This originally appeared at https://pubmed.ncbi.nlm.nih.gov/37199732/
Impact of Marijuana Smoking on COPD Progression in a Cohort of Middle-Aged and Older Persons
Igor Barjaktarevic 1 , Christopher B Cooper 1 , Tracie Shing 2 , Russell G Buhr 1 3 , Eric A Hoffman 4 , Prescott G Woodruff 5 , M Bradley Drummond 6 , Richard E Kanner 7 , MeiLan K Han 8 , Nadia N Hansel 9 , Russell P Bowler 10 , Gregory L Kinney 11 , Sean Jacobson 11 , Madeline A Morris 12 , Fernando J Martinez 13 , Jill Ohar 14 , David Couper 2 , Donald P Tashkin 1
PMID: 37199732 DOI: 10.15326/jcopdf.2022.0378
Abstract
Background: Limited data are available regarding marijuana smoking’s impact on development or progression of chronic obstructive pulmonary disease (COPD) in middle-aged or older adults with a variable history of tobacco cigarette smoking.
Methods: We divided ever-tobacco smoking participants in the Subpopulations and Intermediate Outcomes in COPD Study (SPIROMICS) into three groups based on self-reported marijuana use: current, former or never marijuana smokers (CMS, FMS or NMS, respectively). Longitudinal data were analyzed in participants with ≥2 visits over a period of ≥52 weeks.
Measurements: We compared CMS, FMS and NMS, and those with varying amounts of lifetime marijuana use. Mixed effects linear regression models were used to analyze changes in spirometry, symptoms, health status and radiographic metrics; zero-inflated negative binomial models were used for exacerbation rates. All models were adjusted for age, sex, race, baseline tobacco smoking amount, and FEV1 %predicted.
Results: Most participants were followed for ≥4 years. Annual rates of change in FEV1, incident COPD, respiratory symptoms, health status, radiographic extent of emphysema or air trapping, and total or severe exacerbations were not different between CMS or FMS versus NMS or between those with any lifetime amount of marijuana use versus NMS.
Conclusions: Among SPIROMICS participants with or without COPD, neither former nor current marijuana smoking of any lifetime amount was associated with evidence of COPD progression or its development. Because of our study’s limitations, these findings underscore the need for further studies to better understand longer term effects of marijuana smoking in COPD.
Keywords: COPD; Exacerbations; HRCT; Marijuana; Spirometry.
Introduction:
The effect of marijuana use on lung health has not been extensively studied, with most data
coming from cross-sectional 1-11 and several longitudinal studies 12-17 . While a significant
association of marijuana smoking with symptoms of chronic bronchitis has been reported in most
studies, associations with changes in lung function or other aspects of lung health over time,
especially in those at risk of or with diagnosed chronic obstructive pulmonary disease (COPD),
has been less studied. Three of the longitudinal analyses of lung function change found no
association with marijuana use12,16,17 , one found a small FEV1 decrement over a 20-year period
in the relatively small number (n=40) of heavy marijuana smokers, i.e., ≥20 joint-years (self-
reported number of joints per day times the number of years smoked)13 , and one found a
decrement in FEV1 only in former but not current marijuana smokers 14 . Analyzing a subgroup
derived from the CanCOLD study18 , Tan et al. found that marijuana smoking was associated
with worse FEV1 decline over a median of 5.9 years in comparison with tobacco-only smokers 15 .
While the latter finding mostly related to individuals with a heavy marijuana smoking history
(hereafter defined as ≥20 joint-years), the design of this study might have influenced the
results 19-20 .
In a cross-sectional analysis of participants with COPD in the Subpopulations and Intermediate
Outcome Measures in COPD Study (SPIROMICS) with a tobacco smoking history of ≥20 pack-
years, Morris et al.10 reported higher values for FEV1 % predicted and a lower percent
emphysema on HRCT images in both former marijuana smokers (FMS) and current marijuana
smokers (CMS), compared with never marijuana smokers (NMS) who smoked tobacco only,
after adjustments for relevant variables. In a preliminary analysis focused on lung function
change, we recently showed that ever marijuana smoking among SPIROMICS participants with
≥3 spirometry visits did not have a deleterious impact on FEV1 decline over time nor on the risk
for developing spirometry-defined COPD in tobacco smokers without COPD at baseline17 .
