Modulation of pulmonary immune function by inhaled cannabis products and consequences for lung disease.

The lungs, in addition to participating in gas exchange, represent the first line of defense against inhaled pathogens and respiratory toxicants. Cells lining the airways and alveoli include epithelial cells and alveolar macrophages, the latter being resident innate immune cells important in surfactant recycling, protection against bacterial invasion and modulation of lung immune homeostasis. Environmental exposure to toxicants found in cigarette smoke, air pollution and cannabis can alter the number and function of immune cells in the lungs. Cannabis (marijuana) is a plant-derived product that is typically inhaled in the form of smoke from a joint. However, alternative delivery methods such as vaping, which heats the plant without combustion, are becoming more common. Cannabis use has increased in recent years, coinciding with more countries legalizing cannabis for both recreational and medicinal purposes. Cannabis may have numerous health benefits owing to the presence of cannabinoids that dampen immune function and therefore tame inflammation that is associated with chronic diseases such as arthritis. The health effects that could come with cannabis use remain poorly understood, particularly inhaled cannabis products that may directly impact the pulmonary immune system. Herein, we first describe the bioactive phytochemicals present in cannabis, with an emphasis on cannabinoids and their ability to interact with the endocannabinoid system. We also review the current state-of-knowledge as to how inhaled cannabis/cannabinoids can shape immune response in the lungs and discuss the potential consequences of altered pulmonary immunity. Overall, more research is needed to understand how cannabis inhalation shapes the pulmonary immune response to balance physiological and beneficial responses with potential deleterious consequences on the lungs.

Receptor-mediated effects of Δ9 -tetrahydrocannabinol and cannabidiol on the inflammatory response of alveolar macrophages.

Δ9 -Tetrahydrocannabinol (Δ9 -THC) and cannabidiol (CBD) are cannabinoids found in Cannabis sativa. While research supports cannabinoids reduce inflammation, the consensus surrounding receptor(s)-mediated effects has yet to be established. Here, we investigated the receptor-mediated properties of Δ9 -THC and CBD on alveolar macrophages, an important pulmonary immune cell in direct contact with cannabinoids inhaled by cannabis smokers. MH-S cells, a mouse alveolar macrophage cell line, were exposed to Δ9 -THC and CBD, with and without lipopolysaccharide (LPS). Outcomes included RNA-sequencing and cytokine analysis. Δ9 -THC and CBD alone did not affect the basal transcriptional response of MH-S cells. In response to LPS, Δ9 -THC and CBD significantly reduced the expression of numerous proinflammatory cytokines including tumor necrosis factor-alpha, interleukin (IL)-1ß and IL-6, an effect that was dependent on CB2 . The anti-inflammatory effects of CBD but not Δ9 -THC were mediated through a reduction in signaling through nuclear factor-kappa B and extracellular signal-regulated protein kinase 1/2. These results suggest that CBD and Δ9 -THC have potent immunomodulatory properties in alveolar macrophages, a cell type important in immune homeostasis in the lungs. Further investigation into the effects of cannabinoids on lung immune cells could lead to the identification of therapies that may ameliorate conditions characterized by inflammation.

Inhalation Toxicology of Vaping Products and Implications for Pulmonary Health.

E-cigarettes have a liquid that may contain flavors, solvents, and nicotine. Heating this liquid generates an aerosol that is inhaled into the lungs in a process commonly referred to as vaping. E-cigarette devices can also contain cannabis-based products including tetrahydrocannabinol (THC), the psychoactive component of cannabis (marijuana). E-cigarette use has rapidly increased among current and former smokers as well as youth who have never smoked. The long-term health effects are unknown, and emerging preclinical and clinical studies suggest that e-cigarettes may not be harmless and can cause cellular alterations analogous to traditional tobacco smoke. Here, we review the historical context and the components of e-cigarettes and discuss toxicological similarities and differences between cigarette smoke and e-cigarette aerosol, with specific reference to adverse respiratory outcomes. Finally, we outline possible clinical disorders associated with vaping on pulmonary health and the recent escalation of acute lung injuries, which led to the declaration of the vaping product use-associated lung injury (EVALI) outbreak. It is clear there is much about vaping that is not understood. Consequently, until more is known about the health effects of vaping, individual factors that need to be taken into consideration include age, current and prior use of combustible tobacco products, and whether the user has preexisting lung conditions such as asthma and chronic obstructive pulmonary disease (COPD).

Population-based case-finding to identify subjects with undiagnosed asthma or COPD.

BACKGROUND: ∼5-10% of adults may have undiagnosed airflow obstruction. The objective of this study was to develop a population-based case-finding strategy to assess the prevalence of undiagnosed airflow obstruction (asthma or COPD) amongst adults with respiratory symptoms in Canada. METHODS: Adults without a previous history of asthma, COPD or lung disease were recruited using random digit-dialling and asked if they had symptoms of dyspnoea, cough, sputum or wheeze within the past 6 months. Those who answered affirmatively completed the Asthma Screening Questionnaire (ASQ), COPD-Diagnostic Questionnaire (COPD-DQ) and COPD Assessment Test (CAT). Those with an ASQ score of ≥6 or a COPD-DQ score of ≥20 underwent pre- and post-bronchodilator spirometry to diagnose asthma or COPD. RESULTS: 12 117 individuals were contacted at home and assessed for study eligibility. Of the 1260 eligible individuals, 910 (72%) enrolled and underwent spirometry. Ultimately, 184 subjects (20% of those enrolled) had obstructive lung disease (73 asthma and 111 COPD). Individuals found to have undiagnosed asthma or COPD had more severe respiratory symptoms and impaired quality of life compared with those without airflow obstruction. The ASQ, COPD-DQ, and CAT had ROC areas for predicting undiagnosed asthma or COPD of 0.49, 0.64 and 0.56, respectively. Four descriptive variables (age, BMI, sex and pack-years smoked) produced better receiver operating characteristic (ROC) values than the questionnaires (ROC area=0.68). CONCLUSION: 20% of randomly selected individuals who report respiratory symptoms in Canada have undiagnosed airflow obstruction due to asthma or COPD. Questionnaires could exclude subjects at low risk but lack the ability to accurately find subjects with undiagnosed disease.