Impact of Marijuana Use on Lung Health.

The widespread use of marijuana in the context of increasing legalization has both short- and long-term health implications. Although various modes of marijuana use-smoked, vaped, or ingested-may lead to a wide scope of potential systemic effects, we focus here on inhalational use of marijuana as the most common mode with the lung as the organ that is most directly exposed to its effects. Smoked marijuana has been associated with symptoms of chronic bronchitis and histopathologic changes in airway epithelium, but without consistent evidence of long-term decline in pulmonary function. Its role in immunomodulation, both for risk of infection and protection against a hyperinflammatory host response to infection, has been suggested in animal models and in vitro without conclusive extrapolation to humans. Marijuana smoke contains carcinogens like those found in tobacco, raising concern about its role in lung cancer, but evidence is mixed and made challenging by concurrent tobacco use. Vaping may offer a potential degree of harm reduction when compared with smoking marijuana with reduction of exposure to several toxins, including carbon monoxide, and reduction in chronic respiratory symptoms. However, these potential benefits are counterbalanced by risks including vaping-associated lung injury, potentially more intense drug exposure, and other yet not well-understood toxicities. As more states legalize marijuana and the federal government considers changing this from a Schedule I to a Schedule III controlled substance, we anticipate an increase in prospective medical studies concerning the risks related to marijuana use. This review is based on currently available data concerning the impact of inhaled marijuana on lung health.

Prevalence and Management of Chronic Obstructive Pulmonary Disease in the Gulf Countries with a Focus on Inhaled Pharmacotherapy.

Background: Chronic obstructive pulmonary disease (COPD) is a preventable, progressive disease and the third leading cause of death worldwide. The epidemiological data of COPD from Gulf countries are very limited, as it remains underdiagnosed and underestimated. Risk factors for COPD include tobacco cigarette smoking, water pipe smoking (Shisha), exposure to air pollutants, occupational dusts, fumes, and chemicals. Inadequate treatment of COPD leads to worsening of disease. The 2024 GOLD guidelines recommend use of inhaled bronchodilators, corticosteroids, and adjunct therapies for treatment and management of COPD patients based on an individual assessment of the severity of symptoms and risk of exacerbations. This article reviews COPD pharmacotherapy in the Gulf countries and explores the role of nebulization in the management of COPD in this region. Methods: To review the COPD pharmacotherapy in the Gulf Countries, literature search was conducted using PubMed, Medline, Cochrane Systematic Reviews, and Google Scholar databases (before December 2022), using search terms such as COPD, nebulization, inhalers/inhalation, aerosols, and Gulf countries. Relevant articles from the reference list of identified studies were reviewed. Consensus statements, expert opinion, and other published review articles were included. Results: In the Gulf countries, pressurized metered-dose inhalers (pMDIs), dry powder inhalers (DPIs), soft mist inhalers, and nebulizers are used for drug delivery to COPD patients. pMDIs and DPIs are most prone to errors in technique and other common device handling errors. Nebulization is another mode of inhalation drug delivery, which is beneficial in certain patient populations such as the elderly and patients with cognitive impairment, motor or neuromuscular disorders, and other comorbidities. Conclusion: There is no major difference between Gulf countries and rest of the world in the approach to management of COPD. Nebulizers should be considered for patients who have difficulties in accessing or using MDIs and DPIs, irrespective of geographical location.

Association between ambient exposure to PM2.5 and upper aerodigestive tract cancer in Los Angeles.

