COPD in People with HIV: Epidemiology, Pathogenesis, Management, and Prevention Strategies.

Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disorder characterized by airflow limitation and persistent respiratory symptoms. People with HIV (PWH) are particularly vulnerable to COPD development; PWH have demonstrated both higher rates of COPD and an earlier and more rapid decline in lung function than their seronegative counterparts, even after accounting for differences in cigarette smoking. Factors contributing to this HIV-associated difference include chronic immune activation and inflammation, accelerated aging, a predilection for pulmonary infections, alterations in the lung microbiome, and the interplay between HIV and inhalational toxins.

Isolated abnormal diffusing capacity for carbon monoxide (iso↓DLco) is associated with increased respiratory symptom burden in people with HIV infection.

Objectives: An isolated reduction in the diffusing capacity for carbon monoxide (DLco; iso↓DLco) is one of the most common pulmonary function test (PFT) abnormalities in people living with HIV (PWH), but its clinical implications are incompletely understood. In this study, we explored whether iso↓DLco in PWH is associated with a greater respiratory symptom burden.

Study Design: Cross-sectional analysis.

Sex modifies the risk of HIV-associated obstructive lung disease in Ugandans postpneumonia.

Objectives: Spirometric abnormalities are frequent, and obstructive lung disease (OLD) is a common comorbidity among people with HIV (PWH). HIV increases the risk of many comorbidities to a greater degree in women than in men. Few studies have evaluated whether sex modifies the HIV-associated risk of OLD.

Ambient air pollution exposure and radiographic pulmonary vascular volumes.

Unlabelled: Exposure to higher levels of ambient air pollution is a known risk factor for cardiovascular disease but long-term effects of pollution exposure on the pulmonary vessels are unknown.

Methods: Among 2428 Framingham Heart Study participants who underwent chest computed tomography (CT) between 2008 and 2011, pulmonary vascular volumes were calculated by image analysis, including the total vascular volume and small vessel volume (cross-sectional area <5 mm; BV5 defined as small vessel volume). Using spatiotemporal models and participant home address, we assigned 1-year (2008) and 5-year (2004-2008) average concentrations of fine particulate matter (PM), elemental carbon (EC), and ground-level ozone (O), and distance to major roadway.

Chronic obstructive pulmonary disease in HIV.

: Chronic obstructive pulmonary disease (COPD) is more prevalent in people with HIV (PWH) than in the general population and leads to an increased burden of morbidity and mortality in this population. The mechanisms behind COPD development and progression in PWH are not fully elucidated, and there are no PWH-specific guidelines for COPD management. : The goal of this broad narrative review is to review the epidemiology of COPD in PWH globally, highlight proposed pathways contributing to increased COPD prevalence and progression in PWH, discuss structural and functional changes in the lungs in this population, assesses the excess mortality and comorbidities in PWH with COPD, and address management practices for this unique population.

Loss of Smooth Muscle α-Actin Leads to NF-κB-Dependent Increased Sensitivity to Angiotensin II in Smooth Muscle Cells and Aortic Enlargement.

Rationale: Mutations in , encoding the smooth muscle isoform of α-actin, cause thoracic aortic aneurysms, acute aortic dissections, and occlusive vascular diseases.

Objective: We sought to identify the mechanism by which loss of smooth muscle α-actin causes aortic disease.

Methods And Results: mice have an increased number of elastic lamellae in the ascending aorta and progressive aortic root dilation as assessed by echocardiography that can be attenuated by treatment with losartan, an angiotensin II (AngII) type 1 receptor blocker.

Cost-effectiveness and clinical efficacy of biliary stents in patients undergoing neoadjuvant therapy for pancreatic adenocarcinoma in a randomized controlled trial.

Background And Aims: The optimal type of stent for the palliation of malignant biliary obstruction in patients with pancreatic adenocarcinoma undergoing neoadjuvant chemoradiotherapy with curative intent is unknown. We performed a prospective trial comparing 3 types of biliary stents-fully covered self-expandable metal (fcSEMS), uncovered self-expandable metal (uSEMS), and plastic-to determine which best optimized cost-effectiveness and important clinical outcomes.

Methods: In this prospective randomized trial, consecutive patients with malignant biliary obstruction from newly diagnosed pancreatic adenocarcinoma who were to start neoadjuvant chemoradiotherapy were randomized to receive fcSEMSs, uSEMSs, or plastic stents during the index ERCP.

Smooth muscle hyperplasia due to loss of smooth muscle α-actin is driven by activation of focal adhesion kinase, altered p53 localization and increased levels of platelet-derived growth factor receptor-β.

Mutations in ACTA2, encoding the smooth muscle cell (SMC)-specific isoform of α-actin (α-SMA), cause thoracic aortic aneurysms and dissections and occlusive vascular diseases, including early onset coronary artery disease and stroke. We have shown that occlusive arterial lesions in patients with heterozygous ACTA2 missense mutations show increased numbers of medial or neointimal SMCs. The contribution of SMC hyperplasia to these vascular diseases and the pathways responsible for linking disruption of α-SMA filaments to hyperplasia are unknown.

Rare, nonsynonymous variant in the smooth muscle-specific isoform of myosin heavy chain, MYH11, R247C, alters force generation in the aorta and phenotype of smooth muscle cells.

Rationale: Mutations in myosin heavy chain (MYH11) cause autosomal dominant inheritance of thoracic aortic aneurysms and dissections. At the same time, rare, nonsynonymous variants in MYH11 that are predicted to disrupt protein function but do not cause inherited aortic disease are common in the general population and the vascular disease risk associated with these variants is unknown.

Objective: To determine the consequences of the recurrent MYH11 rare variant, R247C, through functional studies in vitro and analysis of a knock-in mouse model with this specific variant, including assessment of aortic contraction, response to vascular injury, and phenotype of primary aortic smooth muscle cells (SMCs).