Helen K. Reddel

An Official American Thoracic Society/European Respiratory Society Statement: Asthma Control and Exacerbations Standardizing Endpoints for Clinical Asthma Trials and Clinical Practice

BACKGROUND The assessment of asthma control is pivotal to the evaluation of treatment response in individuals and in clinical trials. Previously, asthma control, severity, and exacerbations were defined and assessed in many different ways. PURPOSE The Task Force was established to provide recommendations about standardization of outcomes relating to asthma control, severity, and exacerbations in clinical trials and clinical practice, for adults and children aged 6 years or older. METHODS A narrative literature review was conducted to evaluate the measurement properties and strengths/weaknesses of outcome measures relevant to asthma control and exacerbations. The review focused on diary variables, physiologic measurements, composite scores, biomarkers, quality of life questionnaires, and indirect measures. RESULTS The Task Force developed new definitions for asthma control, severity, and exacerbations, based on current treatment principles and clinical and research relevance. In view of current knowledge about the multiple domains of asthma and asthma control, no single outcome measure can adequately assess asthma control. Its assessment in clinical trials and in clinical practice should include components relevant to both of the goals of asthma treatment, namely achievement of best possible clinical control and reduction of future risk of adverse outcomes. Recommendations are provided for the assessment of asthma control in clinical trials and clinical practice, both at baseline and in the assessment of treatment response. CONCLUSIONS The Task Force recommendations provide a basis for a multicomponent assessment of asthma by clinicians, researchers, and other relevant groups in the design, conduct, and evaluation of clinical trials, and in clinical practice.

A new perspective on concepts of asthma severity and control

Concepts of asthma severity and control are important in the evaluation of patients and their response to treatment but the terminology is not standardised and the terms are often used interchangeably. This review, arising from the work of an American Thoracic Society/European Respiratory Society Task Force, identifies the need for separate concepts of control and severity, describes their evolution in asthma guidelines and provides a framework for understanding the relationship between current concepts of asthma phenotype, severity and control. “Asthma control” refers to the extent to which the manifestations of asthma have been reduced or removed by treatment. Its assessment should incorporate the dual components of current clinical control (e.g. symptoms, reliever use and lung function) and future risk (e.g. exacerbations and lung function decline). The most clinically useful concept of asthma severity is based on the intensity of treatment required to achieve good asthma control, i.e. severity is assessed during treatment. Severe asthma is defined as the requirement for (not necessarily just prescription or use of) high-intensity treatment. Asthma severity may be influenced by the underlying disease activity and by the patients phenotype, both of which may be further described using pathological and physiological markers. These markers can also act as surrogate measures for future risk.

A summary of the new GINA strategy: a roadmap to asthma control

Over the past 20 years, the Global Initiative for Asthma (GINA) has regularly published and annually updated a global strategy for asthma management and prevention that has formed the basis for many national guidelines. However, uptake of existing guidelines is poor. A major revision of the GINA report was published in 2014, and updated in 2015, reflecting an evolving understanding of heterogeneous airways disease, a broader evidence base, increasing interest in targeted treatment, and evidence about effective implementation approaches. During development of the report, the clinical utility of recommendations and strategies for their practical implementation were considered in parallel with the scientific evidence. This article provides a summary of key changes in the GINA report, and their rationale. The changes include a revised asthma definition; tools for assessing symptom control and risk factors for adverse outcomes; expanded indications for inhaled corticosteroid therapy; a framework for targeted treatment based on phenotype, modifiable risk factors, patient preference, and practical issues; optimisation of medication effectiveness by addressing inhaler technique and adherence; revised recommendations about written asthma action plans; diagnosis and initial treatment of the asthma−chronic obstructive pulmonary disease overlap syndrome; diagnosis in wheezing pre-school children; and updated strategies for adaptation and implementation of GINA recommendations. This paper summarises key changes in the GINA global strategy report, a practical new resource for asthma care http://ow.ly/ObvYi

Differences between asthma exacerbations and poor asthma control

BACKGROUND Increased variation in peak expiratory flow (PEF) is characteristic of poorly controlled asthma, and measurement of diurnal variability of PEF has been recommended for assessment of asthma severity, including during exacerbations. We aimed to test whether asthma exacerbations had the same PEF characteristics as poor asthma control. METHODS Electronic PEF records from 43 patients with initially poorly controlled asthma were examined for all exacerbations that occurred after PEF reached a plateau with inhaled corticosteroid treatment. Diurnal variability of PEF was compared during exacerbations, run-in (poor asthma control), and the period of stable asthma before each exacerbation. FINDINGS Diurnal variability was 21.3% during poor asthma control and improved to 5.3% (stable asthma) with inhaled corticosteroid treatment. 40 exacerbations occurred in 26 patients over 2-16 months; 38 (95%) of exacerbations were associated with symptoms of clinical respiratory infection. During exacerbations, consecutive PEF values fell linearly over several days then improved linearly. However, diurnal variability during exacerbations (7.7%) was not significantly higher than during stable asthma (5.4%, p=0.1). PEF data were consistent with impaired response to inhaled beta2-agonist during exacerbations but not during poorly controlled asthma. INTERPRETATION Asthmatics remain vulnerable to exacerbations during clinical respiratory infections, even after asthma is brought under control. Calculation of diurnal variability may fail to detect important changes in lung function. PEF variation is strikingly different during exacerbations compared with poor asthma control, suggesting differences in beta2-adrenoceptor function between these conditions.

