Drug-induced Lung Disease in the Oncology Patient: From Cytotoxic Agents to Immunotherapy.

Drug-induced lung disease is commonly encountered, especially in the oncology setting. Diagnosis is challenging because clinical and radiologic findings are nonspecific, often overlapping with other lung pathologies in these patients due to underlying neoplasia, infection, or other treatment effects such as radiotherapy. Furthermore, oncology patients often receive multiple antineoplastic agents concurrently, and virtually every agent has an association with lung injury. In this article, we will review a variety of antineoplastic agents that are associated with drug-induced injury and discuss incidence, their typical timing of onset, and imaging features.

Pulmonary rehabilitation in Iranian outpatients with mustard gas lung disease: a randomised controlled trial.

OBJECTIVE: People with mustard gas lung disease experience cough, sputum, breathlessness and exercise limitation. We hypothesised that pulmonary rehabilitation (PR) would be beneficial in this condition. DESIGN: An assessor-blind, two-armed, parallel-design randomised controlled clinical trial. SETTING: Secondary care clinics in Iran. PARTICIPANTS: 60 men with breathlessness due to respiratory disease caused by documented mustard gas exposure, mean (SD) age 52.7 (4.36) years, MRC dyspnoea score 3.5 (0.7), St. George's Respiratory Questionnaire (SGRQ) 72.3 (15.2). INTERVENTIONS: Participants were allocated either to a 6-week course of thrice-weekly PR (n=31) or to usual care (n=29), with 6-week data for 28 and 26, respectively. OUTCOME MEASURES: Primary endpoint was change in cycle endurance time at 70% baseline exercise capacity at 6 weeks. Secondary endpoints included 6 min walk distance, quadriceps strength and bulk, body composition and health status. For logistical reasons, blood tests that had been originally planned were not performed and 12-month follow-up was available for only a small proportion. RESULTS: At 6 weeks, cycle endurance time increased from 377 (140) s to 787 (343) s with PR vs 495 (171) s to 479 (159) s for usual care, effect size +383 (231) s (p<0.001). PR also improved 6 min walk distance+103.2 m (63.6-142.9) (p<0.001), MRC dyspnoea score -0.36 (-0.65 to -0.07) (p=0.016) and quality of life; SGRQ -8.43 (-13.38 to -3.48) p<0.001, as well as quadriceps strength+9.28 Nm (1.89 to 16.66) p=0.015. CONCLUSION: These data suggest that PR can improve exercise capacity and quality of life in people with breathlessness due to mustard gas lung disease and support the wider provision of this form of care. TRIAL REGISTRATION NUMBER: IRCT2016051127848N1.

Transient pulmonary and gastric bleeding after iopamidol administration in a patient with marginal zone lymphoma: a case report.

BACKGROUND: Iopamidol is a non-ionic, water-soluble iodine contrast agent that is considered safe for intravenous or intra-arterial administration and is widely used both in the general population and in patients undergoing oncological treatment. While adverse reactions to iopamidol have been documented, to date, no pulmonary and gastric hemorrhages induced by iopamidol have been reported in oncology patients. We report the first case of this complication. CASE PRESENTATION: We report the case of a 60-year-old woman with marginal zone lymphoma who was receiving antineoplastic therapy. As part of the investigation for the condition, she underwent chest enhancement CT with iopamidol. Shortly thereafter(within five minutes), she experienced hemoptysis and hematemesis. She was intubated and admitted to the intensive care unit. Pre- and post-contrast images demonstrated the course of the hemorrhage. Flexible bronchoscopy and gastroscopy on the following day showed no active bleeding, and the patient recovered completely after antiallergy treatment. We speculate that contrast-induced hypersensitivity was the most likely cause of the transient pulmonary and gastric bleeding. CONCLUSION: Although rare, the complications of iopamidol, which may cause allergic reactions in the lungs and stomach, should be considered.

Lung-delivered IL-10 therapy elicits beneficial effects via immune modulation in organic dust exposure-induced lung inflammation.

