[show abstract][hide abstract] ABSTRACT: Patterns of health-care use and comorbidities present in patients in the period before diagnosis of chronic obstructive pulmonary disease (COPD) are unknown. We investigated these factors to inform future case-finding strategies.
We did a retrospective analysis of a clinical cohort in the UK with data from Jan 1, 1990 to Dec 31, 2009 (General Practice Research Database and Optimum Patient Care Research Database). We assessed patients aged 40 years or older who had an electronically coded diagnosis of COPD in their primary care records and had a minimum of 3 years of continuous practice data for COPD (2 years before diagnosis up to a maximum of 20 years, and 1 year after diagnosis) and at least two prescriptions for COPD since diagnosis. We identified missed opportunites to diagnose COPD from routinely collected patient data by reviewing patterns of health-care use and comorbidities present before diagnosis. We assessed patterns of health-care use in terms of lower respiratory consultations (infective and non-infective), lower respiratory consultations with a course of antibiotics or oral steroids, and chest radiography. If these events did not lead to a diagnosis of COPD, they were deemed to be missed opportunities. This study is registered with ClinicalTrials.gov, number NCT01655667.
We assessed data for 38 859 patients. Opportunities for diagnosis were missed in 32 900 (85%) of 38 859 patients in the 5 years immediately preceding diagnosis of COPD; in 12 856 (58%) of 22 286 in the 6-10 years before diagnosis, in 3943 (42%) of 9351 in the 11-15 years before diagnosis; and in 95 (8%) of 1167 in the 16-20 years before diagnosis. Between 1990 and 2009, we noted decreases in the age at diagnosis (0·05 years of age per year, 95% CI 0·03-0·07) and yearly frequency of lower respiratory prescribing consultations (rate ratio 0·982 opportunities per year, 95% CI 0·979-0·985). Prevalence of all comorbidities present at COPD diagnosis increased except for asthma and bronchiectasis, which decreased between 1990 and 2007, from 281 (33·4%) of 842 patients to 451 of 1465 (30·8%) for asthma, and from 53 of 842 (6·3%) to 53 of 1465 (3·6%) for bronchiectasis. In the 2 years before diagnosis, of 6897 patients who had had a chest radiography, only 2296 (33%) also had spirometry.
Opportunities to diagnose COPD at an earlier stage are being missed, and could be improved by case-finding in patients with lower respiratory tract symptoms and concordant long-term comorbidities.
UK Department of Health, Research in Real Life.
The lancet. Respiratory medicine. 04/2014; 2(4):267-76.
[show abstract][hide abstract] ABSTRACT: Cigarette smoking among asthma patients is associated with worsening symptoms and accelerated decline in lung function. Smoking asthma is also characterized by increased levels of neutrophils and macrophages, and greater small airway remodeling, resulting in increased airflow obstruction and impaired response to corticosteroid therapy. As a result, smokers are typically excluded from asthma randomized controlled trials (RCTs). The strict inclusion/exclusion criteria used by asthma RCTs limits the extent to which their findings can be extrapolated to the routine care asthma population and to reflect the likely effectiveness of therapies in subgroups of particular clinical interest, such as smoking asthmatics. The inclusion of smokers in observational asthma studies and pragmatic trials in asthma provides a way of assessing the relative effectiveness of different treatment options for the management of this interesting clinical subgroup. Exploratory studies of possible treatment options for smoking asthma suggest potential utility in: prescribing higher-dose ICS; targeting the small airways of the lungs with extra-fine particle ICS formulations; targeting leukotreines, and possibly also combinations of these options. However, further studies are required. With the paucity of RCT data available, complementary streams of evidence (those from RCTs, pragmatic trials and observational studies) need to be combined to help guide judicious prescribing decisions in smokers with asthma.