Fine particulate matter (PM2.5 ) contains carcinogens similar to those generated by tobacco smoking, which may increase the risks of developing smoking-related cancers, such as upper aerodigestive track (UADT) cancers, for both smokers and never-smokers. Therefore, it is imperative to understand the relation between ambient PM2.5 exposure and risk of UADT cancers. A population-based case-control study involving 565 incident UADT cancer cases and 983 controls was conducted in Los Angeles County from 1999 to 2004. The average residential PM2.5 concentration 1 year before the diagnosis date for cases and the reference date for controls was assessed using a chemical transport model. The association between ambient PM2.5 and the UADT cancers was estimated by unconditional logistic regression, adjusting for confounders at the individual and block-group level. Stratified analyses were conducted by sex, tobacco smoking status and UADT subsites. We also assessed the interaction between PM2.5 and tobacco smoking on UADT cancers. PM2.5 concentrations were associated with an elevated odds of UADT cancers (adjusted odds ratio = 1.21 per interquartile range [4.5 µg/m3 ] increase; 95% confidence interval: 1.02, 1.44). The association between PM2.5 and UADT cancers was similar across UADT subsites, sex and tobacco smoking status. The interaction between PM2.5 and tobacco smoking on UADT cancers was approximately additive on the odds scale. The effect estimate for PM2.5 and UADT cancers was similar among never smokers. Our findings support the hypothesis that exposure to PM2.5 increases the risk of UADT cancers. Improvements in air quality may reduce the risk of UADT cancers.

Eosinophil recovery in hospitalized COVID-19 patients is associated with lower rates of ICU admission and in-hospital mortality: An observational cohort analysis.

BACKGROUND: Admission eosinopenia (<100 cells/µL) is associated with poor clinical outcomes in hospitalized COVID-19 patients. However, the effects of eosinophil recovery (defined as reaching ≥50 eosinophils/µL) during hospitalization on COVID-19 outcomes have been inconsistent. METHODS: The study included 1,831 patients admitted to UCLA hospitals between February 2020 and February 2021 with PCR-confirmed COVID-19. Using competing risk regression and modeling eosinophil recovery as a time-dependent covariate, we evaluated the longitudinal relationship between eosinophil recovery and in-hospital outcomes including ICU admission, need for mechanical ventilation, and in-hospital mortality. All analyses were adjusted for covariates including age, BMI, tobacco smoke exposure, comorbidities known to be risk factors for COVID-19 mortality, and treatments including dexamethasone and remdesivir. RESULTS: Eosinophil recovery was evaluated in patients with <50 eosinophils/µL on admission (n = 1282). These patients cumulatively amassed 11,633 hospital patient-days; 3,985 of those days qualified as eosinophil recovery events, which were represented by 781 patients achieving at least one instance of eosinophil recovery during hospitalization. Despite no significant difference in the rate of mechanical ventilation, eosinophil recoverers had significantly lower rates of in-hospital mortality (aHR: 0.44 [0.29, 0.65], P = 0.001) and ICU admission (aHR: 0.25 [0.11, 0.61], P = 0.002). CONCLUSION: Trending eosinophil counts during hospitalization is simple and can be performed in resource-limited healthcare settings to track the inflammatory status of a patient. Lack of eosinophil recovery events can identify those at risk for future progression to severe COVID.

Longitudinal Follow-Up of Participants With Tobacco Exposure and Preserved Spirometry.

