Circulating 1,3-Beta-D-Glucan is Associated with Lung Function, Respiratory Symptoms, and Mediators of Matrix Degradation in Chronic Obstructive Pulmonary Disease.

Introduction: Factors beyond cigarette smoke likely contribute to chronic obstructive pulmonary disease (COPD) pathogenesis. Prior studies demonstrate fungal colonization of the respiratory tract and increased epithelial barrier permeability in COPD. We sought to determine whether 1,3-beta-d-glucan (BDG), a polysaccharide component of the fungal cell wall, is detectable in the plasma of individuals with COPD and associates with clinical outcomes and matrix degradation proteins. Methods: BDG was measured in the plasma of current and former smokers with COPD. High BDG was defined as a value greater than the 95th percentile of BDG in smokers without airflow obstruction. Pulmonary function, emphysema, and symptoms were compared between COPD participants with high versus low BDG. The relationship between plasma BDG, matrix metalloproteinases (MMP) 1, 7, and 9, and tissue inhibitor of matrix metalloproteinases (TIMP) 1, 2, and 4 was assessed adjusting for age, sex, and smoking status. Results: COPD participants with high BDG plasma levels (19.8%) had lower forced expiratory volume in 1 second to forced vital capacity ratios (median 31.9 versus 39.3, p=0.025), higher St George's Respiratory Questionnaire symptom scores (median 63.6 versus 57.4, p=0.016), and greater prevalence of sputum production (69.4% versus 52.0%) and exacerbations (69.4% versus 48%) compared to COPD participants with low BDG. BDG levels directly correlated with MMP1 (r=0.27, p<0.001) and TIMP1 (r=0.16, p=0.022) in unadjusted and adjusted analyses. Conclusions: Elevated plasma BDG levels correlate with worse lung function, greater respiratory morbidity, and circulating markers of matrix degradation in COPD. These findings suggest that targeting dysbiosis or enhancing epithelial barrier integrity may have disease-modifying effects in COPD.

Brief Report: Association Between Pain, Pulmonary Function, and Respiratory Symptoms in People With HIV.

BACKGROUND: People with HIV (PWH) experience chronic pain and respiratory symptoms, which are closely related in the general population. Pain may affect the impaired pulmonary function seen in PWH beyond its association with HIV alone. Our objective was to investigate the relationship of pain severity to pulmonary function, respiratory symptoms, and sleep disturbance in PWH. SETTING: Study sites included the University of Pittsburgh, University of California San Francisco, and University of Washington. METHODS: Pain, dyspnea, and sleep were assessed using the Brief Chronic Pain Questionnaire, St. George's Respiratory Questionnaire, and Pittsburgh Sleep Quality Index. Participants performed prebronchodilator and postbronchodilator spirometry and 6-minute walk test. Associations between pain severity, lung function, dyspnea, and sleep were assessed with bivariate and multiple quantile regression analysis adjusted for age, sex, race, body mass index, and smoking status. RESULTS: Of 159 PWH, the median age was 56 years with 30.8% women. Two-thirds experienced pain in the past week, with 40.3% reporting chronic pain. Pain severity was higher with female sex (P = 0.038), non-White race (P = 0.005), current smoking (P = 0.003), and lower CD4+ count (P = 0.035). In adjusted analysis, higher pain severity was correlated with reduced postbronchodilator forced expiratory volume in 1 second %predicted (P = 0.008), reduced postbronchodilator forced vital capacity %predicted (P = 0.019), and chronic obstructive pulmonary disease (P = 0.032). Greater pain severity was strongly associated with a higher St. George's Respiratory Questionnaire score (P < 0.001) and sleep disturbance (P < 0.001). CONCLUSIONS: In PWH, pain is common and associated with airflow obstruction, dyspnea, and sleep disturbance. Future studies assessing pain severity and pulmonary function over time could clarify the direction of this association and the impact on quality of life.

CT Imaging and Comorbidities in COPD: Beyond Lung Cancer Screening.

Comorbidities significantly contribute to morbidity, mortality, and health-care costs in individuals with COPD. Comorbidity prevalence does not always correlate with lung disease severity, and the elevated risk of certain comorbidities is often independent of shared risk factors such as tobacco burden. Although COPD management guidelines recognize the importance of identifying and treating comorbidities as part of the comprehensive management of COPD patients, little guidance is provided regarding best screening practices. Whereas universal comorbidity screening in COPD patients is likely not cost-effective, targeted early screening and treatment in those at highest risk may have a significant impact on COPD outcomes. Recent studies suggest that certain radiographic features on thoracic imaging may serve as surrogate markers of comorbidity in patients with COPD. This review evaluates these studies in the context of the growing availability of chest CT scans in the lung cancer screening era and discusses how chest CT imaging can be leveraged to identify those COPD patients at highest risk for comorbid disease.

Obstructive Lung Disease in HIV-Phenotypes and Pathogenesis.

PURPOSE OF REVIEW: In the antiretroviral therapy era, people living with HIV (PLWH) are surviving to older ages. Chronic illnesses such as chronic obstructive pulmonary disease (COPD) occur more frequently. COPD is often described as a single entity, yet multiple manifestations may be considered phenotypes. HIV is an independent risk factor for certain COPD phenotypes, and mechanisms underlying pathogenesis of these phenotypes may differ and impact response to therapy. RECENT FINDINGS: Impaired diffusing capacity, airflow obstruction, and radiographic emphysema occur in PLWH and are associated with increased mortality. Age, sex, tobacco, and HIV-specific factors likely modulate the severity of disease. An altered lung microbiome and residual HIV in the lung may also influence phenotypes. COPD is prevalent in PLWH with multiple phenotypes contributing to the burden of disease. HIV-specific factors and the respiratory microbiome influence disease pathogenesis. As tobacco use remains a significant risk factor for COPD, smoking cessation must be emphasized for all PLWH.