[show abstract][hide abstract] ABSTRACT: Observational studies and pragmatic trials can complement classical randomized controlled trials (RCTs) by providing data more relevant to the circumstances under which medicine is routinely practiced, thereby providing practical guidance for clinicians. The bearing of RCT findings on day-to-day practice can be weighted and the data more meaningfully interpreted by practicing clinicians if evidence is integrated from a variety of different study designs and methodologies. The advent of observational studies and pragmatic trials, often referred to as "real-life studies," has met with a degree of cynicism, but their role and value is gaining widespread recognition and support among clinicians. This article discusses where observational studies and pragmatic trials have utility, namely: in addressing clinical questions that are unanswered and/or unanswerable by RCTs; in testing new hypotheses and possible license extensions; and in helping to differentiate between available therapies for a given indication. Moreover, it seeks to highlight how the different approaches fit within a conceptual framework of evidence relevant to clinical practice, a step-change in the traditional view of medical evidence.
Annals of the American Thoracic Society. 02/2014; 11 Suppl 2:S92-8.
[show abstract][hide abstract] ABSTRACT: Fractional exhaled nitric oxide (FeNO) is a surrogate marker of eosinophilic airway inflammation and good predictor of corticosteroid response.Aim: To evaluate how FeNO is being used to guide primary care asthma management in the United Kingdom (UK) with a view to devising practical algorithms for the use of FeNO in the diagnosis of steroid-responsive disease and to guide on-going asthma management.
Eligible patients (n = 678) were those in the Optimum Patient Care Research Database (OPCRD) aged 4--80 years who, at an index date, had their first FeNO assessment via NIOX MINO(R) or Flex(R). Eligible practices were those using FeNO measurement in at least ten patients during the study period. Patients were characterized over a one-year baseline period immediately before the index date. Outcomes were evaluated in the year immediately following index date for two patient cohorts: (i) those in whom FeNO measurement was being used to identify steroid-responsive disease and (ii) those in whom FeNO monitoring was being used to guide on-going asthma management. Outcomes for cohort (i) were incidence of new ICS initiation at, or within the one-month following, their first FeNO measurement, and ICS dose during the outcome year. Outcomes for cohort (ii) were adherence, change in adherence (from baseline) and ICS dose.Outcomes: In cohort (i) (n = 304) the higher the FeNO category, the higher the percentage of patients that initiated ICS at, or in the one month immediately following, their first FeNO measurement: 82%, 46% and 26% of patients with high, intermediate and low FeNO, respectively. In cohort (ii) (n = 374) high FeNO levels were associated with poorer baseline adherence (p = 0.005) but greater improvement in adherence in the outcome year (p = 0.017). Across both cohorts, patients with high FeNO levels were associated with significantly higher ICS dosing (p < 0.001).
In the UK, FeNO is being used in primary practice to guide ICS initiation and dosing decisions and to identify poor ICS adherence. Simple algorithms to guide clinicians in the practical use of FeNO could improved diagnostic accuracy and better tailored asthma regimens.
Clinical and translational allergy. 11/2013; 3(1):37.
[show abstract][hide abstract] ABSTRACT: BACKGROUND: Beclometasone dipropionate is an inhaled corticosteroid (ICS) available in both extrafine and larger-particle hydrofluoroalkane formulations. Extrafine beclometasone has greater small airway distribution and inhalation technique tolerance than larger-particle beclometasone; therefore, its use may be associated with improved asthma outcomes at population levels. The study objective was to compare real-life effectiveness of extrafine and larger-particle beclometasone. METHODS: Retrospective matched cohort study including primary care patients with asthma (ages 12-60 and non-smokers 61-80 years) prescribed extrafine or larger-particle beclometasone by metered-dose inhaler. We studied patients receiving their first ICS (initiation population, n = 11,289) or switched from another ICS without dose change (switch population, n = 19,065). The extrafine and larger-particle beclometasone cohorts were matched in each population for demographic and database measures of asthma control during a baseline year; and endpoints assessed during 1 outcome year were adjusted for residual confounding factors. RESULTS: The odds of no loss of asthma control (no asthma-related hospital attendance, consultation for lower respiratory tract infection, or oral corticosteroids) were significantly higher in the extrafine beclometasone cohorts of both initiation population (adjusted odds ratio [aOR] 1.12; 95% CI 1.02-1.23) and switch population (aOR 1.10; 95% CI 1.01-1.19). The odds of better adherence to ICS therapy were also significantly higher in both extrafine beclometasone cohorts (initiation population, aOR 1.64; 95% CI 1.52-1.75 and switch population, aOR 1.35; 95% CI 1.27-1.43). CONCLUSIONS: These findings are consistent with the hypothesis that delivery of beclometasone in extrafine particle size produces real-life asthma treatment benefits. Clinical trials no. NCT01400217.
