Topographic diversity of the respiratory tract mycobiome and alteration in HIV and lung disease.

RATIONALE: Microbiome studies typically focus on bacteria, but fungal species are common in many body sites and can have profound effects on the host. Wide gaps exist in the understanding of the fungal microbiome (mycobiome) and its relationship to lung disease. OBJECTIVES: To characterize the mycobiome at different respiratory tract levels in persons with and without HIV infection and in HIV-infected individuals with chronic obstructive pulmonary disease (COPD). METHODS: Oral washes (OW), induced sputa (IS), and bronchoalveolar lavages (BAL) were collected from 56 participants. We performed 18S and internal transcribed spacer sequencing and used the neutral model to identify fungal species that are likely residents of the lung. We used ubiquity-ubiquity plots, random forest, logistic regression, and metastats to compare fungal communities by HIV status and presence of COPD. MEASUREMENTS AND MAIN RESULTS: Mycobiomes of OW, IS, and BAL shared common organisms, but each also had distinct members. Candida was dominant in OW and IS, but BAL had 39 fungal species that were disproportionately more abundant than in the OW. Fungal communities in BAL differed significantly by HIV status and by COPD, with Pneumocystis jirovecii significantly overrepresented in both groups. Other fungal species were also identified as differing in HIV and COPD. CONCLUSIONS: This study systematically examined the respiratory tract mycobiome in a relatively large group. By identifying Pneumocystis and other fungal species as overrepresented in the lung in HIV and in COPD, it is the first to determine alterations in fungal communities associated with lung dysfunction and/or HIV, highlighting the clinical relevance of these findings. Clinical trial registered with www.clinicaltrials.gov (NCT00870857).

Pulmonary Function in HIV-Infected Recreational Drug Users in the Era of Anti-Retroviral Therapy.

BACKGROUND: Individuals with HIV infection commonly have pulmonary function abnormalities, including airflow obstruction and diffusion impairment, which may be more prevalent among recreational drug users. To date, the relationship between drug use and pulmonary function abnormalities among those with HIV remains unclear. OBJECTIVE: To determine associations between recreational drug use and airflow obstruction, diffusion impairment, and radiographic emphysema in men and women with HIV. METHODS: Cross-sectional analysis of pulmonary function and self-reported recreational drug use data from a cohort of 121 men and 63 women with HIV. Primary outcomes were the presence (yes/no) of: 1) airflow obstruction, (pre- or post-bronchodilator forced expiratory volume in 1 second/forced vital capacity<0.70); 2) moderate diffusion impairment (diffusing capacity for carbon monoxide <60% predicted); and 3) radiographic emphysema (>1% of lung voxels <-950 Hounsfield units). Exposures of interest were frequency of recreational drug use, recent (since last study visit) drug use, and any lifetime drug use. We used logistic regression to determine associations between recreational drug use and the primary outcomes. RESULTS: HIV-infected men and women reported recent recreational drug use at 56.0% and 31.0% of their study visits, respectively, and 48.8% of men and 39.7% of women reported drug use since their last study visit. Drug use was not associated with airway obstruction or radiographic emphysema in men or women. Recent crack cocaine use was independently associated with moderate diffusion impairment in women (odds ratio 17.6; 95% confidence interval 1.3-249.6, p=0.03). CONCLUSIONS: In this cross-sectional analysis, we found that recreational drug use was common among HIV-infected men and women and recent crack cocaine use was associated with moderate diffusion impairment in women. Given the increasing prevalence of HIV infection, any relationship between drug use and prevalence or severity of chronic pulmonary diseases could have a significant impact on HIV and chronic disease management.

Sociodemographic characteristics of cannabis smokers and the experience of cannabis withdrawal.

