Emphysema has been suggested to occur more frequently and at younger age in people living with HIV (PLWH) than in uninfected controls. Risk factors for emphysema include smoking and alpha-1 antitrypsin (AAT) deficiency, but recent evidence suggest that inflammation may also play a role. We investigated whether elevated cytokine concentrations (interleukin(IL)-1?, IL-1 receptor antagonist (IL-1RA), IL-2, IL-4, IL-6, IL-10, IL-17A, tumor necrosis factor-alpha (TNF?), interferon-gamma (IFN?), soluble CD14 (sCD14) and sCD163) are independently associated with radiographic emphysema in PLWH.
We included PLWH without hepatitis B and C co-infection with a plasma sample and a chest computed tomography scan available from the Copenhagen Comorbidity in HIV Infection (COCOMO) Study. Radiographic emphysema plus trace emphysema was defined as percentage of low attenuation area under 950 Hounsfield units (%LAA-950) using a cut-off at 5%. Cytokine concentrations were measured by ELISA or Luminex immunoassays, and an elevated cytokine concentration was defined as above the 75th percentile. Logistic regression analyses were performed to explore associations between elevated cytokine concentrations and radiographic emphysema plus trace emphysema in PLWH.
Of 783 PLWH, 147 (18.8%) had emphysema plus trace emphysema. PLWH were predominantly male (86.0%) and 743 (94.9%) had undetectable viral load. PLWH with emphysema plus trace emphysema had higher concentrations of TNF? (median (IQR): 8.2 (6.4-9.8) versus 7.1 (5.7-8.6) pg/ml, p<0.001), IL-1? (median (IQR): 0.21 (0.1-0.4) versus 0.17 (0.1-0.3) pg/ml, p=0.004) and IL-6 (median (IQR): 3.6 (2.6-4.9) versus 3.1 (2.0-4.3) pg/ml, p=0.023) than PLWH without. AAT deficiency (<1.0 g/L) was rare and equally prevalent in the two groups (p=0.291). In models adjusted for age, sex, ethnicity, smoking status, BMI and CD4 nadir, elevated TNF? (adjusted odds ratio (aOR): 1.91 [95%CI: 1.23-2.95], p=0.004) and IL-1? (aOR: 1.93 [95%CI: 1.25-3.00], p=0.003) were associated with emphysema plus trace emphysema (Table 1). The association between IL-1? and emphysema was modified by smoking (p-interaction=0.018) with a more pronounced association in never smokers (aOR: 4.87 [95%CI: 2.22-10.69], p<0.001).
Two markers of systemic inflammation, TNF? and IL-1?, were independently associated with radiographic emphysema plus trace emphysema in PLWH and may be involved in the pathogenesis of emphysema.