Respiratory medicine 05/2013; · 2.33 Impact Factor
[show abstract][hide abstract] ABSTRACT: BACKGROUND: Characteristics of inhaled corticosteroids (ICSs) differ, but data comparing the real-life effectiveness of various ICSs for asthma are lacking. OBJECTIVE: We sought to compare real-life asthma outcomes and costs of extrafine hydrofluoroalkane (HFA)-beclomethasone and fluticasone administered through a pressurized metered-dose inhaler. METHODS: This retrospective matched cohort study examined database markers of asthma control from a large US longitudinal health care claims database over 1 baseline and 1 outcome year for 10,312 patients with asthma aged 12 to 80 years receiving their first ICS as HFA-beclomethasone or fluticasone and matched on baseline demographic characteristics and asthma severity. RESULTS: Patients started on HFA-beclomethasone had significantly higher odds (adjusted odds ratio, 1.19; 95% CI; 1.08-1.31) of achieving overall control (risk and impairment), which was defined as no hospital attendance for asthma, oral corticosteroids, or antibiotics for lower respiratory tract infection and less than 2 puffs per day of short-acting β-agonist; they also experienced a lower rate of respiratory-related hospitalizations or referrals (adjusted rate ratio, 0.82; 95% CI, 0.73-0.93) than patients started on fluticasone. Other database outcome measures were similar in the 2 cohorts. Prescribed HFA-beclomethasone doses were lower (P < .001) than fluticasone doses (median, 320 μg/d [interquartile range, 160-320 μg/d] vs 440 μg/d [interquartile range, 176-440 μg/d]). Adjusted respiratory-related health care costs were significantly lower for HFA-beclomethasone than fluticasone (mean, $1869 [95% CI, $1727-$2032] vs $2259 [95% CI, $2111-$2404]), representing a mean annual savings of $390 (95% CI, $165-$620) per patient prescribed HFA-beclomethasone rather than fluticasone. CONCLUSIONS: Asthma treatment outcomes were similar or better with HFA-beclomethasone prescribed at significantly lower doses and with lower costs than fluticasone.
The Journal of allergy and clinical immunology 04/2013; · 12.05 Impact Factor
[show abstract][hide abstract] ABSTRACT: BACKGROUND: Patient preference is an important factor when choosing an inhaler device for asthma or chronic obstructive pulmonary disease (COPD). AIMS: To identify characteristics of patients with asthma or COPD who prefer a once-daily controller medication regimen. METHODS: This retrospective observational study used electronic patient records and linked outcomes from patient-completed questionnaires in a primary care database. We compared the characteristics of patients indicating a preference for once-daily therapy with those who were unsure or indicating no preference. RESULTS: Of 3,731 patients with asthma, 2,174 (58%) were women; the mean age was 46 years (range 2-94). Of 2,138 patients with COPD, 980 (46%) were women; the mean age was 70 years (range 35-98). Approximately half of the patients in each cohort indicated once-daily preference, one-quarter were unsure, and one-quarter did not prefer once-daily therapy. In patients with asthma or COPD, the preference for once-daily controller medication was significantly associated with poor adherence and higher concerns about medication. In asthma, good control and low self-perceived controller medication need were associated with once-daily preference. By contrast, in COPD, a high self-perceived need for controller medication was associated with once-daily preference. There was no significant relationship between once-daily preference and age, sex, disease severity, or exacerbation history. CONCLUSIONS: Understanding patient preferences may help prescribers to individualise therapy better for asthma and COPD.
