Pulmonary Symptoms and Diagnoses Are Associated with HIV in the MACS and WIHS Cohorts

Supplemental material

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

Matthew R. Gingo MD, MS1, G. K. Balasubramani PhD2, Thomas B. Rice MD, MS1, Lawrence Kingsley DrPH2,3, Eric C. Kleerup MD4, Roger Detels MD4, Eric Seaberg PhD, MPH5, Ruth M. Greenblatt MD6,7,8, Susan Holman RN, MS9, Laurence Huang MD, MAS7, Sarah H. Sutton MD10, Marnie Bertolet, PhD2, Alison Morris MD, MS1,11

1Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA

2Epidemiology Data Center, Department of Epidemiology, School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA

3Department of Infectious Diseases and Microbiology, School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA

4Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA

5Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA

6Department of Clinical Pharmacy, School of Pharmacy, University of California, San Francisco, CA, USA

7Department of Medicine, School of Medicine, University of California, San Francisco, CA, USA

8Department of Epidemiology and Biostatistics, School of Medicine, University of California, San Francisco, CA, USA

9Department of Medicine, SUNY Downstate Medical Center, Brooklyn, NY, USA

10Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA

11Department of Immunology, School of Medicine, University of Pittsburgh, PA, USA

Additional file 1: Table S1: Comparison of participants who completed the pulmonary related questionnaire vs. participants enrolled in the MACS and WIHS studies who did not complete the questionnaire.

MACS / WIHS
Questionnaire complete? / Yes (n=1896) / No (n=223) / p-value / Yes (n=1976) / No (n=488) / p-value
HIV-infected, n (%) / 907 (47.8) / 102 (45.7) / 0.55 / 1405 (71.1) / 357 (73.2) / 0.37
Age, mean (SD) / 50.8 (9.9) / 34.5 (8.2) / <0.001 / 43.4 (9.3) / 39.8 (9.2) / <0.001
African American, n (%) / 482 (25.4) / 74 (33.2) / 0.01 / 1183 (59.9) / 319 (66.1) / 0.01
Hispanic, n (%) / 170 (9.0) / 27 (12.1) / 0.13 / 541 (27.4) / 86 (17.8) / <0.001
Smoking Status, n (%) / 0.43 / 0.003
Never / 480 (25.6) / 51 (27.3) / 577 (29.5) / 166 (34.9)
Former / 894 (47.7) / 80 (42.8) / 543 (27.8) / 98 (20.6)
Current / 501 (26.7) / 56 (29.9) / 835 (42.7) / 212 (44.5)
Pack year-Median (Q1-Q3) / 2.2 (0-21) / 4.3 (0-21) / 0.27 / 13 (0-25.9) / 13 (0-26) / 0.72
Alcohol use, n (%) / 0.83 / 0.002
None / 356 (19.0) / 39 (21.7) / 1170 (59.9) / 242 (50.8)
Light / 940 (50.2) / 86 (47.8) / 529 (27.1) / 149 (31.3)
Moderate / 429 (22.9) / 42 (23.3) / 184 (9.4) / 56 (11.8)
Heavy / 147 (7.9) / 13 (7.2) / 72 (3.6) / 29 (6.1)
Intravenous drug use-ever, n (%) / 233 (12.3) / 3 (1.7) / <0.001 / 495 (25.1) / 11 (2.3) / <0.001
Cocaine use-ever, n (%) / 947 (49.9) / 11 (6.2) / <0.001 / 1102 (55.8) / 14 (2.9) / <0.001
HIV POSITIVE ONLY
CD4 count (cells/µL)-current, mean (SD) / 571.8 (277.8) / 516.8 (252.4) / 0.29 / 502 (291.2) / 529.6 (287.7) / 0.12
Plasma HIV RNA level (copies/mL), median (Q1-Q3) / 40 (40-136) / 40 (40-14900) / <0.001 / 80 (80-2400) / 80 (48-2430) / <0.001
Plasma HIV RNA undetectable, n (%)* / 590 (70.0) / 42 (51.9) / 0.001 / 764 (56.0) / 185 (54.6) / 0.64

* HIV RNA level at baseline pulmonary questionnaire visit available in 924 MACS (843 who completed the questionnaire, 81 who did not complete the questionnaire) and 1704 WIHS participants (1365 who completed the questionnaire, 339 who did not complete the questionnaire). Undetectable level was <40 copies/mL in the MACS cohort and <80 copies/mL in the WIHS cohort.