Efficacious therapeutic options capable of resolving inflammatory lung disease associated with environmental and occupational exposures are lacking. This study sought to determine the preclinical therapeutic potential of lung-delivered recombinant interleukin (IL)-10 therapy following acute organic dust exposure in mice. Here, C57BL/6J mice were intratracheally instilled with swine confinement organic dust extract (ODE) (12.5%, 25%, 50% concentrations) with IL-10 (1 µg) treatment or vehicle control intratracheally-administered three times: 5 hr post-exposure and then daily for 2 days. The results showed that IL-10 treatment reduced ODE (25%)-induced weight loss by 66% and 46% at Day 1 and Day 2 post-exposure, respectively. IL-10 treatment reduced ODE (25%, 50%)-induced lung levels of TNFα (-76%, -83% [reduction], respectively), neutrophil chemoattractant CXCL1 (-51%, -60%), and lavage fluid IL-6 (-84%, -89%). IL-10 treatment reduced ODE (25%, 50%)-induced lung neutrophils (-49%, -70%) and recruited CD11cintCD11b+ monocyte-macrophages (-49%, -70%). IL-10 therapy reduced ODE-associated expression of antigen presentation (MHC Class II, CD80, CD86) and inflammatory (Ly6C) markers and increased anti-inflammatory CD206 expression on CD11cintCD11b+ cells. ODE (12.5%, 25%)-induced lung pathology was also reduced with IL-10 therapy. In conclusion, the studies here showed that short-term, lung-delivered IL-10 treatment induced a beneficial response in reducing inflammatory consequences (that were also associated with striking reduction in recruited monocyte-macrophages) following acute complex organic dust exposure.

Association between cooking fuel exposure and respiratory health: Longitudinal evidence from the China Health and Retirement Longitudinal Study (CHARLS).

The epidemiological evidences for the association between cooking fuel exposure and respiratory health were inconsistent, and repeated-measures prospective evaluation of cooking fuel exposure was still lacking. We assessed the longitudinal association of chronic lung disease (CLD) and lung function with cooking fuel types among Chinese adults aged ≥ 40 years. In this prospective, nationwide representative cohort of the China Health and Retirement Longitudinal Study from 2011 to 2018, 9004 participants from 28 provinces in China were included. CLD was identified based on self-reported physician diagnosis in 2018. Lung function was assessed by peak expiratory flow (PEF) in 2011, 2013 and 2015. Multivariable logistic and linear mixed-effects repeated-measures models were conducted to measure the associations of CLD and PEF with cooking fuel types. Three-level mixed-effects model was performed as sensitivity analysis. Among the participants, 3508 and 3548 participants used persistent solid and clean cooking fuels throughout the survey, and 1948 participants who used solid cooking fuels at baseline switched to clean cooking fuels. Use of persistent clean cooking fuels (adjusted odds ratio [aOR] = 0.73, 95 % confidence interval [CI]: 0.61, 0.88) and switch of solid fuels to clean fuels (aOR = 0.81, 95 % CI: 0.67, 0.98) were associated with lower risk of CLD. The use of clean cooking fuels throughout the survey and switch of solid fuels to clean fuels in 2013 were also significantly associated with higher PEF level. Similar results were observed in stratified analyses and different statistical models. The evidence from CHARLS cohort suggested that reducing solid cooking fuel exposure was associated with lower risk of CLD and better lung function. Given the recent evidence, improving household air quality will reduce the burden of chronic lung diseases.

Saharan dust induces the lung disease-related cytokines granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor.

Desert dust exposure is associated with adverse respiratory health effects. Desert dust is a complex pollutant mixtures that includes respirable crystalline and amorphous particles, metals, and microbial constituents. Given the health effects of desert dust and its heterogeneity, as yet unidentified harmful biological pathways may be triggered. Therefore, we exposed human in vitro air-liquid interface co-cultures of alveolar epithelial A549 cells and THP-1 macrophages to Saharan dust (SD). For comparison, we used the known pulmonary toxicant DQ12 quartz dust. Via RNA sequencing, we identified that SD but not DQ12 increased the gene expression of granulocyte-macrophage colony-stimulating factor (GMCSF) and granulocyte colony-stimulating factor (GCSF). These findings were confirmed by quantitative reverse transcriptase PCR. SD dose-dependently upregulated GMCSF and GCSF expression with significant 7 and 9-fold changes, respectively, at the highest tested concentration of 31 µg/cm2. Furthermore, we observed that SD significantly enhanced the secretion of GM-CSF and G-CSF by 2-fold. Both cytokines have previously been associated with lung diseases such as asthma and fibrosis. Hence, we present two molecular messengers that may contribute to the adverse health effects of desert dust and might serve as drug targets for this globally relevant non-anthropogenic air pollutant.

