Background
In the developed world, mortality from HIV/AIDS has decreased significantly since the introduction of highly active anti-retroviral therapy (HAART) in 1996 [
1]. Consequently, people are living with HIV/AIDS longer than ever. In this context, chronic diseases, whether HIV/AIDS related or not, are increasingly of concern amongst the HIV-positive population, and for clinicians caring for them.
Prior to 2001, annual smoking prevalence in the Ontario Cohort Study (OCS) of HIV-positive adult subjects was more than 70%, and steadily decreased to 58% in 2007 (data unpublished), which was constantly about three times higher than that in the Ontario general population from 1999 to 2007 [
2]. A smoking prevalence of 60% or more in HIV-positive subjects has been reported in other studies [
3‐
7]. Therefore, smoking-related outcomes, such as lung function problems, respiratory symptoms and lung diseases, are likely to increase in this population.
We hypothesized that HIV infection would accelerate smoking-related respiratory symptoms and diseases. Studies have shown that HIV-positive subjects were more likely to have respiratory symptoms and diseases compared to their HIV negative counterparts [
3,
8,
9]. Moreover, some studies showed among HIV-positive subjects, smokers were more likely to have respiratory problems [
8,
10]. Other studies found that HIV-positive subjects had similar lung function compared to their HIV negative counterparts [
11,
12], and they had similar changes of lung function over time [
13,
14]. Although in the general population, the effects of cigarette smoking on lung function has been well demonstrated in the general population, using different measurements of smoking and lung function [
15‐
21], no study has been done to address whether cigarette smoking affects lung function in a similar way in HIV-positive population.
Hence, the literature is unclear on the effects of smoking on lung function in HIV-positive subjects, particularly whether lung function decline would be greater in HIV-positive subjects compared to the general population. The primary objective of this study was to determine the association between smoking and lung function amongst HIV-positive subjects. The secondary objective was to examine the association between smoking and respiratory symptoms and diseases amongst HIV-positive subjects.
Discussion
We did not find excessive decline of %FEV
1 in HIV-positive subjects compared with published reference ranges for the general population. In our study ten pack-years %FEV
1 change was -2.1% (95% CI: -3.6%, -0.6%). In a population-based cross-sectional study, the %FEV
1 before salbutamol in 2050 white people decreased by 0.29% (95% CI: -0.33%, -0.25%) for every one pack-years increment [
17], which would equal an %FEV
1 change of -2.9% (95% CI -3.3%, -2.5%) per ten pack-years. The findings in our study are comparable to that in the general population. Similar results were reported in previous studies, where HIV-positive subjects had similar loss of lung function as their HIV-negative counterparts [
13,
14], which did not support the hypothesis that lung function decline is greater in the HIV-positive population.
We should keep in mind that our study was cross-sectional and the effect of smoking we found might not apply to a cohort study [
16,
29]. In a cross-sectional study, for every one pack-years of smoking increment FEV
1decreased by 7.4 ml (95% CI: 6.4, 8.4) in a typical male (173 cm tall) and by 4.4 ml (95% CI: 3.2, 5.6) in a typical female (161 cm tall) respectively [
16]. While in this same population after 6-year follow up, the longitudinal analysis showed that among smokers, for every one pack/day of cigarette smoking, the rate of FEV
1 decrease was 12.6 ml/year (95% CI: 9.7, 15.5) for men and 7.2 ml/year (95% CI: 4.8, 9.6) for women [
29]. Therefore we should not extrapolate the same coefficient of pack-years of smoking found in a cross-sectional study to a prospective cohort study. In other words, we could not predict an HIV-positive smoker would decrease %FEV
1 by 2.1% if s/he continued smoking for another 10 pack-years.
In the multiple regression model for %FEV
1, the coefficient of gender was not significant (p = 0.640), and the point estimate of coefficient of pack-years did not change regardless of adjustment for gender, suggesting that gender did not affect %FEV
1 in this HIV positive population. Similar results were reported in a meta-regression analysis where eight large population-based cross-sectional studies were synthesized: neither gender nor race affected the association of cigarette smoking with lung function measured by residual FEV
1 (observed - expected value) [
18]. However, other population-based studies showed that smoking affected the annual decrease of FEV
1 significantly more in males than in females [
16,
19,
29]. Further study is needed to compare the result in our study to the general population.
Our study found that current smokers had significantly higher odds of cough and sputum than either non-smokers or former smokers, while the difference between non-smokers and former smokers was not significant, after controlling for possible confounders. The findings were consistent with other studies [
8,
30,
31]. Therefore, effective smoking cessation projects would help HIV-positive smokers to have less cough and sputum. Moreover, the prevalence of smoking in our study was 2.4 (95% CI: 2.0, 3.0) times higher than that in Ontario general population in 2007 [
2], which reinforced the need for smoking cessation programmes in the HIV-positive population. Fortunately 20 (38%) of current smokers were trying to quit smoking at the time of study. Fifteen (65%) former smokers quit smoking successfully without medication or counselling, implying insufficient involvement of health care providers in terms of helping smokers quit. Further, our study showed an association of smoking with childhood household smoking environment (p = 0.023): current smokers accounted for 7 (24%) of those subjects whose parents did not smoke, 12 (33%) if the father smoked, 6 (60%) if the mother smoked and 27 (63%) if both parents smoked. Therefore, an effective smoking cessation program should target not only current smokers, but also health professionals and families.
