6 June 2018
More testing for alpha-1 antitrypsin deficiency is needed in the UK
Chronic obstructive pulmonary disease (COPD) is a major cause of chronic morbidity and the third leading cause of death worldwide. Alpha-1-antitrypsin (AAT) deficiency significantly increases the risk of developing COPD. AAT deficiency (AATD) is a genetic disorder characterized by low serum levels of AAT, which at normal levels protects the lung alveoli from damage. Severe AATD can lead to pulmonary emphysema. Global guidance from the World Health Organization, European Respiratory Society and the Global Initiative for Chronic Obstructive Lung Disease recommends testing AAT levels in blood serum of all COPD patients.
In the UK, previous estimates of the prevalence of AATD are outdated and suggest that it is underdiagnosed. In May 2018, a REG study was published in the European Respiratory Journal that determined recent trends in testing and diagnosing AATD among COPD patients in the UK from 1990 to 2014. The Optimum Patient Care Research Database was used to identify patients with a diagnostic code for COPD from about 550 UK general practices. Analysis focused on those diagnosed with COPD before the age of 60 years.
The study identified over 100,000 patients with COPD, of whom over a quarter were diagnosed before 60 years of age. Between 1994 and 2013 the incidence of AATD diagnosis increased among all age groups and both genders, mostly due to an increase in new testing for AATD from around 0% in 1994 to around 1.3% in 2013. However, despite the increase in testing, still only 2.2% of COPD diagnosed before the age of 60 were ever tested for AATD in the period 1990-2014. Of those tested, 24% were diagnosed with AATD. These findings indicate that AATD remains markedly underdiagnosed in COPD patients in the UK and that more testing is needed.
- Soriano JB, Lucas SJ, Jones R, Miravitlles M, Carter V, Small I, Price D, Mahadeva R. Trends of testing for and diagnosis of alpha-1 antitrypsin deficiency in the UK: more testing is needed. Eur Respir J. 2018 May 31. pii: 1800360.
COPD Baseline Control
In Chronic Obstructive Pulmonary Disease (COPD) the aim of treatment is to reduce symptoms and the occurrence of acute exacerbations. The concept of control in COPD has been developed to guide treatment decisions and indicate prognosis. COPD can be considered controlled if the disease is demonstrated to have both a low impact (i.e. a low level of symptoms) and clinical stability (i.e. no exacerbations or deterioration in COPD Assessment Test (CAT)/ Clinical COPD Questionnaire (CCQ) scores)1.
This concept of control requires validation; hence the REG COPD Working Group have begun an international, multicentre, prospective study, following COPD patients over a 21-month period. An analysis of the data collected from 314 patients during the screening and baseline visits has recently published in Respiratory Medicine.
Most patients in the study are being managed in specialised centres (85%), while the remainder are managed in primary care. The mean age of the patients was 68.5 years, 73% were male, mean FEV1 was 53% of predicted, and based on the BODEx index (Body mass index, Obstruction, Dyspnea and Exacerbations) 88% were classified as having mild-moderate COPD and 12% as severe COPD. According to the prespecified criteria 21% of patients were classified as controlled, all of them with mild-moderate COPD. The main reasons for patients not being classified as controlled were having a high level of dyspnea, a high CAT score or an exacerbation in the previous 3 months. Being female, having chronic bronchitis and having exacerbations in the previous year were associated with having uncontrolled COPD.
These initial study findings suggest the currently proposed criteria for clinical control in COPD are too restrictive. It is hoped the follow-up phase of this prospective study will allow the criteria for control to be refined to improve their ability to predict poor outcomes.
- Soler-Cataluña JJ, Alcazar-Navarrete B, Miravitlles M. The concept of control in COPD: a new proposal for optimising therapy. Eur Respir J. 2014; 44: 1072-1075.
Blood eosinophil count and exacerbation risk in patients with COPD
Chronic obstructive pulmonary disease (COPD) is an important public health challenge as it is a major cause of chronic morbidity and the 4th leading cause of death worldwide1. In patients with COPD, exacerbations are a major contributor to worsening lung function, impaired quality of life, emergency healthcare use and COPD-related mortality. A large observational study, led by Prof. David Price of the Observational and Pragmatic Research Institute and supported by the Respiratory Effectiveness Group (REG), helps to identify those at increased risk of COPD exacerbations.
