A clinical prediction model for hospitalized COPD exacerbations based on “treatable traits”

10.2147/COPD.S194922International Journal of COPD14719-72

Withdrawal of inhaled corticosteroids versus continuation of triple therapy in patients with COPD in real life : Observational comparative effectiveness study

FUNDING The study was funded by a grant from Boehringer Ingelheim. ACKNOWLEDGMENTS The study was designed and conducted by the Respiratory Effectiveness Group (REG; www.regresearchnetwork.org; Ely, UK) and data was delivered by Optimum Patient Care (OPC; www.optimumpatientcare.org) with support from Derek Skinner.Peer reviewedPublisher PD

Airway inflammation contributes to health status in COPD:a cross-sectional study

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by irreversible airflow limitation and airway inflammation, accompanied by decreased health status. It is still unknown which factors are responsible for the impaired health status in COPD. We postulated that airway inflammation negatively contributes to health status in COPD. METHODS: In 114 COPD patients (99 male, age: 62 ± 8 yr, 41 [31–55] pack-years, no inhaled or oral corticosteroids, postbronchodilator FEV(1): 63 ± 9% pred, FEV(1)/IVC: 48 ± 9%) we obtained induced sputum and measured health status (St. George's respiratory questionnaire (SGRQ)), postbronchodilator FEV(1), hyperinflation (RV/TLC), and airway hyperresponsiveness to methacholine (PC(20)). Sputum was induced by hypertonic saline and differential cell counts were obtained in 102 patients. RESULTS: Univariate analysis showed that SGRQ total and symptom score were positively associated with % sputum macrophages (r = 0.20, p = 0.05; and r = 0.20, p = 0.04, respectively). Multiple regression analysis confirmed these relationships, providing significant contributions of % sputum macrophages (B = 0.25, p = 0.021) and RV/TLC (B = 0.60, p = 0.002) to SGRQ total score. Furthermore, SGRQ symptom score was associated with % sputum macrophages (B = 0.30, p = 0.03) and RV/TLC (B = 0.48, p = 0.044), whilst SGRQ activity score was associated with % sputum macrophages (B = 0.46, p = 0.002), RV/TLC (B = 0.61, p = 0.015), and PC(20 )(B = -9.3, p = 0.024). Current smoking and FEV(1 )were not significantly associated with health status in the multiple regression analysis. CONCLUSION: We conclude that worse health status in COPD patients is associated with higher inflammatory cell counts in induced sputum. Our findings suggest that airway inflammation and hyperinflation independently contribute to impaired health status in COPD. This may provide a rationale for anti-inflammatory therapy in this disease

Corticosteroid Resistance in Smokers—A Substudy Analysis of the CORTICO-COP Randomised Controlled Trial

From MDPI via Jisc Publications RouterHistory: accepted 2021-06-16, pub-electronic 2021-06-21Publication status: PublishedFunder: Danish Regions Medical Fund; Grant(s): 5894/16Funder: Sundhed og Sygdom, Det Frie Forskningsråd; Grant(s): 6110-00268BThe CORTICO-COP trial showed that eosinophil-guided corticosteroid-sparing treatment for acute exacerbation of chronic obstructive pulmonary disease was non-inferior to standard of care and decreased the accumulated dose of systemic corticosteroids that patients were exposed to by approximately 60%. Smoking status has been shown to affect corticosteroid responsiveness. This post hoc analysis investigated whether eosinophil-guided treatment is non-inferior to conventional treatment in current smokers. The main analysis of current smokers showed no significant difference in the primary endpoint, days alive, and out of hospital within 14 days between the control group (mean, 9.8 days; 95% confidence interval (CI), 8.7–10.8) and the eosinophil-guided group (mean, 8.7 days; 95% CI, 7.5–9.9; p = 0.34). Secondary analyses of the number of exacerbations or deaths, the number of intensive care unit admissions or deaths, lung function improvement, and change in health-related quality of life also showed no significant differences between the two groups. The results of a sensitivity analysis of ex-smokers are consistent with the main analysis. Our results suggest that eosinophil-guided treatment is non-inferior to standard of care in current smokers and ex-smokers. Because data on the impact of smoking status on eosinophil-guided treatments are sparse, more randomised trials are needed to confirm our results

Predictive value of control of COPD for risk of exacerbations : An international, prospective study

