Z.H. Hoo

Idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis is a progressive lung disease that carries a poor prognosis and for which there are no effective therapies. Although the excessive deposition of extracellular matrix, combined with evidence of recurrent injury to the alveolar epithelium, are well-described there is a pressing need to understand these processes better at a molecular level and thus to identify potential therapeutic targets in this intractable disease. This review considers some recent advances published in Thorax and elsewhere that have improved our understanding of the pathophysiology of idiopathic pulmonary fibrosis, using data both from human cells and tissue and from animal models of pulmonary fibrosis. The studies particularly address the fate of the alveolar epithelial cell and mechanisms of fibrogenesis, and identify mechanistic pathways shared with co-existing conditions such as lung cancer and pulmonary hypertension. The concepts of physiological biomarkers of disease progression and prognosis are also discussed.

Airway clearance techniques used by people with cystic fibrosis in the UK

OBJECTIVES To describe the current use of airway clearance techniques among people with cystic fibrosis (CF) in the UK, and the baseline characteristics for users of different airway clearance techniques. DESIGN Analysis of the UK CF Registry 2011 data. SETTING AND PARTICIPANTS All people with CF in the UK aged ≥11 years (n=6372). RESULTS Of the 6372 people on the UK CF registry in 2011, 89% used airway clearance techniques. The most commonly used primary techniques were forced expiratory techniques (28%) and oscillating positive expiratory pressure (PEP) (23%). Postural drainage and high-frequency chest wall oscillation were used by 4% and 1% of people with CF, respectively. The male:female ratio of individuals who used exercise as their primary airway clearance technique was 2:1, compared with 1:1 for other techniques. Individuals with more severe lung disease tended to use devices such as non-invasive ventilation or high-frequency chest wall oscillation. CONCLUSIONS Forced expiratory techniques and oscillating PEP are the most common airway clearance techniques used by people with CF in the UK, and postural drainage and high-frequency chest wall oscillation are the least common techniques. This is significant in terms of planning airway clearance technique trials, where postural drainage has been used traditionally as the comparator. The use of airway clearance techniques varies between countries, but the reasons for these differences are unknown.

Accurate reporting of adherence to inhaled therapies in adults with cystic fibrosis: methods to calculate “normative adherence”

Background Preventative inhaled treatments in cystic fibrosis will only be effective in maintaining lung health if used appropriately. An accurate adherence index should therefore reflect treatment effectiveness, but the standard method of reporting adherence, that is, as a percentage of the agreed regimen between clinicians and people with cystic fibrosis, does not account for the appropriateness of the treatment regimen. We describe two different indices of inhaled therapy adherence for adults with cystic fibrosis which take into account effectiveness, that is, “simple” and “sophisticated” normative adherence. Methods to calculate normative adherence Denominator adjustment involves fixing a minimum appropriate value based on the recommended therapy given a person’s characteristics. For simple normative adherence, the denominator is determined by the person’s Pseudomonas status. For sophisticated normative adherence, the denominator is determined by the person’s Pseudomonas status and history of pulmonary exacerbations over the previous year. Numerator adjustment involves capping the daily maximum inhaled therapy use at 100% so that medication overuse does not artificially inflate the adherence level. Three illustrative cases Case A is an example of inhaled therapy under prescription based on Pseudomonas status resulting in lower simple normative adherence compared to unadjusted adherence. Case B is an example of inhaled therapy under-prescription based on previous exacerbation history resulting in lower sophisticated normative adherence compared to unadjusted adherence and simple normative adherence. Case C is an example of nebulizer overuse exaggerating the magnitude of unadjusted adherence. Conclusion Different methods of reporting adherence can result in different magnitudes of adherence. We have proposed two methods of standardizing the calculation of adherence which should better reflect treatment effectiveness. The value of these indices can be tested empirically in clinical trials in which there is careful definition of treatment regimens related to key patient characteristics, alongside accurate measurement of health outcomes.

Moving cystic fibrosis care from rescue to prevention by embedding adherence measurement in routine care

Cystic fibrosis [CF] is a chronic disease in which preventative treatment with nebulised antibiotics can reduce pulmonary exacerbations that otherwise require rescue therapy. However, adherence is low. Making adherence to maintenance treatment visible is a crucial step towards improving adherence. In this article, we discuss how adherence data can be used to support Quality Improvement in CF through behaviour change in both people with cystic fibrosis and their clinical teams.

Promoting adherence to nebulized therapy in cystic fibrosis: poster development and a qualitative exploration of adherence

Background Cystic fibrosis (CF) health care professionals recognize the need to motivate people with CF to adhere to nebulizer treatments, yet little is known about how best to achieve this. We aimed to produce motivational posters to support nebulizer adherence by using social marketing involving people with CF in the development of those posters. Methods The Sheffield CF multidisciplinary team produced preliminary ideas that were elaborated upon with semi-structured interviews among people with CF to explore barriers and facilitators to the use of nebulized therapy. Initial themes and poster designs were refined using an online focus group to finalize the poster designs. Results People with CF preferred aspirational posters describing what could be achieved through adherence in contrast to posters that highlighted the adverse consequences of nonadherence. A total of 14 posters were produced through this process. Conclusion People with CF can be engaged to develop promotional material to support adherence, providing a unique perspective differing from that of the CF multidisciplinary team. Further research is needed to evaluate the effectiveness of these posters to support nebulizer adherence.