Importance: People who smoked cigarettes may experience respiratory symptoms without spirometric airflow obstruction. These individuals are typically excluded from chronic obstructive pulmonary disease (COPD) trials and lack evidence-based therapies. Objective: To define the natural history of persons with tobacco exposure and preserved spirometry (TEPS) and symptoms (symptomatic TEPS). Design, Setting, and Participants: SPIROMICS II was an extension of SPIROMICS I, a multicenter study of persons aged 40 to 80 years who smoked cigarettes (>20 pack-years) with or without COPD and controls without tobacco exposure or airflow obstruction. Participants were enrolled in SPIROMICS I and II from November 10, 2010, through July 31, 2015, and followed up through July 31, 2021. Exposures: Participants in SPIROMICS I underwent spirometry, 6-minute walk distance testing, assessment of respiratory symptoms, and computed tomography of the chest at yearly visits for 3 to 4 years. Participants in SPIROMICS II had 1 additional in-person visit 5 to 7 years after enrollment in SPIROMICS I. Respiratory symptoms were assessed with the COPD Assessment Test (range, 0 to 40; higher scores indicate more severe symptoms). Participants with symptomatic TEPS had normal spirometry (postbronchodilator ratio of forced expiratory volume in the first second [FEV1] to forced vital capacity >0.70) and COPD Assessment Test scores of 10 or greater. Participants with asymptomatic TEPS had normal spirometry and COPD Assessment Test scores of less than 10. Patient-reported respiratory symptoms and exacerbations were assessed every 4 months via phone calls. Main Outcomes and Measures: The primary outcome was assessment for accelerated decline in lung function (FEV1) in participants with symptomatic TEPS vs asymptomatic TEPS. Secondary outcomes included development of COPD defined by spirometry, respiratory symptoms, rates of respiratory exacerbations, and progression of computed tomographic-defined airway wall thickening or emphysema. Results: Of 1397 study participants, 226 had symptomatic TEPS (mean age, 60.1 [SD, 9.8] years; 134 were women [59%]) and 269 had asymptomatic TEPS (mean age, 63.1 [SD, 9.1] years; 134 were women [50%]). At a median follow-up of 5.76 years, the decline in FEV1 was -31.3 mL/y for participants with symptomatic TEPS vs -38.8 mL/y for those with asymptomatic TEPS (between-group difference, -7.5 mL/y [95% CI, -16.6 to 1.6 mL/y]). The cumulative incidence of COPD was 33.0% among participants with symptomatic TEPS vs 31.6% among those with asymptomatic TEPS (hazard ratio, 1.05 [95% CI, 0.76 to 1.46]). Participants with symptomatic TEPS had significantly more respiratory exacerbations than those with asymptomatic TEPS (0.23 vs 0.08 exacerbations per person-year, respectively; rate ratio, 2.38 [95% CI, 1.71 to 3.31], P < .001). Conclusions and Relevance: Participants with symptomatic TEPS did not have accelerated rates of decline in FEV1 or increased incidence of COPD vs those with asymptomatic TEPS, but participants with symptomatic TEPS did experience significantly more respiratory exacerbations over a median follow-up of 5.8 years.

Three-Month Variability of Commonly Evaluated Biomarkers in Clinically Stable COPD.

Introduction: Clinical decisions in chronic obstructive pulmonary disease (COPD) treatment often utilize serially assessed physiologic parameters and biomarkers. To better understand the reliability of these tests, we evaluated changes in commonly assessed biomarkers over 3 months in patients with clinically stable COPD. Methods: We performed an observational prospective cohort study of 89 individuals with clinically stable COPD, defined as no exacerbation history within 3 months of enrollment. Biomarkers included lung function and functional performance status, patient-reported outcomes of symptoms and health status, and blood markers of inflammation. The correlation between testing at baseline and at 3-month follow-up was reported as the intraclass correlation coefficient (ICC). "Outliers" had significant variability between tests, defined as >1.645 standard deviations between the two measurements. Differences in clinical features between outliers and others were compared. Results: Participants with COPD (n = 89) were 70.5 ± 6.7 years old, 54 (61%) male, had a 40 pack-year smoking history with 24.7% being current smokers, and postbronchodilator forced expiratory volume in one second (FEV1) 62.3 ± 22.7% predicted. The biomarkers with excellent agreement between the initial and the follow-up measurements were FEV1 (ICC = 0.96), Saint George's Respiratory Questionnaire (SGRQ) (ICC = 0.98), COPD Assessment Test (CAT) (ICC = 0.93) and C-reactive protein (CRP) (ICC = 0.90). By contrast, parameters showing less robust agreement were 6-minute walking distance (ICC = 0.75), eosinophil count (ICC = 0.77), erythrocyte sedimentation rate (ICC = 0.75) and white blood cell count (ICC = 0.48). Individuals with greater variability in biomarkers reported chronic bronchitis more often and had higher baseline SGRQ and CAT scores. Conclusion: Our study evaluated the stability of commonly assessed biomarkers in clinically stable COPD and showed excellent agreement between baseline and three-month follow-up values for FEV1, SGRQ, CAT and CRP. Individuals with chronic bronchitis and more symptomatic disease at baseline demonstrated greater variability in 3-month interval biomarkers.

