Key questions on AsthmaPosted on: 19 Dec 2018
This module will update you on the key questions in managing asthma, including:
- The value of FeNO testing
- Common differential diagnoses and diagnostic tests to rule them out
- Improving the safety of managing acute asthma
- Managing asthma in pregnancy
There is no gold standard diagnostic test for asthma. The diagnosis is based on clinical history in combination with investigations and response to anti-asthma treatment. While it’s excellent that NICE are recommending more objective testing in the process of diagnosing asthma, this has been a feature of the evidence-based British Thoracic Society (BTS)/Scottish Intercollegiate Guidelines (SIGN)1 guideline as well as the strategy document published by the Global Initiative for Asthma (GINA)2 for many years. The more rigorous and meticulous the clinician is in trying to reach a diagnosis of asthma, and the more objective evidence, the better.
I’m not sure if there is evidence that performing more diagnostic tests improves diagnosis, though common sense tells us that more evidence improves the confidence with which we make a diagnosis. The problem with confirming an asthma diagnosis lies in the variable nature of the disease, where asthma is defined as a condition that includes ‘symptoms such as wheezing, shortness of breath, chest tightness and cough that vary over time in their occurrence, frequency and intensity and are associated with variable expiratory airflow.’2 However it ultimately boils down to clinical judgement based on the history, objective measurements and the experience and skills of the doctor or asthma-trained nurse who the patient consults.
There are a number of different asthma phenotypes including eosinophilic, non-eosinophilic, late-onset, asthma with fixed airflow obstruction and asthma in obesity.2 Patients with eosinophilic airway inflammation usually respond to inhaled corticosteroids and, conversely, others with little or no eosinophilic inflammation may also respond to inhaled corticosteroids. Direct tests for evidence of eosinophilic inflammation of the airways are quite invasive and the FeNO test is a surrogate method for a non-invasive measurement of eosinophilic inflammation. In theory this is a good idea but as the symptoms of asthma vary, the levels of eosinophilia do likewise, and multiple tests may be required if initial testing is negative. Furthermore, as above, patients with a low (or normal) FeNO result may still benefit from inhaled corticosteroids and this is one of the reasons for the current controversy.
A positive FeNO test means that the patient will probably respond to inhaled steroids. However, one size doesn’t fit all and a negative or low FeNO result does not mean that a patient with evidence suggestive of asthma should not be prescribed inhaled corticosteroids and also a recent systematic review of 32 studies (24 in adults) concluded, in contrast with NICE3, that use of a single test (FeNO, blood eosinophilia or IgE) could give misleading results.4 FeNO equipment is relatively expensive (between £1500 and £2500) and there are added costs, including disposables, time for staff to set up the equipment, and training in interpretation.
Bronchial airway hyperreactivity or ‘direct challenge’ testing has been used in research for many years to demonstrate airflow obstruction in response to histamine or methacholine. Both of these substances induce bronchospasm, however in asthma this occurs at a lower dose. The test needs to be performed by clinicians or technicians with appropriate facilities and expertise (and resuscitation equipment). This test is only available in specialist centres, which would require referral and is expensive, and is not used in first line diagnosis of asthma. It does have a place where there is diagnostic uncertainty.
In summary, no I don’t think we should be campaigning for these tests at local level. In my view they should be available for specialists to try and establish the diagnosis in more complex patients who do not respond to adequate levels of medication, are adhering to therapy and who are able to use their inhaler devices.
It can be very difficult to diagnose asthma in some individuals. This was demonstrated very nicely by the NICE feasibility study to test the algorithm recommended for GPs to use.5 Despite having state of the art FeNO equipment, access to quality assured spirometry, and funding for staff time, many of the patients with suspected asthma assessed by the chosen seven practices, were not diagnosed. In addition, less than a third of those eventually diagnosed with asthma had evidence of airflow obstruction. In someone suspected of having asthma on the basis of a good clinical history who doesn’t respond to treatment, efforts should first be made to ensure the patient is adhering to treatment, is able to use their inhaler correctly and has been prescribed adequate doses.
Spirometry is more accurate than peak expiratory flow (PEF) but it’s not practical to keep testing someone with suspected asthma with spirometry until reversible airflow obstruction is demonstrated. My advice for GPs is therefore to provide those patients with a PEF meter and home diary chart, and ask the patient to record the best of three readings twice a day and review after two weeks. This could be combined with treatment and instruction to record additional readings before and after taking salbutamol when needed for symptoms. Variation of over 20% confirms reversible airflow obstruction and in combination with a suggestive history of asthma helps to diagnose asthma. If, despite these efforts, a patient still fails to respond or persists with features of uncontrolled asthma, then expert advice should be sought. The patient may still have asthma or they may have a different, or comorbid, condition requiring further investigation.
