Hormonal contraception and the risk of severe asthma exacerbation: 17-year population-based cohort study.

BACKGROUND: Longitudinal studies investigating impact of exogenous sex steroids on clinical outcomes of asthma in women are lacking. We investigated the association between use of hormonal contraceptives and risk of severe asthma exacerbation in reproductive-age women with asthma. METHODS: We used the Optimum Patient Care Research Database, a population-based, longitudinal, anonymised primary care database in the UK, to construct a 17-year (1 January 2000-31 December 2016) retrospective cohort of reproductive-age (16-45 years, n=83 084) women with asthma. Using Read codes, we defined use, subtypes and duration of use of hormonal contraceptives. Severe asthma exacerbation was defined according to recommendations of the European Respiratory Society/American Thoracic Society as asthma-related hospitalisation, accident and emergency department visits due to asthma and/or oral corticosteroid prescriptions. Analyses were done using multilevel mixed-effects Poisson regression with QR decomposition. RESULTS: The 17-year follow-up resulted in 456 803 person-years of follow-up time. At baseline, 34% of women were using any hormonal contraceptives, 25% combined (oestrogen/progestogen) and 9% progestogen-only contraceptives. Previous (incidence rate ratio (IRR) 0.94, 95% CI 0.92 to 0.97) and current (IRR 0.96, 95% CI 0.94 to 0.98) use of any, previous (IRR 0.92, 95% CI 0.87 to 0.97) and current use of combined (IRR 0.93, 95% CI 0.91 to 0.96) and longer duration of use (3-4 years: IRR 0.94, 95% CI 0.92 to 0.97; 5+ years: IRR 0.91, 95% CI 0.89 to 0.93) of hormonal contraceptives, but not progestogen-only contraceptives, were associated with reduced risk of severe asthma exacerbation compared with non-use. CONCLUSIONS: Use of hormonal contraceptives may reduce the risk of severe asthma exacerbation in reproductive-age women. Mechanistic studies investigating the biological basis for the influence of hormonal contraceptives on clinical outcomes of asthma in women are required. PROTOCOL REGISTRATION NUMBER: European Union electronic Register of Post-Authorisation Studies (EUPAS22967).

Differences in severe exacerbations rates and healthcare utilisation in COPD populations in the UK and France.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality in Europe; however, it is important to understand how clinical practice patterns differ between countries and how this might relate to disease outcomes, to identify ways of improving local disease management. We aimed to describe and compare the management of patients with COPD in the UK and France between 2008 and 2017. METHODS: We used data from the Clinical Practice Research Datalink GOLD and Hospital Episode Statistics in the UK and the Echantillon Généraliste des Bénéficiaire in France to identify patients with COPD each year between 2008 and 2017. We compared patient characteristics, all-cause mortality and COPD exacerbations each year between 2008 and 2017 for patients in the UK and France separately. Health care utilisation and COPD exacerbations in 2017 were compared between France and the UK using t-tests and χ2 tests. RESULTS: Patients with COPD were similar in gender and comorbidities in both countries. Incidence of COPD exacerbations remained stable in the UK and France between 2007 and 2017. In 2017, the proportion of all-cause and COPD-related hospitalisations was greater in the UK than in France (43.9% vs 32.8% and 8.3% vs 4.9%, respectively; p<0.001) as was the proportion of patients visiting accident and emergency (A&E) (39.8% vs 16.2%, respectively; p<0.001). In addition, the mean length of stay in hospital for COPD-related causes was shorter in the UK than in France (6.2 days (SD 8.4) vs 10.5 days (SD 9.1), respectively; p<0.001). DISCUSSION: Overall, UK patients were more likely to go to A&E, be hospitalised for COPD-related causes and stay in hospital for fewer days after being admitted for COPD-related reasons compared with patients in France, illustrating a difference in health-seeking behaviours and access to healthcare.

The challenge of recruiting in primary care for a trial of telemonitoring in asthma: an observational study.

AIM: Achieving target recruitment in randomized controlled trials (RCTs) is challenging. This paper compares our experience of recruiting for an RCT with the predictions made in our proposal. METHODS: Participating UK primary care practices searched their computer databases to identify patients (12 years and over) with asthma who may be poorly controlled. Postal invitations were sent to all patients identified. Respondees were prescreened by phone, to assess their asthma control and establish their mobile phone suitability. Potentially eligible patients were booked for a trial recruitment visit. RESULTS: We recruited 288 patients (2.4% of those invited) across 32 practices, with a total list size of 311,926 patients. This compares to our predicted recruitment of 312 patients from a population of 72,000 patients in six to eight practices. In addition to the recognized problem of poor response rates, the major challenges were insufficiently discriminating computer searches and incompatibilities between mobile phone handsets, networks and the asthma application. CONCLUSION: Our data have implications for clinicians, managers, and researchers in primary care. Researchers in this area may wish to consider our data when designing their recruitment strategies. Improved coding of asthma morbidity data in clinical practice would ease identification of poorly controlled patients, both for clinical interventions and recruitment to trials. If telehealth is to become mainstream, there needs to be standardization of applications, operating platforms, and network capabilities.

