Simplifying Asthma Management in Primary Care EDUCATIONAL SERIES RECOMMENDATIONS from the 2020 NZ ASTHMA GUIDELINES

Simplifying asthma management

A RESEARCH REVIEW™ in primary care EDUCATIONAL SERIES RECOMMENDATIONS FROM THE 2020 NZ ASTHMA GUIDELINES

Making Education Easy 2021

About the expert This review is intended as an educational resource for primary healthcare professionals. It discusses the new Asthma and Respiratory Foundation NZ Adolescent and Adult Asthma Guidelines, published in the NZ Medical Professor Journal in June 2020, and how these may be implemented in primary care. The guidelines, which have Richard Beasley been developed by a multidisciplinary group of respiratory health experts, were last updated in 2016. Since CNZM, DSc(Otago), DM(Southampton), that time there have been significant advances in the understanding of how to best manage patients with MBChB, FRCP(London), FRACP, FAAAAI, FFOM(Hon), FAPSR(New Zealand), FERS, asthma. Taking into account the latest findings and incorporating recommendations from the Global Initiative FThorSoc, FRSNZ. for Asthma (GINA) Update strategy, the new guidelines provide simple, practical and evidenced-based recommendations for the diagnosis, assessment and management of asthma. Healthcare professionals may Richard Beasley is a physician at Wellington need to review the management of their asthma patients in light of the new guidelines. Regional Hospital, Director of the Medical Research Institute of New Zealand, and The 2020 Asthma and Respiratory Foundation NZ Adolescent and Adult Asthma Guidelines and a number of Professor of Medicine at Victoria University key clinical resources discussed in this review can be downloaded here. of Wellington. He is an Adjunct Professor at the University of Otago and Visiting Professor, University of Southampton, United Kingdom. Asthma: A major public health issue He is the Chair of the Asthma and Respiratory Foundation of New Zealand Adolescent and The prevalence of asthma in NZ is amongst the highest in the world, with up to 20% of children and adults affected Adult Asthma Guidelines. His research interests and over 610,000 individuals taking medication for this respiratory disease.1,2 Asthma is estimated to cost NZ in respiratory medicine are primarily in the fields over $1 billion annually and the disease has significant socioeconomic impacts.3 Optimal asthma management is of epidemiology and clinical management. essential to relieve the burden of asthma not only for the individual patient and their family, but for society as a whole. Providing health professionals with current best practice guidance in the area of asthma management is a key priority for the Asthma and Respiratory Foundation NZ. Abbreviations used in this review AIR = anti-inflammatory reliever therapy COPD = chronic obstructive pulmonary disease What’s new in the guidelines?1 ED = Emergency Department The inclusion of adolescents (aged ≥12 years) in the adult guidelines FEV1 = forced expiratory volume in 1 second • FVC = forced vital capacity • The recommendation to avoid SABA-only treatment in the long-term management of asthma ICS = inhaled corticosteroid The use of budesonide/formoterol reliever, with or without maintenance budesonide/formoterol, is IgE = immunoglobulin E • IL = interleukin preferred to SABA reliever, with or without maintenance ICS or ICS/LABA, across the spectrum of asthma severity LABA = long-acting β2-agonist LAMA = long-acting muscarinic antagonist • The introduction of the terminology ‘anti-inflammatory reliever (AIR)’ therapy to describe the use of NSAIDs = non-steroidal anti-inflammatory drugs budesonide/formoterol as a reliever, either alone or together with budesonide/formoterol maintenance PEF = peak expiratory flow therapy RCT = randomised controlled trial • Two new stepwise asthma management algorithms SABA = short-acting β2-agonist SMART = single inhaler maintenance and reliever • A clinical allergy section therapy • Recommendations for LAMA add-on therapy in severe asthma ABOUT RESEARCH REVIEW • The use of omalizumab for severe allergic asthma Research Review is an independent medical publishing • The use of mepolizumab for severe eosinophilic asthma. organisation producing electronic publications in a wide variety of specialist areas. Research Review publications are intended for New Zealand medical professionals. Educational Series are a summary of the most important Diagnosing asthma international and local literature which impacts on treatment of a specific medical condition. These Reviews provide information on a disease, current treatment and The advice regarding the diagnosis of asthma remains unchanged since the previous NZ guidelines were published local/international guidelines. They are intended as an in 2016. The diagnosis of suspected asthma is made by taking a focused history, examination, and lung function educational tool. testing if available. A useful algorithm for the diagnosis of asthma from the NZ guidelines is shown in Figure 1.1 Publications are free to receive for health care Certain clinical features increase or decrease the likelihood of asthma (Table 1).1 professionals, keeping them up to date with their Traditionally, a cut-point of a ≥12% increase in FEV1 from baseline following bronchodilator therapy has been chosen clinical area. used as a diagnostic criterion for asthma.1 The 2020 NZ Adolescent and Adult Asthma Guidelines recommend that a specific cut-point is not used, due to its poor sensitivity and specificity for a diagnosis of asthma, but instead recognise that the greater the degree of bronchodilator reversibility the more likely it is that the patient has asthma.1

