Paradigms in chronic obstructive pulmonary disease: phenotypes, immunobiology, and therapy with a focus on vascular disease.

Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous syndrome that represents a major global health burden. COPD phenotypes have recently emerged based on large cohort studies addressing the need to better characterize the syndrome. Though comprehensive phenotyping is still at an early stage, factors such as ethnicity and radiographic, serum, and exhaled breath biomarkers have shown promise. COPD is also an immunological disease where innate and adaptive immune responses to the environment and tobacco smoke are altered. The frequent overlap between COPD and other systemic diseases, such as cardiovascular disease, has influenced COPD therapy, and treatments for both conditions may lead to improved patient outcomes. Here, we discuss current paradigms that center on improving the definition of COPD, understanding the immunological overlap between COPD and vascular inflammation, and the treatment of COPD-with a focus on comorbid cardiovascular disease

Vascular Remodeling Is Airway Generation-Specific in a Primate Model of Chronic Asthma

Rationale: Changes in the density of bronchial vessels have been proposed as a part of airway remodeling that occurs in chronic asthma

SMAD Signaling in the Airways of Healthy Rhesus Macaques versus Rhesus Macaques with Asthma Highlights a Relationship Between Inflammation and Bone Morphogenetic Proteins

Bone morphogenetic protein (BMP) signaling is important for correct lung morphogenesis, and there is evidence of BMP signaling reactivation in lung diseases. However, little is known about BMP signaling patterns in healthy airway homeostasis and inflammatory airway disease and during epithelial repair. In this study, a rhesus macaque (Macaca mulatta) model of allergic airway disease was used to investigate BMP signaling throughout the airways in health, disease, and regeneration. Stereologic quantification of immunofluorescent images was used to determine the expression of BMP receptor (BMPR) Ia and phosphorylated SMAD (pSMAD) 1/5/8 in the airway epithelium. A pSMAD 1/5/8 expression gradient was found along the airways of healthy juvenile rhesus macaques (n = 3, P , 0.005). Membrane-localized BMPRIa expression was also present in the epithelium of the healthy animals. After exposure to house dust mite allergen and ozone, significant down-regulation of nuclear pSMAD 1/5/8 occurs in the epithelium. When the animals were provided with a recovery period in filtered air, proliferating cell nuclear antigen, pSMAD 1/5/8, and membrane-localized BMPRIa expression were significantly increased in the epithelium of conducting airways (P , 0.005). Furthermore, in the asthmatic airways, altered BMPRIa localization was evident. Because of the elevated eosinophil presence in these airways, we investigated the effect of eosinophil-derived proteins on BMPRIa trafficking in epithelial cells. Eosinophil-derived proteins (eosinophil-derived neurotoxin, eosinophil peroxidase, and major basic protein) induced transient nuclear translocation of membrane-bound BMPRIa. This work mapping SMAD signaling in the airways of nonhuman primates highlights a potential mechanistic relationship between inflammatory mediators and BMP signaling and provides evidence that basal expression of the BMP signaling pathway may be important for maintaining healthy airways

Implementation, Maintenance, and Outcomes of an Electronic Referral to a Tobacco Quitline Across Five Health Systems

