Julia Walters

Adverse Effects of β-Agonists

Inhaled β2-adrenoceptor agonists (β2-agonists) are the most commonly used asthma medications in many Western countries. Minor adverse effects such as palpitations, tremor, headache and metabolic effects are predictable and dose related. Time series studies suggested an association between the relatively nonselective β-agonist fenoterol and asthma deaths. Three case-control studies confirmed that among patients prescribed fenoterol, the risk of death was significantly elevated even after controlling for the severity of asthma. The Saskatchewan study not only found an increased risk of death among patients dispensed fenoterol, but also suggested this might be a class effect of β2-agonists. However, in subsequent studies, the long-acting β2-agonist salmeterol was not associated with increased asthma mortality. In a case-control study blood albuterol (salbutamol) concentrations were found to be 2.5 times higher among patients who died of asthma compared with controls. It is speculated that such toxic concentrations could cause tachyarrhythmias under conditions of hypoxia and hypokalemia.The risk of asthma exacerbations and near-fatal attacks may also be increased among patients dispensed fenoterol, but this association may be largely due to confounding by severity. Although salmeterol does not appear to increase the risk of near-fatal attacks, there is a consistent association with the use of nebulized β2-agonists. Nebulized and oral β2-agonists are also associated with an increased risk of cardiovascular death, ischemic heart disease and cardiac failure. Caution should be exercised when first prescribing a β-agonist for patients with cardiovascular disease.A potential mechanism for adverse effects with regular use of β2-agonists is tachyphylaxis. Tachyphylaxis to the bronchodilator effects of long-acting β2-agonists can occur, but has been consistently demonstrated only for formoterol (eformoterol) a full agonist, rather than salmeterol, a partial agonist. Tachyphylaxis to protection against induced bronchospasm occurs with both full and partial β2-agonists, and probably within a matter of days at most. Underlying airway responsiveness to directly acting bronchoconstricting agents is not increased when the bronchodilator effect of the regular β2-agonist has been allowed to wear off, although there may be an increase in responsiveness to indirectly acting agents. While there has been speculation that underlying airway inflammation in asthma may be made worse by regular use of short-acting β2-agonists, in contradistinction, a number of studies have shown that long-acting β2-agonists have positive anti-inflammatory effects.An Australian Cochrane Airways Group systematic review of the randomized, controlled trials of short-acting β-agonists found only minimal and clinically unimportant differences between regular use and use as needed. Regular short-acting treatment was better than placebo. However, a subsequent systematic review has found that regular use of long-acting β-agonists had significant advantages over regular use of short-acting β-agonists. More studies and data are needed on the regular use of β2-agonists in patients not taking inhaled corticosteroids, and in potentially vulnerable groups, such as the elderly and those with particular genotypes for the β-receptor, who might be more prone to adverse effects.

Stability of the EasyOne ultrasonic spirometer for use in general practice.

Objective and background:  Spirometry is recommended for the diagnosis and management of chronic respiratory diseases in the community. Spirometer accuracy is critical, but few general practitioners meet the American Thoracic Society and European Respiratory Society (ATS/ERS) recommendation for daily calibration. The aim of this study was to assess the accuracy and stability of a portable ultrasonic spirometer (EasyOne) that the manufacturer claims does not require regular calibration.

Exploring the Viability of Using Online Social Media Advertising as a Recruitment Method for Smoking Cessation Clinical Trials

INTRODUCTION The aim of the present study was to explore the viability of using social media as a recruitment tool in a clinical research trial. Sociodemographic data and smoking characteristics were assessed in 266 participants recruited to investigate the effectiveness of a behavioral support program for smoking cessation. METHODS For analysis, participants were separated into 2 groups based on whether they were recruited either using traditional means (flyers, word of mouth, or newspaper advertisement; n = 125, 47.0%) or by advertisements in online social media (n = 138, 51.9%). RESULTS Participants recruited via social media were significantly younger, but there were no differences in other socioeconomic variables or smoking characteristics compared with participants recruited via other traditional means. CONCLUSIONS The findings of the present study suggest that using online social media is a viable recruitment method for smoking studies and compliments other more traditional recruitment methods.

Erythropoietin as a treatment of anemia in heart failure: Systematic review of randomized trials

BACKGROUND Anemia in heart failure is both common and associated with worse symptoms and increased mortality. Several small randomized controlled trials (RCTs) have assessed erythropoiesis-stimulating agents (ESAs), but definitive evaluation and clinical guidance are required. We sought to systematically review the effects of ESAs in chronic heart failure. METHODS An extensive search strategy identified 11 RCTs with 794 participants comparing any ESA with control over 2 to 12 months of follow-up. Published and additionally requested data were incorporated into a Cochrane systematic review (CD007613). RESULTS Nine studies were placebo controlled, and 5, double blinded. Erythropoiesis-stimulating agent treatment significantly improved exercise duration by 96.8 seconds (95% CI 5.2-188.4, P = .04) and 6-minute walk distance by 69.3 m (95% CI 17.0-121.7, P = .009) compared with control. Benefit was also noted for peak oxygen consumption (+2.29 mL/kg per minute, P = .007), New York Heart Association class (-0.73, P < .001), ejection fraction (+5.8%, P < .001), B-type natriuretic peptide (-226.99 pg/mL, P < .001), and quality-of-life indicators with a mean increase in hemoglobin level of 2 g/dL. There was a significantly lower rate of heart failure-related hospitalizations with ESA therapy (odds ratio 0.56, 95% CI 0.37-0.84, P = .005). No associated increase in adverse events or mortality (odds ratio 0.58, 95% CI 0.34-0.99, P = .047) was observed, although the number of events was limited. CONCLUSION Meta-analysis of small RCTs suggests that ESA treatment can improve exercise tolerance, reduce symptoms, and have benefits on clinical outcomes in anemic patients with heart failure. Confirmation requires larger, well-designed studies with careful attention to dose, attained hemoglobin level, and long-term outcomes.

