Table 2

Summary of observational studies on marijuana exposure and lung function

Author [ref.]	Subjects n	Study design	Outcomes measured	Results
Cruickshank [11]	60	Cross-sectional	FEV₁, FVC, P_O2, P_CO2	No significant differences found in FEV₁ and FVC among cannabis smokers.
Tashkin [12]	74	Cross-sectional	Respiratory symptoms, FEV₁, FVC, FEF_25–75%, R_aw, CV, ΔN₂_750–1250	No differences in spirometry results. A significant increase was noted in R_aw and decrease in sG_aw. FVC was raised compared to both controls but not significant.
Hernandez [13]	23	Cross-sectional	FEV₁, FVC, FEF_25–75%, R_aw, PD₅₀R_aw	Spirometry results of marijuana smokers were not significantly different to controls. No significant difference in histamine reactivity.
Tilles [14]	68	Cross-sectional	FEV₁, FVC, PEFR, FRC, T_LCO	Cannabis smoking±tobacco smoking was associated with a reduction in T_LCO. In marijuana and marijuana+tobacco smokers, both the FEV₁ and FVC were significantly increased compared to nonsmokers.
Bloom [15]	990	Cross-sectional	Respiratory symptoms, depth of inhalation, FEV₁, FVC, V′_max	Significant increase in respiratory symptoms of phlegm and wheeze, but not cough or shortness of breath, in non-tobacco cigarette smokers regardless of tobacco smoking status. Significant decrease in FEV₁/FVC compared to controls. No significant changes in FEV₁ in any non-tobacco smoking category.
Tashkin [16]	446	Cross-sectional	Respiratory symptoms, FEV₁, FVC, FEF_25–75%, R_aw, sG_aw, D_LCO	Smokers of marijuana±tobacco had significantly increased rates of chronic cough, wheeze and sputum production. FEV₁ and FVC of marijuana smokers not significantly different from controls.
Sherrill [17]	856	Observational cohort	Respiratory symptoms, FEV₁, FVC, V′_max50	Non-tobacco smoking was associated with chronic cough, chronic phlegm and wheeze. Significant reduction in FEV₁ and FEV₁/FVC with previous non-tobacco smoking but not with current smoking.
Sherman [18]	63	Cross-sectional	Macrophage oxidant release, small airway integrity, FEV₁, FVC, T_LCO	Macrophage oxidant release, small airway integrity, and alveolar gas exchange similar in both nonsmokers and marijuana smokers. No significant difference in lung function between marijuana only smokers and nonsmokers. Marijuana and tobacco concurrent smokers showed a decrease in FEV₁, FVC and T_LCO.
Tashkin [19]	542	Cross-sectional	AHR	No significant difference in AHR to methacholine found in nonsmokers and marijuana smokers without tobacco. However, logistic regression showed a significant response to methacholine with marijuana smoking. No dose–response relationship was found between AHR and lifetime marijuana use.
Tashkin [20]	394	Observational cohort	FEV₁	Marijuana smoking was not associated with FEV₁ decline.
Taylor [21]	1037	Observational cohort	Respiratory symptoms, AHR, FEV₁, FVC	Cannabis users had an increase in wheezing, exercise-related shortness of breath, nocturnal wakening with chest tightness and morning sputum production. Cannabis users had decreased FEV₁/FVC compared to nonsmokers. No significant increase in AHR in tobacco or cannabis users.
Taylor [22]	1037	Observational cohort	FEV₁, FVC	After stratifying by use of cannabis, at each age increasing cannabis use was associated with a decline in FEV₁/FVC. After adjustments of other covariates, cannabis as a predictor was only marginally significant.
Moore [9]	6728	Cross-sectional	Respiratory symptoms, examination, FEV₁, FVC	Marijuana use was significantly associated with chronic bronchitis symptoms, coughing on most days, phlegm production, wheezing, and chest sounds without a cold. Cannabis smoking was not associated with an FEV₁/FVC ratio <70%.
Aldington [23]	339	Cross-sectional	Emphysema by CT, FEV₁, FVC, TLC, FRC, MMEF, SVC, RV, T_LCO, sG_aw, V_A	Both cannabis and tobacco smoking groups showed a reduction in the FEV₁/FVC. Tobacco reduced FEV₁, while cannabis smoking had no effect on FEV₁. Tobacco smoking was associated with macroscopic emphysema by CT, but not cannabis-only smoking.
Tan [24]	878	Observational cohort	Respiratory symptoms, COPD by spirometry	Marijuana only smokers had no significant increase in risk of COPD as defined by symptoms and spirometry. However, tobacco and marijuana concurrent use produced an increased risk of respiratory symptoms and COPD.
Hancox [25]	1037	Observational cohort	FEV₁, FVC, TLC, RV, V_A, T_LCO, R_aw, sG_aw	Cannabis exposure was associated with increased FVC and TLC, but no significant association with FEV₁ or FEV₁/FVC. Marijuana smoking associated with increased R_aw and lower sG_aw.
Pletcher [26]	5119	Observational cohort	FEV₁, FVC	Marijuana exposure was non-linearly associated with lung function, unlike tobacco. Cannabis exposure showed an increase in FEV₁ over time at up to 7 joint-years and declining thereafter. FVC was significantly elevated in users up to 20 joint-years. Both FEV₁ and FVC were increased at all exposure levels.
Kempker [27]	7716	Cross-sectional	FEV₁_, FVC	For cannabis smokers with 1–5 and 6–20 joint-years, there was no association with an FEV₁/FVC <70%. Those with >20 joint-years did have an association. Use of marijuana in the past month was associated with increased FVC (0.13±0.03%, p=0.0001) for each additional day but no decrease in FEV₁.
Macleod [28]	500	Observational cohort	Respiratory symptoms, FEV₁, FVC	Cannabis and tobacco use together was associated with increased cough, sputum production and wheeze. After adjustment for tobacco use, age, sex and deprivation, each additional joint year of cannabis was associated with 0.3% increase in prevalence of an FEV₁/FVC <70%.

P_O2: oxygen tension; P_CO2: carbon dioxide tension; FEF_25–75%: forced expiratory flow at 25–75% of FVC; R_aw: airway resistance; CV: closing volume; ΔN₂_750–1250: percentage change in nitrogen concentration between 750 and 1250 mL of expired volume; PD₅₀R_aw: provocative dose required to achieve a 50% increase in airway resistance; PEFR: peak expiratory flow rate; FRC: functional residual capacity; T_LCO: transfer factor of the lung for carbon monoxide; V′_max: oxygen uptake; sG_aw: specific airway conductance; D_LCO: diffusing capacity of the lung for carbon monoxide; V′_max50: flow rate at 50% of the expired FVC; AHR: airway hyperresponsiveness; CT: computed tomography; TLC: total lung capacity; MMEF: maximum mid-expiratory flow; SVC: slow vital capacity; RV: residual volume; V_A: alveolar volume. Reproduced with modification from [2].