Common differential diagnoses (and comorbid conditions) in adults include COPD and cardiac failure. Evidence of airflow obstruction is required for diagnosing COPD. This is usually defined as a ratio of the forced expiratory volume in one second to the vital capacity (FEV1/VC) below 0.7,6 or preferably below the lower limit of normal.7 With confirmed airflow obstruction, features suggestive of COPD rather than asthma include: onset over the age of 40, exposure to cigarette smoke or biomass fuels, fixed airflow obstruction or limited reversibility of obstruction, progressive disease, abnormal x-ray findings, abnormal spirometry in between exacerbations (see detailed chart in GINA chapter 5).2 Cardiac disease diagnosis would need investigations such as ECG, cardiac echocardiogram, chest x-rays, and BNP.
In children with recurrent wheezy episodes, consider cystic fibrosis as a possible diagnosis. A sweat test and referral to a respiratory paediatric specialist may help.
Early studies suggested that there were risks associated with inhaled LABA medication. The key question that arose was whether the LABA itself was responsible for deaths or the fact that in some of the early studies, LABAs were used alone either without prescription or without taking inhaled corticosteroids into account. These studies were done at a time when it was not commonplace in the USA to routinely use inhaled corticosteroids as first line preventer treatment for asthma. However subsequent studies that were designed specifically to compare inhaled corticosteroid in combination with LABAs with inhaled corticosteroids alone confirmed that deaths and severe attacks were reduced in the groups taking combined ICS/LABA.8,9 So the answer to the question is that LABA should not be prescribed without ICS for patients with asthma, because LABAs alone are insufficient to control asthma, rather than being dangerous in themselves.
Ideally LABAs should only be prescribed for people with asthma in combination with an inhaled corticosteroid in a single inhaler. A practical problem for GPs is that between 10 and 20% of people with COPD have comorbid asthma, the risk being that these patients may be prescribed unopposed bronchodilator therapy.
Like all drugs, the dose prescribed for oral corticosteroids depends on age (and weight in children and some adult cases). Between 40 and 50mg per day is the recommended adult dose though sometimes in larger adults or more severe cases of acute asthma, a higher dose may be required (https://www.medicines.org.uk/emc/product/5887/smpc). The dose for children is 1-2mg/kg per day up to maximum of 40mg per day. The most important thing about oral corticosteroid therapy for acute asthma, which has been highlighted in guidelines, is that the drug should be continued until the attack has resolved. As stated in NICE and the BTS/SIGN guideline it usually takes three or five days for children and adults respectively for an attack to resolve, however oral corticosteroids should be continued until the attack has resolved. I personally issue my patients a peak flow meter and instructions on completion of a chart with advice to continue the tablets until the peak flow stabilises and there is no longer a need for rescue salbutamol. (see http://www.consultmarklevy.com/webcasts/actionplans/player.html)
There is evidence that it is unnecessary to tail off the dose, i.e. it can be stopped suddenly, unless more than 14 days treatment is needed to resolve the attack. In this case the oral corticosteroid should be tailed off. Ideally this is done using objective measurement such as peak flow measurement.
Maintenance and intermittent reliever therapy (SMART or MART) in adults over the age of 18 years is a treatment option listed in the BTS/SIGN guidelines. As corticosteroid drugs (oral or inhaled depending on severity) are prescribed when asthma symptoms flare up, research has demonstrated that patients may be able to abort attacks, and reduce the need for oral corticosteroids, by increasing their inhaled corticosteroids at the first signs of flare ups, signified by increased onset of asthma symptoms. Patients are advised, in addition to using their combined ICS/LABA inhaler regularly (i.e. maintenance therapy), to take extra doses of their inhaler when symptoms occur.
In the UK there are only four licenced preparations (containing either budesonide or beclomethasone inhaled corticosteroids plus formoterol) for maintenance and intermittent reliever therapy (SMART or MART) in adults over the age of 18 years. These are Symbicort 100 and 200mcg (SMART), and Fostair 100mcg and Duoresp Spiromax 160 strength (MART). The evidence for benefit of SMART or MART, according to two Cochrane reviews10,11 includes that the quantity of inhaled steroids (mean daily dose), including puffs taken for relief from symptoms, was consistently lower than for the comparison groups, fewer people using this regime had acute exacerbations requiring oral corticosteroids and fewer had exacerbations requiring hospitalisation or a visit to A&E.
Assessment of asthma control comprises two domains: testing intermittently for the presence of current symptom control and identifying risk of future attacks. There are a number of tests and methods available for assessing current symptom control including:
- A validated asthma control test such as the ACT, comprising five questions in adults and nine in children.
- The unvalidated RCP 3 Questions (which count for QOF).
- The partially validated GINA current assessment, which is the RCP 3 Questions plus a question on reliever usage.
- A home PEF diary (see my website consultmarklevy.com for examples).
All of these assess information on current control, however someone may be at risk even if they are well on the day of assessment. Therefore, in addition, treatment should be guided by the presence (or absence) of risk factors for future attacks such as previous life threatening attack, attacks in the last year, comorbid conditions like COPD, pregnancy, food allergy (see table 2-2 GINA Strategy document and table 11 SIGN/BTS 153).
A trial period of six to twelve weeks would be appropriate. If the patient hasn’t improved, you may need to seek a specialist opinion.
