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People living with HIV (PLWH) are at increased risk for noncommunicable diseases such as lung disease in part due to opportunistic infections including pneumonia. HIV infection is associated with increased prevalence of impaired lung function and abnormal gas exchange. Alcohol use disorder (AUD) is exceedingly common in PLWH and is associated with higher risk of pneumonia in PLWH. Alcohol use may lead to lung damage through several mechanisms. Data on the long-term effect of AUD on pulmonary function in PLWH are sparse and conflicting. To evaluate this relationship, we conducted a cross-sectional analysis of adult PLWH in care in Louisiana. We hypothesized that chronic alcohol use would be associated with subsequent pulmonary dysfunction in a dose-dependent fashion. All participants performed standardized spirometry on study entry. In total, 350 participants with acceptable spirometry were included in this analysis. Thirty-one percent of participants were female. Women reported less lifetime alcohol use and less smoking; however, they reported more chronic respiratory symptoms. In adjusted models, total lifetime alcohol use was not associated with spirometry measures of pulmonary function. HIV-related variables (CD4 count and viral load) were also not associated with measures of pulmonary function. We then conducted sex-stratified analyses to eliminate residual confounding of sex and similarly found no association of total lifetime alcohol use and pulmonary function. We found no association of AUDIT score or early life alcohol use and pulmonary function. In latent class factor analysis, current heavy alcohol use was associated with lower measures of pulmonary function as compared to former heavy alcohol use. In summary, in this cohort of New Orleanian men and women living with HIV with robust measures of alcohol use, though total lifetime alcohol use and early life alcohol use were not associated with pulmonary function, current heavy alcohol use was associated with impaired pulmonary function., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The intestinal microbiota generates many different metabolites which are critical for the regulation of host signaling pathways. In fact, a wide-range of diseases are associated with increased levels of local or systemic microbe-derived metabolites. In contrast, certain bacterial metabolites, such as tryptophan metabolites, are known to contribute to both local and systemic homeostasis. Chronic alcohol consumption is accompanied by alterations to intestinal microbial communities, and their functional capacities. However, little is known about the role of alcohol-associated dysbiosis on host defense against bacterial pneumonia. Our previous work using fecal transplantation demonstrated that alcohol-associated intestinal dysbiosis, independent of ethanol consumption, increased susceptibility to Klebsiella pneumonia. Here, we demonstrate that intestinal microbiota treatments mitigate the increased risk of alcohol-associated pneumonia. Treatment with the microbial metabolite indole or with probiotics reduced pulmonary and extrapulmonary bacterial burden, restored immune responses, and improved cellular trafficking required for host defense. Protective effects were, in part, mediated by aryl hydrocarbon receptors (AhR), as inhibition of AhR diminished the protective effects. Thus, alcohol appears to impair the production/processing of tryptophan catabolites resulting in immune dysregulation and impaired cellular trafficking. These data support microbiota therapeutics as novel strategies to mitigate the increased risk for alcohol-associated bacterial pneumonia., (© 2021. The Author(s).)

People living with the human immunodeficiency virus (PLWH) may be particularly vulnerable to the consequences of non-tuberculous mycobacteria (NTM) given their defective T cell-mediated immunity and high rates of structural lung disease. To determine the prevalence of NTM in PLWH hospitalized with pneumonia and to assess the potential predictors of NTM isolation. Secondary data analysis of a prospective cohort study (2007-2011) of early bronchoscopy in PLWH presenting with suspected pneumonia was undertaken. Subjects with any species of NTM, henceforth described as 'NTM of undetermined significance' (NTM-US), isolated from sputum or bronchoalveolar lavage fluid (BALF), were included in the analysis. Potential predictors were chosen a priori. Among 196 HIV-infected subjects hospitalized with pneumonia, 96 had respiratory samples positive for NTM-US, with 91% of all NTM-US isolated from sputum compared with BALF. The overall prevalence of NTM-US was 49% (96/196). More NTM subjects were smokers ( P = 0.08), with a history of chronic obstructive pulmonary disease ( P = 0.08). Among those with pathogenic NTM, 39% (34/88) would have met American Thoracic Society microbiologic criteria for NTM pulmonary disease (17% of total cohort). Respiratory cultures, predominantly sputum samples, were positive for NTM-US in 45% of HIV-infected subjects admitted to hospital for pneumonia. Further research is needed to characterize the prevalence of NTM in PLWH and help establish specific diagnostic criteria in this population. .