This research uses the Optimum Patient Care Research Database (OPCRD; www.optimumpatientcare.org), which comprises a large patient population drawn from geographically and socioeconomically diverse practices throughout the UK. The benefit of this approach is the inclusion of a diverse spectrum of COPD patients, many of whom would not meet the eligibility criteria for randomised controlled trials despite being representative of those regularly seen by clinicians.
In ex-smokers with stable COPD an elevated blood eosinophil count was associated with higher rate of exacerbations in the following year. No increase in exacerbation rate was seen with elevated eosinophil levels in current smokers. The increased exacerbation rate with elevated blood eosinophil levels was found in patients treated with ICS, which is consistent with previous research where ICS treatment failed to lower the blood eosinophil count2.
These findings, published in the European Respiratory Journal, identify a population, ex-smokers with stable COPD but elevated eosinophil levels, where a specific treatment of eosinophilic inflammation may be beneficial in minimising the risk for individual patients.
- Lozano R, Naghavi M, Foreman, K, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012; 380 (9859):2095-128
- Barnes NC, Sharma R, Lettis S, et al. Blood eosinophils as a marker of response to inhaled corticosteroids in COPD. Eur Respir J. 2016; 47: 1374–1382.
Validating the Concept of COPD Control
Chronic Obstructive Pulmonary Disease (COPD) is a major cause of chronic morbidity and mortality worldwide. COPD is considered to be controlled if treatment is minimising symptoms and reducing the risk of acute exacerbations. The concept of control in COPD has been developed as a tool to aid physicians in modifying individual patient’s treatment in order to optimise the patient’s outcomes.
This REG study, published in COPD: Journal of Chronic Obstructive Pulmonary Disease, has investigated the association between COPD control status and clinical outcomes. A retrospective, observational cohort study was conducted using electronic medical records and linked patient questionnaire data from the UK Optimum Patient Care Research Database (OPCRD).
When using the definition of COPD control proposed by Soler-Cataluña et al (2014)1, it was found that only a small proportion of patients in this UK study could be classed as having controlled COPD. Despite this the UK patient population did not have an increased risk of exacerbations, indicating that the proposed definition of control may be too strict.
Patients with mild to moderate COPD that were categorised as having uncontrolled disease experienced exacerbations sooner than patients with controlled disease.
This finding highlights the importance of having a measure of control in COPD; identifying those patients with uncontrolled disease allows treatment to be stepped up so that future exacerbations are reduced. However, the results of this study suggest that further work is still required to optimise the sensitivity and specificity of the proposed COPD control definition.
- Soler-Cataluña JJ, Alcazar-Navarrete B, Miravitlles M. The concept of control in COPD: a new proposal for optimising therapy. Eur Respir J. 2014; 44:1072–1075.
Evidence for Health Decision Making – Beyond Randomised Controlled Trials
In August 2017, the New England Journal of Medicine published a review of the use of randomised controlled trials (RCTs) and observational studies by Thomas R Frieden, former Director of the US Centres for Disease Control and Prevention. The author highlights some of the known issues with RCTs and calls for the improved use of multiple data sources in decision making. Using examples ranging from influenza vaccines to type 2 diabetes treatments, the author sets out a compelling argument for the use of observational studies and real world evidence to supplement, support and strengthen evidence garnered from RCTs. The review also highlights specific scenarios where conducting an observational study may be more appropriate than conducting an RCT.
The Respiratory Effectiveness Group welcomes this article, and its recognition of the role of real life data can play in improving the evidence base for clinical practice.
“Elevating RCTs at the expense of other potentially highly valuable sources of data is counterproductive. A better approach is to clarify the health outcome being sought and determine whether existing data are available that can be rigorously and objectively evaluated, independently of or in comparison with data from RCTs, or whether new studies (RCT or otherwise) are needed”.