Opium, phencyclidine, and crack cocaine smoking associations with lung and upper aerodigestive tract cancers: exploratory findings from a case-control study in Los Angeles County.

Background: Illicit drug use has become a global epidemic, yet it is unclear if drug smoking increases the risk of tobacco-related cancers.Objectives: We aimed to evaluate hypothesized associations between smoking three drugs - opium, phencyclidine (PCP) and crack cocaine and lung and upper aerodigestive tract (UADT) cancers.Methods: A population-based case-control study with 611 lung cancer cases (50% male), 601 UADT cancers cases (76% male), and 1,040 controls (60% male) was conducted in Los Angeles County (1999-2004). Epidemiologic data including drug smoking histories were collected in face-to-face interviews. Associations were estimated with logistic regressions.Results: Adjusting for potential confounders, ever vs. never crack smoking was positively associated with UADT cancers (aOR = 1.56, 95% CI: 1.05, 2.33), and a dose-response relationship was observed for lifetime smoking frequency (p for trend = .024). Heavy (> median) vs. never crack smoking was associated with UADT cancers (aOR = 1.81, 95% CI: 1.07, 3.08) and lung cancer (aOR = 1.58, 95% CI: 0.88, 2.83). A positive association was also observed between heavy PCP smoking and UADT cancers (aOR = 2.29, 95% CI: 0.91, 5.79). Little or no associations were found between opium smoking and lung cancer or UADT cancers.Conclusion: The positive associations between illicit drug use and lung and/or UADT cancers suggest that smoking these drugs may increase the risk of tobacco-related cancers. Despite the low frequency of drug smoking and possible residual confounding, our findings may provide additional insights on the development of lung and UADT cancers.

Impact of Marijuana Smoking on COPD Progression in a Cohort of Middle-Aged and Older Persons.

Background: Limited data are available regarding marijuana smoking's impact on the 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 3 groups based on self-reported marijuana use: current, former, or never marijuana smokers (CMSs, FMSs or NMSs, respectively). Longitudinal data were analyzed in participants with ≥2 visits over a period of ≥52 weeks. Measurements: We compared CMSs, FMSs, and NMSs, 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 forced expiratory volume in 1 second (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 CMSs or FMSs versus NMSs or between those with any lifetime amount of marijuana use versus NMSs. 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.

Isolated abnormal FEF75% detects unsuspected bronchiolar obstruction in CF children.

BACKGROUND: Physiologic detection of bronchiolar obstruction in children with cystic fibrosis (CF) may be clinically unsuspected because of normal routine spirometry despite bronchiectasis on lung CT. METHODS: Children from two accredited CF facilities had spirometry obtained every 3 months when clinically stable. Pre-bronchodilator maximum expiratory flow volume curves were retrospectively analyzed over 16 years to detect an isolated abnormal FEF75%, despite normal routine spirometry. RESULTS: At Miller Children's and Women's Hospital (MCWH), an abnormal FEF75% was initially detected in 26 CF children at age 7.5 ± 4 (SD) years despite normal routine spirometry initially. FEF75% remained an isolated abnormality for 2.5 ± 1.5 years after it was initially detected in these 26 CF children. At Cohen Children's Medical Center (CCMC), despite normal routine spirometry initially, abnormal FEF75% occurred in 13 children at age 11.7 ± 4.5 years, and abnormal FEF25-75% in 10 children at age 11.8 ± 5.3 years. CONCLUSIONS: FEF75% was most sensitive spirometric test for diagnosing both early and isolated progressive bronchiolar obstruction. Data from CCMC in older children demonstrated the simultaneous detection of abnormal FEF75% and FEF25-75% values consistent with greater bronchiolar obstruction when serial spirometry was initiated at an older age. IMPACT: There is very little published spirometric data regarding diagnosis of isolated small airways obstruction in CF children. FEF75% can easily detect unsuspected small airways obstruction in CF children with normal routine spirometry and bronchiectasis on lung CT and optimize targeted modulatory therapies.