This is not a myth. Generally spacer devices should not be wiped dry after washing in warm soapy water as this increases static electricity with the result that drug adheres to the surface and can’t be inhaled. See our mythbuster paper on inhaler facts and fantasies.12
There is increased risk of asthma attacks in pregnancy, particularly in the second and third trimester, and the risk increases with increasing severity of underlying asthma. Furthermore, uncontrolled asthma and asthma attacks in pregnancy are associated with worse outcomes for mother and foetus. It is therefore very important for pregnant women with asthma to take their preventer medication (inhaled corticosteroid) throughout pregnancy.
The question regarding lung function is a bit more complicated. From my reading of the literature, it seems that PEF and FVC increase from 14 weeks gestation onwards. Whether this is of clinical significance or not is unknown. The problem for clinicians lies in interpreting these data because firstly, there are no ‘normal’ spirometry or PEF values for pregnancy (or for that matter for pregnant women by ethnicity and secondly PEF meters may vary, as could different spirometers, particularly if not regularly calibrated. So a common sense approach would be to assess lung function regularly throughout pregnancy, in my view using a daily PEF chart (there is one on my website) and regular assessment of current asthma control using ACT, RCP 3 Qs or GINA symptom assessment.
I wouldn’t! I suggest consult a respiratory specialist if you are considering prescribing any of these drugs. In my view a doctor would find the death of an asthma patient prescribed a beta-blocker extremely difficult to defend.
This question needs a lot more space to answer than allowed in this article. I suggest reading the recommendations in the National Review of Asthma Deaths, and the sections on acute asthma management in the BTS/SIGN guideline and the GINA strategy document.
In essence, we must ensure we are aware of any risk factors present in a patient presenting with acute uncontrolled asthma. (Table 2-2 in GINA and Table 11 in BTS/SIGN). Ensure that objective tests are done to ascertain the severity of the attack, (Tables 12 and 14 BTS/SIGN) and refer anyone with severe or life-threatening features. Treatment should follow the guidelines and in most cases include a short course of oral corticosteroids to be continued until the attack has resolved – see question on oral corticosteroids above. In addition, and perhaps most importantly, assess the patient within two working days of treatment (or discharge from hospital inpatients or A&E or UCC) to ascertain whether the attack is over and secondly whether there are any remediable preventable risk factors that need attention.
Dr Mark L Levy is a respiratory GPSI in North London and the clinical respiratory lead for Harrow CCG. He was the clinical lead for the National Review of Asthma Deaths from 2011-2014.
- British Thoracic Society, Scottish Intercollegiate Guideline Network. SIGN 153 – The British Guideline on the Management of Asthma. 2016 [Available from: https://www.brit-thoracic.org.uk/document-library/clinical-information/asthma/btssign-asthma-guideline-2016/
- The Global Strategy for Asthma Management and Prevention, Global Initiative for Asthma (GINA).2017. Available from: http://www.ginasthma.org.
- Commissioned by the National Institute for Health and Care Excellence (NICE). Asthma: diagnosis and monitoring of asthma in adults, children and young people.NICE guideline NG80. Methods, evidence and recommendations 2017 [Available from: https://www.nice.org.uk/guidance/ng80/evidence/full-guideline-asthma-diagnosis-and-monitoring-pdf-4656178047
- Korevaar DA, Westerhof GA, Wang J et al. Diagnostic accuracy of minimally invasive markers for detection of airway eosinophilia in asthma: a systematic review and meta-analysis. The Lancet Respiratory Medicine. 2015;3(4):290-300.
- Commissioned by the National Institute for Health and Care Excellence (NICE). Asthma: diagnosis and monitoring of asthma in adults, children and young people. NICE guideline NG80 Appendices A – R 2017 [Available from: https://www.nice.org.uk/guidance/ng80/evidence/appendices-a-r-pdf-4656178048
- The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2016 [Available from: www.goldcopd.org.
- Miller MR, Levy ML. Chronic obstructive pulmonary disease: Missed diagnosis versus misdiagnosis. BMJ (Online). 2015;351:h3021.
- Stempel DA, Raphiou IH, Kral KM et al. Serious Asthma Events with Fluticasone plus Salmeterol versus Fluticasone Alone. New England Journal of Medicine. 2016;374(19):1822-30.
- Peters SP, Bleecker ER, Canonica GW et al. Serious Asthma Events with Budesonide plus Formoterol vs. Budesonide Alone. New England Journal of Medicine. 2016;375(9):850-60.
- Cates CJ, Karner C. Combination formoterol and budesonide as maintenance and reliever therapy versus current best practice (including inhaled steroid maintenance), for chronic asthma in adults and children. Cochrane Database Syst Rev. 2013(4):Cd007313.
- Kew KM, Karner C, Mindus SM, Ferrara G. Combination formoterol and budesonide as maintenance and reliever therapy versus combination inhaler maintenance for chronic asthma in adults and children. Cochrane Database Syst Rev. 2013(12):Cd009019.
- ML, Dekhuijzen PNR, Barnes PJ et al. Inhaler technique: facts and fantasies. A view from the Aerosol Drug Management Improvement Team (ADMIT). Npj Primary Care Respiratory Medicine. 2016;26:16017.
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