Dr Mark L Levy gives his personal view of the differences between recommendations from NICE and those presented in previous guidelines from BTS/SIGN and GINA
Read this article to learn more about:
- the key differences in recommendations from NICE for diagnosis and treatment
- suggested use of short-acting beta2 agonists and leukotriene receptor antagonists
- the author’s summary on how to avoid conflict between guidelines and improve asthma care.
In November 2017, NICE published a guideline on Asthma: diagnosis, monitoring and chronic asthma management, comprising a short summary,1 which draws on information in the accompanying evidence documents,2,3 and appendices,4,5 totalling over 2500 pages. Most GPs are too busy to read this much material in order to understand the rationale underlying the NICE recommendations.
NICE spent nearly 4 years producing its guideline, which only deals with some aspects of asthma care, and contradicts the British Thoracic Society (BTS)/Scottish Intercollegiate Guideline Network (SIGN) ‘gold standard’ British guideline on the management of asthma6 in a number of important areas (see discussion below). Post-publication critiques of this NICE guideline by the BTS7 and the Primary Care Respiratory Society8 address key differences between its conclusions and recommendations, and those in the BTS/SIGN guideline. I focus upon some further issues in this short personal view, including diagnosis and two areas related to asthma treatment:
- use of initial reliever medication alone
- addition of leukotriene receptor antagonists (LTRAs) as first line for those patients poorly controlled on low-dose inhaled corticosteroids (ICS).
The NICE guideline
NICE methodology involves agreeing guideline questions, followed by focused literature searches, and clinical and health economic evaluation to produce recommendations.9 Randomised controlled trials (RCTs) are the main source of evidence used to provide graded evidence (see www.gradeworkinggroup.org), and clearly a considerable amount of work has been undertaken by the experts involved. The detailed summary tables of the outcomes in the NICE Appendices illustrate the wide ranges of responses among study subjects;4,5 this is important because the average response to medication used in RCTs does not apply to all patients. For me, old-fashioned clinical judgment by properly trained healthcare professionals is often more important in deciding on medication options. Furthermore, perusal of the evidence tables in the appendices indicates that a large proportion of outcomes evaluated are graded as ‘low’ or ‘very low’ quality,4,5 so what value can we place on the recommendations?
There is no single gold standard test for diagnosing asthma. The diagnosis is based on evidence of a clinical history suggestive of asthma, in conjunction with tests aimed at establishing the presence of variable or reversible airflow obstruction (using spirometry and/or peak expiratory flow [PEF], both before and after taking a bronchodilator); response to medication; atopy; and allergy (bronchial hyper-responsiveness [BHR] to direct methacholine challenge testing). In the case of asthma, these tests may not be practical or available in general practice or in hospital settings. Quality assured spirometry is available in hospital respiratory departments and in patches within primary care settings employing trained technicians; challenge testing is only done in specialist centres. Furthermore, as the test results vary, it may take numerous consultations, with repeated objective measurements, to confirm the likelihood of the diagnosis of asthma.
NICE has produced fairly detailed diagnosis algorithms for patients aged over 5 years with asthma.1 These emphasise the use of objective measurement (quality assured spirometry, bronchodilator reversibility [BDR], fractional exhaled nitric oxide [FeNO], PEF, and BHR to methacholine challenge) to aid diagnosis,1 which is, in theory, a very good idea, but fails to take into account the variable nature of asthma, where test results will vary from time to time. The use of FeNO, as advocated by NICE, in diagnosing asthma is highly contentious,6,10 and is advised against in a recent systematic review,11 which included most of the studies evaluated by NICE. A feasibility study was conducted by NICE to test the algorithms and this is reported in the guideline Appendix Q.4 The results demonstrated many implementation challenges in the current NHS, including: a need for considerable staff training and time; and long delays to diagnose asthma.4 Out of the 143 patients with suspected asthma, 137 started the spirometry part of the algorithm. Asthma was confirmed in 35 (24.5%), and, surprisingly, less than one-third of these patients diagnosed with asthma had evidence of airflow obstruction on spirometry. Of the 143 patients, an alternative diagnosis was made in 19 (16.1%), and 85 (59.4%) had an uncertain diagnosis4 and presumably needed referral to specialist clinics for further evaluation. In my opinion, these findings should have been sufficient to reject the recommendation of this asthma diagnosis system in the UK.