Effects of telephone health mentoring in community-recruited chronic obstructive pulmonary disease on self-management capacity, quality of life and psychological morbidity: a randomised controlled trial

Objectives To assess benefits of telephone-delivered health mentoring in community-based chronic obstructive pulmonary disease (COPD). Design Cluster randomised controlled trial. Setting Tasmanian general practices: capital city (11), large rural (3), medium rural (1) and small rural (16). Participants Patients were invited (1207) from general practitioner (GP) databases with COPD diagnosis and/or tiotropium prescription, response rate 49% (586), refused (176) and excluded (criteria: smoking history or previous study, 68). Spirometry testing (342) confirmed moderate or severe COPD in 182 (53%) patients. Randomisation By random numbers code, block stratified on location, allocation by sequentially numbered, opaque and sealed envelopes. Intervention Health mentor (HM) group received regular calls to manage illness issues and health behaviours from trained community health nurses using negotiated goal setting: problem solving, decision-making and action planning. Control: usual care (UC) group received GP care plus non-interventional brief phone calls. Outcomes Measured at 0, 6 and 12 months, the Short Form 36 (SF-36) and St George’s Respiratory Questionnaire (SGRQ, primary); Partners In Health (PIH) Scale for self-management capacity, Hospital Anxiety and Depression Scale (HADS), Center for Epidemiologic Studies-Depression (CES-D) questionnaire, Post-Traumatic Stress Disorder Checklist, Satisfaction with life and hospital admissions (secondary). Results 182 participants with COPD (age 68±8 years, 62% moderate COPD and 53% men) were randomised (HM=90 and UC=92). Mixed model regression analysis accounting for clustering, adjusting for age, gender, smoking status and airflow limitation assessed efficacy (regression coefficient, β, reported per 6-month visit). There was no difference in quality of life between groups, but self-management capacity increased in the HM group (PIH overall 0.15, 95% CI 0.03 to 0.29; knowledge domain 0.25, 95% CI 0.00 to 0.50). Anxiety decreased in both groups (HADS A 0.35; 95% CI −0.65 to −0.04) and coping capacity improved (PIH coping 0.15; 95% CI 0.04 to 0.26). Conclusions Health mentoring improved self-management capacity but not quality of life compared to regular phone contact, which itself had positive effects where decline is generally expected.

National survey of spirometer ownership and usage in general practice in Australia

Objectives and background:  Despite the lack of data, it is believed that spirometry is underutilized in general practice. The aim of the present study was to determine the availability of spirometry and the level of spirometry training in general practice throughout Australia and compare with international data.

Supporting health behaviour change in chronic obstructive pulmonary disease with telephone health-mentoring: insights from a qualitative study

BackgroundAdoption and maintenance of healthy behaviours is pivotal to chronic disease self-management as this influences disease progression and impact. This qualitative study investigated health behaviour changes adopted by participants with moderate or severe chronic obstructive pulmonary disease (COPD) recruited to a randomised controlled study of telephone-delivered health-mentoring.MethodsCommunity nurses trained as health-mentors used a patient-centred approach with COPD patients recruited in general practice to facilitate behaviour change, using a framework of health behaviours; ‘SNAPPS’ Smoking, Nutrition, Alcohol, Physical activity, Psychosocial well-being, and Symptom management, through regular phone calls over 12 months. Semi-structured interviews in a purposive sample sought feedback on mentoring and behaviour changes adopted. Interviews were analysed using iterative thematic and interpretative content approaches by two investigators.ResultsOf 90 participants allocated to health-mentoring, 65 (72%) were invited for interview at 12-month follow up. The 44 interviewees, 75% with moderate COPD, had a median of 13 mentor contacts over 12 months, range 5–20. Interviewed participants (n = 44, 55% male, 43% current smokers, 75% moderate COPD) were representative of the total group with a mean age 65 years while 82% had at least one additional co-morbid chronic condition. Telephone delivery was highly acceptable and enabled good rapport. Participants rated ‘being listened to by a caring health professional’ as very valuable. Three participant groups were identified by attitude to health behaviour change: 14 (32%) actively making changes; 18 (41%) open to and making some changes and 12 (27%) more resistant to change. COPD severity or current smoking status was not related to group category. Mentoring increased awareness of COPD effects, helping develop and personalise behaviour change strategies, even by those not actively making changes. Physical activity was targeted by 43 (98%) participants and smoking by 14 (74%) current smokers with 21% reporting quitting. Motivation to maintain changes was increased by mentor support.ConclusionsTelephone delivery of health-mentoring is feasible and acceptable to people with COPD in primary care. Health behaviours targeted by this population, mostly with moderate disease, were mainly physical activity and smoking reduction or cessation. Health-mentoring increased motivation and assisted people to develop strategies for making and sustaining beneficial change.Trial registrationACTR12608000112368

Compliance with an EMA monitoring protocol and its relationship with participant and smoking characteristics.

