Participants were followed until their first incident diagnosis, loss to follow-up, death, or end of study in 2014, whichever came first. For each outcome, models were fit separately for HIV+ and HIV− participants using two time-varying variables for marijuana and tobacco smoking: Model 1, current marijuana smoking and prior two-year average tobacco smoking , and Model 2, prior two-year average marijuana smoking and prior two year average tobacco smoking . Models were adjusted by time-invariant baseline education status, race, and baseline calendar period to adjust for potential differences in participant composition between MACS recruitment periods. Models for HIV+ participants were also adjusted by time-varying CD4 T cell count, and by time-varying self-reported ART use in models of infectious diagnoses; 65 participants with no CD4 data during follow-up were omitted from these analyses. Age was used as the time variable in all models . Continuous variables summarizing marijuana and tobacco smoking were right skewed and therefore square-root transformed and reported as back transformed estimates in their original scale. Additional analyses were performed with models for HIV+ participants using: a) visits restricted to CD4 count ≥200 cells/μl, b) time-varying cumulative exposures of marijuana and tobacco smoking in the prior ten years , and c) visits restricted to HIV viral load b400 copies/ml. Cumulative hazard curves estimating risk differences by marijuana and tobacco smoking were constructed by holding other model co-variates at their mean values. Generalized estimating equation logistic regression models were used to assess the association between marijuana smoking and infectious pulmonary diagnoses while including repeated measures and potentially multiple diagnoses within the same individual.
To minimize the potential for duplicate reports of a single diagnosis, only the first of identical diagnoses at consecutive visits were included. Exposure and adjustment variables were the same as for Cox models, except time varying,cannabis drying racks continuous duration in study, and baseline age were included. All analyses were performed with R .Marijuana smokers were more likely to report one or more infectious or non-infectious pulmonary diagnosis compared to nonsmokers during follow-up among HIV+ participants,while there was no association between marijuana smoking and either diagnosis among HIV− participants . Given the high prevalence of tobacco smoking among participants, frequencies of diagnoses were determined after stratifying participants by marijuana and tobacco smoking during follow-up. The proportion of HIV+ participants with one or more infectious pulmonary diagnosis was elevated among marijuana smokers and participants reporting any tobacco smoking in follow-up. Influenza and viral pneumonia and other pneumonias were among diagnoses occurring more frequently in marijuana smokers: other pneumonias were reported in 22% and 23·9% of participants smoking marijuana only, or both marijuana and tobacco, respectively, compared to non-smokers.Among HIV− participants, infectious diagnoses were more prevalent in individuals smoking both marijuana and tobacco, and non-infectious diagnoses were elevated among tobacco but not marijuana smokers. The majority of diagnoses were assessed from ICD coding data, while chronic bronchitis diagnoses were predominantly assessed from self-report .In this prospective study of 2704 MSM contributing over 53,000 person-visits, marijuana smoking was associated with increased risk of both infectious and non-infectious pulmonary diagnoses among 1352 HIV-infected participants independent of tobacco smoking, CD4 count, ART adherence, and demographic factors. To our knowledge, this study is the largest investigation of smoked marijuana and pulmonary diagnoses in HIV-infected individuals to date. In multi-variable Cox models, current daily or weekly marijuana smoking and increased average marijuana smoking over the prior two years were associated with elevated risk of infectious pulmonary diagnoses in HIV+ participants; these results were confirmed in GEE logistic regression models allowing for repeated diagnoses within the same individual.
Current marijuana smoking was also associated with increased risk of chronic bronchitis in multi-variable Cox models, while increased average marijuana smoking in the prior two years was marginally associated with these outcomes . Marijuana and tobacco smoking were independent risk factors in Cox models, and the predicted additive risk of smoking both substances was markedly higher than smoking either substance alone. In contrast, there were no significant associations between marijuana use and infectious pulmonary diagnoses or chronic bronchitis in multi-variable models of 1352 HIV− participants adjusted by tobacco smoking, age, race, education, and calendar period. These findings confirm the known association between HIV infection and increased prevalence of pulmonary disease, and provide evidence that HIV-infected individuals may be more vulnerable to marijuana’s effects on lung disease compared to uninfected participants with similar exposures. In contrast to the well-studied effects of tobacco smoking, the effects of marijuana smoking on lung function and health in the general population remain unclear, though multiple studies reported an increased prevalence of chronic respiratory symptoms in frequent marijuana smokers. Spirometric forced expiratory volume , forced vital capacity , and their ratio are measures of airflow obstruction; FEV1/FVC is reduced in tobacco smokers compared to non-smokers, while studies of marijuana smokers have reported conflicting results. Likewise, a cross sectional study of pulmonary function among HIV-infected recreational drug users in the U.S. reported no association between marijuana smoking and airflow obstruction or radiographic emphysema. In the U.S., marijuana remains an illegal Schedule 1 substance nationally, and is not regulated by the Food and Drug Administration. Marijuana contains substantial variation in the quantity of psychoactive delta-9 tetrahydrocannabinol and other combustible components, complicating systematic comparisons based on observational studies. While marijuana and tobacco smoke contain many of the same toxic constituents, previous studies reported higher concentrations of hydrogen cyanide, ammonia, and polycyclic aromatic hydrocarbons in marijuana smoke, and higher concentrations of blood carboxyhemoglobin concentrations, greater depth of inhalation, and greater puff volume in marijuana compared to tobacco smokers.