IntroductionElectronic referral (e-referral) to quitlines helps connect tobacco-using patients to free, evidence-based cessation counseling. Little has been published about the real-world implementation of e-referrals across U.S. health systems, their maintenance over time, and the outcomes of e-referred patients.Aims and methodsBeginning in 2014, the University of California (UC)-wide project called UC Quits scaled up quitline e-referrals and related modifications to clinical workflows from one to five UC health systems. Implementation strategies were used to increase site readiness. Maintenance was supported through ongoing monitoring and quality improvement programs. Data on e-referred patients (n = 20 709) and quitline callers (n = 197 377) were collected from April 2014 to March 2021. Analyses of referral trends and cessation outcomes were conducted in 2021-2022.ResultsOf 20 709 patients referred, the quitline contacted 47.1%, 20.6% completed intake, 15.2% requested counseling, and 10.9% received it. In the 1.5-year implementation phase, 1813 patients were referred. In the 5.5-year maintenance phase, volume was sustained, with 3436 referrals annually on average. Among referred patients completing intake (n = 4264), 46.2% were nonwhite, 58.8% had Medicaid, 58.7% had a chronic disease, and 48.8% had a behavioral health condition. In a sample randomly selected for follow-up, e-referred patients were as likely as general quitline callers to attempt quitting (68.5% vs. 71.4%; p = .23), quit for 30 days (28.3% vs. 26.9%; p = .52), and quit for 6 months (13.6% vs. 13.9%; p = .88).ConclusionsWith a whole-systems approach, quitline e-referrals can be established and sustained across inpatient and outpatient settings with diverse patient populations. Cessation outcomes were similar to those of general quitline callers.ImplicationsThis study supports the broad implementation of tobacco quitline e-referrals in health care. To the best of our knowledge, no other paper has described the implementation of e-referrals across multiple U.S. health systems or how they were sustained over time. Modifying electronic health records systems and clinical workflows to enable and encourage e-referrals, if implemented and maintained appropriately, can be expected to improve patient care, make it easier for clinicians to support patients in quitting, increase the proportion of patients using evidence-based treatment, provide data to assess progress on quality goals, and help meet reporting requirements for tobacco screening and prevention

Percent Emphysema and Daily Motor Activity Levels in the General Population Multi-Ethnic Study of Atherosclerosis

BackgroundCOPD is associated with reduced physical capacity. However, it is unclear whether pulmonary emphysema, which can occur without COPD, is associated with reduced physical activity in daily life, particularly among people without COPD and never smokers. We hypothesized that greater percentage of emphysema-like lung on CT scan is associated with reduced physical activity assessed by actigraphy and self-report.MethodsThe Multi-Ethnic Study of Atherosclerosis (MESA) enrolled participants free of clinical cardiovascular disease from the general population. Percent emphysema was defined as percentage of voxels < -950 Hounsfield units on full-lung CT scans. Physical activity was measured by wrist actigraphy over 7 days and a questionnaire. Multivariable linear regression was used to adjust for age, sex, race/ethnicity, height, weight, education, smoking, pack-years, and lung function.ResultsAmong 1,435 participants with actigraphy and lung measures, 47% had never smoked, and 8% had COPD. Percent emphysema was associated with lower activity levels on actigraphy (P = .001), corresponding to 1.5 hour less per week of moderately paced walking for the average participant in quintile 2 vs 4 of percent emphysema. This association was significant among participants without COPD (P = .004) and among ever (P = .01) and never smokers (P = .03). It was also independent of coronary artery calcium and left ventricular ejection fraction. There was no evidence that percent emphysema was associated with self-reported activity levels.ConclusionsPercent emphysema was associated with decreased physical activity in daily life objectively assessed by actigraphy in the general population, among participants without COPD, and nonsmokers

Paradigms in chronic obstructive pulmonary disease: phenotypes, immunobiology, and therapy with a focus on vascular disease

Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous syndrome that represents a major global health burden. COPD phenotypes have recently emerged based on large cohort studies addressing the need to better characterize the syndrome. Though comprehensive phenotyping is still at an early stage, factors such as ethnicity and radiographic, serum, and exhaled breath biomarkers have shown promise. COPD is also an immunological disease where innate and adaptive immune responses to the environment and tobacco smoke are altered. The frequent overlap between COPD and other systemic diseases, such as cardiovascular disease, has influenced COPD therapy, and treatments for both conditions may lead to improved patient outcomes. Here, we discuss current paradigms that center on improving the definition of COPD, understanding the immunological overlap between COPD and vascular inflammation, and the treatment of COPD-with a focus on comorbid cardiovascular disease