Beta2-adrenoreceptor agonists and long-term risk of Parkinson's disease.

INTRODUCTION: There is limited information on how the association between Parkinson's disease and the use of beta2-adrenoreceptor (ß2AR) agonists varies among groups of short-, long-, and ultra-long-acting ß2AR agonists (SABA, LABA and ultraLABA). METHODS: In this prospective study of the Norwegian population, we estimated the incidence of Parkinson's disease according to exposure to ß2AR agonists as a time-dependent variable by means of Cox regression. We adjusted for educational level, comorbidity and performed a sensitivity analysis excluding individuals with chronic obstructive pulmonary disease (COPD), all factors associated with smoking. Anticholinergics and corticosteroids as drugs with the same indication were analyzed for comparison. RESULTS: In the follow-up period from 2005 to 2019, 15,807 incident Parkinson's cases were identified. After adjustments for sex, education and age as the timescale, SABA (Hazard ratio (HR) = 0.84; 95%CI: 0.79, 0.89; p < 0.001), LABA (HR = 0.85; 95%CI: 0.81, 0.90; p < 0.001) and ultraLABA (HR = 0.6; 95%CI: 0.49, 0.73; p < 0.001) were all associated with a lower risk of Parkinson's disease. After exclusion of COPD patients, corticosteroids and anticholinergics were no longer inversely associated, whereas ß2AR agonists remained associated. CONCLUSION: Of drugs with the same indication of use, only ß2AR agonists remained inversely associated with PD risk after all adjustments, with ultraLABA displaying the overall strongest association. Although the precision of the estimate is limited by the modest number of exposed PD cases without COPD, the association is intriguing and suggest that longer-acting, more lipophilic, and thus likely more brain-penetrant ß2AR agonists could be prioritized for further studies.

The Relationship of Educational Attainment with Pulmonary Emphysema and Airway Wall Thickness.

RATIONALE: Low educational attainment is a risk factor of chronic obstructive pulmonary disease (COPD). There is limited knowledge on the relationship between educational level and computed tomography measures of emphysema and airway wall thickness (AWT). OBJECTIVES: We hypothesized that low educational attainment is associated with increased emphysema and AWT in ever-smokers with and without COPD. METHODS: We included 462 and 485 ever-smokers with and without COPD in a cross-sectional study, aged 40-86 years. The sample was divided into groups reflecting educational attainment: primary, secondary, and university. We performed linear regression to examine associations between educational attainment and both emphysema and AWT separately for those with and without COPD. We adjusted for sex, age, smoking status, age of onset of smoking, pack-years, height, and body mass index. MEASUREMENTS AND MAIN RESULTS: Compared with university education, in subjects with COPD, primary education was associated with a 68.1% (95% confidence interval = 14.2-147.6%; P = 0.01) relative increase in emphysema and secondary education was associated with a 50.6% (95% confidence interval = 5.7-114.6%; P = 0.02) relative increase. There was a nonsignificant trend toward an association between lower educational attainment and increased emphysema among those without COPD (P = 0.18), yet greater age appeared to modify this association (P = 0.01). We did not detect significant linear relationships between educational attainment and AWT in subjects with or without COPD. CONCLUSIONS: Lower educational attainment was associated with increased emphysema among adults with COPD. Among those without COPD, this association was more pronounced with increasing age. No significant linear relationship between educational attainment and AWT was found. Clinicians treating adults with emphysema should keep in mind that factors related to low education beyond that of smoking and occupational dust exposure might be of importance to the disease.

Quantitative CT: Associations between Emphysema, Airway Wall Thickness and Body Composition in COPD.

