Do self-management interventions in COPD patients work and which patients benefit most? An individual patient data meta-analysis.

BACKGROUND: Self-management interventions are considered effective in patients with COPD, but trials have shown inconsistent results and it is unknown which patients benefit most. This study aimed to summarize the evidence on effectiveness of self-management interventions and identify subgroups of COPD patients who benefit most. METHODS: Randomized trials of self-management interventions between 1985 and 2013 were identified through a systematic literature search. Individual patient data of selected studies were requested from principal investigators and analyzed in an individual patient data meta-analysis using generalized mixed effects models. RESULTS: Fourteen trials representing 3,282 patients were included. Self-management interventions improved health-related quality of life at 12 months (standardized mean difference 0.08, 95% confidence interval [CI] 0.00-0.16) and time to first respiratory-related hospitalization (hazard ratio 0.79, 95% CI 0.66-0.94) and all-cause hospitalization (hazard ratio 0.80, 95% CI 0.69-0.90), but had no effect on mortality. Prespecified subgroup analyses showed that interventions were more effective in males (6-month COPD-related hospitalization: interaction P=0.006), patients with severe lung function (6-month all-cause hospitalization: interaction P=0.016), moderate self-efficacy (12-month COPD-related hospitalization: interaction P=0.036), and high body mass index (6-month COPD-related hospitalization: interaction P=0.028 and 6-month mortality: interaction P=0.026). In none of these subgroups, a consistent effect was shown on all relevant outcomes. CONCLUSION: Self-management interventions exert positive effects in patients with COPD on respiratory-related and all-cause hospitalizations and modest effects on 12-month health-related quality of life, supporting the implementation of self-management strategies in clinical practice. Benefits seem similar across the subgroups studied and limiting self-management interventions to specific patient subgroups cannot be recommended.

Effects of older age and age of asthma onset on clinical and inflammatory variables in severe refractory asthma.

BACKGROUND: Asthma in the elderly as well as asthma of adult-onset has been associated with increased morbidity, but little is known specifically about the effects of age on clinical and inflammatory outcomes in severe refractory asthma. The aims of the study were to examine the effects of age [<65 versus ≥65 years] and age of onset of asthma [childhood-onset, <18 versus adult-onset, ≥18 years] on clinical and inflammatory variables in patients with severe asthma. METHODS: In 1042 subjects with refractory asthma recruited to the British Thoracic Society Severe Asthma Registry, we compared patient demographics, disease characteristics and biomarkers of inflammation in patients aged <65 years (n = 896) versus ≥65 years (n = 146) and onset at age <18 years (n = 430) versus ≥18 years (n = 526). RESULTS: Severe asthma patients aged ≥65 years had improved symptom control, better asthma quality of life and in the last year, less emergency visits and rescue oral steroid courses [3 (1-6) versus 5 (2-7), p < 0.001] than severe asthmatics aged <65 years. Blood eosinophils were lower in the elderly group. Patients with severe adult-onset asthma had similar symptom control, lung function and health-care utilization compared to severe childhood-onset asthma. Adult-onset asthmatics had higher blood eosinophils and were less atopic. CONCLUSIONS: Patients with severe refractory asthma aged ≥65 years exhibit better clinical and health care outcomes and have lower blood eosinophils compared to those aged <65 years. Severe refractory adult-onset asthma is associated with similar levels of asthma control, higher blood eosinophils and less atopy than severe refractory childhood-onset asthma.

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.

Characteristics of effective self-management interventions in patients with COPD: individual patient data meta-analysis.

It is unknown whether heterogeneity in effects of self-management interventions in patients with chronic obstructive pulmonary disease (COPD) can be explained by differences in programme characteristics. This study aimed to identify which characteristics of COPD self-management interventions are most effective.Systematic search in electronic databases identified randomised trials on self-management interventions conducted between 1985 and 2013. Individual patient data were requested for meta-analysis by generalised mixed effects models.14 randomised trials were included (67% of eligible), representing 3282 patients (75% of eligible). Univariable analyses showed favourable effects on some outcomes for more planned contacts and longer duration of interventions, interventions with peer contact, without log keeping, without problem solving, and without support allocation. After adjusting for other programme characteristics in multivariable analyses, only the effects of duration on all-cause hospitalisation remained. Each month increase in intervention duration reduced risk of all-cause hospitalisation (time to event hazard ratios 0.98, 95% CI 0.97-0.99; risk ratio (RR) after 6 months follow-up 0.96, 95% CI 0.92-0.99; RR after 12 months follow-up 0.98, 95% CI 0.96-1.00).Our results showed that longer duration of self-management interventions conferred a reduction in all-cause hospitalisations in COPD patients. Other characteristics are not consistently associated with differential effects of self-management interventions across clinically relevant outcomes.

