Can We Use Lung Function Thresholds and Respiratory Symptoms to Identify Pre-Chronic Obstructive Pulmonary Disease? A Prospective, Population-based Cohort Study.

Rationale: The term "pre-chronic obstructive pulmonary disease" ("pre-COPD") refers to individuals at high risk of developing COPD who do not meet conventional spirometric criteria for airflow obstruction. New approaches to identifying these individuals are needed, particularly in younger populations. Objectives: To determine whether lung function thresholds and respiratory symptoms can be used to identify individuals at risk of developing COPD. Methods: The Tasmanian Longitudinal Health Study comprises a population-based cohort first studied in 1968 (at age 7 yr). Respiratory symptoms, pre- and post-bronchodilator (BD) spirometry, diffusing capacity, and static lung volumes were measured in a subgroup at age 45, and the incidence of COPD was assessed at age 53. For each lung function measure, z-scores were calculated using Global Lung Function Initiative references. The optimal threshold for best discrimination of COPD incidence was determined by the unweighted Youden index. Measurements and Main Results: Among 801 participants who did not have COPD at age 45, the optimal threshold for COPD incidence by age 53 was pre-BD FEV1/FVC z-score less than -1.264, corresponding to the lowest 10th percentile. Those below this threshold had a 36-fold increased risk of developing COPD over an 8-year follow-up period (risk ratio, 35.8; 95% confidence interval, 8.88 to 144), corresponding to a risk difference of 16.4% (95% confidence interval, 3.7 to 67.4). The sensitivity was 88%, and the specificity was 87%. Positive and negative likelihood ratios were 6.79 and 0.14, respectively. Respiratory symptoms, post-BD spirometry, diffusing capacity, and static lung volumes did not improve on the classification achieved by pre-BD FEV1/FVC alone. Conclusions: This is the first study, to our knowledge, to evaluate the discriminatory accuracy of spirometry, diffusing capacity, and static lung volume thresholds for COPD incidence in middle-aged adults. Our findings support the inclusion of pre-BD spirometry in the physiological definition of pre-COPD and indicate that pre-BD FEV1/FVC at the 10th percentile accurately identifies individuals at high risk of developing COPD in community-based settings.

Exposure to household air pollution over 10†years is related to asthma and lung function decline.

INTRODUCTION: We investigated if long-term household air pollution (HAP) is associated with asthma and lung function decline in middle-aged adults, and whether these associations were modified by glutathione S-transferase (GST) gene variants, ventilation and atopy. MATERIALS AND METHODS: Prospective data on HAP (heating, cooking, mould and smoking) and asthma were collected in the Tasmanian Longitudinal Health Study (TAHS) at mean ages 43 and 53 years (n=3314). Subsamples had data on lung function (n=897) and GST gene polymorphisms (n=928). Latent class analysis was used to characterise longitudinal patterns of exposure. Regression models assessed associations and interactions. RESULTS: We identified seven longitudinal HAP profiles. Of these, three were associated with persistent asthma, greater lung function decline and % reversibility by age 53 years compared with the "Least exposed" reference profile for those who used reverse-cycle air conditioning, electric cooking and no smoking. The "All gas" (OR 2.64, 95% CI 1.22-5.70), "Wood heating/smoking" (OR 2.71, 95% CI 1.21-6.05) and "Wood heating/gas cooking" (OR 2.60, 95% CI 1.11-6.11) profiles were associated with persistent asthma, as well as greater lung function decline and % reversibility. Participants with the GSTP1 Ile/Ile genotype were at a higher risk of asthma or greater lung function decline when exposed compared with other genotypes. Exhaust fan use and opening windows frequently may reduce the adverse effects of HAP produced by combustion heating and cooking on current asthma, presumably through increasing ventilation. CONCLUSIONS: Exposures to wood heating, gas cooking and heating, and tobacco smoke over 10 years increased the risks of persistent asthma, lung function decline and % reversibility, with evidence of interaction by GST genes and ventilation.

Early menarche is associated with lower adult lung function: A longitudinal cohort study from the first to sixth decade of life.