BACKGROUND: Cannabis withdrawal can be a negative reinforcer for relapse, but little is known about its association with demographic characteristics. OBJECTIVES: Evaluate the association of demographic characteristics with the experience of cannabis withdrawal. METHODS: Retrospective self-report of a "serious" cannabis quit attempt without formal treatment in a convenience sample of 104 non-treatment-seeking, adult cannabis smokers (mean age 35 years, 52% white, 78% male) with no other current substance use disorder (except tobacco) or chronic health problems. Reasons for quitting, coping strategies to help quit, and 18 specific withdrawal symptoms were assessed by questionnaire. RESULTS: Among withdrawal symptoms, only anxiety, increased sex drive, and craving showed significant associations with age, race, or sex. Women were more likely than men to report a physical withdrawal symptom (OR = 3.2, 95% CI = .99-10.4, p = .05), especially upset stomach. There were few significant demographic associations with coping strategies or reasons for quitting. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: This small study suggests that there are few robust associations between demographic characteristics and cannabis withdrawal. Future studies with larger samples are needed. Attention to physical withdrawal symptoms in women may help promote abstinence.

Quitting among non-treatment-seeking marijuana users: reasons and changes in other substance use.

This study examines the self-reported reasons for quitting marijuana use, changes in other substance use during the quit attempt, and reasons for the resumption of use in 104 non-treatment-seeking adult marijuana smokers. Reasons for quitting were shown to be primarily motivated by concerns about the negative impact of marijuana on health and on self- and social image. The spontaneous quitting of marijuana use is often associated with an increase in the use of legal substances such as alcohol, tobacco, and sleeping aids, but not with the initiation of new substance use. These findings suggest areas for further research on spontaneous recovery from marijuana use.

Cannabis withdrawal among non-treatment-seeking adult cannabis users.

This study investigates the clinical significance of a cannabis withdrawal syndrome in 104 adult, non-treatment-seeking, primarily cannabis users who reported at least one serious attempt to stop using cannabis. Retrospective self-report data were obtained on eighteen potential cannabis withdrawal symptoms derived from the literature, including co-occurrence, time course, and any actions taken to relieve the symptom. Study findings provide evidence for the clinical significance of a cannabis withdrawal syndrome, based on the high prevalence and co-occurrence of multiple symptoms that follow a consistent time course and that prompt action by the subjects to obtain relief, including serving as negative reinforcement for cannabis use.

Strategies for quitting among non-treatment-seeking marijuana smokers.

This study examines self-reported quitting strategies used by adult, non-treatment-seeking marijuana smokers. Sixty-five subjects rated the use and effectiveness of thirteen strategies on a self-developed instrument, the Marijuana Quit Questionnaire. The strategies clustered into three categories/factors, whether grouped by principal components analysis, mean helpfulness rating, or frequency of endorsement: Change Environment, Seeking Organized/Professional Help, and Social Support. Changing one's environment was rated as most helpful while seeking help from professionals was the least helpful. Clinicians are likely to see marijuana users in their practice and should be proactive in offering assistance, incorporating the strategies reported here into treatment plans for their marijuana-using patients.

A pilot study of all-trans-retinoic acid for the treatment of human emphysema.

Emphysema results from progressive destruction of alveolar septae and was considered irreversible until all-trans-retinoic acid (ATRA) was shown to reverse anatomic and physiologic signs of emphysema in a rat model. To evaluate the feasibility of ATRA as a clinical therapy, 20 patients with severe emphysema were enrolled into a randomized, double-blind, placebo-controlled pilot study. Participants included 16 male and 4 female former smokers, two with alpha(1)-antitrypsin deficiency. Patients were treated with either 3 mo of ATRA (50 mg/m(2)/d) or 3 mo of placebo, followed by a 3-mo crossover phase. Plasma drug levels were followed and outcome measures included serial pulmonary function tests, blood gases, lung compliance, computed tomography (CT) imaging, and quality of life questionnaires. In general, treatment was well tolerated and associated with only mild side effects including skin changes, transient headache, hyperlipidemia, transaminites, and musculoskeletal pains. Plasma drug levels varied considerably between subjects and decreased significantly over time in 35% of the participants. Physiologic and CT measurements did not change appreciably in response to therapy. We conclude that ATRA is well tolerated in patients with emphysema, and trials evaluating higher doses, longer treatment, or different dosing schedules are feasible.