MACS - Multicenter AIDS Cohort Study; WIHS - Women’s Interagency HIV Study; SD - standard deviation; n - number; % - percentage; Q1 - quartile 1; Q3 - quartile 3

Additional file 1: Table S2. Proportion of participants with prevalent symptoms, diagnostic testing, and diagnoses comparing HIV-infected and HIV-uninfected by cohort.

MACS / WIHS
HIV-uninfected / HIV-infected / HIV-uninfected / HIV-infected
n=989 / n=907 / p-value / n=571 / n=1405 / p-value
Symptoms
Cough, n (%) / 372 (38.6) / 377 (42.6) / 0.08 / 332 (58.2) / 758 (54.2) / 0.10
Dyspnea, n (%) / 93 (9.4) / 123 (13.8) / 0.003 / 209 (36.7) / 508 (36.3) / 0.88
Wheezing, n (%) / 127 (12.9) / 140 (15.6) / 0.10 / 127 (22.3) / 343 (24.6) / 0.28
Phlegm production, n (%) / 291 (29.8) / 314 (34.9) / 0.02 / 222 (39.0) / 570 (40.8) / 0.47
Any symptom, n (%) / 479 (49.5) / 497 (56.2) / 0.004 / 385 (67.7) / 926 (66.3) / 0.56
Inhaler use, n (%) / 218 (22.1) / 247 (27.4) / 0.008 / 212 (37.2) / 559 (39.9) / 0.25
Oxygen use, n (%) / 10 (1.0) / 16 (1.8) / 0.16 / 6 (1.1) / 34 (2.4) / 0.049
Diagnostic testing
Chest computed tomography, n (%) / 224 (23.7) / 294 (34.4) / <0.001 / 71 (12.5) / 224 (16.1) / 0.04
Bronchoscopy, n (%) / 27 (2.8) / 59 (6.6) / <0.001 / 14 (2.5) / 56 (4.0) / 0.09
Pulmonary function tests, n (%) / 368 (39.1) / 340 (38.6) / 0.84 / 152 (26.7) / 366 (26.2) / 0.81
Lung surgery, n (%) / 10 (1.0) / 16 (1.8) / 0.16 / 6 (1.1) / 16 (1.1) / 0.97
Sputum sample, n (%) / 52 (5.4) / 154 (17.3) / <0.001 / 39 (6.8) / 284 (20.3) / <0.001
Polysomnography, n (%) / 152 (15.5) / 155 (17.2) / 0.33 / 37 (6.5) / 83 (5.9) / 0.64
Echocardiogram, n (%) / 275 (29.0) / 259 (29.4) / 0.84 / 87 (15.3) / 222 (15.9) / 0.72
Diagnoses
Asthma, n (%) / 120 (12.2) / 122 (13.5) / 0.38 / 146 (25.7) / 320 (22.9) / 0.18
COPD, n (%) / 66 (6.7) / 73 (8.1) / 0.25 / 59 (10.4) / 215 (15.4) / 0.004
Chronic bronchitis, n (%) / 53 (5.4) / 57 (6.3) / 0.39 / 54 (9.5) / 182 (13.0) / 0.03
Sleep apnea / 107 (10.8) / 94 (10.5) / 0.79 / 16 (2.8) / 60 (4.3) / 0.12
Pulmonary hypertension / 6 (0.6) / 4 (0.4) / 0.62 / 4 (0.7) / 14 (1.0) / 0.53
Interstitial pulmonary fibrosis, n (%) / - / 2 (0.2) / - / - / 3 (0.2) / -
Sarcoidosis, n (%) / 4 (0.4) / 2 (0.2) / 0.48 / 1 (0.2) / 13 (0.9) / 0.07
Pulmonary embolism, n (%) / 5 (0.5) / 9 (1.0) / 0.21 / 2 (0.4) / 10 (0.7) / 0.35

COPD - chronic obstructive pulmonary disease.