BACKGROUND AND OBJECTIVE: Early menarche is increasing in prevalence worldwide, prompting clinical and public health interest on its links with pulmonary function. We aimed to investigate the relationship between early menarche and lung function in middle age. METHODS: The population-based Tasmanian Longitudinal Health Study (born 1961; n = 8583), was initiated in 1968. The 5th Decade follow-up data (mean age: 45 years) included age at menarche and complex lung function testing. The 6th Decade follow-up (age: 53 years) repeated spirometry and gas transfer factor. Multiple linear regression and mediation analyses were performed to determine the association between age at menarche and adult lung function and investigate biological pathways, including the proportion mediated by adult-attained height. RESULTS: Girls reporting an early menarche (<12 years) were measured to be taller with greater lung function at age 7 years compared with those reporting menarche ≥12 years. By 45 years of age, they were shorter and had lower post-bronchodilator (BD) forced expiratory volume in 1 s (adjusted mean difference: -133 mL; 95% CI: -233, -33), forced vital capacity (-183 mL; 95% CI: -300, -65) and functional residual capacity (-168 mL; 95% CI: -315, -21). Magnitudes of spirometric deficits were similar at age 53 years. Forty percent of these total effects were mediated through adult-attained height. CONCLUSION: Early menarche was associated with reduced adult lung function. This is the first study to investigate post-BD outcomes and quantify the partial role of adult height in this association.

Pragmatic randomised controlled trial of a personalised intervention for carers of people requiring home oxygen therapy.

We used a pragmatic randomised controlled trial to evaluate a behavioural change strategy targeting carers of chronically hypoxaemic patients using long-term home oxygen therapy. Intervention group carers participated in personalised educational sessions focusing on motivating carers to take actions to assist patients. All patients received usual care. Effectiveness was measured through a composite event of patient survival to hospitalisation, residential care admission or death to 12 months. Secondary outcomes at baseline, 3, 6 and 12 months included carer and patient emotional and physical well-being. No difference between intervention (n = 100) and control (n = 97) patients was found for the composite outcome (hazard ratio (HR) 1.22, 95% confidence interval (CI) = 0.89, 1.68; p = 0.22). Improved fatigue, mastery, vitality and general health occurred in intervention group patients (all p values < 0.05). No benefits were seen in carer outcomes. Mortality was significantly higher in intervention patients (HR = 2.01, 95% CI = 1.00, 4.14; p = 0.05; adjusted for Australia-modified Karnofsky Performance Status), with a significant diagnosis-intervention interaction (p = 0.028) showing higher mortality in patients with COPD (HR 4.26; 95% CI = 1.60, 11.35) but not those with interstitial lung disease (HR 0.83; 95% CI = 0.28, 2.46). No difference was detected in the primary outcome, but patient mortality was higher when carers had received the intervention, especially in the most disabled patients. Trials examining behavioural change interventions in severe disease should stratify for functionality, and both risks and benefits should be independently monitored. Trial registration: Australian New Zealand Clinical Trials Registry (ACTRN12607000177459).

Exacerbation action plans for patients with COPD and comorbidities: a randomised controlled trial.

This international randomised controlled trial evaluated whether COPD patients with comorbidities, trained in using patient-tailored multidisease exacerbation action plans, had fewer COPD exacerbation days than usual care (UC).COPD patients (Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification II-IV) with ≥1 comorbidity (ischaemic heart disease, heart failure, diabetes, anxiety, depression) were randomised to a patient-tailored self-management intervention (n=102) or UC (n=99). Daily symptom diaries were completed for 12 months. The primary outcome "COPD exacerbation days per patient per year" was assessed using intention-to-treat analyses.No significant difference was observed in the number of COPD exacerbation days per patient per year (self-management: median 9.6 (interquartile range (IQR) 0.7-31.1); UC: median 15.6 (IQR 3.0-40.3); incidence rate ratio (IRR) 0.87 (95% CI 0.54; 1.39); p=0.546). There was a significantly shorter duration per COPD exacerbation for self-management (self-management: median 8.1 (IQR 4.8-10.1) days; UC: median 9.5 (IQR 7.0-15.1) days; p=0.021), with no between-group differences in the total number of respiratory hospitalisations (IRR 0.76 (95% CI 0.42; 1.35); p=0.348), but a lower probability of ≥1 for respiratory-related hospitalisation compared to UC (relative risk 0.55 (95% CI 0.35; 0.87); p=0.008). No between-group differences were observed in all-cause hospitalisations (IRR 1.07 (95% CI 0.66; 1.72)) or mortality (self-management: n=4 (3.9%); UC: n=7 (7.1%); relative risk 0.55 (95% CI 0.17; 1.84)).Patient-tailored exacerbation action plans for COPD patients with comorbidities did not significantly reduce exacerbation days, but reduced the duration per COPD exacerbation and the risk of having at least one respiratory-related hospitalisation during follow-up, without excess all-cause mortality.

Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease: the GOLD science committee report 2019.

Precision medicine is a patient-specific approach that integrates all relevant clinical, genetic and biological information in order to optimise the therapeutic benefit relative to the possibility of side-effects for each individual. Recent clinical trials have shown that higher blood eosinophil counts are associated with a greater efficacy of inhaled corticosteroids (ICSs) in chronic obstructive pulmonary disease (COPD) patients. Blood eosinophil counts are a biomarker with potential to be used in clinical practice, to help target ICS treatment with more precision in COPD patients with a history of exacerbations despite appropriate bronchodilator treatment.The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 pharmacological treatment algorithms, based on the ABCD assessment, can be applied relatively easily to treatment-naive individuals at initial presentation. However, their use is more problematic during follow-up in patients who are already on maintenance treatment. There is a need for a different system to guide COPD pharmacological management during follow-up.Recent large randomised controlled trials have provided important new information concerning the therapeutic effects of ICSs and long-acting bronchodilators on exacerbations. The new evidence regarding blood eosinophils and inhaled treatments, and the need to distinguish between initial and follow-up pharmacological management, led to changes in the GOLD pharmacological treatment recommendations. This article explains the evidence and rationale for the GOLD 2019 pharmacological treatment recommendations.

Efficacy and safety of the direct switch to indacaterol/glycopyrronium from salmeterol/fluticasone in non-frequently exacerbating COPD patients: The FLASH randomized controlled trial.

BACKGROUND AND OBJECTIVE: Combination long-acting ß2 -agonist/long-acting muscarinic antagonist (LABA/LAMA) has demonstrated superior clinical outcomes over LABA/inhaled corticosteroid (ICS) in chronic obstructive pulmonary disease (COPD) patients; however, data from blinded randomized controlled trials on direct switching from LABA/ICS to LABA/LAMA are lacking. FLASH (Assessment of switching salmeterol/Fluticasone to indacateroL/glycopyrronium in A Symptomatic COPD patient coHort) investigated if direct switch, without a washout period, from salmeterol/fluticasone (SFC) to indacaterol/glycopyrronium (IND/GLY) in COPD patients improves lung function and is well tolerated. METHODS: In this 12-week, multicentre, double-blind study, patients with moderate-to-severe COPD and up to one exacerbation in previous year, receiving SFC for ≥3 months, were randomized to continue SFC 50/500 µg twice daily (bd) or switch to IND/GLY 110/50 µg once daily (od). Primary endpoint was pre-dose trough forced expiratory volume in 1 s (FEV1 ) at Week 12. RESULTS: In total, 502 patients were randomized (1:1) to IND/GLY or SFC. Patients switched to IND/GLY demonstrated superior lung function (pre-dose trough FEV1 ) versus SFC at Week 12 (treatment difference (Δ) = 45 mL; P = 0.028). IND/GLY provided significant improvements in pre-dose trough forced vital capacity (FVC; Δ = 102 mL; P = 0.002) and numerical improvements in transition dyspnoea index (TDI; Δ = 0.46; P = 0.063). Rescue medication use and COPD assessment test (CAT) scores were comparable between groups. Both treatments had similar safety profiles. CONCLUSION: FLASH demonstrated that a direct switch to IND/GLY from SFC improved pre-dose FEV1 and FVC in COPD patients with up to one exacerbation in the previous year. No new safety signals were identified.

Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease 2017 Report. GOLD Executive Summary.

