HIV Infection Is Independently Associated with Increased CT Scan Lung Density

Rationale and Objectives

Noninfectious pulmonary complications are common among HIV-infected individuals and may be detected early by quantitative computed tomography (CT) scanning. The association of HIV disease markers with CT lung density measurement remains poorly understood.

Materials and Methods

One hundred twenty-five participants free of spirometry-defined lung disease were recruited from a longitudinal cohort study of HIV-infected and HIV-uninfected individuals to undergo standardized CT scan of the chest. Parenchymal density for the entire lung volume was 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 to HIV-uninfected participants (−815 Hounsfield unit [HU] 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 to HIV-uninfected individuals (34% vs 17% [ P = 0.045] and 27% vs 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.

Introduction

With the initiation of antiretroviral therapy (ART), noninfectious pulmonary complications of HIV infection including chronic obstructive pulmonary disease, pulmonary fibrosis, lung cancer, and pulmonary hypertension have increasingly been recognized as key contributors to the morbidity and mortality of the HIV-infected population . A focus of many studies has been to understand how different tools (ie, spirometry, diffusing capacity, chest imaging) can detect HIV-associated lung changes earlier in the course of the pulmonary disease . Qualitative and quantitative computed tomography (CT) permits the assessment of lung changes that 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 . 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 . 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 unit [HU]). 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 . 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 have not been reported.

The Study of HIV Infection in the Etiology of Lung Diseases (SHIELD) is a National Institutes of Health-funded longitudinal cohort study of HIV-infected and HIV-uninfected participants followed to understand how HIV may enhance susceptibility to lung disease. Within this study, both HIV-infected and uninfected individuals undergo standardized spirometry testing and research lung CT imaging. In this analysis, we determine the independent association of HIV infection with quantitative lung density from 125 SHIELD participants with normal lung function (assessed via spirometry testing). Using a standardized qualitative CT review, we assess the relationship between qualitative and quantitative CT changes to identify processes contributing to lung CT changes in HIV infection.

Materials and Methods

Study Cohort

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Data Collection

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Acquisition of CT Data

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Statistical Analysis

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Results

Participant Characteristics

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Table 1

Clinical and Demographic Characteristics of Study Participants

N Total Cohort

125 HIV Infected

83 HIV Uninfected

42P Value ‡ Age, years 51.0(6.5) 51.3(5.4) 50.3(8.2) 0.42 Male, n (%) 84(67) 57(69) 27(64) 0.62 Black race, n (%) 119(95) 82(98) 37(88) 0.01 Smoking Status, n (%) \* Current 99(79) 64(77) 35(83) Former 17(14) 12(14) 5(12) Never 9(7) 7(8) 2(5) 0.67 Smoking, pack-years 17(13–33) 16.5(12.6–33.0) 19.7(13.5–37) 0.23 FEV 1 Absolute, L 2.74(0.73) 2.72(0.72) 2.78(0.76) 0.69 % Predicted 91.1(15.1) 90.6(15.1) 92.0(15.5) 0.62 FVC Absolute, L 3.51(0.94) 3.48(0.94) 3.58(0.96) 0.58 % Predicted 93.4(15.7) 92.7(16.1) 94.8(15.0) 0.48 FEV 1 /FVC Absolute 0.78(0.05) 0.78(0.04) 0.78(0.05) 0.43 Total lung capacity, L 5.53(1.06) 5.54(1.07) 5.51(1.06) 0.89 DLco, mL/min/mm Hg 20.5(5.92) 19.9(5.94) 21.8(5.73) 0.10 HIV markers CD4+ cell count, cells/mm 3 349(190–485) Undetectable viral load, n (%) 47(56) HIV-1 RNA level, copies/mL † 7547(779–56200) ART use, n (%) \* 66(80) Mean lung density, HU −822(−840to−799) −815(−836to−792) −837(−844to−809) 0.002

ART, antiretroviral therapy; DLco, diffusion capacity of carbon monoxide; FEV 1 , forced expiratory volume in 1 second; FVC, forced vital capacity; HU, Hounsfield unit.

Values presented as mean(SD) or median(IQR) unless indicated otherwise.

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Table 2

Drug and Pneumonia Cohort Characteristics

N Total Cohort

125 HIV Infected

83 HIV Uninfected

42P Value † Injection drug use, n (%) \* 29(23) 16(19) 13(31) 0.14 Injection drug use frequency, n (%) \* None 96(77) 67(81) 29(69) Less than daily 21(17) 11(13) 10(24) Daily 8(6) 5(6) 3(7) 0.30 Marijuana use, n (%) \* 19(15) 12(14) 7(17) 0.75 Crack cocaine use, n (%) \* 26(21) 16(19) 10(24) 0.55 Other smoked drugs, n (%) \* 37(30) 23(28) 14(33) 0.52 Prior pneumonia, n (%) 21(17) 19(23) 2(5) 0.01 Number of prior pneumonias, n (%) 0 104(83) 64(77) 40(95) 1 14(11) 13(16) 1(2) 2+ 7(6) 6(7) 1(2) 0.19 Prior pneumocystis, n (%) 6(5) 6(7) 0(0) 0.07 Number of prior pneumocystis, n (%) 0 119(95) 77(93) 42(100) 1 3(2) 3(4) 0(0) 2+ 3(2) 3(4) 0(0) 0.53

Values presented as mean(SD) or median(IQR) unless indicated otherwise.