INTRODUCTION Arguably, the greatest advantage of ecological momentary assessment (EMA) studies is that data are collected repeatedly in real-time and real-world situations, which reduces recall and situational biases and thus improves the accuracy and validity of the data collected. However, the validity of EMA data is contingent upon compliance rates. If participant characteristics are related to missing data, analyses should control for these factors, or they should be targeted in EMA training sessions. This study evaluates the impact of demographic and smoking-related participant characteristics on compliance to an EMA smoking study protocol. METHODS Prequit-day data were taken from the control arm of an ongoing randomized controlled trial of a smoking-cessation program. After training, 119 participants were asked to carry a mobile device with them at all times for ~6 days and to log every cigarette they smoked in addition to completing randomly scheduled assessments. Different types of compliance were assessed: the percentage of completed random prompts (signal-contingent compliance), the percentage of logged cigarettes per day compared to a timeline follow-back measure, and the correlation between logged cigarettes and a carbon monoxide assessment 2 hr later (both event-contingent compliance). RESULTS Overall compliance rates were 78.48% for event-contingent and 72.17% for signal-contingent compliance. None of the demographic or smoking-related participant characteristics predicted signal-contingent compliance; however, female participants showed higher event-contingent compliance than male participants, and Caucasian participants showed higher event-contingent compliance than non-Caucasian participants. CONCLUSIONS Compliance did not depend on smoking-related characteristics. EMA is a valid method for assessing smoking behavior in real-time and real-world settings.

Diagnosis and early detection of COPD using spirometry

The standard respiratory function test for case detection of chronic obstructive pulmonary disease (COPD) is spirometry. The criterion for diagnosis defined in guidelines is based on the FEV1/FVC ratio forced expiratory ratio (FER) and its severity is based on forced expiratory volume in one second (FEV1) from measurements obtained during maximal forced expiratory manoeuvres. Spirometry is a safe and practical procedure, and when conducted by a trained operator using a spirometer that provides quality feedback, the majority of patients can be coached to provide acceptable and repeatable results. This allows potentially wide application of testing to improve recognition and diagnosis of COPD, such as for case finding in primary care. However, COPD remains substantially under diagnosed in primary care and a major reason for this is underuse of spirometry. The presence of symptoms is not a reliable indicator of disease and diagnosis is often delayed until more severe airflow obstruction is present. Early diagnosis is worthwhile, as it allows risk factors for COPD such as smoking to be addressed promptly and treatment optimised. Paradoxically, investigation of the patho-physiology in COPD has shown that extensive small airway disease exists before it is detectable with conventional spirometric indices, and methods to detect airway disease earlier using the flow-volume curve are discussed.

A randomized controlled trial of telephone-mentoring with home-based walking preceding rehabilitation in COPD

Purpose With the limited reach of pulmonary rehabilitation (PR) and low levels of daily physical activity in chronic obstructive pulmonary disease (COPD), a need exists to increase daily exercise. This study evaluated telephone health-mentoring targeting home-based walking (tele-rehab) compared to usual waiting time (usual care) followed by group PR. Patients and methods People with COPD were randomized to tele-rehab (intervention) or usual care (controls). Tele-rehab delivered by trained nurse health-mentors supported participants’ home-based walking over 8–12 weeks. PR, delivered to both groups simultaneously, included 8 weeks of once-weekly education and self-management skills, with separate supervised exercise. Data were collected at three time-points: baseline (TP1), before (TP2), and after (TP3) PR. The primary outcome was change in physical capacity measured by 6-minute walk distance (6MWD) with two tests performed at each time-point. Secondary outcomes included changes in self-reported home-based walking, health-related quality of life, and health behaviors. Results Of 65 recruits, 25 withdrew before completing PR. Forty attended a median of 6 (4) education sessions. Seventeen attended supervised exercise (5±2 sessions). Between TP1 and TP2, there was a statistically significant increase in the median 6MWD of 12 (39.1) m in controls, but no change in the tele-rehab group. There were no significant changes in 6MWD between other time-points or groups, or significant change in any secondary outcomes. Participants attending supervised exercise showed a nonsignificant improvement in 6MWD, 12.3 (71) m, while others showed no change, 0 (33) m. The mean 6MWD was significantly greater, but not clinically meaningful, for the second test compared to the first at all time-points. Conclusion Telephone-mentoring for home-based walking demonstrated no benefit to exercise capacity. Two 6-minute walking tests at each time-point may not be necessary. Supervised exercise seems essential in PR. The challenge of incorporating exercise into daily life in COPD is substantial.