However, in order to examine the impact of marijuana smoking on progression of respiratory
symptoms, health status, HRCT metrics or frequency of exacerbations in addition to the change
in lung function, we analyzed a larger subgroup of SPIROMICS participants with ≥2 spirometry
visits and an ever-marijuana smoking history as well as a heavy marijuana smoking history (≥20
joint-years) compared to those with ≥3 spirometry visits as previously reported 17 . We aimed to
determine whether SPIROMICS FMS and CMS exhibit higher rates of change in respiratory
symptoms, HRCT metrics and lung function over time (2-10 years) compared to NMS, and
whether the reported cumulative lifetime exposure to marijuana would affect these changes. In
addition, we evaluated whether self-reported marijuana smoking among SPIROMICS
participants without spirometric evidence of COPD at baseline would affect the subsequent
development of COPD.
Methods:
Study population
SPIROMICS is a prospective cohort study (N= 2979 participants) aiming to identify new COPD
subgroups and intermediate markers of disease progression21 . Participants were followed
annually over three years in SPIROMICS I and had an additional in-person visit in SPIROMICS
II. Enrolled participants were 40-80 years old and had either normal spirometry and no tobacco
smoking history or had ≥20 pack-years of tobacco smoking; the latter subgroup was further
divided based on a post-bronchodilator FEV1/FVC ratio ≥0.70 or <0.70. Current asthma was an exclusionary criterion. For the present analysis data were obtained from ever tobacco-smoking SPIROMICS participants who had spirometry at the baseline visit and at least one follow-up visit, reported marijuana use or nonuse at the baseline visit and had no missing covariate information (n=1863). These participants were divided into the following three groups based on their self-reported history of marijuana use: never marijuana smokers (NMS, n=933), former marijuana smokers, i.e., no marijuana smoking within the last 30 days (FMS; n=775) or current marijuana smokers, i.e., marijuana smoking within the last 30 days (CMS; n=155). Based on their baseline frequency and duration of marijuana use, participants were further categorized by their cumulative lifetime history of marijuana smoking defined in terms of joint-years, calculated as the number of joints smoked per day times the number of years that marijuana was regularly smoked. Recognizing that marijuana is smoked using a variety of devices, we equated a bowlful of marijuana smoked via a pipe or a bong to one joint. Participants were not asked at the baseline visit about alternative modalities of inhaled marijuana such as vaping, hookah and “dabbing” Patients were also categorized into four joint-years groups as follows: 0 (n=933, i.e., NMS); >0-
<10 (n=314); 10-<20 (n=66); and ≥20 (n=137) joint-years. Longitudinal data over a period of at
least 52 weeks were compared between the three groups defined by marijuana smoking status
(NMS, FMS, CMS) as well as between the four subgroups defined by the number of joint-years.
Clinical Data
The study design of SPIROMICS has been described previously21 . The data included baseline
demographic and clinical characteristics, post-bronchodilator spirometry following 2005
ATS/ERS criteria [22], St. George’s Respiratory Questionnaire (SGRQ)23 , modified Medical
Research Council (mMRC) scale24 , COPD Assessment Test (CAT)25 and exacerbations of
COPD, ascertained at quarterly follow-up phone visits. HRCT metrics captured at enrollment
and the one-year follow up visit included emphysema defined by percent-voxels <-950
Hounsfield units at total lung capacity (% emphysema), air trapping using percent-voxels <-856
HU at residual volume, airway wall thickness at an internal perimeter of 10 mm (Pi10)26 and
parametric response mapping (PRM), a dynamic image registration technique assessing extent
functional small airways disease (PRM fsad ) and emphysema (PRM emphysema )27-28 .
Data Analysis
We used linear mixed effects models to assess changes in continuous outcomes over time: post-
bronchodilator FEV1 , post-bronchodilator FVC, SGRQ total score, CAT score, and HRCT
metrics. Linear mixed-effects models, specifically proportional odds models, were used to assess
changes in respiratory symptoms over time.