Bronchodilator Responsiveness in Tobacco-Exposed People With or Without COPD.

BACKGROUND: Bronchodilator responsiveness (BDR) in obstructive lung disease varies over time and may be associated with distinct clinical features. RESEARCH QUESTION: Is consistent BDR over time (always present) differentially associated with obstructive lung disease features relative to inconsistent (sometimes present) or never (never present) BDR in tobacco-exposed people with or without COPD? STUDY DESIGN AND METHODS: We retrospectively analyzed data from 2,269 tobacco-exposed participants in the Subpopulations and Intermediate Outcome Measures in COPD Study with or without COPD. We used various BDR definitions: change of ≥ 200 mL and ≥ 12% in FEV1 (FEV1-BDR), change in FVC (FVC-BDR), and change in in FEV1, FVC or both (ATS-BDR). Using generalized linear models adjusted for demographics, smoking history, FEV1 % predicted after bronchodilator administration, and number of visits that the participant completed, we assessed the association of BDR group: (1) consistent BDR, (2) inconsistent BDR, and (3) never BDR with asthma, CT scan features, blood eosinophil levels, and FEV1 decline in participants without COPD (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 0) and the entire cohort (participants with or without COPD). RESULTS: Both consistent and inconsistent ATS-BDR were associated with asthma history and greater small airways disease (%parametric response mapping functional small airways disease) relative to never ATS-BDR in participants with GOLD stage 0 disease and the entire cohort. We observed similar findings using FEV1-BDR and FVC-BDR definitions. Eosinophils did not vary consistently among BDR groups. Consistent BDR was associated with FEV1 decline over time relative to never BDR in the entire cohort. In participants with GOLD stage 0 disease, both the inconsistent ATS-BDR group (OR, 3.20; 95% CI, 2.21-4.66; P < .001) and consistent ATS-BDR group (OR, 9.48; 95% CI, 3.77-29.12; P < .001) were associated with progression to COPD relative to the never ATS-BDR group. INTERPRETATION: Demonstration of BDR, even once, describes an obstructive lung disease phenotype with a history of asthma and greater small airways disease. Consistent demonstration of BDR indicated a high risk of lung function decline over time in the entire cohort and was associated with higher risk of progression to COPD in patients with GOLD stage 0 disease.

Clinical Implications of Low Absolute Blood Eosinophil Count in the SPIROMICS COPD Cohort.

BACKGROUND: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) considers blood eosinophil counts < 100 cells/µL (BEC≤100) in people with COPD to predict poor inhaled corticosteroid (ICS) responsiveness. However, the BEC≤100 phenotype is inadequately characterized, especially in advanced COPD. RESEARCH QUESTION: Are there differences between GOLD group D patients with high BEC and those with low BEC regarding baseline characteristics and longitudinal outcomes? STUDY DESIGN AND METHODS: We used multivariable mixed models and logistic regression to contrast clinical characteristics and outcomes of BEC≤100 vs BEC > 100 (BEC100+) in all subjects with COPD (n = 1,414) and GOLD group D subjects (n = 185) not receiving ICS. RESULTS: We identified n = 485 with BEC≤100 (n = 61 GOLD group D) and n = 929 people with BEC100+ (n = 124 GOLD group D). BEC≤100 status was stable at 6 weeks and approximately 52 weeks (intraclass correlations of 0.78 and 0.71, respectively). Compared with BEC100+, BEC≤100 comprised more women, with greater current smoking, and less frequent childhood asthma. Among all analyzed participants, the two BEC-defined subsets showed similar rates of lung function decline (mean slope, BEC≤100 vs BEC100+, -50 vs -39 mL/y; P = .140), exacerbations (0.40 vs 0.36/y; P = .098), subsequent ICS initiation (2.5% vs 4.4%; P = .071), and mortality (7.8% vs 8.4%; P = .715). However, in GOLD group D, people with BEC≤100 showed higher exacerbation rates within 365 days of enrollment (0.62 vs 0.33/y; P = .002) and total follow-up (1.16 vs 0.83/y; P = .014). They also had greater lung function decline (mean slope of -68 mL/y vs -23 mL/y; P = .036) and had greater emphysema at baseline (voxels < 950 Hounsfield units at total lung capacity of 7.46% vs 4.61%; P = .029). INTERPRETATION: In non-ICS-treated GOLD group D COPD, people with BEC≤100 had more baseline emphysema, prospective exacerbations, and lung function decline. Our analysis has identified a particularly vulnerable subpopulation of people with COPD, suggesting the need for studies focused specifically on their therapeutic treatment. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT01969344; URL: www. CLINICALTRIALS: gov.

