Eoin Hunt

A study to assess inhaler technique and its potential impact on asthma control in patients attending an asthma clinic

Abstract Objectives: The aim of this study was to evaluate inhaler technique and symptom control in patients with poorly controlled asthma at baseline and at follow-up in a dedicated asthma clinic in a tertiary hospital. We also investigated the impact of asthma on these patients’ quality of life. Methods: Patients referred to a newly established asthma clinic in Cork University Hospital were prospectively recruited over a 6-month period. Their inhaler technique was assessed by a pulmonary nurse specialist using a validated scoring system. They received instruction on inhaler usage when scores were suboptimal. Patients completed a validated asthma control questionnaire (ACQ) and asthma quality of life questionnaire (AQLQ). At follow-up 3–4 months later, the inhaler technique was reassessed and the ACQ questionnaire repeated. Results: Forty-six patients were recruited (female = 74%), and 40/46 were followed up. Mean [SD] FEV1 % predicted at baseline = 76.5% [21.5]. About 63% of the patients were classified as incorrectly using their inhaler at their initial assessment. This decreased to 20% at follow-up, indicating an overall significant improvement in inhaler usage post-training (p = 0.003). ACQ scores improved significantly from median [interquartile range] 2.70 [1.66] to 2.00 [1.90] (p = 0.002). Baseline measurement indicated that patients’ quality of life was moderately affected by asthma, with a median AQLQ score of 4.75 [1.97]. Conclusion: This study demonstrates the importance of educating and formally assessing inhaler technique in patients with asthma as a part of their ongoing clinical review.

A randomised clinical trial of feedback on inhaler adherence and technique in patients with severe uncontrolled asthma

In severe asthma, poor control could reflect issues of medication adherence or inhaler technique, or that the condition is refractory. This study aimed to determine if an intervention with (bio)feedback on the features of inhaler use would identify refractory asthma and enhance inhaler technique and adherence. Patients with severe uncontrolled asthma were subjected to a stratified-by-site random block design. The intensive education group received repeated training in inhaler use, adherence and disease management. The intervention group received the same intervention, enhanced by (bio)feedback-guided training. The primary outcome was rate of actual inhaler adherence. Secondary outcomes included a pre-defined assessment of clinical outcome. Outcome assessors were blinded to group allocation. Data were analysed on an intention-to-treat and per-protocol basis. The mean rate of adherence during the third month in the (bio)feedback group (n=111) was higher than that in the enhanced education group (intention-to-treat, n=107; 73% versus 63%; 95% CI 2.8%–17.6%; p=0.02). By the end of the study, asthma was either stable or improved in 54 patients (38%); uncontrolled, but poorly adherent in 52 (35%); and uncontrolled, but adherent in 40 (27%). Repeated feedback significantly improved inhaler adherence. After a programme of adherence and inhaler technique assessment, only 40 patients (27%) were refractory and adherent, and might therefore need add-on therapy. On a period of monitored adherence only 27% of patients were refractory and adherent and thus need add-on therapy http://ow.ly/ddQr30gTpmb

A protocol for a randomised clinical trial of the effect of providing feedback on inhaler technique and adherence from an electronic device in patients with poorly controlled severe asthma

Introduction In clinical practice, it is difficult to distinguish between patients with refractory asthma from those with poorly controlled asthma, where symptoms persist due to poor adherence, inadequate inhaler technique or comorbid diseases. We designed an audio recording device which, when attached to an inhaler, objectively identifies the time and technique of inhaler use, thereby assessing both aspects of adherence. This study will test the hypothesis that feedback on these two aspects of adherence when passed on to patients improves adherence and helps clinicians distinguish refractory from difficult-to-control asthma. Methods This is a single, blind, prospective, randomised, clinical trial performed at 5 research centres. Patients with partially controlled or uncontrolled severe asthma who have also had at least one severe asthma exacerbation in the prior year are eligible to participate. The effect of two types of nurse-delivered education interventions to promote adherence and inhaler technique will be assessed. The active group will receive feedback on their inhaler technique and adherence from the new device over a 3-month period. The control group will also receive training in inhaler technique and strategies to promote adherence, but no feedback from the device. The primary outcome is the difference in actual adherence, a measure that incorporates time and technique of inhaler use between groups at the end of the third month. Secondary outcomes include the number of patients who remain refractory despite good adherence, and differences in the components of adherence after the intervention. Data will be analysed on an intention-to-treat and a per-protocol basis. The sample size is 220 subjects (110 in each group), and loss to follow-up is estimated at 10% which will allow results to show a 10% difference (0.8 power) in adherence between group means with a type I error probability of 0.05. Trial registration number NCT01529697; Pre-results.