In assessing whether marijuana use among tobacco-smoking participants without COPD at
baseline increased the risk of subsequent development of COPD, the primary outcome was time
to development of airflow obstruction, defined by a post-bronchodilator FEV1/FVC<0.70.
Survival curves and hazard ratios were computed from models fitted with and without covariates.
We used zero-inflated negative binomial models to compare the rate of exacerbations between
CMS, FMS and NMS. Exacerbations were classified as moderate (defined as an increase in
symptoms of COPD requiring treatment with oral corticosteroids and/or antibiotics by a health
care provider), severe (defined as an increase in symptoms of COPD requiring hospitalization or
leading to death) and total (defined as moderate and/or severe exacerbations). To assess dose-
response relationships, the same models were used with the primary predictor of interest being
categorical joint-years history at baseline.
Results:
Baseline characteristics
A consort diagram describing the derivation of the study cohort is shown in Figure 1. At
enrollment, CMS, when compared with NMS, tended to be younger and more often current
tobacco smokers, men, and Black (Table 1 and e-Table 1). They also had fewer exacerbations
during the year prior to enrollment, had better FEV1 , less frequent airflow obstruction and less
emphysema and air trapping, but had similar levels of respiratory symptoms. Similar findings
were noted on comparison of FMS with NMS. Due to incomplete reporting, calculating
cumulative lifetime amount of marijuana use in joint-years was not possible for all participants,
so that the number of those classified by joint-year category (n=1450) is lower than that of the
total analysis sample. Among those with the heaviest marijuana use (≥20 joint-years),
directionally similar baseline differences were noted in age, sex, proportion of Black participants
and current tobacco-smoking status compared to those with 0 joint-years, as were found in
comparison between CMS and FMS with NMS (Table 2 and e-Table 2).
Follow-up visits
All three marijuana use groups (NMS, FMS and CMS) had similar numbers of in-person clinic
visits (median [IQR] 3[1-2]) and follow-up time in years (mean [SD] 4.2[2.2]) (e-Table 3). All
four joint-year groups also had similar numbers of follow-up clinic visits (median [IQR] 3[1-2])
and years of follow-up time (mean [SD] 4.2[2.1-2.2]) (e-Table 4). E-Tables 5 and 6 show the
median (25 th , 75th ) number of non-missing follow-up data points for each outcome variable by
marijuana smoking status and joint-year category, respectively.
Marijuana-smoking effect on change in lung function, symptoms and health status during follow-
up
The estimated rates of change in continuous outcomes by baseline marijuana-smoking status are
shown in Table 3A. While numerically higher annual rates of FEV1 and FVC decline and higher
rates of worsening CAT and total SGRQ scores were found comparing CMS (but not FMS) with
NMS, these differences were neither clinically nor statistically significant (e-Table 7). Similar
rates of change in these parameters were found on comparison of FMS with NMS. Estimated
rates of change in continuous outcomes between joint-years-based categories were similar across
all joint-years groups (Table 3B) and between-groups (e-Table 8). Estimated annualized FEV1
decline during follow-up by marijuana joint-years stratified by former and current tobacco-
smoking history were similar, irrespective of tobacco-smoking status (Figure 2). Estimated
subject-specific yearly changes in odds for worsening respiratory symptoms (cough, sputum,
wheeze and dyspnea) during follow-up compared to the baseline visit by baseline marijuana
status and baseline joint-years are shown in e-Table 9A and B and e-Figures 1 and 2,
respectively. The odds over time of more cough and sputum, but not more wheeze or dyspnea,
were significantly higher in CMS compared to FMS or NMS (e-Figure 1), while no significant
differences were found across the different joint-year categories that included both CMS and
FMS (e-Figure 2). Estimated yearly changes in CAT and SGRQ scores were not significantly
different across marijuana smoking status and joint-year categories as shown both in Tables 3A
and B, respectively, and e-Tables 5 and 6, respectively.