Additional file 1: Table S3a. Final adjusted Poisson regression results for factors associated with prevalent pulmonary outcomes in the HIV-infected subgroup for each cohort.

MACS / WIHS
Adjusted PR (95%CI) / p-value / Adjusted PR (95%CI) / p-value
Outcomes / Independent Variable
Symptoms
Cough / HAART use (ref=Never) / 0.14 / 0.18
Past / 1.69 (0.97-2.95) / 0.96 (0.71-1.29)
Current / 1.37 (0.80-2.36) / 0.81 (0.61-1.07)
Smoking (ref=Never) / <0.001
Current / 1.78 (1.26-2.50)
Former / 1.02 (0.75-1.38)
Dyspnea / HAART use (ref=Never) / 0.17 / 0.23
Past / 2.25 (0.76-6.66) / 1.24 (0.84-1.82)
Current / 1.47 (0.50-4.29) / 1.00 (0.69-1.45)
Cocaine use, ever / 1.37 (1.06-1.77) / 0.01
BMI (per 3 units) / 1.05 (1.01-1.08) / 0.01
Age (per 5 Years) / 0.84 (0.75-0.95) / 0.004
Wheeze / HAART use (ref=Never) / 0.39 / 0.09
Past / 2.04 (0.68-6.10) / 1.59 (0.98-2.58)
Current / 1.57 (0.54-4.59) / 1.23 (0.76-1.97)
Smoking (ref=Never) / 0.05 / 0.001
Current / 1.66 (0.89-3.11) / 1.85 (1.16-2.96)
Former / 0.98 (0.56-1.73) / 1.07 (0.71-1.63)
Cocaine use, ever / 1.60 (1.06-2.42) / 0.03 / 1.43 (1.05-1.96) / 0.02
Smoking (per 10 pack years) / 1.14 (1.04-1.25) / 0.007
BMI (per 3 units) / 1.07 (1.03-1.12) / 0.001
Sputum / HAART use (ref=Never) / 0.53 / 0.47
Past / 1.29 (0.71-2.35) / 0.94 (0.66-1.34)
Current / 1.07 (0.60-1.91) / 0.84 (0.60-1.17)
Smoking (ref=Never) / 0.01 / 0.01
Current / 1.55 (1.07-2.25) / 1.71 (1.21-2.41)
Former / 1.00 (0.72-1.39) / 1.33 (1.00-1.78)
Any symptom / HAART use (ref=Never) / 0.31 / 0.48
Past / 1.42 (0.88-2.30) / 0.96 (0.72-1.27)
Current / 1.23 (0.77-1.96) / 0.87 (0.67-1.14)
Smoking (ref=Never) / 0.01 / 0.03
Current / 1.45 (1.08-1.95) / 1.40 (1.07-1.83)
Former / 1.03 (0.79-1.33) / 1.14 (0.91-1.43)
BMI (per 3 units) / 1.03 (1.00-1.06) / 0.03
Inhaler use / HAART use (ref=Never) / 0.57 / 0.66
Past / 1.44 (0.71-2.91) / 1.03 (0.70-1.51)
Current / 1.24 (0.63-2.44) / 1.14 (0.79-1.63)
Smoking (ref=Never) / 0.03
Current / 1.52 (1.06-2.18)
Former / 1.16 (0.85-1.58)
Cocaine use, ever / 1.51 (1.19-1.93) / 0.001
BMI (per 3 units) / 1.06 (1.03-1.10) / 0.002
Oxygen use 1 / HAART use (ref=Never) / 0.13 / 0.78
Past / 1.01 (0.69-1.47)
Current / 0.34 (0.09-1.36) / 1.09 (0.77-1.55)
Smoking (ref=Never) / 0.01
Current / 1.72 (1.21-2.45)
Former / 1.35 (1.01-1.82)
IDU, ever / 1.23 (1.00-1.51) / 0.05
Nadir in CD4 count (per 200 counts) / 0.30 (0.11-0.81) / 0.02
Diagnostic testing
Chest CT / HAART use (ref=Never) / 0.48 / 0.72
Past / 1.44 (0.74-2.80) / 0.95 (0.50-1.81)
Current / 1.19 (0.63-2.26) / 1.13 (0.63-2.03)
IDU, ever / 1.40 (1.01-1.94) / 0.04
Age (per 5 Years) / 1.11 (1.01-1.22) / 0.03