Overall asthma control: The relationship between current control and future risk

BACKGROUND Asthma guidelines emphasize both maintaining current control and reducing future risk, but the relationship between these 2 targets is not well understood. OBJECTIVE This retrospective analysis of 5 budesonide/formoterol maintenance and reliever therapy (Symbicort SMART Turbuhaler(*)) studies assessed the relationship between asthma control questionnaire (ACQ-5) and Global Initiative for Asthma-defined clinical asthma control and future risk of instability and exacerbations. METHODS The percentage of patients with Global Initiative for Asthma-defined controlled asthma over time was assessed for budesonide/formoterol maintenance and reliever therapy versus the 3 maintenance therapies; higher dose inhaled corticosteroid (ICS), same dose ICS/long-acting beta(2)-agonist (LABA), and higher dose ICS/LABA plus short-acting beta(2)-agonist. The relationship between baseline ACQ-5 and exacerbations was investigated. A Markov analysis examined the transitional probability of change in control status throughout the studies. RESULTS The percentage of patients achieving asthma control increased with time, irrespective of treatment; the percentage Controlled/Partly Controlled at study end was at least similar to budesonide/formoterol maintenance and reliever therapy versus the 3 maintenance therapies: higher dose ICS (56% vs 45%), same dose ICS/LABA (56% vs 53%), and higher dose ICS/LABA (54% vs 54%). Baseline ACQ-5 score correlated positively with exacerbation rates. A Controlled or Partly Controlled week predicted at least Partly Controlled asthma the following week (>or=80% probability). The better the control, the lower the risk of an Uncontrolled week. The probability of an exacerbation was related to current state and was lower with budesonide/formoterol maintenance and reliever therapy. CONCLUSIONS Current control predicts future risk of instability and exacerbations. Budesonide/formoterol maintenance and reliever therapy reduces exacerbations versus comparators and achieves at least similar control.

Complementary and alternative medicine use in asthma: Who is using what?

Abstract:  Consumer interest in complementary and alternative medicine (CAM) has grown dramatically in Western countries in the past decade. However, very few patients volunteer information about CAM use unless directly questioned by their health‐care practitioner. Therefore, by being informed about the prevalence and modality of CAM use for asthma, as well as characteristics of users, health‐care practitioners may be better able to identify patients who use CAM. In turn, this may facilitate proactive discussion and optimization of the patient’s overall asthma management. This review aims to summarize the current knowledge about use of CAM by people with asthma, and to assess the applicability of the available studies to the broader asthmatic population. Computerized literature searches were conducted on Medline, Embase, Cochrane and Allied and Complementary Medicine (AMED) databases from their inception to 13 April 2005. Search terms included: complementary medicine/therapies, alternative medicine/therapies and asthma. The bibliographies of accessible articles were searched for further papers. Seventeen studies have examined the use of CAM by people with asthma. The reported level of use for adults ranged from 4% to 79%, and for children from 33% to 89%. Among the most commonly used CAMs were: breathing techniques, herbal products, homeopathy and acupuncture. There is no strong evidence for effectiveness for any of these modalities. There is little consistency among available prevalence studies making conclusions difficult. Nevertheless, the high rates of CAM use reported in some studies indicate that CAM use should be taken into account when managing patients with asthma.

Evaluation of a novel educational strategy, including inhaler-based reminder labels, to improve asthma inhaler technique

OBJECTIVE To evaluate the feasibility, acceptability and effectiveness of a brief intervention about inhaler technique, delivered by community pharmacists to asthma patients. METHODS Thirty-one pharmacists received brief workshop education (Active: n=16, CONTROL: n=15). Active Group pharmacists were trained to assess and teach dry powder inhaler technique, using patient-centered educational tools including novel Inhaler Technique Labels. Interventions were delivered to patients at four visits over 6 months. RESULTS At baseline, patients (Active: 53, CONTROL: 44) demonstrated poor inhaler technique (mean+/-S.D. score out of 9, 5.7+/-1.6). At 6 months, improvement in inhaler technique score was significantly greater in Active cf. CONTROL patients (2.8+/-1.6 cf. 0.9+/-1.4, p<0.001), and asthma severity was significantly improved (p=0.015). Qualitative responses from patients and pharmacists indicated a high level of satisfaction with the intervention and educational tools, both for their effectiveness and for their impact on the patient-pharmacist relationship. CONCLUSION A simple feasible intervention in community pharmacies, incorporating daily reminders via Inhaler Technique Labels on inhalers, can lead to improvement in inhaler technique and asthma outcomes. PRACTICE IMPLICATIONS Brief training modules and simple educational tools, such as Inhaler Technique Labels, can provide a low-cost and sustainable way of changing patient behavior in asthma, using community pharmacists as educators.

