BACKGROUND: While 16S ribosomal RNA (rRNA) sequencing has been used to characterize the lung's bacterial microbiota in human immunodeficiency virus (HIV)-infected individuals, taxonomic studies provide limited information on bacterial function and impact on the host. Metabolic profiles can provide functional information on host-microbe interactions in the lungs. We investigated the relationship between the respiratory microbiota and metabolic profiles in the bronchoalveolar lavage fluid of HIV-infected and HIV-uninfected outpatients. RESULTS: Targeted sequencing of the 16S rRNA gene was used to analyze the bacterial community structure and liquid chromatography-high-resolution mass spectrometry was used to detect features in bronchoalveolar lavage fluid. Global integration of all metabolic features with microbial species was done using sparse partial least squares regression. Thirty-nine HIV-infected subjects and 20 HIV-uninfected controls without acute respiratory symptoms were enrolled. Twelve mass-to-charge ratio (m/z) features from C18 analysis were significantly different between HIV-infected individuals and controls (false discovery rate (FDR) = 0.2); another 79 features were identified by network analysis. Further metabolite analysis demonstrated that four features were significantly overrepresented in the bronchoalveolar lavage (BAL) fluid of HIV-infected individuals compared to HIV-uninfected, including cystine, two complex carbohydrates, and 3,5-dibromo-L-tyrosine. There were 231 m/z features significantly associated with peripheral blood CD4 cell counts identified using sparse partial least squares regression (sPLS) at a variable importance on projection (VIP) threshold of 2. Twenty-five percent of these 91 m/z features were associated with various microbial species. Bacteria from families Caulobacteraceae, Staphylococcaceae, Nocardioidaceae, and genus Streptococcus were associated with the greatest number of features. Glycerophospholipid and lineolate pathways correlated with these bacteria. CONCLUSIONS: In bronchoalveolar lavage fluid, specific metabolic profiles correlated with bacterial organisms known to play a role in the pathogenesis of pneumonia in HIV-infected individuals. These findings suggest that microbial communities and their interactions with the host may have functional metabolic impact in the lung.

Pulmonary Arterial Hypertension (PAH) is overrepresented in People Living with Human Immunodeficiency Virus (PLWH). HIV protein gp120 plays a key role in the pathogenesis of HIV-PAH. Genetic changes in HIV gp120 determine viral interactions with chemokine receptors; specifically, HIV-X4 viruses interact with CXCR4 while HIV-R5 interact with CCR5 co-receptors. Herein, we leveraged banked samples from patients enrolled in the NIH Lung HIV studies and used bioinformatic analyses to investigate whether signature sequences in HIV-gp120 that predict tropism also predict PAH. Further biological assays were conducted in pulmonary endothelial cells in vitro and in HIV-transgenic rats. We found that significantly more persons living with HIV-PAH harbor HIV-X4 variants. Multiple HIV models showed that recombinant gp120-X4 as well as infectious HIV-X4 remarkably increase arachidonate 5-lipoxygenase (ALOX5) expression. ALOX5 is essential for the production of leukotrienes; we confirmed that leukotriene levels are increased in bronchoalveolar lavage fluid of HIV-infected patients. This is the first report associating HIV-gp120 genotype to a pulmonary disease phenotype, as we uncovered X4 viruses as potential agents in the pathophysiology of HIV-PAH. Altogether, our results allude to the supplementation of antiretroviral therapy with ALOX5 antagonists to rescue patients with HIV-X4 variants from fatal PAH.

Hyperinflammation is associated with increased mortality in coronavirus disease 2019 (COVID-19). In this retrospective, uncontrolled patient cohort with moderate -severe COVID-19, treatment with baricitinib plus hydroxychloroquine was associated with recovery in 11 of 15 patients. Baricitinib for the treatment of COVID-19 should be further investigated in randomized, controlled clinical trials.

Objective: Bronchoscopy and bronchoalveolar lavage (BAL) are common procedures in intensive care units; however, no contemporaneous safety and outcomes data have been reported, particularly for critically ill patients. Design: This is a retrospective analysis of prospectively collected data from teaching hospital adult intensive care units. Interventions: One hundred mechanically ventilated patients with severe sepsis, septic shock, acute lung injury (ALI), and/or acute respiratory distress syndrome underwent bronchoscopy with unilateral BAL. Data collected included demographics, presence of sepsis or ALI, Pao2 to Fio2 ratio, positive end-expiratory pressure, Acute Physiology and Chronic Health Evaluation score, Sequential Organ Failure Assessment score, and peri- or postprocedural complications. Results: Men comprised 51% of the patients; 81% of the patients were black, and 15% were white. The mean age was 52 (SD, ±. 16) years. The mean Acute Physiology and Chronic Health Evaluation score was 22 (±. 7.5), whereas the median Sequential Organ Failure Assessment score was 9 (interquartile range, 5-12). Ten patients (10%) had complications during or immediately after the procedure. Hypoxemia during or immediately after the BAL was the most common complication. Ninety percent of the complications were related to transient hypoxemia, whereas bradycardia and hypotension each occurred in 1 patient. Age, female sex, and higher positive end-expiratory pressure were associated with complications. Conclusions: Bronchoscopy with BAL in critically ill patients with sepsis and ALI is well tolerated with low risk of complications, primarily related to manageable hypoxemia.

