Pulmonary symptoms and diagnoses are associated with HIV in the MACS and WIHS cohorts

Gingo, Matthew R.; Balasubramani, Goundappa K.; Rice, Thomas B.; Kingsley, Lawrence A.; Kleerup, Eric C.; Detels, Roger; Seaberg, Eric C.; Greenblatt, Ruth M.; Holman, Susan; Huang, Laurence; Sutton, Sarah H.; Bertolet, Marnie; Morris, Alison

doi:10.1186/1471-2466-14-75

Cited by 57 publications

(52 citation statements)

References 42 publications

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“…Several cohort studies have addressed respiratory symptoms in HIV-positive individuals with access to ART in the USA: the Women's Interagency HIV Study (WIHS); Multicentre AIDS Cohort Study and the EXHALE substudy of the Veterans Aging Cohort Study 32 36. Tobacco use was high in these cohorts, and smoking was more frequent in the HIV-positive than HIV-negative groups (reported in 39%–64% and 23%–58%, respectively).…”

Section: Resultsmentioning

confidence: 99%

Respiratory symptoms in people living with HIV and the effect of antiretroviral therapy: a systematic review and meta-analysis

Brown

Roy

Harris

et al. 2016

Thorax

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BackgroundAntiretroviral therapy (ART) has significantly altered the pattern of acute and chronic HIV-related disease. However, it is not clear what this means in terms of respiratory symptoms. We sought to investigate the association between HIV status and respiratory symptoms and how these have changed with the availability of ART.MethodsWe searched Cochrane, Medline and Embase databases for studies published between 1946 and August 2015 comparing the prevalence of respiratory symptoms in populations with and without HIV infection. We undertook random effects meta-analysis of the main symptoms reported. We studied heterogeneity and completed sensitivity analyses and funnel plots.ResultsFrom 5788 unique references identified, 24 papers provided relevant data: 18 documented the prevalence of cough and 11 examined the prevalence of breathlessness among other symptoms reported. Compared with the HIV negative, people living with HIV (PLWH) were more likely to have respiratory symptoms with pooled ORs for the prevalence of cough of 3.05 (95% CI 2.24 to 4.16) in resource-limited populations without access to ART; 2.18 (1.56 to 3.18) in resource-rich populations without access to ART and 1.11 (0.99 to 1.24) in resource-rich populations with access to ART. In resource-rich settings, although the availability of ART was associated with a reduction in the difference between HIV-positive and HIV-negative individuals, PLWH were more likely to report breathlessness, OR 1.39 (95% CI 1.11 to 1.73).ConclusionsRespiratory symptoms are more common in PLWH than controls. This association persists although at a reduced level in populations with access to ART.

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Section: Resultsmentioning

confidence: 99%

Respiratory symptoms in people living with HIV and the effect of antiretroviral therapy: a systematic review and meta-analysis

Brown

Roy

Harris

et al. 2016

Thorax

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“…HIV appears to be an independent risk factor for these diseases, as these associations have been demonstrated despite consideration of known risk factors for chronic pulmonary disease such as smoking, prior pneumonia history, or injection drug use[2–4, 7, 14]. The biologic mechanisms that underlie pulmonary function abnormalities in this vulnerable population remain incompletely described.…”

Section: Introductionmentioning

confidence: 99%

Novel relationships of markers of monocyte activation and endothelial dysfunction with pulmonary dysfunction in HIV-infected persons

Fitzpatrick

Nouraie

Gingo

et al. 2016

Aids

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Objective Chronic obstructive pulmonary disease (COPD) is a common co-morbidity in HIV, with prevalence and severity of disease incompletely explained by risk factors such as smoking and age. Unique HIV-associated factors, including microbial translocation, monocyte activation, and endothelial dysfunction, have been described in other co-morbidities, but have not been investigated in relation to pulmonary abnormalities in HIV. This study assessed the relationship of these pathologic processes to pulmonary function in HIV-infected and uninfected individuals and determined if relationships were unique to HIV. Design Longitudinal observational study Methods 274 participants completed pulmonary function testing. Markers of inflammation (IL-6, IL-8, TNF-α), microbial translocation (lipopolysaccharide, sCD14), monocyte activation (sCD163, sCD14, and IL-2 receptor), and endothelial dysfunction (endothelin-1) were measured at baseline. Cross-sectional and longitudinal analyses were performed, adjusting for pertinent covariates. Results In HIV-infected individuals, higher IL-6 and endothelin-1 associated with worse FEV1 percent-predicted, and higher sCD163 associated with worse FEV1/FVC. IL-6, TNF-α, lipopolysaccharide, sCD163, IL-2 receptor, and endothelin-1 associated with diffusing impairment. sCD163 and endothelin-1 interacted with HIV status in relationship to pulmonary function. In HIV-infected individuals only, baseline endothelin-1 was associated with lower FEV1, and sCD163 and endothelin-1 were associated with lower diffusing capacity during follow-up. Conclusions Circulating markers of HIV-associated humoral abnormalities are associated with airflow obstruction and diffusing impairment, and baseline measures of monocyte activation and endothelial dysfunction associate with lower pulmonary function over time in HIV-infected persons. These findings suggest mechanisms of the disproportionate burden of COPD in HIV-infected persons.

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“…The median VACS Index was 29 in PLWH compared to [18][19][20][21][22][23][24][25][26][27] in the uninfected (p<0.001). There was a trend towards higher pack years of smoking in PLWH.…”

Section: Resultsmentioning

confidence: 97%

“…COPD may be associated with a higher symptom burden in PLWH, [22,23,47] and PLWH are more likely to have acute exacerbations and hospitalizations related to COPD. [48,49] Those who are admitted with COPD-related diagnoses may face higher in-hospital mortality.…”

Section: Discussionmentioning

confidence: 99%

“…[10][11][12][13][14][15] This is largely due to more smoking in PLWH, but there may be an independent contribution related to HIV infection. [16][17][18][19] COPD is associated with increased symptoms, hospitalization and frailty in PLWH, [20][21][22][23] but an association with mortality has not been determined. Understanding the impact of COPD on mortality in HIV is important in considering the public health impact and clinical significance of COPD in this population and to support smoking cessation interventions and early COPD diagnosis and management.…”

Section: Introductionmentioning

confidence: 99%

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

Triplette

Justice

Attia

et al. 2018

Aids

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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.

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Pulmonary symptoms and diagnoses are associated with HIV in the MACS and WIHS cohorts

Cited by 57 publications

References 42 publications

Respiratory symptoms in people living with HIV and the effect of antiretroviral therapy: a systematic review and meta-analysis

Respiratory symptoms in people living with HIV and the effect of antiretroviral therapy: a systematic review and meta-analysis

Novel relationships of markers of monocyte activation and endothelial dysfunction with pulmonary dysfunction in HIV-infected persons

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

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