All Wales Adult Asthma Management and Prescribing Guideline

This Guidelines summary of the All Wales Medicines Strategy Group’s adult asthma management and prescribing guideline encompasses core principles of asthma management, inhaler selection and use, and referral guidance.

Core Principles

Inhaler Principles

• Choice of inhaler is based on patient’s preference and technique
• Whenever possible, choose a device with low global warming potential
• Only choose inhalers that you have observed the patient using correctly
• If more than one inhaler is being prescribed, both the ICS and SABA inhalers should be of the same type, that is, do not mix metered-dose inhalers (MDIs) and dry-powder inhalers (DPIs) whenever possible
• Where indicated in Algorithm 1, the MDIs should be inhaled via a spacer device such as an AeroChamber flow-vu
• Always prescribe by brand to ensure consistent device
• ICSs and long-acting bronchodilators (LABAs) MUST be prescribed as a combination product to obviate the risk of patients inadvertently taking the LABA as monotherapy, which has been associated with increased risk of mortality.

Indications for Referral

• Diagnostic uncertainty
• Complex comorbidity
• Suspected occupational asthma
• Poor control following treatment at step four
• 2 or more courses of oral steroids per year, despite optimising therapy in primary care.

Prescribing Guidance

Algorithm 1: Prescribing Guidance

Diagnosis

• The diagnosis of asthma is a clinical diagnosis supported by tests of airway hyper-responsiveness and airway inflammation. All patients with suspected asthma should undergo objective testing including spirometry/reversibility and peak flow diary monitoring to document evidence of variable airflow obstruction
• Exhaled nitric oxide (where available) is a simple breath test that can identify airway inflammation that is likely to respond to inhaled corticosteroids. An elevated exhaled nitric oxide level (FeNO) is supportive (but not diagnostic) of asthma
• It should be usual practice to perform objective testing prior to starting therapy for asthma. If inhalers have already been prescribed, these will need to be withheld prior to performing bronchodilator reversibility testing
• Most inhaled corticosteroid/long-acting beta₂ agonists (ICS/LABAs) will need to be withheld for more than 12 hours; however, once daily preparations (for example, Relvar) will need to be withheld for more than 24 hours
• SABAs need to be withheld for more than 4 hours and long-acting anti-muscarinic agents (LAMAs) for more than 36 hours
• Inhalers do not need to be withheld prior to performing FeNO; however, levels of FeNO will be reduced by inhaled corticosteroids. Ideally, objective tests should be performed prior to starting inhaled therapy
• Reversibility to either inhaled or oral corticosteroids could also be considered if initial spirometry is obstructive (forced expiratory volume in 1 second [FEV₁]/forced vital capacity [FVC] ratio less than 0.7 or below lower limit of normal). A change in FEV₁ of more than 12% and 200 ml confirms reversibility and supports an asthma diagnosis.

Asthma–COPD Overlap

• Some patients with chronic obstructive pulmonary disease (COPD) also show reversibility, and asthma and COPD can coexist (asthma–COPD overlap syndrome)
• Clinical history is important in distinguishing asthma from COPD
• When diagnostic uncertainty remains, or both COPD and asthma are present, use the following findings to help identify asthma:
  • a large (over 400 ml) response to bronchodilators
  • a large (over 400 ml) response to 30 mg oral prednisolone daily for 2 weeks
  • serial peak flow measurements showing 20% or greater diurnal or day-to-day variability
• Clinically significant COPD is not present if the FEV₁ and FEV₁/FVC ratio return to normal with drug therapy.

General Principles of Management

• Recent guidelines (British Thoracic Society/Scottish Intercollegiate Guidelines Network [BTS/SIGN] and NICE [diagnosis and monitoring, and chronic asthma management]) have highlighted the need to treat all individuals symptomatic of asthma with inhaled corticosteroids
• The practice of using a short-acting bronchodilator as monotherapy is now outdated and reports such as the National Review of Asthma Deaths have highlighted the potential dangers of this practice, with underuse of inhaled corticosteroids and overreliance on beta-agonists a contributory factor in a number of deaths
• For individuals with mild, intermittent asthma there is increasing support for the use of inhaled corticosteroid taken together with short-acting bronchodilators on an ‘if and when required’ basis. This is only recommended for individuals with symptoms less than twice per month
• If an individual has more frequent symptoms, they should take regular inhaled corticosteroid to reduce their risk of exacerbation and asthma-related death.