Introduction Critical illnesses continue to be major causes of morbidity and mortality worldwide. Recent investigations show that stem cells may be beneficial as prognostic biomarkers and novel therapeutic strategies in these syndromes. This article reviews the use of stem cells in sepsis and acute lung injury as prognostic biomarkers and also as a potential for exogenous cell-based therapy. Methods A directed search of the medical literature was done using PubMed and OVID to evaluate topics related to pathophysiology of sepsis and acute lung injury, in addition to the characterization and utilization of stem cells in these diseases. Conclusions Stem cells have shown significant promise in the field of critical care medicine both for prognostication and treatment strategies. Although recent studies have been done to describe the mechanistic pathways of stem cells in critical illness, further investigation is necessary to fully delineate the mechanisms behind a stem cell’s immunomodulatory characteristics and its ability to mobilize and engraft in tissues.

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Pulmonary Complications of HIV summarizes current practices for diagnosing and treating common HIV-related pulmonary complications. It is a well-written, educational work that will interest anyone managing the care of HIV-infected persons. The content and amount of information packed into this easy-to-read textbook is impressive. Each chapter is well organized and well referenced, and important concepts and definitions are laid out clearly.

Despite antiretroviral therapy, lung disease is a leading cause of death in individuals infected with human immunodeficiency virus type 1 (HIV). Individuals infected with HIV are susceptible to serious bacterial and viral infections, such as pneumococcus and influenza, which are particularly problematic for lung health, resulting in lung injury. Additionally, HIV-infected individuals are susceptible to a number of pulmonary diseases for unknown reasons. Alcohol, the most commonly abused drug in the world, continues to exact an enormous toll on morbidity and mortality in individuals living with HIV. Chronic alcohol abuse has been shown to affect lung immunity, resulting in significant lung injury. There is a paucity of literature on the additive effects of HIV and alcohol, two diseases of immune senescence, in the lung. This chapter begins by discussing the latest literature evaluating the epidemiology of HIV, alcohol use, and lung health focusing on two prevalent infections, tuberculosis and pneumococcal pneumonia. In parallel, we discuss the interactions of alcohol and HIV on the risk for acute lung injury and subsequent morbidity and mortality. We then discuss the pathophysiology of how these two diseases of immune dysfunction affect the lung, with a focus on the oxidative stress, alveolar macrophage host immune capacity, and immunomodulatory role of zinc in the airway. Finally, we review the latest literature on how HIV and alcohol affect other pulmonary disorders including chronic obstructive pulmonary disease, pulmonary hypertension, and lung cancer.

Background:The US Preventive Services Task Force (USPSTF) 2021 updated recommendations on lung cancer screening with chest computed tomography to apply to individuals 50-80 years of age (previously 55-80 years), with a ≥20 pack-year history (previously ≥30), whether currently smoking or quit ≤15 years ago. Despite being at higher risk for lung cancer, persons with HIV (PWH) were not well-represented in the National Lung Screening Trial, which informed the USPSTF 2013 recommendations. It is unknown or unclear how PWH are affected by the 2021 recommendations.Setting:This study was a retrospective analysis of PWH with and without lung cancer in the Women's Interagency HIV Study and the Multicenter AIDS Cohort Study.Methods:We identified PWH, ages 40-80 years, who currently or previously smoked, with (cases) and without lung cancer (noncases). The sensitivity and specificity of the old, new, and alternative screening criteria were evaluated in each cohort.Results:We identified 52 women and 19 men with lung cancer and 1950 women and 1599 men without lung cancer. Only 11 women (22%) and 6 men (32%) with lung cancer met 2013 screening criteria; however, more women (22; 44%) and men (12; 63%) met 2021 criteria. Decreased age and tobacco exposure thresholds in women further increased sensitivity of the 2021 criteria.Conclusions:The 2021 USPSTF lung cancer screening recommendations would have resulted in more PWH with lung cancer being eligible for screening at the time of their diagnosis. Further investigation is needed to determine optimal screening criteria for PWH, particularly in women.

IMPORTANCE: SARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or other health effects after the acute phase of infection; termed post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are ill-defined. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC in Adults (RECOVER-Adult) are to: (1) characterize PASC prevalence; (2) characterize the symptoms, organ dysfunction, natural history, and distinct phenotypes of PASC; (3) identify demographic, social and clinical risk factors for PASC onset and recovery; and (4) define the biological mechanisms underlying PASC pathogenesis. METHODS: RECOVER-Adult is a combined prospective/retrospective cohort currently planned to enroll 14,880 adults aged ≥18 years. Eligible participants either must meet WHO criteria for suspected, probable, or confirmed infection; or must have evidence of no prior infection. Recruitment occurs at 86 sites in 33 U.S. states, Washington, DC and Puerto Rico, via facility- and community-based outreach. Participants complete quarterly questionnaires about symptoms, social determinants, vaccination status, and interim SARS-CoV-2 infections. In addition, participants contribute biospecimens and undergo physical and laboratory examinations at approximately 0, 90 and 180 days from infection or negative test date, and yearly thereafter. Some participants undergo additional testing based on specific criteria or random sampling. Patient representatives provide input on all study processes. The primary study outcome is onset of PASC, measured by signs and symptoms. A paradigm for identifying PASC cases will be defined and updated using supervised and unsupervised learning approaches with cross-validation. Logistic regression and proportional hazards regression will be conducted to investigate associations between risk factors, onset, and resolution of PASC symptoms. DISCUSSION: RECOVER-Adult is the first national, prospective, longitudinal cohort of PASC among US adults. Results of this study are intended to inform public health, spur clinical trials, and expand treatment options. REGISTRATION: NCT05172024.