NICE recommends consideration of asthma ‘diagnostic hubs’, staffed by experts with access to objective tests;1,2 however in the cash-strapped NHS, directed nationally with commissioning devolved locally, this recommendation is unlikely to be widely implemented. NICE has recognised this major obstacle by recommending a ‘phased introduction’ of their algorithms.1,2
In the majority of cases, NICE has recommended similar treatment options for chronic asthma to those detailed in the BTS/SIGN6 and other guidelines.10 However NICE recommendations for treatment of chronic asthma differ in two major areas.
First, NICE recommends that doctors offer a short-acting beta2 agonist bronchodilator (SABA) as initial reliever therapy for all patients with newly diagnosed asthma.1 This is an illogical recommendation in my view, particularly as asthma is defined as an inflammatory condition and this bronchodilator treatment, which is not anti-inflammatory, only offers up to 4 hours of relief from bronchoconstriction. Most importantly, this contradicts the long-standing evidence12 that many patients with moderate or severe asthma may not be classified and may, therefore, be untreated. Furthermore, it directly contradicts the BTS/SIGN guideline where SABAs have been removed from the stepwise treatment of asthma and recommended as rescue/reliever treatment only,6 on the basis of the confirmatory finding in the Royal College of Physicians National Review of Asthma Deaths13 that patients are at risk if prescribed excess reliever medication.14 NICE does not present any evidence to support the recommendation on SABA. It seems for children they relied on a discussion point in a study15 that was abandoned due to poor recruitment. It is difficult to understand why NICE states in citing this study that ‘the absolute risk of severe exacerbations remains low in mild asthma when treated with reliever therapy alone’3). The problem with this assertion is that severity of asthma, as defined by NICE and others,10,16,17 is not often evaluated or recorded by many clinicians.13
The second major difference in NICE recommendations, to the astonishment of many of us with expertise in primary care asthma management, is recommendation of LTRAs as first-line add-on therapy for people with asthma uncontrolled on low-dose ICS.1 This recommendation contradicts the BTS/SIGN guideline,6 GINA strategy,10 and a systematic review of adult treatment.18 The NICE recommendation for children aged 5–16 years is based on one inconclusive study that was abandoned due to poor recruitment.19 The main role of NICE, as I see it, is to evaluate the cost-effectiveness of available medication. However, in the case of this recommendation it seems clear that the cheapest add-on drug (£1.02 for 28 × 10 mg montelukast tablets, versus for example £29 for 120 doses of salmeterol by inhaler or £30 for 100 doses of formoterol by inhaler20), rather than the most clinically effective ones, was chosen. Perhaps 4 years of work could have been saved had NICE simply been asked by NHS England, ’Which “add on” asthma drug is the cheapest?’
There is insufficient space here to discuss all the other questions the NICE guideline on asthma has raised for me. What would be sensible, however, rather than the production and dissemination of conflicting, confusing guidelines for asthma, would be for agreement to be reached to accept one cohesive, clear guideline for asthma management in the UK. Furthermore, what is needed, as was so successfully achieved in Finland,21 is a long-term, sustainable system for training and supporting appropriate healthcare professionals to manage asthma.
Dr Mark L Levy FRCGP
Member of the BTS/SIGN Acute Asthma Guideline Group
Member of the Executive Board of the Global Initiative on Asthma (GINA)
Clinical Lead National Review of Asthma Deaths (2011–2014)
Respiratory Clinical Lead, Harrow Clinical Commissioning Group
- Detailed summary tables in NICE Guideline 80 on Asthma: diagnosis, monitoring and chronic asthma management Appendices illustrate the wide ranges of responses among study subjects, which is important because the average response to medication used in RCTs does not apply to all patients:
- unfortunately the evidence is graded mainly ‘low’ or ‘very low’ quality, which brings into question its value
- NICE recommends FeNO testing to aid diagnosis, but this approach is contradicted by other guidelines
- NICE suggests diagnostic hubs staffed by experts to implement objective testing, although it recognises difficulty in implementing this and therefore recommends a ‘phased introduction’ of the algorithms
- Treatment recommendations from NICE are largely similar to those from BTS/SIGN, but key differences in NICE are:
- that doctors should offer a SABA as initial reliever therapy for all patients with newly diagnosed asthma
- the use of LTRAs as first-line add-on therapy for people with asthma uncontrolled on low-dose ICS
- To avoid confusion between conflicting guidelines, it would be sensible to accept one cohesive, clear guideline for asthma management in the UK, as well as to implement a long-term sustainable system for training and supporting appropriate healthcare professionals to manage asthma.
RCT=randomised controlled trial; FeNO=fractional exhaled nitric oxide; BTS/SIGN=British Thoracic Society/Scottish Intercollegiate Guidelines Network; SABA=short-acting beta2 agonist bronchodilator; LTRA=leukotriene receptor antagonist; ICS=inhaled corticosteroid.