Primary care respiratory journal: journal of the General Practice Airways Group 03/2013;
[show abstract][hide abstract] ABSTRACT: Correct use of inhaler devices is fundamental to effective asthma management but represents an important challenge for patients. The correct inhalation manoeuvre differs markedly for different inhaler types. The objective of this study was to compare outcomes for patients prescribed the same inhaler device versus mixed device types for asthma controller and reliever therapy.
This retrospective observational study identified patients with asthma (ages 4-80 years) in a large primary care database who were prescribed an inhaled corticosteroid (ICS) for the first time. We compared outcomes for patients prescribed the same breath-actuated inhaler (BAI) for ICS controller and salbutamol reliever versus mixed devices (BAI for controller and pressurised metered-dose inhaler [pMDI] for reliever). The 2-year study included 1 baseline year before the ICS prescription (to identify and correct for confounding factors) and 1 outcome year. Endpoints were asthma control (defined as no hospital attendance for asthma, oral corticosteroids, or antibiotics for lower respiratory tract infection) and severe exacerbations (hospitalisation or oral corticosteroids for asthma).
Patients prescribed the same device (n=3,428) were significantly more likely to achieve asthma control (adjusted odds ratio, 1.15; 95% confidence interval [CI], 1.02-1.28) and recorded significantly lower severe exacerbation rates (adjusted rate ratio, 0.79; 95% CI, 0.68-0.93) than those prescribed mixed devices (n=5,452).
These findings suggest that, when possible, the same device should be prescribed for both ICS and reliever therapy when patients are initiating ICS.
[show abstract][hide abstract] ABSTRACT: Classical randomized controlled trials are the gold standard in medical evidence because of their high internal validity. However, their necessarily strict design can limit their external validity and the ability to extrapolate these data to real world patients. Therefore, alternatively designed studies may play a complementary role in evaluating the comparative effectiveness of therapies in nonidealized patients in more naturalistic, real world settings. Observational studies have high external validity and can evaluate real world outcomes. Their strength lies in hypothesis generation and testing and in identifying areas in which further clinical trials may be required. Pragmatic trials are designed to maximize applicability of trial results to usual care settings by relying on clinically important outcomes and enrolling a wide range of participants. A combination of these approaches is preferable and necessary.
Current Allergy and Asthma Reports 09/2011; 11(6):526-38. · 2.75 Impact Factor
[show abstract][hide abstract] ABSTRACT: The extrafine-particle formulation of hydrofluoroalkane-beclometasone (EF HFA-BDP; Qvar®) demonstrates improved total and small airway deposition compared with large-particle chlorofluorocarbon (CFC)-BDP. In some short-term studies, EF HFA-BDP provides greater effects on lung function than CFC-BDP, and hence is recommended to be prescribed at a lower dose, but whether there are differences in asthma outcomes during long-term treatment is unknown.
To compare the effectiveness of EF HFA-BDP vs. CFC-BDP over 1 year.
This retrospective matched cohort study examined outcomes in a large primary care database for patients aged 5-60 years with asthma receiving their first inhaled corticosteroid (ICS) prescription (initiation population) or first ICS dose increase (step-up population) by a pressurized metered-dose inhaler (pMDI) as EF HFA-BDP or CFC-BDP. Patients were matched on baseline demographic and asthma severity measures in EF HFA-BDP:CFC-BDP ratios of 1:3 and 1:2 for initiation and step-up populations, respectively. Step-up patients were matched also on ICS dose during a baseline year. Co-primary endpoints were asthma control (composite measure comprising no recorded hospital attendance for asthma, oral corticosteroids, or antibiotics for lower respiratory infection) and exacerbation rate during the outcome year.