The effect of marijuana smoking on annual rate of change in HRCT metrics
Our analysis showed nominally less emphysema, air trapping and functional small airways
disease progression without statistical significance among CMS compared to NMS. Similarly,
comparison between NMS, FMS and CMS showed no significantly different changes in HRCT
metrics, except for unadjusted increased total tissue volume loss among FMS compared to NMS
(Table 3A and e-Table 7). No difference in tissue volume loss between CMS and NMS was
found.
Estimated rates of change in HRCT metrics were generally similar across all joint-years groups
(Table 3B), except for a higher rate of increase in PRM fsad on comparison of those with ≥20
joint-years (coefficient 1.030; 95% CI: 0.686,1.375) versus 0 joint-years (coefficient 0. 638; 95%
CI: 0.504,0.771), with a between-group difference 0.393 (95% C.I. 0.023, 0.762; p=0.037) when
unadjusted for multiple testing (e-Table 8).
Rate of exacerbations
Estimated yearly rates of one or more total (moderate and severe) or severe exacerbations during
the first 365 days or the total follow-up period by baseline marijuana smoking status and
marijuana joint-years are shown in Table 4 A and B and e-Figures 3 and 4. While rates of total
and severe exacerbations were numerically lower among both CMS and FMS versus NMS
during the first follow-up year, and severe exacerbation rates were slightly higher among CMS
versus NMS during the total follow-up period, none of these differences were statistically
significant (e-Figure 3). Estimated rates of total and severe exacerbations were numerically
higher among those with ≥20 versus those with 0 joint-years during the first follow-up year.
During the total follow-up period, rates of total exacerbations, but not severe exacerbations, were
slightly higher among those with ≥20 versus those with 0 joint-years. However, none of these
between-group differences were statistically significant (e-Figure 6).
Longitudinal effect of marijuana exposure on development of COPD
Estimated hazard ratios for development of COPD during follow-up by baseline marijuana-
smoking status and joint-years among participants without spirometric evidence of COPD at
baseline are shown in Table 5 and e-Figures 5 and 6. The odds of developing COPD by
spirometric criteria were lower among CMS and FMS versus NMS, as well as among those with
≥20 versus those with 0 joint-years, although these differences were not statistically significant.
Discussion:
The increasing prevalence of marijuana smoking among adolescents and adults 29 , including
ageing adults 30 , in the wake of a growing number of states legalizing marijuana use underscores
the need to better understand the impact of marijuana use on lung health. This need is
particularly evident among adult tobacco smokers in mid- and older life who have been
understudied previously. The current analysis of the pulmonary consequences of marijuana
smoking in the SPIROMICS cohort of current and former tobacco smokers with or at high risk of
developing COPD is a longitudinal extension of a cross-sectional analysis of the baseline
findings in the same cohort. 10 While the latter cross-sectional study failed to identify deleterious
effects of concomitant marijuana smoking on lung function or baseline structural radiographic
abnormalities when compared with the effect of tobacco smoking alone, it could not answer the
question whether marijuana affects changes in these outcomes over one to several years of
follow-up. In addition, the current study overlaps to some extent with a recent longitudinal
analysis focused mainly on the trajectory of lung function in SPIROMICS participants limited to
those with ≥ 3 spirometry visits.17 By including all those participants with ≥ 2, rather than only ≥3, spirometry visits at least one year apart, the current study has the advantage of including in theanalysis larger numbers of CMS and FMS, most importantly of those heavy MS with ≥ 20 joint-years, in an effort to achieve greater statistical power in examining the influence of marijuanasmoking on lung function decline. Furthermore, the current study examined changes inrespiratory symptoms and HRCT metrics during follow-up that were not included in the previousreport.Our study revealed trends toward higher rates of decline in post-bronchodilator FEV1 andworsening CAT and SGRQ scores among CMS (but not FMS) compared with NMS andcontrastingly, smaller rates of change in % emphysema and functional small airways disease.However, none of these differences were statistically significant. Similarly, when we compareddifferent categories of lifetime cumulative amounts of marijuana smoking, no significantdifferences were noted in rates of change in lung function, CAT or SGRQ scores, or HRCTmetrics, except for an increase in PRM fsad among the heaviest marijuana-smoking category (≥20joint-years) in comparison to those with 0 joint-years. It is noteworthy that significantly higherodds of worsening cough and sputum were noted among CMS in comparison with both NMSand FMS, but not between FMS and NMS. The latter finding is consistent with previous datashowing a significant reduction in symptoms of chronic bronchitis after cessation of marijuanasmoking 31,32 . Although some numerical differences were noted in rates of exacerbations acrossmarijuana-use status and joint-years categories, none of the between-group differences werestatistically significant. Finally, while the probability of subsequently developing COPD amongtobacco smokers without COPD at baseline was lower among CMS and FMS compared withNMS, as well as between the heaviest marijuana smokers versus those no history of marijuanasmoking, none of these differences reached statistical significance. Taken together, theaforementioned data failed to demonstrate that marijuana smoking of any lifetime cumulativeamount had a demonstrable effect on changes over time in clinical outcomes relevant to COPD,including respiratory symptoms, health status, HRCT metrics or frequency of exacerbations.Our failure to find any impact of even heavy marijuana smoking (≥20 joint-years) on lungfunction decline in ever-tobacco smokers with or at risk of COPD differs substantially from the
findings of Tan et al.15 . The latter authors demonstrated a dose-response effect of marijuana on
lung function decline in the CanCOLD subcohort with a significantly greater rate of decline in
FEV1 only among those with ≥20 joint-years (40.2 ml/year) compared to those who never used
marijuana (10.7 ml/year). Surprisingly, in the same study, among those with ≥20 joint-years of
marijuana smoking, the rates of FEV1 decline were very similar for CMS and FMS, compared to
NMS. In contrast, the average rate of FEV1 decline among the heaviest former tobacco smoking
was substantially lower than that of the current tobacco smokers. Since tobacco smokers with
COPD have a substantial reduction in the rate of FEV1 decline after sustained smoking
cessation33 , the disparate findings of Tan et al.15 comparing the impact of quitting marijuana with
that of quitting tobacco is surprising. The absence of a difference in the rates of decline between
their current and former marijuana smoking participants, most of whom were dual smokers of
marijuana and tobacco, may be a reflection of the impact of continuing tobacco smoking among
those who had quit using marijuana rather than of an enduring effect of marijuana among the
quitters.. It is also noteworthy that the number of SPIROMICS participants who were
particularly heavy marijuana smokers (≥20 joint-years) (n=137) was almost three times higher
than the number of CanCOLD participants with a heavy marijuana smoking history (n=51),
suggesting that our analysis of the impact of heavy marijuana use on lung function decline had
greater statistical power. Finally, while the reference control group in our analysis of FEV1
decline in relation to marijuana smoking consisted of NMS with a history of at least 20 pack-
years of tobacco smoking, the reference group in the analysis reported by Tan et al. 15 was
comprised solely of never smokers of either substance. Thus, our aim was to examine whether
marijuana smoking had an impact on the progression or development of COPD in current or
former smokers of tobacco who already had COPD or were at increased risk of developing
COPD, while Tan et al. evaluated whether marijuana smoking led to an accelerated decline in
lung function in a population of whom 43% were non-smokers of tobacco.
Our findings are also at odds with the results of another recent study by Winhusen et al. 1 Using
data from electronic health records of patients treated in an integrated healthcare system located
in Northeast Ohio, the latter authors reported a significantly greater risk for COPD, defined using
ICD-9/10 codes, among persons with a diagnosis of cannabis use disorder compared to
propensity-matched controls in a subgroup of patients with a diagnosis of tobacco use disorder
(adjusted OR 1.44 (C.I. 1.56-1.73; p=0.0001). These findings imply an additive effect of
cannabis on top of tobacco use. However, limitations of the latter study include misclassification
of COPD in the absence of spirometry data, suggested by the relatively young average age of the
authors’ analysis population (42 years) versus ours (64 years), as well as the absence of data on
the route of cannabis administration and the intensity and duration of its use. The marked
disparity of these results with ours underscores the need for additional study.