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Assessing asthma control, Presentation with suspected asthma severity and future risk The level of asthma control, severity and future risk must be assessed.1 The Asthma Control Test™ Clinical assessment (ACT) is a simple clinically validated test that • History and examination provides a very useful tool for monitoring a patient’s 4 • Measurement of PEF or FEV1 including brochodilator responsiveness asthma. The test can be filled in by patients in the clinic waiting room and has the added value that it educates patients about their asthma control. Is asthma likely? The online version of the ACT is available from: www.asthmacontroltest.com YES NO The test asks straightforward questions relating to Poor the patient’s asthma, including activity limitation, Start asthma treatment and response Consider alternative diagnosis 4,5 review response shortness of breath, reliever medication etc. A score is generated and pre-defined cut-off levels indicate the level of asthma control (Figure 2). Good response Alternative diagnosis confirmed Continue to monitor and treat YES NO ACT “cut-off” levels Treat Consider further investigations accordingly and/or specialist referral Poorly Well or or not Somewhat completely controlled controlled controlled ≤15 16-19 ≥20 FEV1 = forced expiratory volume in one second; PEF = peak expiratory flow

Figure 1. NZ Adolescent and Adult Asthma Guideline’s approach to the diagnosis of asthma1

Table 1. Clinical features that make asthma more or less likely1 Figure 2. Asthma Control Test score cut-off levels indicating the degree of asthma control. A. Asthma more likely • Two or more of these symptoms: Identifying high-risk patients in - Wheeze (most sensitive and specific symptom of asthma) primary care - Breathlessness The identification of high-risk asthma patients - Chest tightness who may require more intensive monitoring and - Cough supervision can be achieved by assessing healthcare • Symptom pattern: utilisation (hospital admissions, ED and emergency - Intermittent primary care visits) and the patient’s need for asthma medication (oral steroids, frequency of SABA - Typically worse at night or in the early morning prescriptions, a greater number of prescriptions - Provoked by exercise, cold air, allergen exposure, irritants, viral infections, beta blockers, for SABA than for ICS).1 The features outlined in aspirin or other non-steroidal anti-inflammatory drugs Table 2 also help to identify asthma patients at - Recurrent or seasonal increased risk of a poor outcome.1 - Began in childhood • History of atopic disorder or family history of asthma • Widespread wheeze heard on chest auscultation TAKE-HOME MESSAGE: In your • Symptoms rapidly relieved by inhaled SABA or budesonide/formoterol clinical practice, an important time to

• Airflow obstruction on spirometry (FEV1/FVC < lower limit of normal) assess risk is when issuing a repeat prescription. If review of the patient’s • Increase in FEV1 following bronchodilator ≥12%; the greater the increase the greater the probability electronic health records indicates that • Variability in PEF over time (highest-lowest PEF/mean) ≥15%; the greater the variability the the patient has had a recent severe greater the probability attack requiring urgent medical care, or is using more than one reliever B. Asthma less likely inhaler every two months, then a formal • Chronic productive cough in absence of wheeze or breathlessness asthma review should be arranged.1,6 • No wheeze when symptomatic • Normal spirometry or PEF when symptomatic • Symptoms beginning later in life, particularly in people who smoke • Increase in FEV following bronchodilator <12%; the lesser the increase the lower the probability 1 New Zealand Research Review subscribers • Variability in PEF over time <15%; the lesser the variability the lower the probability can claim CPD/CME points for time spent reading • No response to trial of asthma treatment our reviews from a wide range of local medical and • Clinical features to suggest an alternative diagnosis nursing colleges. Find out more on our CPD page.

