Here we document what we believe is the first known case of pulmonary mucormycosis associated with medical marijuana use.A 66-year-old man presented to the emergency department with a two-month history of shortness of breath, cough, rust-colored sputum, night sweats and a 20 pound unintentional weight loss. He had a history of poorly controlled type 2 diabetes mellitus and chronic lower back pain. He was a 1-pack-per-day smoker for thirty years. Three months prior to presentation, he had started smoking medical marijuana for relief of his chronic back pain. The marijuana was obtained from a medical dispensary. He previously worked as an auto mechanic but had retired six months prior to presentation. On physical examination, respiratory rate was 24 breaths per minute with an SpO2 of 98% on high flow oxygen.There were bilateral coarse breath sounds on pulmonary examination. White blood cell count was 17.3 × 103 /μL. Blood glucose was 348 mg/dL and hemoglobin A1c was 10.0%. Plain film chest x-ray showed multiple large oval opacities in both lungs. Computed tomography of the chest showed multiple bilateral large ground glass opacities with surrounding areas of consolidation. Infectious workup including blood, urine and sputum cultures was negative.Vasculitis and autoimmune workups were negative. Bronchoalveolar lavage cultures grew normal oral flora. The patient was treated with a broad spectrum antibiotic regimen including vancomycin, piperacillin-tazobactam and levofloxacin without clinical improvement. The patient was intubated and underwent video-assisted thoracoscopic surgery on hospital day 7. The lungs were noted to have areas of severely friable and inflamed lung parenchyma and pleura.Culture of the biopsied lung tissue grew Rhizopus species.He was started on liposomal amphotericin B and micafungin. His oxygen requirements decreased and he was extubated on post-operative day 12.

He received two weeks of parenteral amphotericin and was then transitioned to oral posaconazole after clinical improvement. Repeat CT one month later showed stable size of the cavities and continued improvement of the patient’s respiratory function. He was readmitted two months later with hemoptysis which stopped spontaneously. One month after discharge from the second hospitalization, he died of massive pulmonary hemorrhage despite continued therapy with posaconazole.Mucormycosis is an angioinvasive disease caused by species of the order Mucorales,grow cannabis most commonly of the genera Rhizopus, Mucor, and Rhizomucor. Mucormycosis most commonly manifests as rhino-orbitalcerebral infection but may also present as pulmonary, cutaneous, gastrointestinal, central nervous system or disseminated infection. Disease is typically seen in immunocompromised patients, including those with Diabetes mellitus, particularly in the setting of diabetic ketoacidosis.High plasma glucose and iron concentrations upregulate expression of glucose-regulated protein 78,a heat shock protein present on host endothelial cells. CotH is a fungal spore coat protein present in pathogenic Mucorales species and acts as the fungal ligand which binds to GRP78, inducing endocytosis and leading to angioinvasion. Mucorales are widespread and are can be found where humid organic matter is exposed to heat, such as in composting vegetation or rotting fruit. Marijuana, though known to contain Mucorales species, has not previously been associated with mucormycosis. Like all Zygomycetes, Mucorales produce spores that are released into the environment where they remain airborne and may eventually gain entry to the body via inhalation. Definitive diagnosis is made by histopathological, cytopathological, or direct microscopic visualization in affected organs. Hyphae of mucorales species are easily damaged during biopsy or tissue preparation and thus microscopic or histopathological examination is usually more useful than culture. In a population studied by Roden et al., diabetics represented 36% of published mucormycosis cases. Among this diabetic population, 43% presented with rhinocerebral involvement and 16% presented with pulmonary involvement. Mortality among all patients was 76% in patients with pulmonary infection. Due to the high mortality, treatment must be initiated as soon as the diagnosis is suspected rather than waiting for definitive diagnosis.