For the initiation population (EF HFA-BDP n=2882; CFC-BDP n=8646), adjusted odds of achieving asthma control with EF HFA-BDP vs. CFC-BDP was 1.15 (95% CI 1.02-1.28). For the step-up population (n=258 and 516), adjusted odds of asthma control with EF HFA-BDP was 1.72 (95% CI 1.14-2.56). EF HFA-BDP was prescribed at a median dose half that of CFC-BDP.
During 1 year after initiating or stepping up ICS therapy by pMDI, patients who received EF HFA-BDP were more likely to achieve asthma control than those receiving CFC-BDP. These findings suggest that ICS formulation, particle size, and deposition characteristics play important roles in real-life effectiveness of asthma therapy. This study shows that an EF-particle formulation of beclometasone can be used at half the dose of the large-particle formulation with at least as good clinical outcomes.
[show abstract][hide abstract] ABSTRACT: Selection of inhaler device type appears to influence real-world effectiveness of inhaled corticosteroids (ICS), but data are lacking on the role of inhaler device in ICS and long-acting β2-agonist (LABA) combination therapy for asthma.
This retrospective matched cohort study compared 1-year asthma outcomes for UK patients initiating fixed-dose combination (FDC) fluticasone-salmeterol delivered by pressurised metered-dose inhaler (pMDI) versus dry powder inhaler (DPI). Patients with asthma aged 4-80 years receiving a first prescription for FDC fluticasone-salmeterol by pMDI or DPI were matched on baseline demographic and asthma severity measures. Co-primary outcomes were asthma control (a composite measure comprising no recorded hospital attendance for asthma, oral corticosteroids, or antibiotics for lower respiratory infection) and exacerbation rate.
Compared with the DPI cohort (n = 1567), patients in the pMDI cohort (n = 1567) had significantly greater odds of achieving asthma control during the outcome year (odds ratio [OR] 1.19; 95% confidence interval [CI] 1.01 to 1.40). Exacerbation rate was lower but not significantly in the pMDI cohort (adjusted rate ratio for pMDI cohort, 0.82; 95% CI 0.66 to 1.00). The odds of treatment success (defined as no exacerbations and no change in asthma therapy) was significantly greater in the pMDI cohort (OR 1.23; 95% CI, 1.07 to 1.42).
For UK primary care patients, pMDIs appear to achieve better asthma control outcomes than DPIs for delivery of FDC fluticasone-salmeterol. Pragmatic trials are needed to further investigate real-world outcomes with different inhaler devices for combination therapy.
Respiratory medicine 05/2011; 105(10):1457-66. · 2.33 Impact Factor
[show abstract][hide abstract] ABSTRACT: Results of randomized controlled trials may not predict effectiveness of inhaled corticosteroids (ICS) in real-world clinical practice, where inhaler technique and device characteristics can influence effectiveness. We compared asthma outcomes for ICS delivered via three different inhaler devices: pressurized metered-dose inhaler (pMDI), breath-actuated MDI (BAI), and dry powder inhaler (DPI).
This retrospective database study evaluated 1-year outcomes for primary care patients with asthma aged 5-60 years prescribed their first ICS (initiation population) by pMDI (n = 39,746), BAI (n = 9809), or DPI (n = 6792), or their first ICS dose increase (step-up population) by pMDI (n = 6245), BAI (n = 1388), or DPI (n = 1536). Co-primary outcome measures were composite proxy measures of asthma control (no hospital attendance for asthma, oral corticosteroids, or antibiotics for lower respiratory infection) and severe exacerbations (unscheduled hospital admission, emergency room attendance, or oral corticosteroids). Outcomes were adjusted for potential confounding factors identified during a baseline year.