Lipid mediators of inhalation exposure-induced pulmonary toxicity and inflammation.

Many inhalation exposures induce pulmonary inflammation contributing to disease progression. Inflammatory processes are actively regulated via mediators including bioactive lipids. Bioactive lipids are potent signaling molecules involved in both pro-inflammatory and resolution processes through receptor interactions. The formation and clearance of lipid signaling mediators are controlled by multiple metabolic enzymes. An imbalance of these lipids can result in exacerbated and sustained inflammatory processes which may result in pulmonary damage and disease. Dysregulation of pulmonary bioactive lipids contribute to inflammation and pulmonary toxicity following exposures. For example, inhalation of cigarette smoke induces activation of pro-inflammatory bioactive lipids such as sphingolipids, and ceramides contributing to chronic obstructive pulmonary disease. Additionally, exposure to silver nanoparticles causes dysregulation of inflammatory resolution lipids. As inflammation is a common consequence resulting from inhaled exposures and a component of numerous diseases it represents a broadly applicable target for therapeutic intervention. With new appreciation for bioactive lipids, technological advances to reliably identify and quantify lipids have occurred. In this review, we will summarize, integrate, and discuss findings from recent studies investigating the impact of inhaled exposures on pro-inflammatory and resolution lipids within the lung and their contribution to disease. Throughout the review current knowledge gaps in our understanding of bioactive lipids and their contribution to pulmonary effects of inhaled exposures will be presented. New methods being employed to detect and quantify disruption of pulmonary lipid levels following inhalation exposures will be highlighted. Lastly, we will describe how lipid dysregulation could potentially be addressed by therapeutic strategies to address inflammation.

Amikacin liposome inhalation suspension for Mycobacterium avium complex pulmonary disease: A subgroup analysis of Japanese patients in the randomized, phase 3, CONVERT study.

BACKGROUND: CONVERT, a randomized, active-controlled, global, Phase 3 trial demonstrated that patients with treatment-refractory Mycobacterium avium complex (MAC) pulmonary disease were more likely to achieve culture conversion with amikacin liposome inhalation suspension (ALIS) plus guideline-based therapy (GBT) versus those continuing on GBT alone. This subgroup analysis reports the efficacy and safety of ALIS in Japanese patients enrolled in CONVERT. METHODS: Japanese patients aged ≥20 years with treatment-refractory MAC pulmonary disease from Japanese sites were included. Patients were randomized to receive once-daily 590 mg ALIS + GBT or GBT alone; patients converting by Month 6 remained in the study to complete 12-month treatment followed by a 12-month off-treatment period. Nonconverters exited the study at Month 8. The primary endpoint was the proportion of patients achieving culture conversion by Month 6. RESULTS: Of the 59 Japanese patients screened, 48 were randomized to receive ALIS + GBT (n = 34) or GBT alone (n = 14), and 41/48 (85.4 %) were women. The mean (standard deviation) age of patients was 64.5 (8.6) years, and 83.3 % of patients had bronchiectasis at baseline. By Month 6, sputum culture conversion was cumulatively achieved in 9/34 (26.5 %) patients receiving ALIS + GBT versus none receiving GBT alone. Treatment-emergent adverse events were reported in 94.1 % and 100.0 % of patients receiving ALIS + GBT and GBT alone, respectively. No deaths were reported. CONCLUSIONS: The efficacy observed in the Japanese subpopulation was largely consistent with that in the overall CONVERT study population, with more patients achieving culture conversion with ALIS + GBT versus GBT alone. Safety profiles were similar between the overall population and the Japanese subpopulation. CLINICAL TRIAL REGISTRATION: NCT02344004.

Predictors of pulmonary dysfunction vis-à-vis the hypertension status of mine workers in Gujarat, western India: A cross-sectional study on the need to further investigate the role of anti-hypertensive drugs.