This Executive Summary of the Global Strategy for the Diagnosis, Management, and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 report focuses primarily on the revised and novel parts of the document. The most significant changes include: (1) the assessment of chronic obstructive pulmonary disease has been refined to separate the spirometric assessment from symptom evaluation. ABCD groups are now proposed to be derived exclusively from patient symptoms and their history of exacerbations; (2) for each of the groups A to D, escalation strategies for pharmacologic treatments are proposed; (3) the concept of deescalation of therapy is introduced in the treatment assessment scheme; (4) nonpharmacologic therapies are comprehensively presented; and (5) the importance of comorbid conditions in managing chronic obstructive pulmonary disease is reviewed.

Comparison of the Dyspnoea-12 and Multidimensional Dyspnoea Profile in people with COPD.

We directly compared convergent, discriminant and concurrent validity of the Dyspnoea-12 (D-12) and Multidimensional Dyspnoea Profile (MDP) in people with chronic obstructive pulmonary disease.Breathlessness measures (D-12, MDP, visual analogue scales and descriptors) were completed for two focal periods (daily life and end of walk test). Instrument structure (D-12 and MDP item grouping) was assessed with factor analysis. Differences between airflow severity stage and focal periods (ANOVA, t-test and Chi-squared test), associations between D-12 and MDP (r, r2 for static pulmonary function, 6-min walk test and self-reported measures of impairment) and individual consistency for comparable items of the D-12 and MDP (McNemar's test) were assessed.In 84 participants (mean±sd age 70±9 years, 47 males, forced expiratory volume in 1 s 48±17% predicted), item groupings were confirmed for both focal periods. Developer-recommended single and subdomain scores were highly correlated, and demonstrated similar convergent, discriminant and concurrent validity. Individual consistency differed between the D-12 and MDP according to item/item groups.At the level of developer-recommended single and subdomain scores, the D-12 and MDP share similar psychometric properties, but these instruments serve different purposes, do not assess the same sensations or emotions and are not interchangeable.

Effects of combined tiotropium/olodaterol on inspiratory capacity and exercise endurance in COPD.

Two replicate, double-blind, 6-week, incomplete-crossover studies (MORACTO 1 and 2) assessed the effects of tiotropium/olodaterol on inspiratory capacity and exercise endurance time in patients with moderate to severe chronic obstructive pulmonary disease.For each patient, four of five treatments were administered once daily for 6 weeks, with a 21-day washout between treatments: tiotropium/olodaterol 2.5/5 µg or 5/5 µg, tiotropium 5 µg, olodaterol 5 µg or placebo, all via the Respimat inhaler. Primary outcomes were inspiratory capacity prior to exercise and exercise endurance time during constant work-rate cycle ergometry to symptom limitation at 75% of peak incremental work rate after 6 weeks (2 h post-dose).295 and 291 patients were treated in MORACTO 1 and 2, respectively. Tiotropium/olodaterol 2.5/5 and 5/5 µg provided significant improvements in inspiratory capacity versus placebo and monotherapies (p<0.0001), and significant improvements in exercise endurance time versus placebo (p<0.0001). Intensity of breathing discomfort was reduced following both doses of tiotropium/olodaterol versus placebo (p<0.0001).Once-daily tiotropium/olodaterol yielded improvements in lung hyperinflation versus placebo and statistically significant improvements versus monotherapies. Tiotropium/olodaterol also showed improvements in dyspnoea and exercise tolerance versus placebo but not consistently versus monotherapies.

Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease 2017 Report: GOLD Executive Summary.

This Executive Summary of the Global Strategy for the Diagnosis, Management, and Prevention of COPD (GOLD) 2017 Report focuses primarily on the revised and novel parts of the document. The most significant changes include: 1) the assessment of chronic obstructive pulmonary disease has been refined to separate the spirometric assessment from symptom evaluation. ABCD groups are now proposed to be derived exclusively from patient symptoms and their history of exacerbations; 2) for each of the groups A to D, escalation strategies for pharmacological treatments are proposed; 3) the concept of de-escalation of therapy is introduced in the treatment assessment scheme; 4) nonpharmacologic therapies are comprehensively presented and; 5) the importance of comorbid conditions in managing COPD is reviewed.

Global Strategy for the Diagnosis, Management and Prevention of Chronic Obstructive Lung Disease 2017 Report: GOLD Executive Summary.