Comorbidity in severe asthma requiring systemic corticosteroid therapy: cross-sectional data from the Optimum Patient Care Research Database and the British Thoracic Difficult Asthma Registry.

OBJECTIVE: To determine the prevalence of systemic corticosteroid-induced morbidity in severe asthma. DESIGN: Cross-sectional observational study. SETTING: The primary care Optimum Patient Care Research Database and the British Thoracic Society Difficult Asthma Registry. PARTICIPANTS: Optimum Patient Care Research Database (7195 subjects in three age- and gender-matched groups)-severe asthma (Global Initiative for Asthma (GINA) treatment step 5 with four or more prescriptions/year of oral corticosteroids, n=808), mild/moderate asthma (GINA treatment step 2/3, n=3975) and non-asthma controls (n=2412). 770 subjects with severe asthma from the British Thoracic Society Difficult Asthma Registry (442 receiving daily oral corticosteroids to maintain disease control). MAIN OUTCOME MEASURES: Prevalence rates of morbidities associated with systemic steroid exposure were evaluated and reported separately for each group. RESULTS: 748/808 (93%) subjects with severe asthma had one or more condition linked to systemic corticosteroid exposure (mild/moderate asthma 3109/3975 (78%), non-asthma controls 1548/2412 (64%); p<0.001 for severe asthma versus non-asthma controls). Compared with mild/moderate asthma, morbidity rates for severe asthma were significantly higher for conditions associated with systemic steroid exposure (type II diabetes 10% vs 7%, OR=1.46 (95% CI 1.11 to 1.91), p<0.01; osteoporosis 16% vs 4%, OR=5.23, (95% CI 3.97 to 6.89), p<0.001; dyspeptic disorders (including gastric/duodenal ulceration) 65% vs 34%, OR=3.99, (95% CI 3.37 to 4.72), p<0.001; cataracts 9% vs 5%, OR=1.89, (95% CI 1.39 to 2.56), p<0.001). In the British Thoracic Society Difficult Asthma Registry similar prevalence rates were found, although, additionally, high rates of osteopenia (35%) and obstructive sleep apnoea (11%) were identified. CONCLUSIONS: Oral corticosteroid-related adverse events are common in severe asthma. New treatments which reduce exposure to oral corticosteroids may reduce the prevalence of these conditions and this should be considered in cost-effectiveness analyses of these new treatments.

Dedicated severe asthma services improve health-care use and quality of life.

BACKGROUND: Systematic assessment of severe asthma can be used to confirm the diagnosis, identify comorbidities, and address adherence to therapy. However, the prospective usefulness of this approach is yet to be established. The objective of this study was to determine whether the systematic assessment of severe asthma is associated with improved quality of life (QoL) and health-care use and, using prospective data collection, to compare relevant outcomes in patients referred with severe asthma to specialist centers across the United Kingdom. METHODS: Data from the National Registry for dedicated UK Difficult Asthma Services were used to compare patient demographics, disease characteristics, and health-care use between initial assessment and a median follow-up of 286 days. RESULTS: The study population consisted of 346 patients with severe asthma. At follow-up, there were significant reductions in health-care use in terms of primary care or ED visits (66.4% vs 87.8%, P < .0001) and hospital admissions (38% vs 48%, P = .0004). Although no difference was noted in terms of those requiring maintenance oral corticosteroids, there was a reduction in steroid dose (10 mg [8-20 mg] vs 15 mg [10-20 mg], P = .003), and fewer subjects required short-burst steroids (77.4% vs 90.8%, P = .01). Significant improvements were seen in QoL and control using the Asthma Quality of Life Questionnaire and the Asthma Control Questionnaire. CONCLUSIONS: To our knowledge, this is the first time that a prospective study has shown that a systematic assessment at a dedicated severe asthma center is associated with improved QoL and asthma control and a reduction in health-care use and oral steroid burden.

The cost of treating severe refractory asthma in the UK: an economic analysis from the British Thoracic Society Difficult Asthma Registry.