Chronic Obstructive Pulmonary Disease is Not Associated with In-Hospital Mortality in COVID-19: An Observational Cohort Analysis.

Background: Chronic obstructive pulmonary disease (COPD) is associated with worsened outcomes in COVID-19 (coronavirus disease 2019). However, data remain fraught with heterogeneity and bias from comorbid conditions. Additionally, data on the impact of COPD-specific factors, such as pre-hospital medications and pulmonologist involvement, remain sparse. Objective: We report a single-center analysis of COPD patients hospitalized with COVID-19 compared to those without COPD. Primary outcomes include ICU admission, mechanical ventilation, and in-hospital mortality. Methods: We evaluated all patients ≥40 years admitted with PCR-confirmed COVID-19 between February 2020 and February 2021. COPD was defined by documented ICD-10 diagnosis of COPD, confirmed smoking history, and active bronchodilator use. We compared outcomes between COPD patients and the remainder of the COVID-19 cohort. Multivariable analyses were adjusted for age, sex, smoking status, and comorbid conditions. Results: Of 1537 hospitalized COVID-19 patients, 122 (7.9%) carried a diagnosis of COPD. The COPD cohort was older (74 ± 13 vs 66 ± 15 years, P < 0.001) and more often former smokers (P < 0.001). Comorbid conditions including diabetes, cardiovascular disease, and kidney disease were more prevalent in the COPD group (P < 0.001). After adjusting for comorbid conditions, the COPD cohort had higher severity scores and trended towards fewer hospital-free days. Among patients with COPD, pre-hospital use of aspirin was associated with decreased ICU admissions (aHR 0.56, P = 0.049) and mechanical ventilation (aHR 0.25, P = 0.008), while LAMAs (long-acting muscarinic antagonists) were associated with decreased in-hospital mortality (aHR 0.34, P = 0.047). Involvement of pulmonology in pre-hospital management of COPD was not found to significantly affect outcomes. Conclusion: When corrected for comorbid illnesses, COPD was associated with more severe disease but not with increased ICU admission, mechanical ventilation, or in-hospital mortality rates. Among COPD patients, prehospital treatment with aspirin and COPD-directed therapies were associated with improved outcomes.

Cannabis consumption is associated with lower COVID-19 severity among hospitalized patients: a retrospective cohort analysis.