The Microbiome and the Pathophysiology of Asthma

Asthma is a chronic respiratory disease whose prevalence is increasing in the western world. Recently research has begun to focus on the role the microbiome plays in asthma pathogenesis in the hope of further understanding this respiratory disorder. Considered sterile until recently, the lungs have revealed themselves to contain a unique microbiota. A shift towards molecular methods for the quantification and sequencing of microbial DNA has revealed that the airways harbour a unique microbiota with apparent, reproducible differences present between healthy and diseased lungs. There is a hope that in classifying the microbial load of the asthmatic airway an insight may be afforded as to the possible role pulmonary microbes may have in propagating an asthmatic airway response. This could potentially pave the way for new therapeutic strategies for the treatment of chronic lung conditions such as asthma.

Roflumilast in COPD

We read with interest the Point and Counterpoint editorials in CHEST (May 2014) by Suissa and Rabe 1 and Rho et al 2 about the appropriateness of industry-sponsored rofl umilast trials. In the editorials, reference was made to the level of patient withdrawal as well as to the level of side eff ects experienced by patients receiving this drug during clinical trials. 2 In our real-world clinical experience, we have found both the reported side eff ect and drug discontinuation rates to be at far higher than reported levels.

The Potential Role of Aspiration in the Asthmatic Airway

BACKGROUND: Many people with asthma remain suboptimally controlled despite current treatments. Reasons include comorbidities that could aggravate asthma, including gastroesophageal reflux. We aimed to investigate whether aspiration occurs in patients with asthma and, if so, does it correlate with asthma control? METHODS: Patients had Asthma Control Questionnaire 7 (ACQ‐7), fractional exhaled nitric oxide, and spirometry performed to characterize their level of asthma control. Barium swallow with provocation was performed to assess for predisposition to aspiration. Patients underwent bronchoscopic investigation, with BAL pepsin measured as a marker of aspiration. RESULTS: Seventy‐eight patients stratified by disease severity (Global Initiative for Asthma) into mild (35.8%), moderate (21.7%) and severe (42.3%) were studied. Pepsin was detectable in BAL in 46/78 (58.9%). There were no differences between pepsin levels in patients with different disease severity. Furthermore, no significant associations were seen between pepsin level and measures of asthma control, FEV1, ACQ‐7 or exacerbation frequency. Similarly no associations were found with adjustments for smoking history, BMI, proton pump inhibitor use, eosinophil count or IgE. When stratified into eosinophilic or neutrophilic asthmatic populations on the basis of BAL, there was no relationship to detected pepsin concentrations. A positive barium swallow (seen in 33/60 patients) did not correlate with BAL pepsin level and we found no significant association between barium swallow result and ACQ‐7, Global Initiative for Asthma, exacerbation frequency or FEV1 using either univariate or multivariate analyses. CONCLUSIONS: This study suggests that the importance of aspiration on current asthma symptom control and exacerbation rate may be overstated. However, this study did not address the role of aspiration and future risk of exacerbation.

In patients with severe uncontrolled asthma, does knowledge of adherence and inhaler technique using electronic monitoring improve clinical decision making? A protocol for a randomised controlled trial.

Introduction Many patients with asthma remain poorly controlled despite the use of inhaled corticosteroids and long-acting beta agonists. Poor control may arise from inadequate adherence, incorrect inhaler technique or because the condition is refractory. Without having an objective assessment of adherence, clinicians may inadvertently add extra medication instead of addressing adherence. This study aims to assess if incorporating objectively recorded adherence from the Inhaler Compliance Assessment (INCA) device and lung function into clinical decision making provides more cost-effective prescribing and improves outcomes. Methods and analysis This prospective, randomised, multicentre study will compare the impact of using information on adherence to influence asthma treatment. Patients with severe uncontrolled asthma will be included. Data on adherence, inhaler technique and electronically recorded peak expiratory flow rate will be used to promote adherence and guide a clinical decision protocol to guide management in the active group. The control group will receive standard inhaler and adherence education. Medications will be adjusted using a protocol based on Global Initiativefor Asthma (GINA) recommendations. The primary outcome is the between-group difference in the proportion of patients who have refractory disease and are prescribed appropriate medications at the end of 32 weeks. A co-primary outcome is the difference between groups in the rate of adherence to salmeterol/fluticasone inhaler over the last 12 weeks. Secondary outcomes include changes in symptoms, lung function, type-2 cytokine biomarkers and clinical outcomes between both groups. Cost-effectiveness and cost-utility analyses of the INCA device intervention will be performed. The economic impact of a national implementation of the INCA-SUN programme will be evaluated. Ethics and dissemination The results of the study will be published as a manuscript in peer-reviewed journals. The study has been approved by the ethics committees in the five participating hospitals. Trial registration NCT02307669; Pre-results.