Marijuana use was evaluated in our study when the effect of smoking was estimated. Marijuana use might be associated with respiratory symptoms such as cough and sputum production. We found current marijuana users tended to use more frequently and for longer time than former users, however we did not know how many joints a subject consumed each time. More measurement of cumulative marijuana consumption might be more helpful to further examine the effect of marijuana use more deeply.
Subjects in our study represented the source population at the SIS clinic fairly well. Only five patients refused participating. In a clinical database of our study population (data unpublished), mean (SD) age among 726 active patients was 43.0 (10.5) years old in 2007, males accounted for 68% (95% CI: 65%, 72%), and smoking prevalence was 48% (95% CI: 44%, 53%). Compared to this clinical database, the subjects in our study was comparable in terms of age (p = 0.718) and smoking prevalence (p = 0.365), however we recruited a slightly greater proportion of males in our study (rate ratio RR = 1.1, 95% CI: 1.0, 1.3). Notably the smoking prevalence of 44% (95% CI: 35%, 53%) in our study was significantly lower than 58% (95% CI: 55%, 61%), the lowest smoking prevalence in OCS over time in 2007 (data unpublished). As OCS was a province-wide study, we considered it the best resource to assess smoking prevalence in Ontario HIV-positive population, although the subjects in OCS might not represent the whole HIV positive population in Ontario due to voluntary participation. Nevertheless the representativeness of our study subjects was limited to our clinic only.
Since we only detected four cases of COPD, we had low power to examine the effect of smoking on COPD. Nevertheless all four COPD cases were smokers, and smokers had a crude OR of 4.0 (95% CI: 0.9, 18.8) of pre-salbutamol obstructive lung function compared to non-smokers in our study. In a prospective observational study with 867 HIV-positive veterans, either former or current smokers were 5.3 times more likely to develop COPD than non-smokers (95% CI was 1.5 to 18.0 for former smokers and 1.6 to 17.0 for current smokers) [
10]. Our study was comparable with these results, albeit underpowered to detect statistically significant difference due to the small number of COPD cases.
We likely would have captured more cases of COPD, if all the subjects with pre-salbutamol obstructive lung function had undergone post-salbutamol testing. According to our preset criteria, all subjects with %FEV
1 < 90% should undergo post salbutamol test, which should have included 46 subjects. However only 27 (59%) of these subjects agreed to salbutamol inhalation followed by repeat spirometry, primarily due to time limitations. As a result, amongst 14 subjects whose spirogram suggested COPD by pre-salbutamol test, 9 (64%) subjects did not undergo post-salbutamol test and could not be confirmed. We might expect 5 to 6 more cases of COPD in our study. In a prospective observational study the prevalence of COPD in 1014 HIV positive veterans was 10% by ICD-9 codes and 15% by self report respectively [
9]. Comparing this HIV-positive veteran population to our study population, the median age of study population was 50 versus 44.0 years old, the median age of COPD cases was 52 (by ICD-9 codes, 51 by self report) versus 49.5 years old. COPD usually is often diagnosed in patients 50 years or older, and longer follow up will be needed to observe development of additional COPD cases.
QC: PhD student in Health Research Methodology Program in Department of Clinical Epidemiology and Biostatistics at McMaster University.
SC: Respiratory technologist at St. Joseph's Healthcare.
AM: Professor in Department of Medicine (respirology) at McMaster University.
FS: Chair, professor in Department of Pathology and Molecular Medicine (microbiology) at McMaster University.
LT: Associate Professor in Department of Clinical Epidemiology and Biostatistics at McMaster University.
MS: Associate Professor in Department of Pathology and Molecular Medicine at McMaster University, and at St. Joseph's Healthcare, Hamilton.
Competing interests
Qu Cui and Marek Smieja are currently leading an open label study sponsored by the Pfizer company, where we offer Champix to HIV-positive smokers to help them quit smoking and we evaluate the effectiveness, safety and tolerability of Champix in this HIV-positive population.
Authors' contributions
QC wrote study protocol, designed the questionnaire, carried out medical chart review, performed the statistical analysis and drafted the manuscript. SC performed the spirometry test, carried out the questionnaire survey and coordinated the study. AM made substantial contributions to interpretation of data, and was involved in revising the draft critically for important intellectual content. FS made substantial contributions to acquisition of data, and was involved in revising the draft critically for important intellectual content. LT made substantial contributions to analyze data, and was involved in revising the draft critically for important intellectual content. MS conceived of the study, participated in its design, made substantial contributions to acquisition of data, and helped to draft the manuscript. All authors read and approved the final manuscript.