BACKGROUND: While cannabis is known to have immunomodulatory properties, the clinical consequences of its use on outcomes in COVID-19 have not been extensively evaluated. We aimed to assess whether cannabis users hospitalized for COVID-19 had improved outcomes compared to non-users. METHODS: We conducted a retrospective analysis of 1831 patients admitted to two medical centers in Southern California with a diagnosis of COVID-19. We evaluated outcomes including NIH COVID-19 Severity Score, need for supplemental oxygen, ICU (intensive care unit) admission, mechanical ventilation, length of hospitalization, and in-hospital death for cannabis users and non-users. Cannabis use was reported in the patient's social history. Propensity matching was used to account for differences in age, body-mass index, sex, race, tobacco smoking history, and comorbidities known to be risk factors for COVID-19 mortality between cannabis users and non-users. RESULTS: Of 1831 patients admitted with COVID-19, 69 patients reported active cannabis use (4% of the cohort). Active users were younger (44 years vs. 62 years, p < 0.001), less often diabetic (23.2% vs 37.2%, p < 0.021), and more frequently active tobacco smokers (20.3% vs. 4.1%, p < 0.001) compared to non-users. Notably, active users had lower levels of inflammatory markers upon admission than non-users-CRP (C-reactive protein) (3.7 mg/L vs 7.6 mg/L, p < 0.001), ferritin (282 µg/L vs 622 µg/L, p < 0.001), D-dimer (468 ng/mL vs 1140 ng/mL, p = 0.017), and procalcitonin (0.10 ng/mL vs 0.15 ng/mL, p = 0.001). Based on univariate analysis, cannabis users had significantly better outcomes compared to non-users as reflected in lower NIH scores (5.1 vs 6.0, p < 0.001), shorter hospitalization (4 days vs 6 days, p < 0.001), lower ICU admission rates (12% vs 31%, p < 0.001), and less need for mechanical ventilation (6% vs 17%, p = 0.027). Using propensity matching, differences in overall survival were not statistically significant between cannabis users and non-users, nevertheless ICU admission was 12 percentage points lower (p = 0.018) and intubation rates were 6 percentage points lower (p = 0.017) in cannabis users. CONCLUSIONS: This retrospective cohort study suggests that active cannabis users hospitalized with COVID-19 had better clinical outcomes compared with non-users, including decreased need for ICU admission or mechanical ventilation. However, our results need to be interpreted with caution given the limitations of a retrospective analysis. Prospective and observational studies will better elucidate the effects cannabis use in COVID-19 patients.

A Close Look at Vaping in Adolescents and Young Adults in the United States.

Vaping by adolescents and young adults is a legitimate concern as there is a risk that some may start smoking and that electronic cigarette (EC) use may have adverse effects in the developing lungs of adolescents. This commentary provides updated information on vaping patterns among adolescents and young adults in the United States, as well as the impact of EC usage on respiratory health. EC use has surged greatly among high school students and young adults over the last decade but fortunately has declined significantly since its peak in 2019. During the same time period, smoking rates have constantly fallen to new low record levels. These trends argue against EC use as a gateway to smoking. Most EC usage is infrequent and unlikely to increase a person's risk of negative health consequences. Furthermore, the majority of EC usage has happened among those who have previously smoked. There is a dearth of data on the long-term health implications of EC usage in adolescents and young adults. We do not know whether short-term or intermittent use of EC in youth can lead to negative health outcomes in adulthood, and long-term high-quality studies in well-defined groups are needed. Although vaping has been linked to respiratory symptoms, they tend to be transient and of uncertain significance. This commentary provides up-to-date information so health care providers can give objective and responsible medical advice on EC usage.

Reversible Airflow Obstruction Predicts Future Chronic Obstructive Pulmonary Disease Development in the SPIROMICS Cohort: An Observational Cohort Study.