BACKGROUND: Mine workers face various health risks from occupational hazards, notably dust-related pulmonary dysfunction. This dysfunction is also attributed to diverse risk factors and health conditions. Despite the variety of underlying mechanisms, conflicting evidence persists regarding hypertension as a potential risk factor for such dysfunction. OBJECTIVE: To determine the predictors of pulmonary dysfunction vis-à-vis the hypertension status of mine workers. METHODS: We conducted a cross-sectional study among 444 mine workers from ten open-cast mines in Gujarat state (western part of India) from November 2020 to February 2022. We collected data on demographics, occupation, addiction, and comorbidities, including measurements like anthropometry, blood pressure, blood sugar, haemoglobin, and lipid levels. Hypertension was confirmed based on self-reported history and/or onsite blood pressure measurement, while pulmonary functions were assessed using a spirometer (expressed as forced expiratory volume in the first second FEV1 and forced vital capacity FVC). Multiple linear regression analysis was performed to determine the significant predictor of FEV1 or FVC vis-à-vis the hypertension status after adjusting for confounding variables. In addition, we assessed the effect of anti-hypertensive medications on pulmonary dysfunction. RESULTS: A total of 41% (95% CI: 36-45%) of mine workers were suffering from hypertension. On multiple linear regression, only being a male and work experience duration were the significant predictors of FEV1 [0.900 (0.475-1.092), p=<0.001; -0.029 (-0.034 - -0.021, p=<0.001] and FVC [1.088 (0.771-1.404), p=<0.001; -0.031 (-0.038 - -0.024, p = 0.001] respectively. While unadjusted analysis indicated hypertension led to FEV1 and FVC reduction, this effect lost significance after adjusting for confounders. Nevertheless, subgroup analysis revealed those on antihypertensive medications had reductions in FEV1 and FVC by -0.263 (95% CI: -0.449 - -0.078, p = 0.006) L and -0.271 (95% CI: -0.476 - -0.067, p = 0.009) L respectively. CONCLUSION: In our study among mine workers, alterations in lung function (FEV1 and FVC) on spirometry were predicted by gender and duration of work experience, while hypertension did not serve as a predictor. It is noteworthy that antihypertensive drugs were found to reduce lung functions on spirometry, highlighting the need for further research.

Advances in the study of silica nanoparticles in lung diseases.

Silicon dioxide nanoparticles (SiNPs) are one of the major forms of silicon dioxide and are composed of the most-abundant compounds on earth. Based on their excellent properties, SiNPs are widely used in food production, synthetic processes, medical diagnostics, drug delivery, and other fields. The mass production and wide application of SiNPs increases the risk of human exposure to SiNPs. In the workplace and environment, SiNPs mainly enter the human body through the respiratory tract and reach the lungs; therefore, the lungs are the most important and most toxicologically affected target organ of SiNPs. An increasing number of studies have shown that SiNP exposure can cause severe lung toxicity. However, studies on the toxicity of SiNPs in ex vivo and in vivo settings are still in the exploratory phase. The molecular mechanisms underlying the lung toxicity of SiNPs are varied and not yet fully understood. As a result, this review summarizes the possible mechanisms of SiNP-induced lung toxicity, such as oxidative stress, endoplasmic reticulum stress, mitochondrial damage, and cell death. Moreover, this study provides a summary of the progression of diseases caused by SiNPs, thereby establishing a theoretical basis for future studies on the mechanisms of SiNP-induced lung toxicity.

Effectiveness and safety of regimens containing linezolid for treatment of Mycobacterium abscessus pulmonary Disease.