Establishing the place in therapy of bilastine in the treatment of allergic rhinitis according to ARIA: evidence review.

BACKGROUND: The ARIA (Allergic Rhinitis and its Impact on Asthma) guidelines development group examined the properties of oral H(1)-antihistamines and made proposals about an 'optimal' drug. Several criteria should be met by oral H(1)-antihistamines in terms of their pharmacological, and clinical efficacy and safety profiles. OBJECTIVE: Bilastine, a new H(1)-antihistamine, has been approved in 28 European countries for the symptomatic treatment of allergic rhinoconjunctivitis and urticaria in adults and children older than 12 years. To determine its potential place in therapy in the treatment of allergic rhinitis, this manuscript examines whether bilastine meets the criteria defined in the European Academy of Allergy and Clinical Immunology (EAACI)/ARIA proposals for oral H(1)-antihistamines. METHODS: The optimal properties of oral H(1)-antihistamines and current ARIA recommendations for their use in allergic rhinitis are presented, as well as relevant pharmacological and clinical data for bilastine obtained from the published literature that specifically address the defined criteria. RESULTS: Bilastine is a potent inhibitor of the histamine H(1) receptor. Data from preclinical studies have confirmed its selectivity for the histamine H(1) receptor over other receptors, and demonstrated antihistaminic properties in vitro and in vivo. Bilastine does not interfere with the cytochrome P450 system and is devoid of cardiac side effects. Studies in healthy volunteers and patients have shown that bilastine does not affect driving ability, cardiac conduction or alertness. In large pivotal randomized, placebo-controlled trials (RCTs), bilastine had a favourable safety profile. Bilastine 20 mg once daily improved all nasal and ocular symptoms of allergic rhinitis with greater efficacy than placebo and comparable to that of cetirizine and desloratadine. Moreover, bilastine was shown to improve quality of life, an important outcome of RCTs in allergic diseases. There were no significant changes in laboratory tests, electrocardiograms or vital signs. A potential limitation of this assessment of bilastine is that it is a literature-based review and the findings are dependent upon the quality of the published evidence. CONCLUSIONS: Bilastine meets current EAACI/ARIA criteria for medications used in the treatment of allergic rhinitis.

Systematic review and meta-analysis of budesonide/formoterol in a single inhaler.

OBJECTIVE: To compare the effectiveness of budesonide/formoterol using fixed dosing (BUD/FORM) with inhaled corticosteroid (ICS) alone or alternative ICS and long-acting beta(2)-agonist (LABA) regimens for adults with moderate/severe asthma. METHODS: BIOSIS, CENTRAL, EMBASE and MEDLINE were searched for abstracts and papers. All searching was completed in July 2006. No restriction was placed on language. Meta-analysis of randomised controlled trials (RCTs) using a fixed effects model. RCTs were included if the comparator with BUD/FORM had an equivalent daily dose of ICS at the start of the trial. The primary outcome measure was, 'treatment failure', defined as: asthma-related serious adverse event, oral glucocorticosteroid treatment, A&E visit and/or admission to hospital, withdrawal due to a need for additional asthma therapy. RESULTS: Of the 330 papers identified in the literature search, 15 met the inclusion criteria. The following alternative treatments were found: ICS alone (BUD), BUD/FORM adjustable maintenance dose (BUD/FORM-AMD), and salmeterol/fluticasone in a single inhaler (SALM/FP). Meta-analysis of treatment failure demonstrated a 50% increase with BUD versus BUD/FORM (Relative Risk [RR] 1.50, 95% confidence interval [95% CI]: 1.12-2.02, p = 0.007; 2 RCTs); a trend in favour of a reduction with BUD/FORM-AMD versus BUD/FORM (RR 0.88, 95% CI: 0.77-1.02, p = 0.09; 11 RCTs); and no evidence of a difference with SALM/FP versus BUD/FORM (RR 0.99, 95% CI: 0.83-1.16, p = 0.86; 3 RCTs). Significant heterogeneity was not detected in the primary analyses. Secondary analyses demonstrated the following significant differences: hospitalisations/A&E visits (49% increased risk with SALM/FP vs. BUD/FORM, RR 1.49, 95% CI: 1.07-2.08, p = 0.02, and 28% reduced risk with BUD/FORM-AMD vs. BUD/FORM, RR 0.72, 95% CI: 0.52-0.99, p = 0.04); and use of oral steroids (51% increase in risk with BUD vs. BUD/FORM, RR 1.51, 95% CI: 1.10-2.09, p = 0.01, and 19% reduced risk with BUD/FORM-AMD vs. BUD/FORM, RR 0.81, 95% CI: 0.70-0.95, p = 0.01). CONCLUSIONS: Fixed-dose BUD/FORM is an effective treatment option for adult patients with moderate/severe asthma when compared to BUD and SALM/FP, with adjustable maintenance dosing demonstrating important advantages over fixed dosing in relation to exacerbation prevention and reduced treatment load.