The possibility of a “dose-response” impact of marijuana exposure is suggested by our finding of
a significantly larger effect of ≥20 joint-years on PRM fsad in comparison with 0 joint-years (i.e.,
NMS), consistent with a deleterious effect of heavy marijuana use on small airways. The latter
observation is consistent with the recently reported finding in a New Zealand birth cohort at age
45 years of an association of lifetime cannabis use, adjusted for tobacco pack-years, with pre-
bronchodilator peripheral airways resistance and reactance using impulse oscillometry 34 .
However, this finding was only significant in women and was weaker and no longer significant
after bronchodilator use. In the same birth cohort at age 45, Hancox et al. further reported a
significant negative association of marijuana joint-years with FEF25-75% , but this association was
only significant in men16 . A “dose-response” effect could also be consistent with previous
findings by Pletcher et al.13 , who followed a cohort of 5015 young adults with a high tobacco-
smoking prevalence for over 20 years and found no evidence that increasing lifetime marijuana
exposure adversely affected lung function except among those with very heavy lifetime exposure
(>40 joint-years).
The findings of the present study should be interpreted in the context of certain limitations.
SPIROMICS was not specifically designed to examine the effects of marijuana smoking, and our
analyses were conducted post hoc; therefore, this analysis may be underpowered due to a
relatively small sample size and short duration of follow-up and our findings should be
considered exploratory. SPIROMICS did not enroll a random sample, so that our results may not
be generalizable. Marijuana is inhaled by various methods besides smoking a joint, including use
of a pipe or bong, hookah, a blunt, dabbing, vaping or administered as edible cannabinoids 35 , all
of which information was not collected at the baseline visit. However, the most common mode
of inhalation of marijuana is via smoking a joint 36 , but the amount of marijuana actually delivered with each use is highly variable and difficult to quantitate so that the method we used
for quantitating the cumulative lifetime amount of marijuana smoked (joint-years, or joint-
equivalent/years) is crude. Besides, marijuana use was self-reported and thus prone to recall or
reporting biases since marijuana use at some sites was illicit at the time of data collection. Our
classification of the participants with respect to marijuana and tobacco use status and the lifetime
amount of use was based on the information collected at baseline that did not take into account
changes in marijuana or tobacco amount or use status during the follow-up period. Moreover, the
groups we compared both by marijuana smoking status (CMS, FMS and NMS) and by joint-
years were quite different, and we could not adequately control for all of the differences.
Therefore, between-group differences in the true amount and modes of exposure to marijuana, as
well as in socioeconomic differences, might explain any effects noted. Finally, since most
participants with a history of marijuana smoking (n=314/547; 57%) were relatively light users
(<10 joint-years), it is possible that the cumulative amount of self-reported marijuana exposure
was insufficient to have a detectably deleterious effect on lung health on top of the impact of a
history of comparatively heavy tobacco smoking.
The present study also has several strengths. Subjects were recruited and followed at twelve
geographically varied sites nationwide, and women and African-Americans were adequately
represented, suggesting at least some measure of generalizability. All subjects had extensive
baseline and longitudinal characterization, allowing assessment of multiple clinical outcomes
over several years. Spirometry and HRCT imaging were performed by strict adherence to
recommended standards and protocols and were interpreted by dedicated reading centers. A
relatively large number of subjects were current marijuana smokers or reported a heavy lifetime
exposure to marijuana, thereby allowing for an assessment of dose-response relationship.
Conclusions:In a cohort of ever-tobacco smokers of ≥20 pack-years with established COPD or at risk ofdeveloping COPD followed over an average of more than 4 years, a history of current and/orformer smoking of marijuana of any cumulative lifetime amount was not found to be associatedwith a significantly deleterious impact on progression of COPD. Among ever-tobacco smokersin the same cohort without COPD at enrollment, self-reported current and/or former concomitant
marijuana smoking, including heavy marijuana smoking, was not found to be associated with an
increased risk of subsequently developing COPD. However, in view of our study’s limitations
and of previously published findings that conflict with our results, additional studies with a
larger sample size and longer duration of follow-up that are specifically designed to evaluate this
issue are needed for a better understanding of potential long-term effects of marijuana smoking
in persons with or at risk of developing COPD.
