Risk Factors Associated With Quantitative Evidence of Lung Emphysema and Fibrosis in an HIV-Infected Cohort

Leader, Joseph K.; Crothers, Kristina; Huang, Laurence; King, Mark A.; Morris, Alison; Thompson, Bruce; Flores, Sonia C.; Drummond, M. Bradley; Rom, William N.; Diaz, Philip T.

doi:10.1097/qai.0000000000000894

Cited by 40 publications

(50 citation statements)

References 75 publications

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“…However, the pattern of spirometry abnormalities observed in our study was mainly restrictive. This might be explained by chronic immune activation causing scarring and fibrosis, resulting in a restrictive lung function abnormality [30–32]. We found a reduced FEV 1 /FVC ratio – a more obstructive pattern – in those with a previous history of infection.…”

Section: Discussionmentioning

confidence: 73%

Chronic lung disease in HIV-infected children established on antiretroviral therapy

Rylance

McHugh

Metcalfe

et al. 2016

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Objective:Respiratory disease is a major cause of morbidity and mortality in HIV-infected children. Despite antiretroviral therapy (ART), children suffer chronic symptoms. We investigated symptom prevalence, lung function and exercise capacity among older children established on ART and an age-matched HIV-uninfected group.Design:A cross-sectional study in Zimbabwe of HIV-infected children aged 6–16 years receiving ART for over 6 months and HIV-uninfected children attending primary health clinics from the same area.Methods:Standardized questionnaire, spirometry, incremental shuttle walk testing, CD4+ cell count, HIV viral load and sputum culture for tuberculosis were performed.Results:A total of 202 HIV-infected and 150 uninfected participants (median age 11.1 years in each group) were recruited. Median age at HIV diagnosis and ART initiation was 5.5 (interquartile range 2.8–7.5) and 6.1 (interquartile range 3.6–8.4) years, respectively. Median CD4+ cell count was 726 cells/μl, and 79% had HIV viral load less than 400 copies/ml. Chronic respiratory symptoms were rare in HIV-uninfected children [n = 1 (0.7%)], but common in HIV-infected participants [51 (25%)], especially cough [30 (15%)] and dyspnoea [30 (15%)]. HIV-infected participants were more commonly previously treated for tuberculosis [76 (38%) vs 1 (0.7%), P < 0.001], had lower exercise capacity (mean incremental shuttle walk testing distance 771 vs 889 m, respectively, P < 0.001) and more frequently abnormal spirometry [43 (24.3%) vs 15 (11.5%), P = 0.003] compared with HIV-uninfected participants. HIV diagnosis at an older age was associated with lung function abnormality (P = 0.025). No participant tested positive for Mycobacterium tuberculosis.Conclusion:In children, despite ART, HIV is associated with significant respiratory symptoms and functional impairment. Understanding pathogenesis is key, as new treatment strategies are urgently required.

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Section: Discussionmentioning

confidence: 73%

Chronic lung disease in HIV-infected children established on antiretroviral therapy

Rylance

McHugh

Metcalfe

et al. 2016

Aids

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“…1–4 A focus of many studies has been to understand how different tools (i.e., spirometry, diffusing capacity, chest imaging) can detect HIV-associated lung changes earlier in the course of the pulmonary disease. 3,5,6 Qualitative and quantitative computed tomography (CT) permits the assessment of lung changes which may develop prior to clinically overt lung disease. Several studies have examined the CT findings in HIV-infected individuals from varying populations with different risk factors for lung disease.…”

Section: Introductionmentioning

confidence: 99%

“…Several studies have examined the CT findings in HIV-infected individuals from varying populations with different risk factors for lung disease. 3,7–10 Qualitative abnormalities, including emphysema, nodules, and bronchiectasis are common in HIV-infected individuals, with one study reporting 55% of HIV-infected individuals having a radiographic abnormality. 7 Quantitative measurements, which use computerized software to calculate the density of each voxel of the lung image, can be employed to determine overall lung density [measured in Hounsfield Units (HU)].…”

Section: Introductionmentioning

confidence: 99%

“…Both decreased lung density (as seen in emphysema) and increased lung density (as seen in fibrotic lung disease) have been reported in HIV-infected populations. 3,8,10 The association of HIV disease markers (viral load, CD4 cell count) with CT lung density measurement remains poorly understood. As well, the qualitative lung CT changes contributing to quantitative changes in HIV has not been reported.…”

Section: Introductionmentioning

confidence: 99%

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HIV Infection Is Independently Associated with Increased CT Scan Lung Density

et al. 2017

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Rationale and Objectives Non-infectious pulmonary complications are common among HIV-infected individuals and may be detected early by quantitative CT scan. The association of HIV disease markers with CT lung density measurement remains poorly understood. Materials and Methods 125 participants free of spirometry-defined lung disease were recruited from a longitudinal cohort study of HIV-infected and HIV negative individuals to undergo standardized CT scan of the chest. Parenchymal densities for the entire lung volumes wer calculated using computerized software. Qualitative assessment of CT scans was conducted by two radiologists masked to HIV status. Linear regression models were developed to determine the independent association of markers of HIV infection on inspiratory scan mean lung density (MLD). Results HIV-infected participants had a significantly higher MLD (denser lung) compared with HIV-uninfected participants (−815 vs. −837 HU; p=0.002). After adjusting for relevant covariates, HIV infection was independently associated with 19.9 HU higher MLD (95% CI 6.04 to 33.7 HU; p=0.005). In qualitative assessment, only ground glass attenuation and cysts were noted more commonly among HIV-infected individuals compared with HIV-uninfected individuals [34% versus 17% (p=0.045) and 27% versus 10% (p=0.03), respectively]. No qualitative radiographic abnormalities attenuated the association between HIV infection and increased MLD. Conclusions HIV infection is independently associated with increased lung density. Although qualitative CT abnormalities were common in this cohort, only ground glass attenuation and cysts were noted more frequently in HIV-infected participants, suggesting that the increased lung density observed among HIV-infected individuals may be associated with subclinical inflammatory lung changes.

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“…Scans also underwent quantitative emphysema analysis using University of Pittsburgh software for lung segmentation followed by density mask technique to quantify percentage of low attenuation areas (Hounsfield units ≤ -950, %LAA) consistent with emphysema. [36][37][38][39] Baseline characteristics were compared by HIV status using Chi-squared testing. We used Cox proportional hazards regression to examine variable associations with mortality, stratified by HIV status.…”

Section: Introductionmentioning

confidence: 99%

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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Risk Factors Associated With Quantitative Evidence of Lung Emphysema and Fibrosis in an HIV-Infected Cohort

Cited by 40 publications

References 75 publications

Chronic lung disease in HIV-infected children established on antiretroviral therapy

Chronic lung disease in HIV-infected children established on antiretroviral therapy

HIV Infection Is Independently Associated with Increased CT Scan Lung Density

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

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