Echocardiogram / HAART use (ref=Never) / 0.34 / 0.03
Past / 1.43 (0.72-2.83) / 0.54 (0.28-1.06)
Current / 1.06 (0.55-2.04) / 1.10 (0.63-1.92)
Black / 0.69 (0.50-0.96) / 0.03
BMI (per 3 units) / 1.08 (1.03-1.14) / 0.002
Age (per 5 Years) / 1.15 (1.06-1.25) / 0.001 / 1.23 (1.13-1.34) / <0.001
Bronchoscopy 1 / HAART use (ref=Never) / 0.47 / 0.29
Past / 0.64 (0.11-3.58)
Current / 1.43 (0.54-3.78) / 1.50 (0.34-6.68
Black / 1.79 (1.00-3.23) / 0.05
Nadir CD4 count (per 200 counts) / 0.43 (0.28-0.67) / 0.002 / 0.58 (0.36-0.92) / 0.02
Polysomnography / HAART use (ref=Never) / 0.91 / 0.80
Past / 1.11 (0.51-2.43) / 0.72 (0.27-1.94)
Current / 0.98 (0.47-2.06) / 0.86 (0.36-2.08)
Black / 1.49 (1.02-2.16) / 0.04
Hispanic / 0.31 (0.11-0.85) / 0.02 / 0.10 (0.03-0.29) / <0.001
BMI (per 3 units) / 1.17 (1.06-1.30) / 0.002 / 1.15 (1.07-1.23) / 0.0002
Age (per 5 Years) / 1.20 (1.07-1.34) / 0.002
Pulmonary function tests / HAART use (ref=Never) / 0.43 / 0.99
Past / 0.91 (0.50-1.65) / 0.98 (0.62-1.56)
Current / 1.19 (0.68-2.07) / 1.00 (0.65-1.54)
Cocaine use, ever / 1.52 (1.13-2.03) / 0.01
Age (per 5 Years) / 1.10 (1.02-1.18) / 0.01
Sputum testing / HAART use (ref=Never) / 0.49 / 0.22
Past / 1.07 (0.45-2.56) / 0.73 (0.41-1.31)
Current / 0.79 (0.34-1.84) / 1.05 (0.63-1.75)
Smoking (ref=Never) / 0.04
Current / 1.99 (1.15-3.45)
Former / 1.51 (0.94-2.43)
Cocaine use, ever / 1.48 (1.04-2.12) / 0.03
Nadir CD4 count (per 200 counts) / 0.67 (0.53-0.86) / 0.001 / 0.81 (0.67-0.98) / 0.03
Age (per 5 Years) / 1.14 (1.04-1.24) / 0.004
Diagnoses
Asthma / HAART use (ref=Never) / 0.87 / 0.61
Past / 0.85 (0.36-1.97) / 1.19 (0.72-1.95)
Current / 0.99 (0.44-2.20) / 1.02 (0.63-1.64)
Smoking (ref=Never) / 0.05
Current / 1.63 (1.01-2.64)
Former / 1.18 (0.77-1.79)
Cocaine use, ever / 1.68 (1.22-2.31) / 0.001
BMI (per 3 units) / 1.08 (1.03-1.12) / 0.001
Age (per 5 Years) / 0.89 (0.80-1.00) / 0.05
Any COPD / HAART use (ref=Never) / 0.93 / 0.54
Past / 0.80 (0.23-2.84) / 0.78 (0.43-1.42)
Current / 0.92 (0.29-2.94) / 0.98 (0.57-1.69)
Cocaine use, ever / 2.09 (1.37-3.21) / 0.001
Viral Load / 1.07 (1.01-1.14) / 0.02
Smoking (per 10 pack years) / 1.23 (1.03-1.47) / 0.02
Sleep apnea / HAART use (ref=Never) / 0.25 / 0.28
Past / 2.50 (0.66-9.45) / 2.09 (0.53-8.19)
Current / 1.51 (0.42-5.44) / 2.81 (0.77-10.3)
BMI (per 3 units) / 1.42 (1.26-1.59) / <0.001 / 1.22 (1.13-1.32) / <0.001
Age (per 5 Years) / 1.29 (1.13-1.48) / 0.0002
Pulmonary hypertension 2 / HAART use (ref=Never/Past) / 0.63 / 0.15
Current / 2.18 (0.09-52.1) / 3.35 (0.64-17.6)
Viral Load / 1.60 (1.07-2.41) / 0.02
Nadir CD4 count (per 200 counts) / 3.95 (1.19-13.1) / 0.03