Severe refractory asthma poses a substantial burden in terms of healthcare costs but relatively little is known about the factors which drive these costs. This study uses data from the British Thoracic Society Difficult Asthma Registry (n=596) to estimate direct healthcare treatment costs from an National Health Service perspective and examines factors that explain variations in costs. Annual mean treatment costs among severe refractory asthma patients were £2912 (SD £2212) to £4217 (SD £2449). Significant predictors of costs were FEV1% predicted, location of care, maintenance oral corticosteroid treatment and body mass index. Treating individuals with severe refractory asthma presents a substantial cost to the health service.

Statistical cluster analysis of the British Thoracic Society Severe refractory Asthma Registry: clinical outcomes and phenotype stability.

BACKGROUND: Severe refractory asthma is a heterogeneous disease. We sought to determine statistical clusters from the British Thoracic Society Severe refractory Asthma Registry and to examine cluster-specific outcomes and stability. METHODS: Factor analysis and statistical cluster modelling was undertaken to determine the number of clusters and their membership (N = 349). Cluster-specific outcomes were assessed after a median follow-up of 3 years. A classifier was programmed to determine cluster stability and was validated in an independent cohort of new patients recruited to the registry (n = 245). FINDINGS: Five clusters were identified. Cluster 1 (34%) were atopic with early onset disease, cluster 2 (21%) were obese with late onset disease, cluster 3 (15%) had the least severe disease, cluster 4 (15%) were the eosinophilic with late onset disease and cluster 5 (15%) had significant fixed airflow obstruction. At follow-up, the proportion of subjects treated with oral corticosteroids increased in all groups with an increase in body mass index. Exacerbation frequency decreased significantly in clusters 1, 2 and 4 and was associated with a significant fall in the peripheral blood eosinophil count in clusters 2 and 4. Stability of cluster membership at follow-up was 52% for the whole group with stability being best in cluster 2 (71%) and worst in cluster 4 (25%). In an independent validation cohort, the classifier identified the same 5 clusters with similar patient distribution and characteristics. INTERPRETATION: Statistical cluster analysis can identify distinct phenotypes with specific outcomes. Cluster membership can be determined using a classifier, but when treatment is optimised, cluster stability is poor.

Clinical outcomes and inflammatory biomarkers in current smokers and exsmokers with severe asthma.

BACKGROUND: Clinical outcomes are worse in current smokers and exsmokers with mild-to-moderate asthma compared with never smokers, but little is known about the influence of smoking status in patients with severe asthma. OBJECTIVES: We sought to examine the association of current or previous cigarette smoking with clinical and inflammatory variables in patients with severe asthma. METHODS: We compared patients' demographics, disease characteristics, and biomarkers of inflammation in current smokers (n=69 [9%]), exsmokers (n=210 [28%]), and never smokers (n=461 [62%]) with severe asthma (n=760) recruited to the British Thoracic Society Severe Asthma Registry. RESULTS: Current smokers had poorer asthma control, more unscheduled health care visits, more rescue courses of oral steroids, and higher anxiety and depression scale scores than exsmokers or never smokers. Current smokers had a reduced proportion of sputum eosinophils compared with never smokers (1% and 4%, respectively) and lower fraction of expired nitric oxide (50 mL/s; 14 ppb and 35 ppb, respectively). Exsmokers compared with never smokers had an increased proportion of sputum neutrophils (59% and 43%, respectively) but a similar proportion of sputum eosinophils (3%) and fraction of expired nitric oxide (50 mL/s; 35 ppb). Both current smokers and exsmokers had reduced serum specific IgE levels to several common environmental allergens. CONCLUSION: Current smokers with severe asthma exhibit worse clinical and health care outcomes compared with exsmokers and never smokers with severe asthma. Their inflammatory profiles in sputum and blood differ.

Obesity-associated severe asthma represents a distinct clinical phenotype: analysis of the British Thoracic Society Difficult Asthma Registry Patient cohort according to BMI.

