Susceptibility to chronic obstructive pulmonary disease (COPD) beyond cigarette smoking is incompletely understood, although several genetic variants associated with COPD are known to regulate airway branch development. We demonstrate that in vivo central airway branch variants are present in 26.5% of the general population, are unchanged over 10 y, and exhibit strong familial aggregation. The most common airway branch variant is associated with COPD in two cohorts ( = 5,054), with greater central airway bifurcation density, and with emphysema throughout the lung. The second most common airway branch variant is associated with COPD among smokers, with narrower airway lumens in all lobes, and with genetic polymorphisms within the gene. We conclude that central airway branch variation, readily detected by computed tomography, is a biomarker of widely altered lung structure with a genetic basis and represents a COPD susceptibility factor.
Patients with multimorbidity and complex health care needs are usually vulnerable elders with several concomitant advanced chronic diseases. Our research aim was to evaluate differences in patterns of multimorbidity by gender in this population and their possible prognostic implications, measured as in-hospital mortality, 1-month readmissions, and 1-year mortality. We focused on a cohort of elderly patients with well-established multimorbidity criteria admitted to a specific unit for chronic complex-care patients. Multimorbidity criteria, the Charlson, PROFUND and Barthel indexes, and the Pfeiffer test were collected prospectively during their stays. A total of 843 patients (49.2% men) were included, with a median age of 84 [interquartile range (IQR) 79-89] years. The women were older, with greater functional dependence [Barthel index: 40 (IQR:10-65) vs. 60 (IQR: 25-90)], showed more cognitive deterioration [Pfeiffer test: 5 (IQR:1-9) vs. 1 (0-6)], and had worse scores on the PROFUND index [15 (IQR:9-18) vs. 11.5 (IQR: 6-15)], all p <0.0001, while men had greater comorbidity measured with the Charlson index [5 (IQR: 3-7) vs. 4 (IQR: 3-6); p = 0.002]. In the multimorbidity criteria scale, heart failure, autoimmune diseases, dementia, and osteoarticular diseases were more frequent in women, while ischemic heart disease, chronic respiratory diseases, and neoplasms predominated in men. In the analysis of grouped patterns, neurological and osteoarticular diseases were more frequent in females, while respiratory and cancer predominated in males. We did not find gender differences for in-hospital mortality, 1-month readmissions, or 1-year mortality. In the multivariate analysis age, the Charlson, Barthel and PROFUND indexes, along with previous admissions, were independent predictors of 1-year mortality, while gender was non-significant. The Charlson and PROFUND indexes predicted mortality during follow-up more accurately in men than in women (AUC 0.70 vs. 0.57 and 0.74 vs. 0.62, respectively), with both p<0.001. In conclusion, our study shows differing patterns of multimorbidity by gender, with greater functional impairment in women and more comorbidity in men, although without differences in the prognosis. Moreover, some of these prognostic indicators had differing accuracy for the genders in predicting mortality.
Emphysema, a component of chronic obstructive pulmonary disease (COPD), is characterized by irreversible alveolar destruction that results in a progressive decline in lung function. This alveolar destruction is caused by cigarette smoke, the most important risk factor for COPD. Only 15%‐20% of smokers develop COPD, suggesting that unknown factors contribute to disease pathogenesis. We postulate that the aryl hydrocarbon receptor (AHR), a receptor/transcription factor highly expressed in the lungs, may be a new susceptibility factor whose expression protects against COPD. Here, we report that Ahr‐deficient mice chronically exposed to cigarette smoke develop airspace enlargement concomitant with a decline in lung function. Chronic cigarette smoke exposure also increased cleaved caspase‐3, lowered SOD2 expression, and altered MMP9 and TIMP‐1 levels in Ahr‐deficient mice. We also show that people with COPD have reduced expression of pulmonary and systemic AHR, with systemic AHR mRNA levels positively correlating with lung function. Systemic AHR was also lower in never‐smokers with COPD. Thus, AHR expression protects against the development of COPD by controlling interrelated mechanisms involved in the pathogenesis of this disease. This study identifies the AHR as a new, central player in the homeostatic maintenance of lung health, providing a foundation for the AHR as a novel therapeutic target and/or predictive biomarker in chronic lung disease.
Background:There is a paucity of information on patient characteristics associated with enrolment under voluntary programs (e.g. incentive payments) implemented within fee-for-service systems. We explored patient characteristics associated with enrolment under these programs in British Columbia and Quebec. Methods:We used linked administrative data and a cross-sectional design to compare people aged 40 years or more enrolled under voluntary programs to those who were eligible but not enrolled. We examined 2 programs in Quebec (enrolment of vulnerable patients with qualifying conditions [implemented in 2003] and enrolment of the general population [2009]) and 3 in BC (Chronic disease incentive [2003], Complex care incentive [2007] and enrolment of the general population [A GP for Me, 2013]). We used logistic regression to estimate the odds of enrolment by neighbourhood income, rural versus urban residence, previous treatment for mental illness, previous treatment for substance use disorder and use of health care services before program implementation, controlling for characteristics linked to program eligibility. Results:In Quebec, we identified 1 569 010 people eligible for the vulnerable enrolment program (of whom 505 869 [32.2%] were enrolled within the first 2 yr of program implementation) and 2 394 923 for the general enrolment program (of whom 352 380 [14.7%] were enrolled within the first 2 yr). In BC, we identified 133 589 people eligible for the Chronic disease incentive, 47 619 for the Complex care incentive and 1 349 428 for A GP for Me; of these, 60 764 (45.5%), 28 273 (59.4%) and 1 066 714 (79.0%), respectively, were enrolled within the first 2 years. The odds of enrolment were higher in higher-income neighbourhoods for programs without enrolment criteria (adjusted odds ratio [OR] comparing highest to lowest quintiles 1.21 [95% confidence interval (CI) 1.20-1.23] in Quebec and 1.67 [95% CI 1.64-1.69] in BC) but were similar across neighbourhood income quintiles for programs with health-related eligibility criteria. The odds of enrolment by urban versus rural location varied by program. People treated for substance use disorders had lower odds of enrolment in all programs (adjusted OR 0.60-0.72). Compared to people eligible but not enrolled, those enrolled had similar or higher numbers of primary care visits and longitudinal continuity of care in the year before enrolment.Interpretation: People living in lower-income neighbourhoods and those treated for substance use disorders were less likely than people in higher-income neighbourhoods and those not treated for such disorders to be enrolled in programs without health-related eligibility criteria. Other strategies are needed to promote equitable access to primary care.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.