Markers of chronic obstructive pulmonary disease are associated with mortality in people living with HIV

Abstract

Objective. Aging people living with HIV (PLWH) face an increased burden of comorbidities, including chronic obstructive pulmonary disease (COPD). The impact of COPD on mortality in HIV remains unclear. We examined associations between markers of COPD and mortality among PLWH and uninfected subjects.Design. Longitudinal analysis of the Examinations of HIV-Associated Lung Emphysema (EXHALE) cohort study.Methods. EXHALE includes 196 PLWH and 165 uninfected smoking-matched subjects who underwent pulmonary function testing and CT scans to define COPD and were followed. We determined associations between markers of COPD with mortality using multivariable Cox regression models, adjusted for smoking and the VACS Index, a validated predictor of mortality in HIV.Results. Median follow-up time was 6.9 years; the mortality rate was 2.7 per 100-person-years among PLWH and 1.7 per 100-person-years among uninfected subjects (p=0.11). The VACS Index was associated with mortality in both PLWH and uninfected subjects. In multivariable models, pulmonary function and CT characteristics defining COPD were associated with mortality in PLWH: those with airflow obstruction (FEV1/FVC<0.7) had 3.1 times the risk of death (HR 3.1 [95% CI 1.4-7.1]), compared to those without; those with emphysema (>10% burden) had 2.4 times the risk of death (HR 2.4 [95% CI 1.1-5.5]) compared to those with ≤10% emphysema. In uninfected subjects, pulmonary variables were not significantly associated with mortality, which may reflect fewer deaths limiting power.Conclusions. Markers of COPD were associated with greater mortality in PWLH, independent of the VACS Index. COPD is likely an important contributor to mortality in contemporary PLWH.

HIV persistence in mucosal CD4+ T cells within the lungs of adults receiving long-term suppressive antiretroviral therapy

“…The accumulation of senescent T cells could impair the cell maintenance and repair capabilities of the lungs and promote lung tissue destruction in the long-term [ 40 ]. In HIV + adults, chronic obstructive pulmonary disease and lung cancers are reported much earlier than in general population and are associated with high mortality independent of smoking [ 1 , 2 ]. Therefore, the high CD4 + T-cell differentiation, activation and senescence could contribute to greater HIV burden and mucosal pro-inflammatory milieu [ 1 ].…”

“…Despite suppressive antiretroviral therapy (ART), HIV-infected individuals suffer from a high burden of bacterial pneumonia, influenza, and tuberculosis [ 1 ], suggesting that lung immunity is not fully restored. The high prevalence of chronic lung diseases, notably chronic obstructive pulmonary disease, among HIV-infected individuals is associated with high mortality rates [ 1 , 2 ]. Importantly, HIV is an independent risk factor from tobacco for altered pulmonary immunity, despite suppressive ART [ 1 ].…”

Associations between baseline biomarkers and lung function in HIV-positive individuals

“…COPD is a leading cause of death worldwide, is common among HIV positive individuals [5,7] and diminishes both quality and duration of life. [8][9][10] COPD is defined by expiratory airflow limitation, when spirometry demonstrates a low ratio of forced expiratory volume in 1s to forced vital capacity (FEV 1 /FVC). FEV 1 is the most common metric to determine severity of COPD and although FEV 1 declines as part of normal aging, faster decline in FEV 1 has been associated with both COPD susceptibility and increased respiratory and all-cause mortality.…”

Respiratory symptoms and chronic bronchitis in people with and without HIV infection

“…Although respiratory symptoms in the general population are associated with negative outcomes, including cardiovascular comorbidity, hospitalization and mortality [28,29], similar studies among PWH are lacking. Some studies have considered associations between lung function and outcomes in PWH, reporting associations of airflow obstruction, impaired diffusing capacity and emphysema with mortality [30,31] and slower gait speed [32], the latter suggesting an association with frailty as also reported in the general population [9]. Whilst lung function is only moderately correlated with respiratory symptoms, these findings do suggest the potential for respiratory symptoms to impact on clinical outcomes, in addition to the strong associations with depressive symptoms and quality of life seen in our study.…”