Rationale: Chronic obstructive pulmonary disease (COPD) is defined by fixed spirometric ratio, FEV1/FVC < 0.70 after inhaled bronchodilators. However, the implications of variable obstruction (VO), in which the prebronchodilator FEV1/FVC ratio is less than 0.70 but increases to 0.70 or more after inhaled bronchodilators, have not been determined. Objectives: We explored differences in physiology, exacerbations, and health status in participants with VO compared with reference participants without obstruction. Methods: Data from the SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study) cohort were obtained. Participants with VO were compared with reference participants without obstruction. Measurements and Main Results: We assessed differences in baseline radiographic emphysema and small airway disease at study entry, baseline, and change in lung function by spirometry, functional capacity by 6-minute walk, health status using standard questionnaires, exacerbation rates, and progression to COPD between the two groups. All models were adjusted for participant characteristics, asthma history, and tobacco exposure. We assessed 175 participants with VO and 603 reference participants without obstruction. Participants with VO had 6.2 times the hazard of future development of COPD controlling for other factors (95% confidence interval, 4.6-8.3; P < 0.001). Compared with reference participants, the VO group had significantly lower baseline pre- and post-bronchodilator (BD) FEV1, and greater decline over time in post-BD FEV1, and pre- and post-BD FVC. There were no significant differences in exacerbations between groups. Conclusions: Significant risk for future COPD development exists for those with pre- but not post-BD airflow obstruction. These findings support consideration of expanding spirometric criteria defining COPD to include pre-BD obstruction. Clinical trial registered with www.clinicaltrials.gov (NCT01969344).

Inhaled Marijuana and the Lung.

Although vaping has recently increased as a mode of inhaling marijuana and has been associated with numerous and sometimes fatal cases of acute severe lung injury, smoking remains the most common method of inhaling marijuana and has been studied more extensively. Smoking marijuana has been shown to produce modest but significant short-term bronchodilation both in healthy subjects and in those with asthma. Long-term effects of habitual marijuana smoking include the following: (1) symptoms of chronic bronchitis (increased cough, sputum production, and wheezing); (2) modest effects on lung function in cross-sectional studies (no significant decrease in FEV1 but mild reductions in FEV1/forced vital capacity ratio, an increase in forced vital capacity and other lung volumes, reductions in specific airway conductance, and variable effects of maximal midexpiratory flow rates and diffusing capacity); and (3) variable effects on age-related decline in FEV1 in longitudinal studies. Most cohort and case-control studies have failed to show that marijuana smoking is a significant risk factor for lung cancer despite the presence of procarcinogenic components in marijuana smoke, although further study is warranted. The question whether marijuana smoking is associated with asthma is unclear and requires further investigation. Although delta-9 tetrahydrocannabinol, the principal psychoactive component of marijuana, has immunomodulatory properties that hypothetically could increase the risk of pneumonia, the few available studies in marijuana smokers have failed to find an increased risk of pneumonia in immunocompetent users, although effects in immunosuppressed individuals have been variable.

The disconnect between visual assessment of air trapping and lung physiology for assessment of small airway disease in scleroderma-related interstitial lung disease: An observation from the Scleroderma Lung Study II Cohort.

Objective: To explore the presence of small airway disease (SAD) and emphysema in scleroderma-related interstitial lung disease (SSc-ILD) and to evaluate the physiologic and clinical correlates of SAD in SSc-ILD. Methods: Thoracic high-resolution computed tomography (HRCT) images obtained from the Scleroderma Lung Study II (SLSII) participants were reviewed by a group of thoracic radiologists. The presence of SAD was assessed by visual assessment for air trapping. HRCT scans were also evaluated for the presence of emphysema. The association of the presence of air trapping and emphysema with physiological measures of airway disease and clinical variables was evaluated. Results: A total of 155 baseline HRCT scans were reviewed. For assessment of air trapping, images needed to be adequate end-expiratory examinations, leaving 123 scans. Air trapping was seen in 13/123 (10.6%) of the SSc-ILD cohort and was independent of smoking history, asthma or the presence of gastroesophageal reflux. Air trapping on HRCT was not associated with physiologic evidence of SAD. We also identified 8/155 (5.2%) patients with emphysema on HRCT, which was independent of SAD and found mostly in prior smokers. Conclusion: We report the first study of air trapping on standardized, high-quality HRCT images as a reflection of SAD in a relatively large, well characterized SSc-ILD cohort. The presence of SAD in non-smoking SSc-ILD patients supports that SSc may cause not only restrictive lung disease (SSc-ILD), but also, to a lesser extent, obstructive disease. Physiologic measures alone may be inadequate to detect airway disease in patients with SSc-ILD.