This Executive Summary of the Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 Report focuses primarily on the revised and novel parts of the document. The most significant changes include: (i) the assessment of chronic obstructive pulmonary disease has been refined to separate the spirometric assessment from symptom evaluation. ABCD groups are now proposed to be derived exclusively from patient symptoms and their history of exacerbations; (ii) for each of the groups A to D, escalation strategies for pharmacological treatments are proposed; (iii) the concept of de-escalation of therapy is introduced in the treatment assessment scheme; (iv)non-pharmacological therapies are comprehensively presented and (v) the importance of co-morbid conditions in managing COPD is reviewed.

Australian and New Zealand Pulmonary Rehabilitation Guidelines.

BACKGROUND AND OBJECTIVE: The aim of the Pulmonary Rehabilitation Guidelines (Guidelines) is to provide evidence-based recommendations for the practice of pulmonary rehabilitation (PR) specific to Australian and New Zealand healthcare contexts. METHODS: The Guideline methodology adhered to the Appraisal of Guidelines for Research and Evaluation (AGREE) II criteria. Nine key questions were constructed in accordance with the PICO (Population, Intervention, Comparator, Outcome) format and reviewed by a COPD consumer group for appropriateness. Systematic reviews were undertaken for each question and recommendations made with the strength of each recommendation based on the GRADE (Gradings of Recommendations, Assessment, Development and Evaluation) criteria. The Guidelines were externally reviewed by a panel of experts. RESULTS: The Guideline panel recommended that patients with mild-to-severe COPD should undergo PR to improve quality of life and exercise capacity and to reduce hospital admissions; that PR could be offered in hospital gyms, community centres or at home and could be provided irrespective of the availability of a structured education programme; that PR should be offered to patients with bronchiectasis, interstitial lung disease and pulmonary hypertension, with the latter in specialized centres. The Guideline panel was unable to make recommendations relating to PR programme length beyond 8 weeks, the optimal model for maintenance after PR, or the use of supplemental oxygen during exercise training. The strength of each recommendation and the quality of the evidence are presented in the summary. CONCLUSION: The Australian and New Zealand Pulmonary Rehabilitation Guidelines present an evaluation of the evidence for nine PICO questions, with recommendations to provide guidance for clinicians and policymakers.