In the initiation population, adjusted odds ratios (95% confidence intervals [CI]) for asthma control, as compared with pMDIs, were significantly better for BAIs (1.08 [1.02-1.14]) and DPIs (1.13 [1.06-1.21]), while adjusted exacerbation rate ratios (95% CI) were 1.00 (0.93-1.08) and 0.88 (0.81-0.95), respectively. In the step-up population, adjusted odds of asthma control were 1.21 (1.05-1.39) for BAIs and 1.13 (0.99-1.29) for DPIs; adjusted exacerbation rate ratios were 0.83 (0.71-0.98) for BAIs and 0.85 (0.74-0.98) for DPIs, compared with pMDIs.
Inhaler device selection may have a bearing on clinical outcomes. Differences in real-world effectiveness among these devices require closer evaluation in well-designed prospective trials.
[show abstract][hide abstract] ABSTRACT: Therapeutic interventions in chronic obstructive pulmonary disease (COPD) shown to reduce exacerbations include smoking cessation, vaccination and appropriate pharmacological therapy. Long-acting bronchodilators are the cornerstone of COPD pharmacotherapy, whereas inhaled corticosteroids and mucolytics have shown benefit in subgroups of patients. Despite management with existing therapies, clinical trials confirm the persistent nature of exacerbations throughout the course of the disease. Roflumilast - a phosphodiesterase-4 (PDE4) inhibitor - received European Marketing Approval in 2010 and represents a new class of drug in the management of COPD. Through selective inhibition of the PDE4 enzyme, roflumilast prevents the breakdown of cyclic AMP, which plays an important role in regulating inflammatory cell activity. Early trials in patients with a forced expiratory volume in one second (FEV1) less than 50% predicted suggest that roflumilast offers sustained and significant improvement in lung function and a reduction in exacerbations compared with placebo, irrespective of concomitant bronchodilator therapy. Common adverse events include headache, diarrhoea and weight loss, with the majority occurring at the beginning of treatment, being transient and not leading to sequelae. Serious adverse events tended to be low across all studies. Roflumilast is currently licensed in Europe, and is indicated as maintenance treatment in severe COPD (i.e. in patients with post-bronchodilator FEV1 <50% predicted) associated with chronic bronchitis in adult patients with a history of frequent exacerbations as an add-on to bronchodilator treatment. Clear identification of patients eligible for roflumilast will require improved characterisation and phenotyping of patients in primary care, including lung function measurement, accurate health status classification, and recording of chronic cough and regular sputum production.
Primary care respiratory journal: journal of the General Practice Airways Group 11/2010; 19(4):342-51.
[show abstract][hide abstract] ABSTRACT: Long-term randomized trials comparing asthma outcomes between inhaled corticosteroids in real-world populations are lacking. As such, rigorously conducted observational studies to complement the findings of randomized trials are needed.
We sought to compare asthma-related outcomes over 1 year as recorded in a large primary care database for patients aged 5 to 60 years receiving a first prescription (initiation population) or dose increase (step-up population) of hydrofluoroalkane (HFA)-beclomethasone or fluticasone.
We used a retrospective matched cohort study in which patients were matched on baseline demographic and disease severity measures. Coprimary outcomes were asthma control (a composite measure comprising no unplanned visit or hospitalization for asthma, oral corticosteroids, or antibiotics for lower respiratory tract infection) and exacerbation rate.
More than 80% of patients in each population achieved asthma control; 10% and 16% of patients in the initiation and step-up populations, respectively, received add-on or combination therapy during the year. Fluticasone was prescribed at significantly higher doses than HFA-beclomethasone for both populations (P <or= .001). In the initiation population (n = 1319 in each cohort) the adjusted odds ratio for achieving asthma control with HFA-beclomethasone was 1.30 (95% CI, 1.02-1.65) relative to fluticasone. In the step-up population (cohorts: n = 250) the adjusted odds ratio for achieving asthma control with HFA-beclomethasone was 1.22 (95% CI, 0.66-2.26). Exacerbation rates were similar between cohorts.
In a real-world setting patients receiving HFA-beclomethasone had a similar or better chance of achieving asthma control at lower prescribed doses than with fluticasone.
The Journal of allergy and clinical immunology 09/2010; 126(3):511-8.e1-10. · 12.05 Impact Factor