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Table 2. Features associated with increased risk of severe asthma exacerbation and mortality1 Managing asthma

Effective communication and patient education are essential for optimal asthma management. Care must be A. Asthma taken to explain and deliver health information in a way that is understandable to the patient and their family. Management goals should be agreed upon and a cycle of repeated assessment, adjustment and review of • Poor symptom control responses to treatment should be undertaken as shown in Figure 3.1,7 • One or more exacerbations requiring oral corticosteroids in the last year Confirmation of diagnosis if • Hospitalisation or emergency department necessary visit in the last year Symptom control & modifiable risk factors (including lung function) • High SABA use (≥3 canisters per year) Comorbidities A • Home nebuliser E SS NS E Inhaler technique & adherence O S P S S • History of sudden asthma attacks Patient (and parent) goals E

• Impaired lung function (FEV W 1 E

Symptoms

<60% predicted)

Exacerbations

• Raised blood eosinophil count

Side-effects

• Intensive Care Unit admission or

Lung function Treatment of modifiable risk intubation (ever) UST Patient (and parent) ADJ factors & comorbidities • Requirement for long-term oral satisfaction Non-pharmacological strategies corticosteroids Education & skills training Asthma medications B. Comorbidity

• Psychotropic medications Figure 3. The cycle of management for asthma patients.1,7 • Major psychosocial problems • Smoking A new approach to therapy • Food allergy/anaphylaxis • SABA reliever as sole therapy (without ICS or ICS/LABA) is no longer recommended in the long-term • Alcohol and drug abuse management of adolescents and adults with asthma1 • Aspirin or other non-steroidal anti- • The use of a single 2-in-1 ICS/fast-acting LABA (budesonide/formoterol) inhaler is recommended as the preferred reliever therapy, either as sole reliever therapy in mild asthma, or as maintenance and reliever inflammatory drug sensitivity therapy in moderate and severe asthma; the budesonide/formoterol 400/12 µg dose should not be used as reliever therapy1 C. Other factors Background • Underuse or poor adherence to ICS In mild asthma, combination budesonide/formoterol reliever therapy has been shown to be superior to SABA treatment (terbutaline or salbutamol)-alone reliever therapy with a reduction in the risk of a severe asthma exacerbation of ≥60%.8,9 • Discontinuity of medical care Also in mild asthma, a number of large RCTs have shown that budesonide/formoterol taken alone and only as • Socioeconomic disadvantage and poor reliever therapy has advantages over regular scheduled maintenance ICS and SABA as-needed for relief, reducing housing the risk of a severe exacerbation by about 20%.8,10-12 • Māori and Pacific ethnicity In patients with moderate and severe persistent asthma, a systematic review and meta-analysis compared the SMART therapy regimen (ICS/formoterol taken as maintenance and reliever therapy) versus the comparable • Occupational asthma dose of ICS/LABA maintenance and SABA reliever therapy.13 The meta-analysis revealed that SMART therapy was associated with a 32% reduced risk of asthma exacerbation compared with conventional therapy using the comparable dose of ICS/LABA maintenance and SABA as quick relief.13 This meta-analysis also showed that the SMART regimen of budesonide/formoterol reduced the exacerbation risk SUBSCRIBE AT NO COST TO by 23% compared with a higher dose of ICS/LABA plus a SABA for relief, suggesting that the timing of ICS use may be more important than the total dose taken.13 ANY RESEARCH REVIEW Budesonide/formoterol taken as reliever therapy, either with or without regular scheduled maintenance budesonide/ Health professionals can subscribe to or download formoterol therapy, is now recommended by the 2020 NZ Adolescent and Adult Asthma Guidelines as the preferred previous editions of Research Review publications option for the treatment of asthma.1 This change represents the largest paradigm shift in the treatment of asthma at www.researchreview.co.nz over the last two decades, and is consistent with the GINA strategy.7

Privacy Policy: Research Review will record your email details on In NZ, the budesonide/formoterol 200 µg/6 µg formulation is registered for use as anti-inflammatory a secure database and will not release them to anyone without your reliever therapy. Please consult relevant data sheets for full indications, dosing, precautions for use and prior approval. Research Review and you have the right to inspect, other prescribing information.14,15 update or delete your details at any time.