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Characteristics Associated with Mean Lung Density (MLD)

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Table 3

Association Between Cohort Characteristics and Mean Lung Density

Covariate Unadjusted Mean HU (95% CI)P Value Adjusted \* Mean HU (95% CI)P Value HIV infected 21.7(9.09,34.4) 0.001 19.9(6.04,33.7) 0.005 Male −21.6(−34.3,−8.83) 0.001 −10.6(−28.3,7.21) 0.24 Black 25.3(−3.56,54.2) 0.085 3.35(−26.4,33.1) 0.82 Current smoker 10.9(−4.35,26.2) 0.16 13.3(−3.37,30.1) 0.12 FEV 1 (liter) −19.0(−26.9,−11.1) <0.001 −9.44(−26.9,8.03) 0.29 TLC(liter) −7.77(−14.0,−1.55) 0.015 1.24(−9.02,11.5) 0.81 DLco(ml/min/mm Hg) −1.76(−2.80,−0.72) 0.001 −0.33(−1.75,1.08) 0.64

DLco, diffusion capacity of carbon monoxide; FEV 1 , forced expiratory volume in 1 second; HU, Hounsfield unit; TLC, total lung capacity.

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Table 4

Adjusted \* Association Between HIV markers and Mean Lung Density

Covariate HIV Serostatus Model Adjusted Mean HU (95% CI) HIV RNA Model Adjusted Mean HU (95% CI) CD4 Count Model Adjusted Mean HU (95% CI) HIV Uninfected Reference Reference Reference HIV Infected 19.1 (6.04, 33.7) † HIV RNA undetectable 22.2 (6.17, 38.2) † HIV RNA detectable 17.6 (1.51, 33.6) † CD4 count ≥350 cells/mm 3 25.0 (9.03, 41.0) † CD4 count <350 cells/mm 3 14.6 (−1.48, 30.7)

HU, Hounsfield unit.

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Qualitative CT Analysis

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Table 5

Qualitative Radiographic Abnormalities Among Cohort Participants

N HIV Infected

83 HIV Uninfected

42P Value Emphysema global severity None 29(35) 21(50) Trace(1–10%) 27(33) 11(26) Mild(11–25%) 22(27) 7(17) Moderate(26–50%) 5(6) 2(5) Severe(51–75%) 0(0) 1(2) Very severe(>75%) 0(0) 0(0) 0.27 Description of emphysema Bullae 9(11) 1(2) 0.10 Centrilobular 45(54) 16(38) 0.09 Distal acinar or paraseptal 38(46) 13(31) 0.11 Bronchiectasis(nontraction) Present 16(19) 9(21) 0.78 Minimal 15(18) 9(21) 0.22 Bronchial wall thickening 13(6) 5(12) 0.57 Traction bronchiectasis 6(7) 1(2) 0.27 Pulmonary artery enlargement 13(16) 3(7) 0.18 Diameter if enlarged, mm 33(32–34) 33(33–34) 0.72 Consolidation 1(1) 0(0) 0.48 Ground glass 28(34) 7(17) 0.045 Mosaic attenuation 46(55) 24(57) 0.89 Cysts 22(27) 4(10) 0.03 Pleural effusion 1(1) 0(0) 0.48 Reticular abnormalities 16(19) 6(14) 0.49 Linear scars 26(31) 8(18) 0.15 Noncalcified nodules Present 44(53) 18(43) 0.11 Number 11(25) 4(22) 1 25(57) 11(61) 2 8(18) 3(17) 3+ 0.96 Mediastinal lymphadenopathy 6(7) 3(7) 0.99 Cavitary lesion 1(1) 0(0) 0.48 Tree-in-bud 4(5) 1(2) 0.51

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Discussion

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Conclusions

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Supplementary Data

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Table S1

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References

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HIV Infection Is Independently Associated with Increased CT Scan Lung Density

Rationale and Objectives

Materials and Methods

Results

Conclusions

Introduction

Materials and Methods

Study Cohort

Data Collection

Acquisition of CT Data

Statistical Analysis

Results

Participant Characteristics

Characteristics Associated with Mean Lung Density (MLD)

Qualitative CT Analysis

Discussion

Conclusions

Supplementary Data

References

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