- NICE. Asthma: diagnosis, monitoring and chronic asthma management. NICE Guideline NG80. NICE, 2017. Available at: www.nice.org.uk/guidance/ng80
- NICE. Asthma: diagnosis and monitoring of asthma in adults, children and young people. NICE Guideline NG80: Methods, evidence and recommendations. NICE, 2017. Available at: www.nice.org.uk/guidance/ng80/evidence/full-guideline-asthma-diagnosis-and-monitoring-pdf-4656178047
- NICE. Chronic asthma: management. NICE Guideline NG80: Methods, evidence and recommendations. NICE, 2017. Available at: www.nice.org.uk/guidance/ng80/evidence/full-guideline-chronic-asthma-management-pdf-4656179345
- NICE. Asthma: diagnosis and monitoring of asthma in adults, children and young people. NICE Guideline NG80: Appendices A–R. NICE, 2017. Available at: www.nice.org.uk/guidance/ng80/evidence/appendices-a-r-pdf-4656178048
- NICE. Chronic asthma: management. NICE Guideline 80: Appendices A–S. NICE, 2017. Available at: www.nice.org.uk/guidance/ng80/evidence/appendices-a-s-pdf-4656179346
- British Thoracic Society, Scottish Intercollegiate Guidelines Network. British guideline on the management of asthma. SIGN 153. BTS/SIGN, 2016. Available at: www.sign.ac.uk/sign-153-british-guideline-on-the-management-of-asthma.html
- White J, Paton J, Niven R, Pinnock H, on behalf of the British Thoracic Society. Guidelines for the diagnosis and management of asthma: a look at the key differences between BTS/SIGN and NICE. Thorax 2018, 0: 1–5.
- Primary Care Respiratory Society UK. Asthma guidelines. PCRS-UK briefing document. 2017. Available at: pcrs-uk.org/briefing-asthma-guidelines
- NICE. Developing NICE guidelines: the manual. NICE PMG20. 2014.
- Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention, updated 2017. GINA, 2017. Available at: ginasthma.org/2017-gina-report-global-strategy-for-asthma-management-and-prevention/
- Korevaar D, Westerhof G, Wang J et al. Diagnostic accuracy of minimally invasive markers for detection of airway eosinophilia in asthma: a systematic review and meta-analysis. Lancet Respir Med 2015; 3 (4): 290–300.
- Speight A, Lee D, Hey E. Underdiagnosis and undertreatment of asthma in childhood. Br Med J Clin Res 1983; 286 (6373): 1253–1256.
- Royal College of Physicians. Why asthma still kills: the National Review of Asthma Deaths (NRAD). London: Royal College of Physicians, 2014. Available at: www.rcplondon.ac.uk/sites/default/files/why-asthma-still-kills-full-report.pdf
- Suissa S, Blais L, Ernst P. Patterns of increasing β-agonist use and the risk of fatal or near-fatal asthma. Eur Respir J 1994; 7 (9): 1602–1609.
- Pauwels R, Pedersen S, Busse W et al. Early intervention with budesonide in mild persistent asthma: a randomised, double-blind trial. Lancet 2003; 361 (9363): 1071–1076.
- Reddel H, Taylor D, Bateman E et al. An official American Thoracic Society/European Respiratory Society statement: Asthma control and exacerbations—Standardizing endpoints for clinical asthma trials and clinical practice. Am J Respir Crit Care Med 2009; 180 (1): 59–99.
- Taylor D, Bateman E, Boulet L-P et al. A new perspective on concepts of asthma severity and control. Eur Respir J 2008; 32 (3): 545–554.
- Chauhan B, Ducharme F. Addition to inhaled corticosteroids of long-acting beta2 -agonists versus anti-leukotrienes for chronic asthma. Cochrane Database Syst Rev 2014, Issue 1. dx.doi.org/10.1002/14651858.CD003137.pub5
- Lenney W, McKay A, Tudur Smith C et al on behalf of the MASCOT Study Group. Management of asthma in school age children on therapy (MASCOT): a randomised, double-blind, placebo-controlled, parallel study of efficacy and safety. Health Technology Assessment 2013; 17 (4): 1–238.
- MIMS. MIMS online. www.mims.co.uk (accessed January 2018).
- Haahtela T, Tuomisto L, Pietinalho A et al. A 10 year asthma programme in Finland: major change for the better. Thorax 2006; 61 (8): 663–670.