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‘AIR’ therapy: The 2020 NZ Adolescent and Adult Asthma Guidelines have Experts’ remarks on the new approach to treatment introduced the term ‘anti-inflammatory reliever (AIR)’ therapy to describe The 2020 NZ Adolescent and Adult Asthma Guidelines are consistent with 1 this new treatment approach. AIR therapy refers to the use of budesonide/ the GINA strategy 2019/2020 updates which recommended that SABAs formoterol as a reliever medication either as monotherapy (no maintenance) should not be used alone as sole therapy without ICS, and that combination or together with regular scheduled budesonide/formoterol (also known ICS/formoterol is preferred to SABA as reliever therapy across the spectrum

as SMART: single inhaler maintenance and reliever therapy). AIR therapy of asthma severity, in adults and adolescents.7 It has been suggested that (including SMART) can only be undertaken with budesonide/formoterol and these recommendations represent the most important change in asthma not other available ICS/LABA combinations, as they do not contain a fast- management for over 30 years.16 acting LABA.1

ICS therapy for all A step-up and step-down approach The 2020 NZ Adolescent and Adult Asthma Guidelines recommend that all asthma A step-up and step-down approach to asthma treatment is well established and patients receive ICS therapy.1 ICS in asthma can be delivered in one of three forms: has been included in asthma guidelines for the past 20 years. With this approach, • As ICS/LABA reliever therapy (AIR) – budesonide/formoterol with or without treatment is stepped up to achieve control and reduce the risk of exacerbation, and maintenance budesonide/formoterol stepped down after a period of prolonged control, in order to find and maintain the 1 • As maintenance ICS together with SABA reliever lowest level of treatment needed. • As maintenance ICS/LABA with SABA reliever The updated 2020 NZ Adolescent and Adult Asthma Guidelines include two 1 The recommended standard daily dose of ICS, when prescribed according to a algorithms for treating adolescents and adults with asthma. Both algorithms regular scheduled maintenance regimen, in adolescent and adult asthma, is detailed comprise three steps of asthma treatment with both maintenance therapy and in Table 3.1 reliever therapy. The first algorithm is for AIR therapy using budesonide/formoterol 200 µg/6 µg (Figure 4). This simply involves the use of one inhaler for maintenance Table 3. Recommended standard maintenance daily dose of ICS in adolescent/ and symptom relief across the spectrum of asthma severity. In the algorithm, Step 1 adult asthma1 relates to patients with intermittent or mild asthma – maintenance is not necessary and they simply take one actuation of the budesonide/formoterol inhaler as required Beclomethasone dipropionate 400-500 μg/day to relieve symptoms. Evidence shows that this will be at least as effective at reducing exacerbation risk as regular maintenance ICS and a SABA reliever.8,10-12 If the patient Beclomethasone dipropionate extrafine 200 μg/day is taking budesonide/formoterol frequently for relief of their symptoms or experience an asthma attack, then it is reasonable to move to Step 2 and if necessary to Budesonide 400 μg/day Step 3, using their budesonide/formoterol as both a regular maintenance and reliever therapy (no more than 6 inhalations should be taken on any single occasion Fluticasone propionate 200-250 μg/day – a total of up to 12 inhalations daily can be used temporarily).1,14,15 The second algorithm is for traditional treatment regimens incorporating SABA Fluticasone furoate 100 g/day μ reliever therapy (Figure 5).1 Step 1 involves the use of standard-dose ICS (see Table 3) and a SABA as required. Step 2 involves the use of a standard-dose ICS/ ICS/LABA therapy LABA combination for maintenance and Step 3 involves a high-dose ICS/LABA combination together with SABA reliever therapy. LABAs should not be prescribed in a separate inhaler from ICS.1 Combination ICS/LABA may be prescribed as:1 • ICS/LABA reliever therapy (AIR) What about patients not controlled at Step 3? Add-on therapies? • ICS/LABA maintenance and reliever therapy (AIR:SMART)* LAMA add-on therapy has demonstrated efficacy in severe asthma with the • Fixed maintenance ICS/LABA and SABA reliever** greatest evidence for tiotropium.17 Tiotropium [Spiriva® Respimat®] as add-on *This is the 2020 NZ Adolescent and Adult Asthma Guidelines preferred regimen for patients at risk of therapy to maintenance ICS/LABA is approved for use in NZ, but is not currently severe exacerbations funded.18 This agent is only funded for patients with coexisting COPD and is **This regimen may be used for patients if their asthma is already well controlled on this regimen, or if therefore an option only for asthma patients with features of COPD who are not they have poor technique with the Turbuhaler® device controlled at Step 3.1 Biologic add-on therapy including omalizumab (anti-IgE) and mepolizumab What do the new recommendations mean for my (anti-IL-5/eosinophils) targets specific inflammatory pathways in severe asthma.1 asthma patients? Omalizumab [XOLAIR®] and mepolizumab [NUCALA] are only approved in NZ for • Adolescents and adults with asthma should not be receiving SABA reliever asthma patients with severe disease meeting specific criteria and need to be as sole therapy (without ICS or ICS/LABA)1 prescribed by a specialist.19,20 • For new asthma patients at risk of severe exacerbation or those requiring a Other measures include smoking cessation, weight loss, exercise, breathing step up in therapy, it is preferable to start them on budesonide/formoterol exercises, avoiding triggers (including aspirin/NSAIDs) and avoiding workplace maintenance and reliever therapy (SMART)1 exposures to asthma triggers.1 • For patients well controlled with no exacerbations on their fixed maintenance ICS (e.g. beclomethasone dipropionate or fluticasone propionate) and a SABA reliever therapy, or ICS/LABA (fluticasone propionate/salmeterol or Who to refer?: Consider referral to a respiratory specialist for review fluticasone furoate/vilanterol) and a SABA reliever therapy, it is reasonable and assessment for biological therapy in patients with severe asthma for them to continue on their regimen. However, if they experience severe who require frequent courses of oral prednisone or who have become exacerbations they should be switched to the SMART regimen.1 dependent on oral prednisone.1