Self-management interventions including action plans for exacerbations versus usual care in patients with chronic obstructive pulmonary disease.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) self-management interventions should be structured but personalised and often multi-component, with goals of motivating, engaging and supporting the patients to positively adapt their behaviour(s) and develop skills to better manage disease. Exacerbation action plans are considered to be a key component of COPD self-management interventions. Studies assessing these interventions show contradictory results. In this Cochrane Review, we compared the effectiveness of COPD self-management interventions that include action plans for acute exacerbations of COPD (AECOPD) with usual care. OBJECTIVES: To evaluate the efficacy of COPD-specific self-management interventions that include an action plan for exacerbations of COPD compared with usual care in terms of health-related quality of life, respiratory-related hospital admissions and other health outcomes. SEARCH METHODS: We searched the Cochrane Airways Group Specialised Register of trials, trials registries, and the reference lists of included studies to May 2016. SELECTION CRITERIA: We included randomised controlled trials evaluating a self-management intervention for people with COPD published since 1995. To be eligible for inclusion, the self-management intervention included a written action plan for AECOPD and an iterative process between participant and healthcare provider(s) in which feedback was provided. We excluded disease management programmes classified as pulmonary rehabilitation or exercise classes offered in a hospital, at a rehabilitation centre, or in a community-based setting to avoid overlap with pulmonary rehabilitation as much as possible. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. We resolved disagreements by reaching consensus or by involving a third review author. Study authors were contacted to obtain additional information and missing outcome data where possible. When appropriate, study results were pooled using a random-effects modelling meta-analysis. The primary outcomes of the review were health-related quality of life (HRQoL) and number of respiratory-related hospital admissions. MAIN RESULTS: We included 22 studies that involved 3,854 participants with COPD. The studies compared the effectiveness of COPD self-management interventions that included an action plan for AECOPD with usual care. The follow-up time ranged from two to 24 months and the content of the interventions was diverse.Over 12 months, there was a statistically significant beneficial effect of self-management interventions with action plans on HRQoL, as measured by the St. George's Respiratory Questionnaire (SGRQ) total score, where a lower score represents better HRQoL. We found a mean difference from usual care of -2.69 points (95% CI -4.49 to -0.90; 1,582 participants; 10 studies; high-quality evidence). Intervention participants were at a statistically significant lower risk for at least one respiratory-related hospital admission compared with participants who received usual care (OR 0.69, 95% CI 0.51 to 0.94; 3,157 participants; 14 studies; moderate-quality evidence). The number needed to treat to prevent one respiratory-related hospital admission over one year was 12 (95% CI 7 to 69) for participants with high baseline risk and 17 (95% CI 11 to 93) for participants with low baseline risk (based on the seven studies with the highest and lowest baseline risk respectively).There was no statistically significant difference in the probability of at least one all-cause hospital admission in the self-management intervention group compared to the usual care group (OR 0.74, 95% CI 0.54 to 1.03; 2467 participants; 14 studies; moderate-quality evidence). Furthermore, we observed no statistically significant difference in the number of all-cause hospitalisation days, emergency department visits, General Practitioner visits, and dyspnoea scores as measured by the (modified) Medical Research Council questionnaire for self-management intervention participants compared to usual care participants. There was no statistically significant effect observed from self-management on the number of COPD exacerbations and no difference in all-cause mortality observed (RD 0.0019, 95% CI -0.0225 to 0.0263; 3296 participants; 16 studies; moderate-quality evidence). Exploratory analysis showed a very small, but significantly higher respiratory-related mortality rate in the self-management intervention group compared to the usual care group (RD 0.028, 95% CI 0.0049 to 0.0511; 1219 participants; 7 studies; very low-quality evidence).Subgroup analyses showed significant improvements in HRQoL in self-management interventions with a smoking cessation programme (MD -4.98, 95% CI -7.17 to -2.78) compared to studies without a smoking cessation programme (MD -1.33, 95% CI -2.94 to 0.27, test for subgroup differences: Chi² = 6.89, df = 1, P = 0.009, I² = 85.5%). The number of behavioural change techniques clusters integrated in the self-management intervention, the duration of the intervention and adaptation of maintenance medication as part of the action plan did not affect HRQoL. Subgroup analyses did not detect any potential variables to explain differences in respiratory-related hospital admissions among studies. AUTHORS' CONCLUSIONS: Self-management interventions that include a COPD exacerbation action plan are associated with improvements in HRQoL, as measured with the SGRQ, and lower probability of respiratory-related hospital admissions. No excess all-cause mortality risk was observed, but exploratory analysis showed a small, but significantly higher respiratory-related mortality rate for self-management compared to usual care.For future studies, we would like to urge only using action plans together with self-management interventions that meet the requirements of the most recent COPD self-management intervention definition. To increase transparency, future study authors should provide more detailed information regarding interventions provided. This would help inform further subgroup analyses and increase the ability to provide stronger recommendations regarding effective self-management interventions that include action plans for AECOPD. For safety reasons, COPD self-management action plans should take into account comorbidities when used in the wider population of people with COPD who have comorbidities. Although we were unable to evaluate this strategy in this review, it can be expected to further increase the safety of self-management interventions. We also advise to involve Data and Safety Monitoring Boards for future COPD self-management studies.

The predictive value of an adjusted COPD assessment test score on the risk of respiratory-related hospitalizations in severe COPD patients.

We evaluated whether a chronic obstructive pulmonary disease (COPD) assessment test (CAT) with adjusted weights for the CAT items could better predict future respiratory-related hospitalizations than the original CAT. Two focus groups (respiratory nurses and physicians) generated two adjusted CAT algorithms. Two multivariate logistic regression models for infrequent (≤1/year) versus frequent (>1/year) future respiratory-related hospitalizations were defined: one with the adjusted CAT score that correlated best with future hospitalizations and one with the original CAT score. Patient characteristics related to future hospitalizations ( p ≤ 0.2) were also entered. Eighty-two COPD patients were included. The CAT algorithm derived from the nurse focus group was a borderline significant predictor of hospitalization risk (odds ratio (OR): 1.07; 95% confidence interval (CI): 1.00-1.14; p = 0.050) in a model that also included hospitalization frequency in the previous year (OR: 3.98; 95% CI: 1.30-12.16; p = 0.016) and anticholinergic risk score (OR: 3.08; 95% CI: 0.87-10.89; p = 0.081). Presence of ischemic heart disease and/or heart failure appeared 'protective' (OR: 0.17; 95% CI: 0.05-0.62; p = 0.007). The original CAT score was not significantly associated with hospitalization risk. In conclusion, as a predictor of respiratory-related hospitalizations, an adjusted CAT score was marginally significant (although the original CAT score was not). 'Previous respiratory-related hospitalizations' was the strongest factor in this equation.