OBJECTIVE: To evaluate the effectiveness and safety of linezolid-containing regimens for treatment of M. abscessus pulmonary disease. METHODS: The records of 336 patients with M. abscessus pulmonary disease who were admitted to Shanghai Pulmonary Hospital from January 2018 to December 2020 were retrospectively analyzed. A total of 164 patients received a linezolid-containing regimen and 172 controls did not. The effectiveness, safety, antibiotic susceptibility profiles, outcomes, culture conversion, cavity closure, and adverse reactions were compared in these two groups. RESULTS: The two groups had similar treatment success (56.1% vs. 48.8%; P > 0.05), but treatment duration was shorter in the linezolid group (16.0 months [inter-quartile ranges, IQR: 15.0-17.0] vs. 18.0 months [IQR: 16.0-18.0]; P < 0.01). The rates of sputum culture conversion were similar (53.7% vs. 46.5%, P > 0.05), but time to conversion was shorter in the linezolid group (3.5 months [IQR: 2.5-4.4] vs. 5.5 months [IQR: 4.0-6.8]; P < 0.01). The linezolid group had a higher rate of cavity closure (55.2% vs. 28.6%, P < 0.05) and a shorter time to cavity closure (3.5 months [IQR: 2.5-4.4] vs. 5.5 months [IQR: 4.0-6.8]; P < 0.01). Anemia and peripheral neuropathy were more common in the linezolid group (17.7% vs. 1.7%, P < 0.01; 12.8% vs. 0.6%, P < 0.01). CONCLUSIONS: The linezolid and control groups had similar treatment success rates. The linezolid group had a shorter treatment duration, shorter time to sputum culture conversion, and higher rate and shorter time to lung cavity closure. More patients receiving linezolid developed anemia and peripheral neuropathy.

First reported case of ANCA-associated vasculitis induced by oxaliplatin, capecitabine, and trastuzumab.

A 68-year-old male, who was undergoing XELOX plus trastuzumab therapy for gastric cancer, developed proteinuria, hematuria, and progressive increase in creatinine after 3 months. Subsequently, the patient also experienced hemoptysis, nasal bleeding. Chest CT examination shown pulmonary hemorrhage. The MRI of the nasopharynx ruled out nasopharyngeal cancer recurrence. The MPO and PR3 were elevated, and renal biopsy confirmed ANCA-related vasculitis, which affected the lungs, kidneys, and nasopharynx. Based on the review of the patient''s medical history and medication, it is believed that ANCA-related vasculitis was caused by XELOX plus trastuzumab chemotherapy, but it is difficult to confirm which specific drug caused it. After stopping XELOX plus trastuzumab chemotherapy, glucocorticoids and cyclophosphamide was given, the patient''s pulmonary hemorrhage and nasal bleeding stopped, and the lung lesions were absorbed. The renal function also improved. The patient later experienced pulmonary infection again, and tNGS indicated Legionella pneumophila and pulmonary tuberculosis infection. Despite anti-infection treatment, steroid dose was rapidly reduced. Ultimately, the patient gave up on treatment and eventually died.

Inhaled toxicants and pulmonary lipid metabolism: biological consequences and therapeutic interventions.

Inhaled toxicants drive the onset of and exacerbate preexisting chronic pulmonary diseases, however, the biological mechanisms by which this occurs are largely unknown. Exposure to inhaled toxicants, both environmental and occupational, drives pulmonary inflammation and injury. Upon activation of the inflammatory response, polyunsaturated fatty acids (PUFAs) are metabolized into predominately proinflammatory lipid mediators termed eicosanoids which recruit immune cells to the site of injury, perpetuating inflammation to clear the exposed toxicants. Following inflammation, lipid mediator class-switching occurs, a process that leads to increased metabolism of hydroxylated derivates of PUFAs. These mediators, which include mono-hydroxylated PUFA derivatives and specialized proresolving lipid mediators, initiate an active process of inflammation resolution by inhibiting the inflammatory response and activating resolution pathways to return the tissue to homeostasis. Exposure to inhaled toxicants leads to alterations in the synthesis of these proinflammatory and proresolving lipid mediator pathways, resulting in greater pulmonary inflammation and injury, and increasing the risk for the onset of chronic lung diseases. Recent studies have begun utilizing supplementation of PUFAs and their metabolites as potential therapeutics for toxicant-induced pulmonary inflammation and injury. Here we will review the current understanding of the lipid mediators in pulmonary inflammation and resolution as well as the impact of dietary fatty acid supplementation on lipid mediator-driven inflammation following air pollution exposure.

Diffuse Alveolar Hemorrhage Synergistically Induced by Amiodarone and Rheumatoid Arthritis.

