HIV infection impairs the host response to Mycobacterium tuberculosis infection by altering surfactant protein D function in the human lung alveolar mucosa.

Tuberculosis is the leading cause of death for people living with HIV (PLWH). We hypothesized that altered functions of innate immune components in the human alveolar lining fluid of PLWH (HIV-ALF) drive susceptibility to Mycobacterium tuberculosis (M.tb) infection. Our results indicate a significant increase in oxidation of innate proteins and chemokine levels and significantly lower levels and function of complement components and Th1/Th2/Th17 cytokines in HIV-ALF versus control-ALF (non-HIV-infected people). We further found a deficiency of surfactant protein D (SP-D) and reduced binding of SP-D to M.tb that had been exposed to HIV-ALF. Primary human macrophages infected with M.tb exposed to HIV-ALF were significantly less capable of controlling the infection, which was reversed by SP-D replenishment in HIV-ALF. Thus, based on the limited number of participants in this study, our data suggest that PLWH without antiretroviral therapy (ART) have declining host innate defense function in their lung mucosa, thereby favoring M.tb and potentially other pulmonary infections.

Emphysema and soluble CD14 are associated with pulmonary nodules in HIV-infected patients: implications for lung cancer screening.

OBJECTIVE: Lung cancer screening may benefit HIV-infected (HIV) smokers because of an elevated risk of lung cancer, but may have unique harms because of HIV-specific risk factors for false-positive screens. This study seeks to understand whether inflammatory biomarkers and markers of chronic lung disease are associated with noncalcified nodules at least 4 mm (NCN) in HIV compared with uninfected patients. DESIGN: This is a cohort study of Examinations of HIV-Associated Lung Emphysema (EXHALE), including 158 HIV and 133 HIV-uninfected participants. METHODS: Participants underwent a laboratory assessment [including measurement of D-dimer, interleukin 6, and soluble CD14 (sCD14)], chest computed tomography (CT), and pulmonary function testing. We created multivariable logistic regression models to determine predictors of NCN in the participants stratified by HIV status, with attention to semiqualitative scoring of radiographic emphysema, markers of pulmonary function, and inflammatory biomarkers. RESULTS: Of the 291 participants, 69 had NCN on chest CT. As previously reported, there was no difference in prevalence of these nodules by HIV status. Emphysema and elevated sCD14 demonstrated an association with NCN in HIV participants independent of smoking status, CD4 cell count, HIV viral load, and pulmonary function. CONCLUSION: Emphysema and sCD14, a marker of immune activation, was associated with a higher prevalence of NCN on chest CT in HIV participants. Patients with chronic immune activation and emphysema may be at higher risk for both false-positive findings and incident lung cancer, thus screening in this group requires further study to understand the balance of benefits and harms.

Enrichment of the lung microbiome with oral taxa is associated with lung inflammation of a Th17 phenotype.

Microaspiration is a common phenomenon in healthy subjects, but its frequency is increased in chronic inflammatory airway diseases, and its role in inflammatory and immune phenotypes is unclear. We have previously demonstrated that acellular bronchoalveolar lavage samples from half of the healthy people examined are enriched with oral taxa (here called pneumotypeSPT) and this finding is associated with increased numbers of lymphocytes and neutrophils in bronchoalveolar lavage. Here, we have characterized the inflammatory phenotype using a multi-omic approach. By evaluating both upper airway and acellular bronchoalveolar lavage samples from 49 subjects from three cohorts without known pulmonary disease, we observed that pneumotypeSPT was associated with a distinct metabolic profile, enhanced expression of inflammatory cytokines, a pro-inflammatory phenotype characterized by elevated Th-17 lymphocytes and, conversely, a blunted alveolar macrophage TLR4 response. The cellular immune responses observed in the lower airways of humans with pneumotypeSPT indicate a role for the aspiration-derived microbiota in regulating the basal inflammatory status at the pulmonary mucosal surface.

Pulmonary artery stenosis secondary to fibrosing mediastinitis: management with cutting balloon angioplasty and endovascular stenting.

Cutting balloon angioplasty is a common treatment modality in the pediatric population for pulmonary artery stenosis. We present an adult with histoplasmosis induced fibrosing mediastinitis resulting in pulmonary artery stenosis that was successfully treated with cutting balloon angioplasty and subsequent stent deployment. Percutaneous endovascular stent placement has be shown to effectively alleviate pulmonary artery stenosis, however in-stent restenosis does limit durability. Pharmacologic therapy is indicated with either mediastinal adenitis or mediastinal granuloma with anti-fungal agents such as amphotericin B and itraconazole. Surgical intervention for histoplasmosis induced fibrosing mediastinitis is rarely indicated and may result in fatal complications that stem from mediastinal fibrosis due to resultant destruction of surgical planes. To our knowledge, this is the first reported case of utilizing cutting balloon angioplasty and stent insertion for the treatment of histoplasmosis induced fibrosing mediastinitis complicated by pulmonary artery stenosis.

Sex, depression, and risk of hospitalization and mortality in chronic obstructive pulmonary disease.

BACKGROUND: We sought to determine whether depressive or anxiety symptoms are associated with chronic obstructive pulmonary disease (COPD) hospitalization or mortality. These data were collected as part of the National Emphysema Treatment Trial (NETT), a randomized controlled trial of lung volume reduction surgery vs continued medical treatment conducted at 17 clinics across the United States between January 29, 1998, and July 31, 2002. METHODS: Prospective cohort study among participants in the NETT with emphysema and severe airflow limitation who were randomized to medical therapy. Primary outcomes were 1- and 3-year mortality, as well as COPD or respiratory-related hospitalization or emergency department visit during the 1-year follow-up period. Of 610 patients randomized to medical therapy, complete data on hospitalization and mortality were available for 3 years of follow-up for 603 patients (98.9%). RESULTS: Depressive symptoms were assessed using the Beck Depression Inventory (BDI) questionnaire, and anxiety was assessed using the State-Trait Anxiety Inventory. Among 610 subjects, 40.8% had at least mild to moderate depressive symptoms. Patients in the highest quintile of BDI score (BDI score, >or=15) had an increased risk of respiratory hospitalization in unadjusted analysis compared with patients in the lowest quintile (BDI score, < 5) (odds ratio [OR], 2.26; 95% confidence interval [CI], 1.30-3.93). After adjustment for disease severity, this relationship was no longer statistically significant. The adjusted risk of 3-year mortality was increased among those in the highest quintile of BDI score (OR, 2.74; 95% CI, 1.42-5.29) compared with those in the lowest quintile. Anxiety was not associated with hospitalization or mortality in this population. CONCLUSIONS: Depressive symptoms are common in patients with severe COPD and are treated in few subjects. Depressive symptoms are associated with increased risk for 3-year mortality but not 1-year mortality or hospitalization.