Four patients with a history of acute exacerbations of COPD: implementing the CHEST/Canadian Thoracic Society guidelines for preventing exacerbations

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/ by/4.0

Multi-component assessment of chronic obstructive pulmonary disease: an evaluation of the ADO and DOSE indices and the global obstructive lung disease categories in international primary care data sets

Acknowledgements We thank Sian Williams of the International Primary Care Respiratory Group for her help and encouragement with the project. The OPCRD database was made available courtesy of the Respiratory Effectiveness Group and RIRL and the data were kindly prepared for analysis by Julie von Ziegenweidt. Funding The International Primary Care Respiratory Group (IPCRG) provided funding for this research project as an UNLOCK group study for which the funding was obtained through an unrestricted grant by Novartis AG, Basel, Switzerland. The latter funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Database access for the OPCRD was provided by the Respiratory Effectiveness Group (REG) and Research in Real Life; the OPCRD statistical analysis was funded by REG. The Bocholtz Study was funded by PICASSO for COPD, an initiative of Boehringer Ingelheim, Pfizer and the Caphri Research Institute, Maastricht University, The Netherlands.Peer reviewedPublisher PD

Use of low-dose oral theophylline as an adjunct to inhaled corticosteroids in preventing exacerbations of chronic obstructive pulmonary disease: study protocol for a randomised controlled trial.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with high morbidity, mortality, and health-care costs. An incomplete response to the anti-inflammatory effects of inhaled corticosteroids is present in COPD. Preclinical work indicates that 'low dose' theophylline improves steroid responsiveness. The Theophylline With Inhaled Corticosteroids (TWICS) trial investigates whether the addition of 'low dose' theophylline to inhaled corticosteroids has clinical and cost-effective benefits in COPD. METHOD/DESIGN: TWICS is a randomised double-blind placebo-controlled trial conducted in primary and secondary care sites in the UK. The inclusion criteria are the following: an established predominant respiratory diagnosis of COPD (post-bronchodilator forced expiratory volume in first second/forced vital capacity [FEV1/FVC] of less than 0.7), age of at least 40 years, smoking history of at least 10 pack-years, current inhaled corticosteroid use, and history of at least two exacerbations requiring treatment with antibiotics or oral corticosteroids in the previous year. A computerised randomisation system will stratify 1424 participants by region and recruitment setting (primary and secondary) and then randomly assign with equal probability to intervention or control arms. Participants will receive either 'low dose' theophylline (Uniphyllin MR 200 mg tablets) or placebo for 52 weeks. Dosing is based on pharmacokinetic modelling to achieve a steady-state serum theophylline of 1-5 mg/l. A dose of theophylline MR 200 mg once daily (or placebo once daily) will be taken by participants who do not smoke or participants who smoke but have an ideal body weight (IBW) of not more than 60 kg. A dose of theophylline MR 200 mg twice daily (or placebo twice daily) will be taken by participants who smoke and have an IBW of more than 60 kg. Participants will be reviewed at recruitment and after 6 and 12 months. The primary outcome is the total number of participant-reported COPD exacerbations requiring oral corticosteroids or antibiotics during the 52-week treatment period. DISCUSSION: The demonstration that 'low dose' theophylline increases the efficacy of inhaled corticosteroids in COPD by reducing the incidence of exacerbations is relevant not only to patients and clinicians but also to health-care providers, both in the UK and globally. TRIAL REGISTRATION: Current Controlled Trials ISRCTN27066620 was registered on Sept. 19, 2013, and the first subject was randomly assigned on Feb. 6, 2014

Simulation-Based Estimates of Effectiveness and Cost-Effectiveness of Smoking Cessation in Patients with Chronic Obstructive Pulmonary Disease

International audienceBACKGROUND: The medico-economic impact of smoking cessation considering a smoking patient with chronic obstructive pulmonary disease (COPD) is poorly documented. OBJECTIVE: Here, considering a COPD smoking patient, the specific burden of continuous smoking was estimated, as well as the effectiveness and the cost-effectiveness of smoking cessation. METHODS: A multi-state Markov model adopting society's perspective was developed. Simulated cohorts of English COPD patients who are active smokers (all severity stages combined or patients with the same initial severity stage) were compared to identical cohorts of patients who quit smoking at cohort initialization. Life expectancy, quality adjusted life-years (QALY), disease-related costs, and incremental cost-effectiveness ratio (ICER: £/QALY) were estimated, considering smoking cessation programs with various possible scenarios of success rates and costs. Sensitivity analyses included the variation of model key parameters. PRINCIPAL FINDINGS: At the horizon of a smoking COPD patient's remaining lifetime, smoking cessation at cohort intitialization, relapses being allowed as observed in practice, would result in gains (mean) of 1.27 life-years and 0.68 QALY, and induce savings of -1824 £/patient in the disease-related costs. The corresponding ICER was -2686 £/QALY. Smoking cessation resulted in 0.72, 0.69, 0.64 and 0.42 QALY respectively gained per mild, moderate, severe, and very severe COPD patient, but was nevertheless cost-effective for mild to severe COPD patients in most scenarios, even when hypothesizing expensive smoking cessation intervention programmes associated with low success rates. Considering a ten-year time horizon, the burden of continuous smoking in English COPD patients was estimated to cost a total of 1657 M£ while 452516 QALY would be simultaneously lost. CONCLUSIONS: The study results are a useful support for the setting of smoking cessation programmes specifically targeted to COPD patients

Budesonide/formoterol as effective as prednisolone plus formoterol in acute exacerbations of COPD A double-blind, randomised, non-inferiority, parallel-group, multicentre study