The effect of inhaled IFN-β on worsening of asthma symptoms caused by viral infections. A randomized trial.

RATIONALE Ex vivo, bronchial epithelial cells from people with asthma are more susceptible to rhinovirus infection caused by deficient induction of the antiviral protein, IFN-β. Exogenous IFN-β restores antiviral activity. OBJECTIVES To compare the efficacy and safety of inhaled IFN-β with placebo administered to people with asthma after onset of cold symptoms to prevent or attenuate asthma symptoms caused by respiratory viruses. METHODS A total of 147 people with asthma on inhaled corticosteroids (British Thoracic Society Steps 2-5), with a history of virus-associated exacerbations, were randomized to 14-day treatment with inhaled IFN-β (n = 72) or placebo (n = 75) within 24 hours of developing cold symptoms and were assessed clinically, with relevant samples collected to assess virus infection and antiviral responses. MEASUREMENTS AND MAIN RESULTS A total of 91% of randomized patients developed a defined cold. In this modified intention-to-treat population, asthma symptoms did not get clinically significantly worse (mean change in six-item Asthma Control Questionnaire <0.5) and IFN-β treatment had no significant effect on this primary endpoint, although it enhanced morning peak expiratory flow recovery (P = 0.033), reduced the need for additional treatment, and boosted innate immunity as assessed by blood and sputum biomarkers. In an exploratory analysis of the subset of more difficult-to-treat, Step 4-5 people with asthma (n = 27 IFN-β; n = 31 placebo), Asthma Control Questionnaire-6 increased significantly on placebo; this was prevented by IFN-β (P = 0.004). CONCLUSIONS Although the trial did not meet its primary endpoint, it suggests that inhaled IFN-β is a potential treatment for virus-induced deteriorations of asthma in difficult-to-treat people with asthma and supports the need for further, adequately powered, trials in this population. Clinical trial registered with www.clinicaltrials.gov (NCT 01126177).

Metered-Dose Inhaler Technique: The Effect of Two Educational Interventions Delivered in Community Pharmacy Over Time

Instruction is critical in order to ensure correct technique with pressurized metered-dose inhalers (pMDIs) by patients. The aim of this study was to compare the effects over time of two educational interventions delivered in community pharmacy to pMDI users. In this randomized controlled parallel-group study, pMDI technique was assessed before and after written and verbal instruction, alone or with physical demonstration, at baseline and 4, 8, and 16 weeks. The study recruited 52 subjects with asthma or chronic obstructive pulmonary disease (COPD). Initially only 1/52 (6%) subject had correct pMDI technique (= checklist score 8/8), with mean baseline score 5 (SD 1) for both groups. Written and verbal information improved pMDI technique at 16 weeks (7 ± 1, p < .05). Addition of physical demonstration resulted in significant improvement at weeks 4, 8, and 16 (7 ± 1, 7 ± 1, 7 ± 1 respectively; p < .05 for each). Subjects receiving written and verbal information alone were less likely to return for follow-up than those receiving physical demonstration (8 weeks: 6/25 versus 19/27; p < .001). By the 8-week visit, 80% subjects in the physical demonstration group had correct technique prior to education, compared with 10% of subjects receiving written and verbal information alone (p < .05). There was some decline in inhaler technique by 16 weeks. The results demonstrate that adding a physical demonstration is more effective in improving pMDI technique than written and verbal instructions alone.

Double blind randomised controlled trial of two different breathing techniques in the management of asthma

Background: Previous studies have shown that breathing techniques reduce short acting β2 agonist use and improve quality of life (QoL) in asthma. The primary aim of this double blind study was to compare the effects of breathing exercises focusing on shallow nasal breathing with those of non-specific upper body exercises on asthma symptoms, QoL, other measures of disease control, and inhaled corticosteroid (ICS) dose. This study also assessed the effect of peak flow monitoring on outcomes in patients using breathing techniques. Methods: After a 2 week run in period, 57 subjects were randomised to one of two breathing techniques learned from instructional videos. During the following 30 weeks subjects practised their exercises twice daily and as needed for relief of symptoms. After week 16, two successive ICS downtitration steps were attempted. The primary outcome variables were QoL score and daily symptom score at week 12. Results: Overall there were no clinically important differences between the groups in primary or secondary outcomes at weeks 12 or 28. The QoL score remained unchanged (0.7 at baseline v 0.5 at week 28, p = 0.11 both groups combined), as did lung function and airway responsiveness. However, across both groups, reliever use decreased by 86% (p<0.0001) and ICS dose was reduced by 50% (p<0.0001; p>0.10 between groups). Peak flow monitoring did not have a detrimental effect on asthma outcomes. Conclusion: Breathing techniques may be useful in the management of patients with mild asthma symptoms who use a reliever frequently, but there is no evidence to favour shallow nasal breathing over non-specific upper body exercises.