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, Flaegstad Trond, Sovershaeva Evgeniya
Paediatric Research Group, Department of Clinical Medicine, Faculty of Health sciences, UiT - The Arctic University of Norway, Tromsø, Norway.
Department of Paediatrics, University Hospital of North Norway, Tromsø, Norway.
HIV Med. 2024 Feb;25(2):223-232. doi: 10.1111/hiv.13565. Epub 2023 Oct 7.
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.
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.
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).
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.
慢性肺病是感染HIV儿童中一种公认的并发症。急性呼吸加重（ARE）在该群体中很常见，并会导致显著的发病率。呼出一氧化氮（eNO）是局部气道炎症的已知标志物。我们研究了eNO与ARE、全身炎症生物标志物之间的关联，以及阿奇霉素对eNO水平的影响。
在津巴布韦哈拉雷，年龄在6至19岁的患有HIV相关慢性肺病的个体被纳入一项安慰剂对照随机试验，该试验研究48周阿奇霉素治疗对肺功能和ARE的影响。在连续入组的一部分参与者中，在入组时和治疗后测量eNO水平和生物标志物。使用线性回归和广义线性模型来研究eNO与ARE、生物标志物之间的关联，以及阿奇霉素对eNO水平的影响。
该亚研究共纳入172名参与者，其中86名来自安慰剂组，86名来自阿奇霉素组。在随访期间经历至少一次ARE的参与者在基线时的eNO水平显著高于未经历的参与者（几何平均比1.13，95%置信区间[CI]1.03 - 1.24，p = 0.015），对试验组、年龄、性别和结核病病史进行了调整。基质金属蛋白酶（MMP）-3、-7和-10与更高的基线eNO水平显著相关。在48周时，阿奇霉素治疗未影响eNO水平（几何平均比0.86，95%CI 0.72 - 1.03，p = 0.103）。
更高的基线eNO水平是ARE的一个危险因素。eNO与先前发现的促炎生物标志物相关，这些生物标志物有助于慢性肺病的发展。在HIV相关慢性肺病中，eNO作为炎症标志物和ARE危险因素的潜在用途需要进一步研究。