Asthma Control

• An objective measure of asthma control should be recorded during each consultation. This would usually include a symptom score, such as the ‘asthma control test’ or a commonly used tool, the Royal College of Physicians’ ‘three questions’, a measure of airflow obstruction (peak flow or spirometry), and an assessment of exacerbation risk and symptoms based on reliever use and any requirement for oral steroids
• Reliever inhalers should not be required more than twice per week. The risk of severe exacerbations and mortality increases incrementally with higher SABA use, independent of treatment step. Prescribing three or more 200-dose SABA inhalers per year, corresponding to daily use, is associated with an increased risk of severe exacerbations and mortality and reflects very poorly controlled asthma. As an initial step, patients prescribed more than six reliever inhalers over the preceding 12 months should be invited for urgent review of their asthma control
• Do not prescribe repeat SABAs without also prescribing an ICS.

Table 1: Levels of Asthma Control and Exacerbation Risk

Assessment of Current Clinical Control (Over Last 4 Weeks)

Device Selection

• Always involve the patient when choosing the device. Take into account individual preference, ease at which the device can be used, and prior success or failure with different preparations
• Ensure continuity of device for individual patients so that only one inhaler technique is required. Whenever possible do not mix MDIs and DPIs as they require radically different inhaler techniques
• MDIs have a higher carbon footprint than DPI devices and BTS guidelines recommend that inhalers with low global-warming potential should be used when they are likely to be equally effective
• MDIs currently contribute an estimated 3.5% of the carbon footprint of the NHS. MDIs comprise 70% of all inhalers prescibed in the UK, but only 14% in Sweden. The default option should be to prescribe a DPI, unless a patient has a better technique, or prefers, an MDI. Patients should also be encouraged to use any locally available inhaler recycling and recovery schemes. Patients can return empty inhalers to their community pharmacy
• DPIs require inspiratory flow rates of 30–90 l/min. The In-Check DIAL device or training whistles should be used to check patients can achieve this
• MDIs should be used with a spacer device (Aerochamber flow-vu or Volumatic) to improve technique and lung deposition. The Flo-Tone device is also useful to optimise MDI technique
• It is important to teach patients that they need to wait 30 seconds between activations of their MDI devices to allow time for the canister to recharge before administering a second dose
• Inhaled corticosteroids and long-acting bronchodilators MUST be prescribed as a combination product to obviate the risk of patients inadvertently taking the LABA as monotherapy, which has been associated with increased risk of mortality
• All inhalers should be prescribed by brand to prevent the wrong inhaler device being inadvertently issued by the pharmacy.

Stepping up Therapy

• It is important to check and address factors known to be associated with poor asthma control at every opportunity, including when considering a step up in treatment. The following factors should be considered:
  • inhaler technique
  • adherence with asthma medication. This can be checked by an open conversation with the patient—it is important to be non-judgemental and explore barriers to concordance with medication (for example, dislike of device, side effects, chaotic lifestyle). The prescription ‘fill rate’ should be reviewed (that is, the actual number of preventative inhalers collected [issued] in a 12-month period compared with the number that should have been collected [issued]). This is a surrogate measure of adherence and can prompt a conversation with a patient
  • smoking status and referral to smoking cessation services
  • triggers and trigger avoidance (including occupation)
  • comorbid conditions—for example, weight management, obstructive sleep apnoea, dysfunctional breathing pattern, rhinitis
• Asthma control should be reassessed within 3 months of a change in therapy.

Maintenance and Reliever Therapy

• A number of combination inhalers are licensed for use in a variable dosing regime termed maintenance and reliever therapy (MART). These include Fostair 100/6 MDI and Nexthaler, Symbicort 200/6 Turbohaler, Fobumix 160/4.5, and Duoresp Spiromax 160/4.5
• Higher strength preparations are not licensed for this use
• The patient should take twice-daily maintenance therapy and then also use the same product and device as a reliever medication if required. This enables the amount of inhaled steroid to be titrated against symptoms
• There is no need to prescribe a separate reliever inhaler if a patient is on this regime
• MART regimes can help overcome poor concordance with ICS inhalers and historic over reliance on beta₂ agonist reliever therapy. There is also evidence these regimes can reduce exacerbation frequency.