Pulmonary disease risk may be increased in HIV-infected vs. uninfected individuals due to HIV-specific factors including lung immune cell depletion and dysfunction, persistent immune cell activation, systemic inflammation, respiratory microbiome alterations, and oxidative stress, or a combination of these effects with modifiable risk factors including tobacco smoking. Previous studies linked marijuana smoke with alveolar macrophage dysfunction in both humans and mouse models, and a potential additive risk of marijuana smoking and HIV disease may explain the increased prevalence of infectious pulmonary diagnoses in our adjusted analyses. The association between HIV infection, low CD4 T cell count, and increased risk of infectious and non-infectious pulmonary disease has been previously reported, and was the strongest predictor of infectious pulmonary diagnoses in HIV+ participants in our study. Low CD4 T cell count was the dominant predictor of infectious pulmonary diagnoses in multi-variable analyses, yet the association between marijuana smoking and infectious pulmonary diagnoses remained significant in adjusted analyses restricted to visits with CD4 ≥ 200 cells/μl, and sensitivity analyses with no CD4 restriction. Tobacco smoking, reported during follow-up for 44% of HIV+ participants, was a stronger risk factor for chronic bronchitis in HIV+ participants compared to marijuana smoking, while for infectious pulmonary diagnoses in HIV+ participants, the risk associated with ≥1/2 pack/day tobacco smoking was comparable to that of daily or weekly marijuana smoking . Strengths of this study included the large sample size, large number of diagnoses reported, and substantial length of follow-up . Men at risk for HIV are recruited by the MACS from four U.S. urban sites, hydroponic cannabis system and thus HIV-infected participants share similar demographic and lifestyle characteristics with uninfected participants. HIV+ and HIV− participants reported substantial daily or weekly marijuana smoking , which allowed assessments of both current and average exposures during follow-up. The sample size allowed for stricter control of tobacco smoking with large numbers of participants in stratified analyses , which may in part explain the lack of association between marijuana smoking and pulmonary disease among HIV− individuals found here compared to previous studies. Injection drug use is a possible risk factor for lung disease among HIV-infected persons, and poly drug use is common in HIV-infected individuals, and we therefore excluded heavy cocaine and heroin users from our analysis to reduce the potential for competing risks from multiple inhaled or injected substances. Limitations of this study include those inherent to longitudinal prospective cohort studies, including the potential for findings to be specific to MSM populations recruited by the MACS, and for nonrandom dropout and ascertainment biases. Measures of marijuana intake were limited to self-report during follow-up, with limited detail regarding exposure prior to MACS enrollment or marijuana potency, source, or quantity. These concerns are mitigated in part by the use of three separate measures of marijuana smoking , all of which were associated with infectious pulmonary diagnoses and chronic bronchitis in models of HIV-infected participants. Furthermore, the proportion of daily or weekly HIV+ marijuana smokers here is comparable to reports from other U.S. cohorts of HIV-infected individuals. The use of self-reported pulmonary symptoms and diagnoses is an additional potential source of bias, and possible under-representation of specific non-infectious diagnoses in the MACS, particularly COPD and pulmonary hypertension, has been reported. Most diagnoses were not assessed from both self-report and ICD-coded sources. This limitation was mitigated in part because most diagnoses were obtained from ICD code data, which consists of more specific diagnosis classifications .
Potential ambiguities regarding terminology for diagnoses, and discordance between highly prevalent pulmonary symptoms and low rate of pulmonary diagnostic testing among HIV-infected persons has been noted in other clinical settings, and is mitigated here in part by use of composite diagnoses. The number of diagnoses reported for several categories, including tuberculosis, lung cancers, and Pneumocystis pneumonia, was small and lacked statistical power to assess an adjusted association with marijuana or tobacco smoking. In summary, we found a significant association between long-term marijuana smoking and risk of infectious lung disease and chronic bronchitis in HIV-infected men on ART, independent of tobacco smoking and other risk factors . In contrast, we detected no association between marijuana smoking and lung disease among HIV-uninfected men while controlling for tobacco smoking and other demographic characteristics. These findings suggest that marijuana smoking is a modifiable risk factor that healthcare providers should consider when seeking to prevent or treat lung disease in people infected with HIV, particularly those with other known risk factors including heavy tobacco smoking, and low CD4 T cell count or advanced HIV disease. Given increasing trends of regular marijuana smoking among HIV-infected people and other high-risk populations in the U.S. and other developed and developing countries, more studies are needed to evaluate potential merits of non-smoked rather than smoked forms of marijuana for medicinal and other purposes.Humboldt County has been an epicenter of cannabis cultivation for decades, and an element of social division has characterized the region: the “back-to-the-landers” versus the born-and-raised locals, the “hippies” versus the “rednecks,” and the pot growers versus the loggers and ranchers . However, as cannabis cultivation has been decriminalized in California, the social dynamics around cannabis have become more complex. Over the last 20 years, new growers from different parts of California, the United States and even outside the United States have moved to Humboldt County and surrounding areas to grow cannabis — a so-called green rush of growers hoping to strike it rich . Growers have come from a host of countries beyond the United States, including Bulgaria, Russia, Mexico and nations in Southeast Asia . Some work independently while others work together in operations that may qualify as more organized. For many Humboldt County residents — “mom-and-pop” cannabis growers and more traditional agricultural producers alike — the near-exponential growth of the industry has been a shock, and it has unleashed numerous social, economic and environmental concerns. This situation is not unique to Humboldt — cannabis cultivation has increased rapidly throughout rural California . California voters, when they legalized cannabis for adult recreational use in 2018, created conditions for competition among agricultural interests and changes in rural social dynamics. Indeed, because new cannabis farming is often conducted near traditional ranching and timber-producing lands , the potential for conflict — or collaboration — between traditional land uses and cannabis production has grown. But little research documents the effects of cannabis production on traditional agricultural producers, and therefore we know little about such producers’ adaptation to change.