Surgical debridement should be considered but is not always feasible, especially when necrotic tissue abuts important anatomic structures, as was the case in our patient.First line treatment is amphotericin B lipid complex at a daily dose of > 5 mg/kg or liposomal amphotericin B at a daily dose of > 3 mg/ kg. Patients with impaired renal function, those who fail treatment with amphotericin or develop major adverse effects should be treated with posaconazole 200 mg four times per day. Isavuconazole is a second-generation triazole that has shown promise in treating invasive pulmonary aspergillosis and mucormycosis and may have a more favorable side effect profile than current first-line drugs. Aggressive surgical resection should be considered in patients who do not show clinical improvement within 48–72 hours of starting appropriate medical therapy. Wedge resection may be considered if disease is limited but a lobectomy is often required and pneumonectomy may be necessary for extensive disease. A review of 87 cases of localized pulmonary mucormycosis without evidence of dissemination showed a 44% overall survival rate with a mortality rate of 55% in patients receiving medical therapy alone versus a mortality rate of 27% in patients who underwent surgery, most of whom also received antifungal therapy. These results may be biased by the fact that patients who have extensive, multilobar disease at the time of diagnosis may not be deemed surgical candidates due to the widespread nature of their infection, as was the case with our patient. Numerous previous case reports have described cases of invasive pulmonary fungal infection associated with marijuana smoking in immunocompromised patients.Most of these patients had hematologic malignancies, a well-known risk factor for invasive fungal disease. Our patient had no known malignancy. However, we suspect that the combination of poorly controlled diabetes and years of cigarette smoking leading to emphysema and increased susceptibility to pulmonary infection put him at increased risk of invasive fungal disease. We hypothesize that he inhaled airborne spores while smoking marijuana, leading to overwhelming pulmonary infection. Unfortunately, we were unable to perform microbiologic testing of the suspect marijuana due to the delayed presentation after onset of symptoms. Patients seeking pain relief by smoking marijuana may have conditions putting them at risk for opportunistic infections. In Canada and the Netherlands, where medical marijuana is dispensed under the regulation of the federal government, gamma-irradiation is used to sterilize medical marijuana before it is distributed to patients.

This practice is not yet commonplace in the United States, where rules and regulations vary state to state.Until sterilization of medical marijuana becomes routine in the United States, physicians should counsel immunocompromised patients, including those with poorly controlled diabetes, that smoking medical marijuana puts them at risk for overwhelming pulmonary infection due to invasive fungi.Tobacco use is the leading cause of preventable morbidity and mortality in the US.Cannabis  is the most prevalent and increasingly used illicit drug in the United States.Accumulating evidence consistently demonstrates that heavy or habitual marijuana use is associated with numerous short- and long-term deleterious health consequences,including but not limited to addiction,altered brain structure and connectivity,impaired memory and neuropsychological decline,psychosis,poor educational attainment,symptoms of chronic bronchitis,impaired motor coordination and traffic collisions,and diminished life satisfaction.Marijuana and tobacco use share potential common environmental influences,common mode of use,and are frequently used together. One study suggested that, during a lifetime period, 57.9% of those who ever used tobacco reported ever using marijuana and 90% of those who ever used marijuana reported ever using tobacco.Another study showed that, during the past month, the prevalence of marijuana use was 17.8% among past-month tobacco users and the prevalence of tobacco use was 69.6% among past-month marijuana users.Across the lifespan, either concurrently or at different times, prior use of either tobacco or marijuana substantially elevates the risk of subsequent initiation of the other and is associated with the progression to tobacco and marijuana dependence.Heightened susceptibility has been linked to genetic predispositions and putative neurobiological mechanisms that may facilitate increased urge and intensity of using each substance,promote progression to other types of illicit drugs,and precipitate relapse or hamper the success of quitting use of either substance.