Rescue therapy within the UK Cystic Fibrosis Registry: An exploration of predictors of intravenous antibiotic use amongst adults with CF: Predictors of i.v. antibiotic use in CF

Intravenous (i.v.) antibiotics are needed for rescue when preventative therapy fails to achieve stability among adults with cystic fibrosis (CF). Understanding the distribution of i.v. days can provide insight into the care that adults with CF need. We aim to determine the baseline characteristics that are associated with higher i.v. use, in particular to test the hypothesis that prior‐year i.v. use is associated with future‐year i.v. use.

Determinants of objective adherence to nebulised medications among adults with cystic fibrosis: an exploratory mixed methods study comparing low and high adherers

ABSTRACT Objectives: Adherence to nebulised treatment is typically low among people with cystic fibrosis (CF). This study sought to identify factors differentiating high or low nebuliser adherence patterns (i.e. ≥80% or <50% of all nebulised treatments over one year) among adults with CF. Design: A mixed methods cross-sectional exploratory comparison of low and high adherers to nebulised medications. Methods: Of 36 eligible adults invited from a UK CF centre, 20 were recruited (10 high, 10 low adherers). Adherence was objectively measured using electronic data capture. Participants completed a self-report questionnaire comprising measures of hypothesised predictors (habit, self-control, life chaos, perceived treatment burden, capability, motivation and opportunity), then took part in a semi-structured interview. Quantitative data were compared between groups, and interview data were thematically analysed. Results: High adherers reported stronger habit and greater opportunities, though habit and perceived opportunity scores were highly positively correlated. No other quantitative measure distinguished between groups. Habitual instigation tendency attenuated the relationship between treatment complexity and perceived treatment burden. Indeed, in interviews, high adherers reported that routinisation and greater automaticity made treatment burden more manageable. Conclusions: High adherers seized more opportunities for nebuliser use, adapted their lives more effectively to using nebulisers and were more likely to make nebuliser use habitual. Nebuliser adherence interventions among adults with CF might usefully target development of routines for instigating nebuliser use, and identification of opportune moments for nebuliser use.

What is an ROC curve

The paper by Body et al is concerned with the evaluation of decision aids, which can be used to identify potential acute coronary syndromes (ACS) in the ED. The authors previously developed the Manchester Acute Coronary Syndromes model (MACS) decision aid, which uses several clinical variables and two biomarkers to ‘rule in’ and ‘rule out’ ACS. However, one of the two biomarkers (heart-type fatty acid bindingprotein, H-FABP) is not widely used so a revised decision aid has been developed (Troponin-only Manchester Acute Coronary Syndromes, T-MACS), which include a single biomarker hs-cTnT. In this issue, the authors show how they derive a revised decision aid and describe its performance in a number of independent diagnostic cohort studies. Decision aids (as well as other types of ‘diagnostic tests’) are often evaluated in terms of diagnostic testing parameters such as the area under the receiver operating characteristic (ROC) curve, sensitivity and specificity. In this article, we explain how the ROC analysis is conducted and why it is an essential step towards developing a test with the desirable levels of sensitivity and specificity.

P278 Is there a role for telemedicine in cystic fibrosis? A systematic review

Background As a result of new medical advances people with CF are now able to live longer but still require frequent specialist care input and support. To cope with an ever increasing complex condition and demand for care, CF centres are having to rethink the way they work. Telemedicine is an evolving field which has the advantage of remote monitoring and real time review and may provide a solution. Objectives To determine whether telemedicine has a role in the management of CF in terms of: 1) Feasibility and acceptability, 2) Early pulmonary exacerbation detection, and 3) Self-management and improving adherence to prescribed therapies. Methods A systematic search was undertaken to identify relevant studies. This involved seven electronic databases, the top four peer reviewed journals reporting on CF and telemedicine, and the three major conference proceedings in CF and telemedicine. Clinical trial registers were searched to find ongoing studies as supplementary evidence. A mixed methods synthesis was performed to combine results from quantitative and qualitative studies. Results 34 studies in total were included in the results synthesis. These consisted of mainly small pilot and feasibility studies. There were 7 RCTs largely reporting interim results rather than efficacy data. Rates of adherence to telemedicine varied between 10.16 to 59% but were generally poor with barriers including frequent measures being a burden, forgetting, and denial of results. There was a general consensus that pulmonary exacerbations can be detected early but no statistical tests of significance performed. There were also only 2 studies predominantly reporting qualitative evidence. After corroborating the results using thematic synthesis this led to 3 main themes (expectations, technical aspects, and impacts of telemedicine) linked to these were barriers and facilitators. Conclusion The findings indicate that telemedicine in CF is feasible but the uptake amongst people with CF may be challenging. This is probably not surprising since adherence to treatment is often poor. Nevertheless telemedicine has the potential to play an important role in the early detection of pulmonary exacerbations and further studies are required.

Role of habit in treatment adherence among adults with cystic fibrosis

Among adults with cystic fibrosis (CF), medication adherence is low and reasons for low adherence are poorly understood. Our previous exploratory study showed that stronger ‘habit’ (ie, automatically experiencing an urge to use a nebuliser) was associated with higher nebuliser adherence. We performed a secondary analysis of pilot trial data (n=61) to replicate the earlier study and determine whether habit–adherence association exists in other cohorts of adults with CF. In this study, high adherers also reported stronger habit compared with low adherers. Habit may be a promising target for self-management interventions. Trial registration number ACtiF pilot, ISRCTN13076797.