<p>Abstract</p> <p>Background</p> <p>Oral corticosteroids and inhaled bronchodilators with or without antibiotics represent standard treatment of COPD exacerbations of moderate severity. Frequent courses of oral steroids may be a safety issue. We wanted to evaluate in an out-patient setting whether a 2-week course of inhaled budesonide/formoterol would be equally effective for treatment of acute COPD exacerbations as standard therapy in patients judged by the investigator not to require hospitalisation.</p> <p>Methods</p> <p>This was a double-blind, randomised, non-inferiority, parallel-group, multicentre study comparing two treatment strategies; two weeks' treatment with inhaled budesonide/formoterol (320/9 μg, qid) was compared with prednisolone (30 mg once daily) plus inhaled formoterol (9 μg bid) in patients with acute exacerbations of COPD attending a primary health care centre. Inclusion criteria were progressive dyspnoea for less than one week, FEV₁30–60% of predicted normal after acute treatment with a single dose of oral corticosteroid plus nebulised salbutamol/ipratropium bromide and no requirement for subsequent immediate hospitalisation, i.e the clinical status after the acute treatment allowed for sending the patient home.</p> <p>A total of 109 patients (mean age 67 years, 33 pack-years, mean FEV₁45% of predicted) were randomized to two weeks' double-blind treatment with budesonide/formoterol or prednisolone plus formoterol and subsequent open-label budesonide/formoterol (320/9 μg bid) for another 12 weeks. Change in FEV₁was the primary efficacy variable. Non-inferiority was predefined.</p> <p>Results</p> <p>Non-inferiority of budesonide/formoterol was proven because the lower limit of FEV₁-change (97.5% CI) was above 90% of the efficacy of the alternative treatment. Symptoms, quality of life, treatment failures, need for reliever medication (and exacerbations during follow-up) did not differ between the groups. No safety concerns were identified.</p> <p>Conclusion</p> <p>High dose budesonide/formoterol was as effective as prednisolone plus formoterol for the ambulatory treatment of acute exacerbations in non-hospitalized COPD patients. An early increase in budesonide/formoterol dose may therefore be tried before oral corticosteroids are used.</p> <p>Clinical trial registration</p> <p>NCT00259779</p

Clinical presentation and predictors of outcome in patients with severe acute exacerbation of chronic obstructive pulmonary disease requiring admission to intensive care unit

BACKGROUND: Severe acute exacerbation of chronic obstructive pulmonary disease (AE-COPD) is a common reason for emergency room (ER) visit about which little has been documented from India. METHODS: Prospective study of the clinical presentation and predictors of outcome in 116 patients presenting with severe AE-COPD requiring admission to the medical intensive care unit between January 2000 and December 2004. RESULTS: Their mean age was 62.1 ± 9.8 years. There were 102 males. Mean duration of COPD was 7.2 ± 5.8 years. All males were smokers (22.3 ± 11.2 pack years); 35.2% smoked cigarettes and 64.8% smoked bidis. All women were exposed to domestic fuel. Associated co-morbid illnesses were present in 81 patients (69.8%); 53(45.7%) had one co-morbid illness and the remaining 28 (54.3%) had two or more co-morbid illnesses. Evidence of past pulmonary tuberculosis (PTB) was present in 28.4% patients; 5 patients who also had type II diabetes mellitus had active PTB. Arterial blood gas analysis revealed respiratory failure in 40 (33.8%) patients (type I 17.5% and type II 82.5%). Invasive mechanical ventilation was required in 18 patients. Sixteen (13.7%) patients died. Stepwise multivariate logistic regression analysis revealed need for invasive ventilation (OR 45.809, 95%CI 607.46 to 3.009;p < 0.001); presence of co-morbid illness (OR 0.126, 95%CI 0.428 to 0.037;p < 0.01) and hypercapnia (OR 0.114, 95%CI 1.324 to 0.010;p < 0.05) were predictors of death. CONCLUSION: Co-morbid conditions and metabolic abnormalities render the diagnosis of AE-COPD difficult and also contribute to mortality. High prevalence of past PTB and active PTB in patients with AE-COPD suggests an intriguing relationship between smoking, PTB and COPD which merits further study

The IRYSS-COPD appropriateness study: objectives, methodology, and description of the prospective cohort

<p>Abstract</p> <p>Background</p> <p>Patients with chronic obstructive pulmonary disease (COPD) often experience exacerbations of the disease that require hospitalization. Current guidelines offer little guidance for identifying patients whose clinical situation is appropriate for admission to the hospital, and properly developed and validated severity scores for COPD exacerbations are lacking. To address these important gaps in clinical care, we created the IRYSS-COPD Appropriateness Study.</p> <p>Methods/Design</p> <p>The RAND/UCLA Appropriateness Methodology was used to identify appropriate and inappropriate scenarios for hospital admission for patients experiencing COPD exacerbations. These scenarios were then applied to a prospective cohort of patients attending the emergency departments (ED) of 16 participating hospitals. Information was recorded during the time the patient was evaluated in the ED, at the time a decision was made to admit the patient to the hospital or discharge home, and during follow-up after admission or discharge home. While complete data were generally available at the time of ED admission, data were often missing at the time of decision making. Predefined assumptions were used to impute much of the missing data.</p> <p>Discussion</p> <p>The IRYSS-COPD Appropriateness Study will validate the appropriateness criteria developed by the RAND/UCLA Appropriateness Methodology and thus better delineate the requirements for admission or discharge of patients experiencing exacerbations of COPD. The study will also provide a better understanding of the determinants of outcomes of COPD exacerbations, and evaluate the equity and variability in access and outcomes in these patients.</p