BACKGROUND: Obesity has emerged as a risk factor for the development of asthma and it may also influence asthma control and airway inflammation. However, the role of obesity in severe asthma remains unclear. Thus, our objective was to explore the association between obesity (defied by BMI) and severe asthma. METHODS: Data from the British Thoracic Society Difficult Asthma Registry were used to compare patient demographics, disease characteristics, and health-care utilization among three BMI categories (normal weight: 18.5-24.99; overweight: 25-29.99; obese: 30) in a well-characterized group of adults with severe asthma. RESULTS: The study population consisted of 666 patients with severe asthma; the group had a median BMI of 29.8 (interquartile range, 22.5-34.0). The obese group exhibited greater asthma medication requirements in terms of maintenance corticosteroid therapy (48.9% vs 40.4% and 34.5% in the overweight and normal-weight groups, respectively), steroid burst therapy, and short-acting b 2 -agonist use per day. Significant differences were seen with gastroesophageal reflux disease (53.9% vs 48.1% and 39.7% in the overweight and normal weight groups, respectively) and proton pump inhibitor use. Bone density scores were higher in the obese group, while pulmonary function testing revealed a reduced FVC and elevated carbon monoxide transfer coefficient. Serum IgE levels decreased with increasing BMI and the obese group was more likely to report eczema, but less likely to have a history of nasal polyps. CONCLUSIONS: Patients with severe asthma display particular characteristics according to BMI that support the view that obesity-associated severe asthma may represent a distinct clinical phenotype.

The impact of normalization of esophageal acid profile by incremental protein pump inhibitors dosing in difficult asthma patients with proven gastro-esophageal acid reflux.

BACKGROUND: GER is common in patients with asthma and some, although not all, studies have shown benefit from identification and treatment of GER. METHODS: patients with persistent symptoms after optimisation of asthma therapy underwent pH monitoring and adjustment of GER therapy based on the results of repeated pH monitoring. Gastrointestinal symptom scores and asthma therapy requirements were recorded. RESULTS: Over a 2 year period, 51 patients with a definite diagnosis of asthma underwent pH monitoring with GER being identified in 32 (63%). Normal oesophageal acid exposure was achieved in 11 patients, 7 requiring a daily PPI dose greater than 20 mg; 8 patients had persisting abnormal oesophageal acid exposure (OAE) despite daily PPI doses up to 80 mg. 13 patients declined further pH studies. 8 (73%) patients with normalisation of OAE had meaningful reductions in long term asthma therapy with 2 patients stopping and 2 patients reducing long term oral corticosteroids and 4 others halving the dose of inhaled corticosteroids. No patient who had persisting GER had asthma therapy reduced, neither did any of the group of patients in whom GER was not identified. CONCLUSION: Tailoring GER therapy with repeated pH studies had a major impact in a subgroup of patients, greater than any other intervention employed in our clinic over the same period. This uncontrolled data adds to the evidence that effective management of GER reduces asthma symptomatology and allows therapy to be reduced in a subgroup of patients with difficult to control asthma.

An observational investigation of dysfunctional breathing and breathing control therapy in a problem asthma clinic.

OBJECTIVES: Dysfunctional breathing (DB) is recognized as an associated problem in patients with asthma and may be identified by the Nijmegen questionnaire. We conducted an observational study to determine if breathing control therapy (BCT) improved Nijmegen scores or asthma-related quality of life in patients attending a problem asthma clinic. METHODS: Nijmegen and Mini Asthma Quality of Life (Mini-AQLQ) questionnaires were completed. Patients with a positive Nijmegen (> or = 23, DB) were referred for BCT and progressive exercise testing (PET) to seek confirmation of dysfunctional breathing. Follow-up questionnaire data were collected at 6 months. RESULTS: A total of 102 patients were studied. The total mean Nijmegen score was 26.4 (range 1-61). Those with a score > or = 23 (DB group, n = 65, 64%) had significantly lower Mini-AQLQ (mean 2.83) than the non-DB group (n = 37, mean 4.12, 95% CI for difference 0.87, 1.87, p < 0.0001). There was a strong relationship between Nijmegen score and Mini-AQLQ (r = -0.63, p < 0.001) at baseline; 10 of 17 DB patients who completed PET showed inappropriate hyperventilation. Follow-up data, available for Nijmegen and Mini-AQLQ in 44 and 46 patients respectively, showed no significant change in either of these parameters. CONCLUSIONS: The strong relationship between Mini-AQLQ and Nijmegen scores and poor relationship between Nijmegen scores and PET-identified inappropriate hyperventilation suggest that a positive Nijmegen score overestimates the presence of dysfunctional breathing in patients with moderate to severe asthma. We found no evidence that a moderate intensity breathing control intervention had any impact on Nijmegen scores or asthma-related quality of life in this patient group.