Models controlled for age, race, smoking status, pack-years smoked, and intravenous drug use.

A variable with ‘blank’ indicates not significant.

1 MACS-Oxygen use/Bronchoscopy - HAART use was classified into two groups only: Never/Past vs. Current, because there were zero frequencies in one of the groups.

2 Pulmonary hypertension - HAART and smoking status were classified into two groups only: Never/former vs. Current for MACS and WIHS.

MACS - Multicenter AIDS Cohort Study; WIHS - Women’s Interagency HIV Study; PR - Prevalent ratio; CI - confidence intervals; HAART – highly active antiretroviral therapy; BMI – body mass index; ICU – injection drug use; COPD - chronic obstructive pulmonary disease.

Additional file 1: Table S3b: Final adjusted Poisson regression results for factors associated with prevalent pulmonary outcomes in the HIV-infected subgroup for each cohort including cardiovascular disease and history of bacterial or Pneumocystis pneumonia in variable selection.

MACS / WIHS
Adjusted PR (95%CI) / p-value / Adjusted PR (95%CI) / p-value
Outcomes / Independent Variable
Symptoms
Cough / HAART use (ref=Never) / 0.14 / 0.17
Past / 1.69 (0.97-2.95) / 0.96 (0.71-1.30)
Current / 1.36 (0.79-2.34) / 0.81 (0.60-1.07)
Smoking (ref=Never) / <0.001
Current / 1.82 (1.29-2.56
Former / 1.03 (0.76-1.39)
Dyspnea / HAART use (ref=Never) / 0.19 / 0.07
Past / 2.17 (0.73-6.41) / 1.31 (0.89-1.94)
Current / 1.44 (0.49-4.21) / 0.98 (0.67-1.42)
Cocaine use, ever / 1.34 (1.04-1.73) / 0.02
BMI (per 3 units) / 1.04 (1.01-1.08) / 0.02
Age (per 5 Years) / 0.84 (0.75-0.95) / 0.004
Cardiovascular disease / 1.49 (1.03-2.18) / 0.04
Bacterial pneumonia, ever / 1.34 (1.08-1.67) / 0.008
Wheeze / HAART use (ref=Never) / 0.39 / 0.04
Past / 1.96 (0.66-5.88) / 1.69 (1.04-2.75)
Current / 1.49 (0.51-4.37) / 1.22 (0.76-1.96)
Smoking (ref=Never) / 0.04 / 0.001
Current / 1.75 (0.94-3.26) / 1.86 (1.17-2.97)