The objective of the present study was to determine the association between CT phenotypes-emphysema by low attenuation area and bronchitis by airway wall thickness-and body composition parameters in a large cohort of subjects with and without COPD. In 452 COPD subjects and 459 subjects without COPD, CT scans were performed to determine emphysema (%LAA), airway wall thickness (AWT-Pi10), and lung mass. Muscle wasting based on FFMI was assessed by bioelectrical impedance. In both the men and women with COPD, FFMI was negatively associated with %LAA. FMI was positively associated with AWT-Pi10 in both subjects with and without COPD. Among the subjects with muscle wasting, the percentage emphysema was high, but the predictive value was moderate. In conclusion, the present study strengthens the hypothesis that the subgroup of COPD cases with muscle wasting have emphysema. Airway wall thickness is positively associated with fat mass index in both subjects with and without COPD.

Quantitative CT measures of emphysema and airway wall thickness are related to D(L)CO.

UNLABELLED: There is limited knowledge on the relationship between diffusing capacity of the lung for carbon monoxide (D(L)CO) and quantitative computed tomography (CT) measures of emphysema and airway wall thickness. STUDY QUESTION: What is the relationship between D(L)CO and the quantitative CT measures of emphysema and airway wall thickness in subjects with and without COPD? METHODS: We included 288 COPD subjects (70% men) and 425 non-COPD subjects (54% men). All subjects were current or ex-smokers older than 40 years and all subjects underwent spirometry, diffusing capacity tests and CT examination. Quantitative CT measures included % low attenuation areas < -950 HU (%LAA) and standardized airway wall thickness (AWT-Pi10). RESULTS: Multiple linear regression analyses showed significant associations between D(L)CO and both %LAA and AWT-Pi10 in the COPD group. The adjusted regression coefficients (SE) for D(L)CO (mmol min(-1) kPa(-1)) were -1.15 (0.11) per 10% increase in %LAA and 0.08 (0.03) per 0.1 mm increase in AWT-Pi10, and the models' adjusted R(2) was 0.65 and 0.49, respectively. CONCLUSIONS: CT measured emphysema explains a large fraction of the variation of D(L)CO among COPD subjects, and more so in men. Airway wall thickness is also significantly associated with D(L)CO, but explains a much smaller fraction of the variation.

Quantitative computed tomography measures of emphysema and airway wall thickness are related to respiratory symptoms.

RATIONALE: There is limited knowledge about the relationship between respiratory symptoms and quantitative high-resolution computed tomography measures of emphysema and airway wall thickness. OBJECTIVES: To describe the ability of these measures of emphysema and airway wall thickness to predict respiratory symptoms in subjects with and without chronic obstructive pulmonary disease (COPD). METHODS: We included 463 subjects with chronic obstructive pulmonary disease (COPD) (65% men) and 488 subjects without COPD (53% men). All subjects were current or ex-smokers older than 40 years. They underwent spirometry and high-resolution computed tomography examination, and completed an American Thoracic Society questionnaire on respiratory symptoms. MEASUREMENTS AND MAIN RESULTS: Median (25th percentile, 75th percentile) percent low-attenuation areas less than -950 Hounsfield units (%LAA) was 7.0 (2.2, 17.8) in subjects with COPD and 0.5 (0.2, 1.3) in subjects without COPD. Mean (SD) standardized airway wall thickness (AWT) at an internal perimeter of 10 mm (AWT-Pi10) was 4.94 (0.33) mm in subjects with COPD and 4.77 (0.29) in subjects without COPD. Both %LAA and AWT-Pi10 were independently and significantly related to the level of dyspnea among subjects with COPD, even after adjustments for percent predicted FEV(1). AWT-Pi10 was significantly related to cough and wheezing in subjects with COPD, and to wheezing in subjects without COPD. Odds ratios (95% confidence intervals) for increased dyspnea in subjects with COPD and in subjects without COPD were 1.9 (1.5-2.3) and 1.9 (0.6-6.6) per 10% increase in %LAA, and 1.07 (1.01-1.14) and 1.11 (0.99-1.24) per 0.1-mm increase in AWT-Pi10, respectively. CONCLUSIONS: Quantitative computed tomography assessment of the lung parenchyma and airways may be used to explain the presence of respiratory symptoms beyond the information offered by spirometry.