Diffuse alveolar hemorrhage (DAH) syndrome is characterized by bleeding into the alveolar spaces of the lungs and occurs when there is an injury to the alveolar microcirculation that leads to hemorrhage from the alveolar capillaries. We report a case of an 82-year-old woman who presented with acute respiratory distress. The patient had a history of rheumatoid arthritis (RA) and was on amiodarone for atrial fibrillation therapy. Initial diagnostic workup, including bronchoscopy and imaging studies, revealed diffuse opacities and the bronchoalveolar lavage fluid consistent with DAH. The patient required aggressive management with supportive care and corticosteroids. Laboratory work showed a synergistic effect between amiodarone and RA in inducing DAH. This makes the report unique as no reports in the literature described a synergic effect of amiodarone and RA in inducing DAH. The primary objective of this report is to guide physicians and remind them to keep DAH at the top of their differential diagnosis in the setting of an RA patient taking amiodarone.

Protective effects of inhaled antioxidants against air pollution-induced pathological responses.

As the public health burden of air pollution continues to increase, new strategies to mitigate harmful health effects are needed. Dietary antioxidants have previously been explored to protect against air pollution-induced lung injury producing inconclusive results. Inhaled (pulmonary or nasal) administration of antioxidants presents a more promising approach as it could directly increase antioxidant levels in the airway surface liquid (ASL), providing protection against oxidative damage from air pollution. Several antioxidants have been shown to exhibit antioxidant, anti-inflammatory, and anti-microbial properties in in vitro and in vivo models of air pollution exposure; however, little work has been done to translate these basic research findings into practice. This narrative review summarizes these findings and data from human studies using inhaled antioxidants in response to air pollution, which have produced positive results, indicating further investigation is warranted. In addition to human studies, cell and murine studies should be conducted using more relevant models of exposure such as air-liquid interface (ALI) cultures of primary cells and non-aqueous apical delivery of antioxidants and pollutants. Inhalation of antioxidants shows promise as a protective intervention to prevent air pollution-induced lung injury and exacerbation of existing lung disease.

Phosphodiesterase inhibitors and lung diseases.

Phosphodiesterase enzymes (PDE) have long been known as regulators of cAMP and cGMP, second messengers involved in various signaling pathways and expressed in a variety of cell types implicated in respiratory diseases such as airway smooth muscle and inflammatory cells making them a key target for the treatment of lung diseases as chronic obstructive pulmonary disease (COPD), asthma, cystic fibrosis, and pulmonary hypertension (PH). The first reported PDE inhibitor was the xanthine, theophylline, described as a non-specific PDE inhibitor and whilst this drug is effective, it also has a range of unwanted side effects. In an attempt to improve the therapeutic window of xanthines, a number of selective PDE inhibitors have been developed for the treatment of respiratory diseases with only the selective PDE 4 inhibitor, roflumilast, being approved for the treatment of severe COPD. However, roflumilast also has a very narrow therapeutic window due to a number of important doses limiting side effects, particularly in the gastrointestinal tract. However, there continues to be research carried out in this field to identify improved selective PDE inhibitors, both by targeting other PDE subtypes (e.g., PDE 7 found in a number of inflammatory and immune cells) and through development of selective PDE inhibitors for pulmonary administration to reduce systemic exposure and improve the side effect profile. This approach has been exemplified by the development of ensifentrine, a dual PDE 3-PDE 4 inhibitor, an inhaled drug that has recently completed two successful Phase III clinical trials in patients with COPD.

Establishment of an artificial particulate matter-induced lung disease model through analyzing pathological changes and transcriptomic profiles in mice.

Particulate matter (PM), an environmental risk factor, is linked with health risks such as respiratory diseases. This study aimed to establish an animal model of PM-induced lung injury with artificial PM (APM) and identify the potential of APM for toxicological research. APM was generated from graphite at 600 °C and combined with ethylene. We analyzed diesel exhaust particulate (DEP) and APM compositions and compared toxicity and transcriptomic profiling in lungs according to the exposure. For the animal study, C57BL/6 male mice were intratracheally administered vehicle, DEP, or APM. DEP or APM increased relative lung weight, inflammatory cell numbers, and inflammatory protein levels compared with the vehicle control. Histological assessments showed an increase in particle-pigment alveolar macrophages and slight inflammation in the lungs of DEP and APM mice. In the only APM group, granulomatous inflammation, pulmonary fibrosis, and mucous hyperplasia were observed in the lungs of some individuals. This is the first study to compare pulmonary toxicity between DEP and APM in an animal model. Our results suggest that the APM-treated animal model may contribute to understanding the harmful effects of PM in toxicological studies showing that APM can induce various lung diseases according to different doses of APM.

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.