Background: Pneumonia is common in persons living with the human immunodeficiency virus (HIV) (PLWH). Alcohol, cocaine, and marijuana impact pneumonia pathogenesis. We hypothesized that substance use was independently associated with pneumonia severity in PLWH and modified the effect of alcohol on pneumonia severity. Methods: Retrospective data analysis of PLWH admitted with a diagnosis of pneumonia was conducted. Alcohol use disorder was defined by the Alcohol Use Disorders Identification Test score ≥14. Drug use was quantified by self-report. Pneumonia severity was defined by the pneumonia severity index (PSI). Multivariable linear regression was used to test independent associations with pneumonia severity and effect modification by sex. Results: Of 196 PLWH, the mean age was 44 (SD = 9) years and the majority were men (71%). Ten percent ( n =  19) of subjects met criteria for an alcohol use disorder (AUD). In subjects reporting alcohol use, 25% reported concomitant crack/cocaine use and 16% reported marijuana use. PSI scores were higher with lifetime use of crack/cocaine (mean PSI: 63.1 vs. 57.3, P  = .06) and/or injection drug use (68.4 vs. 54.9, P  = .04). PSI scores were lower with active marijuana use (51.5 vs. 62.2, P  = .01). There was no significant difference in clinical outcomes. Sex modified the effect of drug use on PSI, with greater PSI scores in women with an AUD (β = 58.1, 95% confidence interval [CI]: 46.7 to 69.5, P  < .01), whereas active marijuana use mitigated the effect of AUD on PSI in men (β = -12.7, 95% CI: -18.8 to -6.6, P  < .01). Conclusions: Active alcohol and/or crack/cocaine use was associated with increased pneumonia severity in PLWH, with less severe pneumonia with marijuana use. Alcohol and marijuana effects on pneumonia severity differed by sex, with increased PSI in women and decreased PSI in men with concomitant marijuana and AUD.

Purpose: Pneumonia is common and more severe in human immunodeficiency virus (HIV)-infected patients. Alcohol consumption in pneumonia patients without HIV is associated with excess mortality and morbidity. However, studies are lacking on the impact of alcohol on pneumonia and HIV. Our goal was to determine if alcohol use was an independent risk factor for pneumonia severity in HIV-infected patients., Methods: Secondary analysis of prospective cohort study data evaluating early bronchoscopy for pneumonia diagnosis in HIV patients between 2007 and 2011 was conducted. We defined AUDs using an alcohol use disorder identification test (AUDIT) score as follows: ≥8 indicates hazardous drinking and ≥14 indicates dependence. We quantified pneumonia severity using the pneumonia severity index (PSI). Multivariable linear regression was used to investigate the independent association between alcohol and pneumonia severity., Results: A total of 196 HIV+ individuals comprised our cohort. Most cohort subjects were middle-aged African American men. Most subjects (70 %) reported not taking antiretroviral therapy. The overall prevalence of hazardous drinking was 24 % in our cohort (48/196) with 10 % (19/196) meeting the criteria for alcohol dependence. Alcohol consumption was significantly associated with pneumonia severity (r = 0.25, p < 0.001). Hazardous drinking (β-coefficient 10.12, 95 % CI 2.95-17.29, p = 0.006) and alcohol dependence (β-coefficient 12.89, 95 % CI 2.59-23.18, p = 0.014) were independent risk factors for pneumonia severity. Reported homelessness and men who have sex with men (MSM) status remained independent risk factors for more severe pneumonia after adjustment for the effects of alcohol., Conclusions: In a cohort of HIV patients with pneumonia, presence of an AUD was an independent risk factor for pneumonia severity. Homelessness and MSM status were associated with greater pneumonia severity in AUD patients.

Respiratory defenses against infection involve a diverse and complex system. Mechanical barriers limit exposure of the respiratory tract to potential pathogenic organisms, whereas the mucociliary apparatus and cough reflexes work to expel any microbes that may bypass the initial defenses. When microorganisms have gained entry to the lower respiratory tract, the alveolar macrophage and recruited phagocytes may eliminate the culprits before active infection can be established. Only after the failure of the innate immune defenses is a specific immune response mounted. Examination of clinical defects in host defense allows one to understand the importance of the multitude of components of the lung's immune defense system.