Self-rated health  is a brief, validated proxy measure of overall health status.Among a variety of populations, SRH is strongly predictive of future morbidity and mortality, even after extensive adjustment for many covariates such as illness, depression status, functional and cognitive decline, and health care utilization.Although SRH is generated through a subjective, contextual, and non-arbitrary process, research shows that individuals with “poor” SRH have a two-fold higher mortality risk than that of those with “excellent” SRH.SRH has been adopted as a chronic disease indicator for overarching conditions and as a Foundation Health Measure for the Healthy People 2020 objectives that monitor progress toward promoting health, preventing disease and disability, eliminating disparities, and improving quality of life.Although epidemiologic studies have evaluated effects of marijuana and tobacco use on many health outcomes, combined patterns of marijuana and tobacco use and their impact on overall health are uncertain. To our knowledge, no study has assessed regular marijuana smoking, with and without current tobacco use, in relation to suboptimal SRH among US adult ever users of marijuana. Ever users of marijuana are an important population of concern. Given that habitual marijuana use may affect health outcomes, and that tobacco use is a serious public health problem,such a study may provide observational evidence to inform prevention efforts. Therefore, we sought to examine patterns of regular marijuana smoking and current tobacco use and their associations with suboptimal SRH among a nationally representative household-based survey sample of US adult ever users of indoor cannabis grow system by analyzing data from the 2009– 2012 National Health and Nutrition Examination Survey .We estimated the crude prevalence for the four mutually exclusive groups of regular marijuana use and current tobacco use, both overall and among age subgroups. We also calculated the age-adjusted prevalence by the direct method to the year 2000 Census population for these patterns among participants and subgroups stratified by sex, race or ethnicity, education, marital status, alcohol use, physical activity, BMI, health care access, and a history of cardiovascular diseases, diabetes, arthritis, and cancer.We produced unadjusted and adjusted prevalence ratios with multivariable generalized linear models for survey data.We used the variable for patterns of regular marijuana smoking and current tobacco use as the predictor and suboptimal SRH as the outcome while adjusting for sociodemographic, behavioral, and health-related risk factors.

To obtain additional information on current regular marijuana smoking, we estimated the prevalence for reporting suboptimal SRH by status of previous 30-day and 60-day regular marijuana smoking among regular marijuana smokers with and without current tobacco use.To estimate relative excess risk due to interaction  between current tobacco use and regular marijuana smoking,additional analyses were performed by using current tobacco use and regular marijuana smoking as two independent variables with their interaction term in regression models. Weighted analyses were performed to account for the complex sampling design to provide nationally representative estimates.Consistent with previous studies, our results show that approximately 40% of ever users of marijuana were currently using tobacco. Our findings further indicate that, when compared to non-regular marijuana smoking without current tobacco use, regular marijuana smoking without current tobacco use was significantly associated with a 34% increased prevalence ratio of reporting suboptimal SRH. A greater prevalence ratio was observed for current tobacco use and regular marijuana smoking,as well as current tobacco use and non-regular marijuana smoking.Results from previous research on effects of marijuana use are inconclusive. One study reported an improvement in capacity for recall of information was associated with cessation of marijuana use.Other studies showed persistent marijuana use was associated with long-lasting cognitive impairment, and that cessation of marijuana use does not fully restore neuropsychological functioning, especially among those marijuana users of adolescentonset.Another study found that marijuana use for up to 20 years was associated with periodontal disease but not with other physical health measures in early midlife.In this study, we did not detect any appreciable difference in reporting suboptimal SRH among regular marijuana smokers with and without current tobacco stratified by status of their past 30- or 60-day regular marijuana smoking. Moreover, the results from this and previous studies show that many unhealthy lifestyle health behaviors  are interrelated. Such behaviors frequently co-occur and are often associated with worse health outcomes.The findings of our study have a number of important public health implications. First, SRH is included in the public health key metrics such as Healthy People 2020 and CDC Healthy Day for guiding disease prevention and health promotion and for measuring health-related quality of life in the US population.Second, reducing tobacco use and initiation among youth and adults is an important public health goal.