Acknowledgements Collaborators/REG Investigators: Spain: Marc Miravitlles, Cristina Esquinas, Miriam Barrecheguren, Alexa Nuñez, Hospital Universitari Vall d'Hebron, Barcelona. Bernardino Alcazar, Hospital de Alta Resolución de Loja. Juan Luis García‐Rivero, Karina Hueso, Hospital Comarcal de Laredo, Cantabria. Miguel Roman‐Rodríguez, Primary Health‐Care Center Son Pisà, IB‐Salut, Palma de Mallorca. Poland: Pawel Sliwinsk, Katarzyna Iwan, Jacek Kolakowski, Institute of Tuberculosis and Lung Diseases, Warsaw. Korea: Chin Kook Rhee, Esther Ahn, St Mary's Hospital, Seoul. Singapore: Jessica Tan, Therese Laperre, Karen Tan Li Leng, Nicole Chia, Ong Thun How, Syifa Binte Shamsuddin, Sherine Lim Shu Gim, Yap Chwee Bee, Soh Rui Ya, Singapore General Hospital. Augustine Tee, Jun Jie Yan, Samuel Hong, William Tan, Changi General Hospital. UK: Victoria Carter, Latife Hardaker, Andrew McLaughlin, Optimum Patient Care, Cambridge. Malta: Caroline Gouder, Mater Dei Hospital. Ireland: Richard W Costello, Royal College of Surgeons, Dublin. The study was funded by an unrestricted grant from Novartis AG. The study was designed and coordinated by the Respiratory Effectiveness Group (REG; www.effectivenessevaluation.org; Cambridge, UK) and delivered by Optimum Patient Care (OPC; www.optimumpatientcare.org).Peer reviewedPostprin

Prediction of Long-Term Benefits of Inhaled Steroids by Phenotypic Markers in Moderate-to-Severe COPD:A Randomized Controlled Trial

BACKGROUND:The decline in lung function can be reduced by long-term inhaled corticosteroid (ICS) treatment in subsets of patients with chronic obstructive pulmonary disease (COPD). We aimed to identify which clinical, physiological and non-invasive inflammatory characteristics predict the benefits of ICS on lung function decline in COPD. METHODS:Analysis was performed in 50 steroid-naive compliant patients with moderate to severe COPD (postbronchodilator forced expiratory volume in one second (FEV1), 30-80% of predicted, compatible with GOLD stages II-III), age 45-75 years, >10 packyears smoking and without asthma. Patients were treated with fluticasone propionate (500 μg bid) or placebo for 2.5 years. Postbronchodilator FEV1, dyspnea and health status were measured every 3 months; lung volumes, airway hyperresponsiveness (PC20), and induced sputum at 0, 6 and 30 months. A linear mixed effect model was used for analysis of this hypothesis generating study. RESULTS:Significant predictors of attenuated FEV1-decline by fluticasone treatment compared to placebo were: fewer packyears smoking, preserved diffusion capacity, limited hyperinflation and lower inflammatory cell counts in induced sputum (p<0.04). CONCLUSIONS:Long-term benefits of ICS on lung function decline in patients with moderate-to-severe COPD are most pronounced in patients with fewer packyears, and less severe emphysema and inflammation. These data generate novel hypotheses on phenotype-driven therapy in COPD. TRIAL REGISTRATION:ClinicalTrials.gov NCT00158847

Smoking cessation and bronchial epithelial remodelling in COPD: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Chronic Obstructive Pulmonary Disease (COPD) is associated with bronchial epithelial changes, including squamous cell metaplasia and goblet cell hyperplasia. These features are partially attributed to activation of the epidermal growth factor receptor (EGFR). Whereas smoking cessation reduces respiratory symptoms and lung function decline in COPD, inflammation persists. We determined epithelial proliferation and composition in bronchial biopsies from current and ex-smokers with COPD, and its relation to duration of smoking cessation.</p> <p>Methods</p> <p>114 COPD patients were studied cross-sectionally: 99 males/15 females, age 62 ± 8 years, median 42 pack-years, no corticosteroids, current (n = 72) or ex-smokers (n = 42, median cessation duration 3.5 years), postbronchodilator FEV₁63 ± 9% predicted. Squamous cell metaplasia (%), goblet cell (PAS/Alcian Blue⁺) area (%), proliferating (Ki-67⁺) cell numbers (/mm basement membrane), and EGFR expression (%) were measured in intact epithelium of bronchial biopsies.</p> <p>Results</p> <p>Ex-smokers with COPD had significantly less epithelial squamous cell metaplasia, proliferating cell numbers, and a trend towards reduced goblet cell area than current smokers with COPD (p = 0.025, p = 0.001, p = 0.081, respectively), but no significant difference in EGFR expression. Epithelial features were not different between short-term quitters (<3.5 years) and current smokers. Long-term quitters (≥3.5 years) had less goblet cell area than both current smokers and short-term quitters (medians: 7.9% vs. 14.4%, p = 0.005; 7.9% vs. 13.5%, p = 0.008; respectively), and less proliferating cell numbers than current smokers (2.8% vs. 18.6%, p < 0.001).</p> <p>Conclusion</p> <p>Ex-smokers with COPD had less bronchial epithelial remodelling than current smokers, which was only observed after long-term smoking cessation (>3.5 years).</p> <p>Trial registration</p> <p>NCT00158847</p