OBJECTIVES
People living with HIV (PLWH) carry increased risk of chronic obstructive pulmonary disease (COPD), yet the underlying mechanisms remain poorly understood. We investigated whether systemic inflammatory profiles differ between PLWH with and without COPD.
METHODS
We analyzed serum samples from 87 PLWH: 38 with COPD and 49 without COPD, matched for age and sex. Inflammatory proteins were measured using the Olink Target 96 Inflammation panel. Modules of co-varying analytes were identified using CytoMod, and associations with clinical features were tested. Key findings were validated using ELISA. A replication analysis was conducted in 158 samples from an independent cohort.
RESULTS
PLWH with COPD showed significantly elevated inflammatory markers. CytoMod analysis identified five modules when adjusting for background levels. Two modules were significantly associated with COPD, and comprised molecules involved in tissue damage and repair. Individual molecules including PD-L1, FGF-23, IL6, and others were significantly dysregulated. ELISA validation confirmed significantly elevated levels of IL-10RB, PD-L1, M-CSF, and IL-6 in PLWH-COPD. Key analytes and directional effects were confirmed in an independent cohort.
CONCLUSIONS
PLWH with COPD exhibit distinct inflammatory signatures characterized by enhanced tissue damage, immune activation, and dysregulated repair mechanisms, providing insights into HIV-related COPD.
Lennart Riemann, Lena Böger, Carina Dahl et al.· Journal of Infection· 0 citations
The relevance of high-sensitivity C-reactive protein (hsCRP), a marker of low-grade systemic inflammation, remains unclear with regard to its association with severity and clinical outcomes in wheeze/asthma. We aimed to assess the role of hsCRP across different phenotypes and severity levels. We studied children with preschool wheeze (≥ 2 episodes), and patients with GINA-defined asthma (school-age/adult) compared with healthy controls (HCs) in the well-characterized ALLIANCE (All Age Asthma Cohort) study. HsCRP was measured (AU5800®-CRP-Latex test) in 944 study participants (pediatric: n = 728; adult: n = 216) at baseline. Age-stratified analyses (age groups 0–5, 6–18, ≥ 18 years) of standardized log10-transformed hsCRP concentrations (age, sex, BMI, site) were performed using univariable tests and regression models. The validated ASSESS score and its dimensions (exacerbations, lung function, inhaled corticosteroids, symptom control) were primary outcomes. Adult patients with asthma showed higher hsCRP than HCs (OR 2.22, 95% CI 1.56–3.24). Across all ages, hsCRP increased with clinical severity of wheeze/asthma. The ASSESS score correlated positively with hsCRP in patients aged ≥ 6 years (R = 0.19, p = 0.007). hsCRP was increased in school-age asthmatics with prior exacerbations (OR 1.37, 95% CI 1.01–1.87), and in adult asthmatics with impaired lung function (R = 0.2, p = 0.013). Inhaled corticosteroid use was associated with lower hsCRP in preschool wheezers (OR 0.66, 95% CI 0.50–0.85) but higher levels in adults (OR 1.99, 95% CI 1.02–4.09). HsCRP was increased in adult asthmatics compared to HCs and was associated with several severity-related clinical characteristics. ICS use was associated with higher hsCRP levels in adults, potentially reflecting greater disease severity, whereas ICS use in preschool wheezers was associated with lower hsCRP levels. These age-dependent effects may mirror varying disease courses across the lifespan and progression of asthma. The association of hsCRP with asthma severity in child- and adulthood may indicate its potential relevance for the course of disease and monitoring clinical outcomes. Future longitudinal studies are needed to assess, whether hsCRP may support therapy monitoring. ClinicalTrials.gov; Pediatric arm: NCT02496468, Registration date: 03 July 2015; Adult arm: NCT02419274, Registration date: 14 April 2015.
Lena Lagally, Lena Ullemeyer, J. Omony et al.· Respiratory Research· 0 citations
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