Gastric Aspiration and Its Role in Airway Inflammation

Gastro-Oesophageal Reflux (GOR) has been associated with chronic airway diseases while the passage of foreign matter into airways and lungs through aspiration has the potential to initiate a wide spectrum of pulmonary disorders. The clinical syndrome resulting from such aspiration will depend both on the quantity and nature of the aspirate as well as the individual host response. Aspiration of gastric fluids may cause damage to airway epithelium, not only because acidity is toxic to bronchial epithelial cells but also due to the effect of digestive enzymes such as pepsin and bile salts. Experimental models have shown that direct instillation of these factors to airways epithelia cause damage with a consequential inflammatory response. The pathophysiology of these responses is gradually being dissected, with better understanding of acute gastric aspiration injury, a major cause of acute lung injury, providing opportunities for therapeutic intervention and potentially, ultimately, improved understanding of the chronic airway response to aspiration. Ultimately, clarification of the inflammatory pathways which are related to micro-aspiration via pepsin and bile acid salts may eventually progress to pharmacological intervention and surgical studies to assess the clinical benefits of such therapies in driving symptom improvement or reducing disease progression.

Pathophysiology in the Lung

This chapter discusses selected aspects of reflux, aspiration and pathophysiology in the lung. It is complimented by reviews that exist in this broad area dealing with adult [1–3] and paediatric patients [4–6].

The Safety of Salt Pipes in Asthmatic Patients

To the Editor, Salt pipes are commercially available products which are advertised for use in a wide range of respiratory conditions, including asthma. They use micronized salt crystals which are inspired into the lungs. Advocats of the device propose that they enhance sputum clearance from the lungs with resultant improvement in breathing. However, there is a lack of robust clinical efficacy and safety data available to support this claim. Airway hyperresponsiveness is a characteristic feature of asthma and results in an exaggerated bronchoconstrictive reaction of the airways to nonspecific stimuli. Only a small volume of hypertonic saline is needed to provoke airway narrowing in patients with asthma. Hence, concern remains that salt pipes may provoke a bronchoconstrictive response particularly in potentially susceptible asthmatic subjects. Our group conducted a short study to evaluate and determine the safety profile of salt pipe inhalers in asthmatic patients. Ethical approval was granted by The Clinical Research Ethics Committee of the Cork Teaching Hospitals. Twelve patients who suffered from asthma (a bronchodilator response of 12% and 200 ml change in FEV1 or a positive methacholine test) were recruited. Mean age was 41.3 (618.9) y, with an average FEV1 of 87.3% predicted and an ACQ-7 score of 1.9 indicative of poor control. Patients did not take their short or long term bronchodilators, in accordance with standard inhaled challenge guidelines. FEV1 was determined by spirometry to obtain a baseline lung function. Each patient then inhaled from the Cisca Easy SaltpipeVR (Cisca Limited, Durham, United Kingdom) for 5 min, performing normal breathing, as per product instructions. Serial FEV1 was conducted at 5, 10, 15 and 30 min after using the salt pipe inhaler. Patients were then asked if they felt there had been any clinical improvement or deterioration. They were asked this again 24 h later. The maximum change in FEV1 over the test’s duration was determined (Figure 1). Baseline and postinhalation FEV1 values were analysed, using a paired t test, with no significant change observed (P5 0.58). The maximum fall in FEV1 was 16.9% from baseline and the mean decrease, among those with a decrease in FEV1, was 3.8%. A maximum increase of 7.2% was recorded and, of those who responded positively to the treatment, the mean increase was 3.0%. Overall, the mean change in FEV1 from baseline was an increase of 0.5%. Of note the patient that had the maximum fall in FEV1 during the study also demonstrated the largest bronchodilator response (20.9%) on formal testing for reversibility prior to study entry. There was no correlation observed between age, sex, BMI, atopic status and response to salt pipe using standard ANOVA. Clinical efficacy was not formally assessed but six patients reported improvement in breathing in the 24 h after using the salt pipe (5/6 of whom had experienced an increase in FEV1 during the test). Three patients reported feeling worse after using the salt pipe, mentioning an unpleasant salty aftertaste, headache and experiencing tightness in the chest. This study was limited by a small sample size but based on the results obtained we would exercise caution when using salt pipe inhalers. While, the device was safe in the majority of our asthmatic subjects, it did cause a decrease in FEV1 of almost 17% in one of the patients.