Definition of a COPD self-management intervention: International Expert Group consensus.

There is an urgent need for consensus on what defines a chronic obstructive pulmonary disease (COPD) self-management intervention. We aimed to obtain consensus regarding the conceptual definition of a COPD self-management intervention by engaging an international panel of COPD self-management experts using Delphi technique features and an additional group meeting.In each consensus round the experts were asked to provide feedback on the proposed definition and to score their level of agreement (1=totally disagree; 5=totally agree). The information provided was used to modify the definition for the next consensus round. Thematic analysis was used for free text responses and descriptive statistics were used for agreement scores.In total, 28 experts participated. The consensus round response rate varied randomly over the five rounds (ranging from 48% (n=13) to 85% (n=23)), and mean definition agreement scores increased from 3.8 (round 1) to 4.8 (round 5) with an increasing percentage of experts allocating the highest score of 5 (round 1: 14% (n=3); round 5: 83% (n=19)).In this study we reached consensus regarding a conceptual definition of what should be a COPD self-management intervention, clarifying the requisites for such an intervention. Operationalisation of this conceptual definition in the near future will be an essential next step.

Glycopyrronium once-daily significantly improves lung function and health status when combined with salmeterol/fluticasone in patients with COPD: the GLISTEN study, a randomised controlled trial.

BACKGROUND: The optimal use of various therapeutic combinations for moderate/severe chronic obstructive pulmonary disease (COPD) is unclear. The GLISTEN trial compared the efficacy of two long-acting anti-muscarinic antagonists (LAMA), when combined with an inhaled corticosteroid (ICS) and a long-acting ß2 agonist (LABA). METHODS: This randomised, blinded, placebo-controlled trial in moderate/severe COPD patients compared once-daily glycopyrronium (GLY) 50 µg, once-daily tiotropium (TIO) 18 µg or placebo (PLA), when combined with salmeterol/fluticasone propionate (SAL/FP) 50/500 µg twice daily. The primary objective was to determine the non-inferiority of GLY+SAL/FP versus TIO+SAL/FP on trough FEV1 after 12 weeks. An important secondary objective was whether addition of GLY to SAL/FP was better than SAL/FP alone. RESULTS: 773 patients (mean FEV1 57.2% predicted) were randomised; 84.9% completed the trial. At week 12, GLY+SAL/FP demonstrated non-inferiority to TIO+SAL/FP for trough FEV1: least square mean treatment difference (LSMdiff) -7 mL (SE 17.4) with a lower limit for non-inferiority of -60 mL. There was significant increase in week 12 trough FEV1 with GLY+SAL/FP versus PLA+SAL/FP (LSMdiff 101 mL, p<0.001). At 12 weeks, GLY+SAL/FP produced significant improvement in St George's Respiratory Questionnaire total score versus PLA+SAL/FP (LSMdiff -2.154, p=0.02). GLY+SAL/FP demonstrated significant rescue medication reduction versus PLA+SAL/FP (LSMdiff -0.72 puffs/day, p<0.001). Serious adverse events were similar for GLY+SAL/FP, TIO+SAL/FP and PLA+SAL/FP with an incidence of 5.8%, 8.5% and 5.8%, respectively. CONCLUSIONS: GLY+SAL/FP showed comparable improvements in lung function, health status and rescue medication to TIO+SAL/FP. Importantly, addition of GLY to SAL/FP demonstrated significant improvements in lung function, health status and rescue medication compared to SAL/FP. TRIAL REGISTRATION NUMBER: NCT01513460.