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Anti-inflammatory reliever therapy based algorithm SABA reliever therapy based algorithm for using budesonide/formoterol 200 μg/6 μg asthma management

STEP UP to achieve control and reduce risk of exacerbations STEP UP to achieve control and reduce risk of exacerbations STEP DOWN after a period of prolonged control to find and maintain lowest required step STEP DOWN after a period of prolonged control to find and maintain lowest required step Step 3 Step 3 Step 2 Step 2 Two actuations One actuation twice daily Step 1 twice daily High dose OR Step 1 Standard ICS/LABA Maintenance two actuations dose ICS/LABA None once daily Maintenance Standard dose ICS Symptom relief One actuation as required Symptom relief SABA 1-2 actuations as required Before stepping up Review inhaler technique, use, and treatable traits. NZ Adolescent and Adult AsthmaBefore Guidelines stepping up Review inhaler technique, use, and treatable traits. If a severe exacerbation of asthma occurs: Review and consider stepping up. If a severe exacerbation of asthma occurs: Review and consider stepping up, or switching to the If asthma remains uncontrolled at Step 3 Anti-inflammatory Reliever (AIR) therapy based algorithm Health professional to consider add-on treatment. May require referral for specialist review. If asthma remains uncontrolled at Step 3 Health professional to consider add-on treatment. such as weight, comorbidities and • Inhaler technique should be routinely May require referral for specialist review. interactions with other medications. assessed at consultations and training • Adherence to treatment should provided as part of self-management be routinely assessed and encour- education. If using a pMDI, it is pref- Figure 4. Algorithm for anti-inflammatory reliever therapy using budesonide/agement providedFigure as part5. Traditionalof the SABA relievererable totherapy-based administer via aalgorithm spacer. for asthma formoterol 200 µg/6 µg.1 self-managementmanagement. education.1 For • A four-step adult asthma consultation, example, encourage patients to link which includes guidance for writing their inhaler use with some other an asthma action plan, is provided in activity such as cleaning their teeth the Appendix. (and then rinsing their mouth). Asthma self-management AIR asthma action plan with budesonide/formoterol reliever ± maintenance therapy Asthma action plans are effective in reducing asthma- related morbidity and mortality.1 The 2020 NZ Adolescent and Adult Asthma Guidelines include three different action plans, including the new AIR therapy plan:1 available here • Asthma plans should be offered to all individuals with asthma • Asthma action plans may be based on symptoms +/- peak flow and comprise 3 or 4 stages • If there is a need for oral prednisone, the usual dose is 40 mg/day for 5 days. An alternative regimen is 40 mg/day until there is definite improvement and then 20 mg/day for the same number of days. The new AIR therapy asthma action plan is specifically for the use of budesonide/formoterol (Figure 6).1 The plan reminds patients that budesonide/formoterol is used for both the prevention and relief of symptoms and should be carried at all times. Instruct the patient to take only one actuation as required for relief, as opposed to their previous use of two actuations of their SABA for relief. Explain that in the situation of an emergency, they should continue to use their 2-in-1 inhaler as needed while seeking urgent medical help. For regular scheduled maintenance therapy with budesonide/ formoterol, either one or two actuations can be taken at a time, depending on asthma severity.1 Figure 6. Anti-inflammatory reliever therapy asthma action plan.2,14