Add-on Therapies

• Step three
  • montelukast may be particularly helpful in those with exercise-induced asthma and in asthma associated with allergic rhinitis. If patients do not benefit from a 6-week trial of this agent, it should be discontinued
  • always treat coexisting allergic rhinitis with a separate nasal steroid with or without antihistamines to prevent asthma triggering from nasal inflammation
• Step five
•  
  • the addition of a long-acting antimuscarinic agent (LAMA) is an option for adult patients who are on maintenance moderate dose ICS/LABA who experience one or more asthma exacerbations in the previous year. This therapy may be of particular benefit in patients who have both asthma and COPD
  • there are now three options available for clinicians and patients: add-on Spiriva Respimat (tiotropium) or combination inhalers Trimbow MDI (beclometasone dipropionate/formoterol/glycopyrronium) and Enerzair Breezhaler (indacaterol/glycopyrronium/ mometasone). Of note, the triple-therapy inhalers (Trimbow/Enerzair Breezhaler) contain different strengths of ICS and caution is needed to ensure that the required dose of ICS is not inadvertently stepped up or down when commencing a triple therapy inhaler
  • oral theophylline is a further add-on therapy that can be trialled at step five. Always review response to add-on therapies and discontinue if ineffective.

Table 2: Dosing and Administration of Add-on Therapies

Referral/Specialist Therapy

• Patients who remain uncontrolled despite moderate dose ICS/LABA with or without additional controller agents have difficult to control or severe asthma. A proportion of these will have an alternative or coexistent condition that is contributing to their symptoms. Objective and structured evaluation can help identify and treat these conditions. Patients with suspected occupational asthma should be referred
• Some individuals will have severe eosinophilic asthma and will require high-dose ICS/LABA combination inhalers. Others may have neutrophilic asthma and may benefit from additional bronchodilator therapy such as Spiriva Respimat
• Patients receiving two or more courses of oral steroids in a 12-month period despite concordance with optimised therapy should be referred
• There are a number of biological therapies licenced for severe asthma. These can be prescribed where appropriate following review by a specialist in severe asthma, and discussion in the All Wales Difficult Asthma multidisciplinary team.

Stepping Down

• All asthma guidelines recommend a step-wise approach including the need to consider stepping down therapy once control is achieved and maintained
• High-dose ICS carries a risk of systemic side effects (adrenal suppression, growth retardation, decrease in bone mineral density, and cataracts) and these risks should be balanced against the benefits
• Reductions in asthma therapy should be considered if a patient has had complete asthma control over a 3-month period
• A decision to step down should take into account how difficult it was to achieve stability and also whether previous step-down attempts have resulted in exacerbations
• Seasonal variation in symptoms should be considered
• Stop or reduce dose of medicines in an order that takes into account the clinical effectiveness when the medicine was introduced, side effects, and the person’s preference
• It is recommended that the dose of ICS is reduced by no more than 50% each time. The risks and benefits of dose reduction should be discussed with patients and their carers.

Self-management and Asthma Control

• Self-management should include a written personalised asthma action plan containing advice on how to recognise a loss of asthma control (peak flow monitoring or symptoms) and what action to take to regain control, including when to start oral steroids and seek emergency advice
• Patients should be prescribed a peak flow meter to aid self-management
• Best peak flow should be ascertained when treatment is optimised and symptoms are stable. Best peak flow is more accurate than predicted peak flow. Trigger points should be individualised, but as a guide, oral steroids are usually required when peak flow reaches 60% or less of best, and emergency review is usually necessary when peak flow reaches 50% or less of best.

For further information on asthma control and action plans, including information on how to achieve a quadrupling in ICS as part of personalised action plan in patients on a fixed-dose combination inhaler, refer to the full guideline.

Also refer to the full guideline for a template for asthma review, additional information on the provision of national steroid treatment cards, and a table on the inhaled steroid dose equivalence of inhalers available to treat asthma.