, Jorunn PaulineFlaegstad, TrondSovershaeva, Evgeniya2024-04-112024-04-112024-02Flygel, T.T., Hameiri-Bowen, D., Simms, V., et al. Exhaled nitric oxide is associated with inflammatory biomarkers and risk of acute respiratory exacerbations in children with HIV-associated chronic lung disease. HIV Medicine 2024; 25(2): 223‐232. doi:10.1111/hiv.13565.1464-2662 (print)1468-1293 (online)10.1111/hiv.13565http://hdl.handle.net/2263/95478SUPPORTING INFORMATION : FIGURE S1. Box plot of eNO at baseline and 48 weeks by trial group and overall. AZM, azithromycin; eNO, exhaled nitric oxide. TABLE S1. Baseline characteristics of participants by trial group. TABLE S2. Effect of azithromycin on levels of eNO after 48 weeks of treatment using a generalized linear model. eNO, exhaled nitric oxide.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.en© 2023 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association. This is an open access article under the terms of the Creative Commons Attribution License.AfricaBiomarkersChronic lung diseaseHuman immunodeficiency virus (HIV)InflammationAcute respiratory exacerbations (ARE)Exhaled nitric oxide (eNO)SDG-03: Good health and well-beingArticle