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NZMJ 26 June 2020, Vol 133 No 1517 14 ISSN 1175-8716 © NZMA www.nzma.org.nz/journal A RESEARCH REVIEW™ Simplifying asthma management in primary care EDUCATIONAL SERIES RECOMMENDATIONS FROM THE 2020 NZ ASTHMA GUIDELINES

Treatable traits in severe asthma The four step asthma consultation1 The concept of treatable traits was introduced in the 2016 NZ Asthma Guidelines and relates to the other factors that may be contributing to a patient’s poor asthma control.1,21 Identifying and managing treatable traits is especially important for patients who are optimally treated for asthma Assess asthma control and risk but still experience marked respiratory symptoms.1,21 Treatable traits include overlapping disorders, Complete the Asthma Control Test comorbidities, environmental and behavioural factors detailed in Table 4.1 www.asthmacontroltest.com Table 4. Treatable traits in asthma1 Review lung function tests (peak flow monitoring and/or spirometry) Overlapping disorders: Comorbidities: Review severe asthma attacks in last 12 months (requiring urgent medical review/oral steroids/bronchodilator • COPD • Obesity nebuliser use) • Bronchiectasis • Gastro-oesophageal reflux disease • Allergic bronchopulmonary aspergillosis • Rhinitis • Dysfunctional breathing, e.g. vocal cord • Chronic rhinosinusitis ± nasal polyps dysfunction • Obstructive sleep apnoea • Depression/anxiety Consider other relevant clinical issues Environmental: Behavioural: Ask about compliance with maintenance treatment Check inhaler technique • Smoking • Adherence Enquire about clinical features associated • Damp, mouldy, cold or crowded housing • Inhaler technique with increased risk • Occupational exposures • Health literacy Consider treatable traits • Provoking factors including aeroallergens Decide if peak flow monitoring is indicated • Drugs such as aspirin, other non-steroidal anti-inflammatory drugs and beta blockers • Insufficient income to access healthcare

TAKE-HOME MESSAGE: In asthma patients with uncontrolled respiratory Decide if increase or decrease in maintenance therapy required symptoms, enquire about overlapping disorders, comorbidities, environmental and behavioural factors before stepping up their asthma treatment. Is a step up in level of treatment required? (asthma not adequately controlled, poor lung function or recent severe exacerbation) Is a step down in the level of treatment possible? (has there been a sustained period of good control?) Is a step across to the SMART regimen required? (in patients prescribed ICS or ICS/LABA who have had a recent severe exacerbation) RESPIRATORY RESEARCH REVIEW

SUBSCRIBE FREE, CLICK HERE to visit www.researchreview.co.nz Complete the asthma action plan and update your subscription to receive Respiratory Research Review. https://www.asthmafoundation.org.nz Peak flow instructions (recommended cut points of <80% for getting worse and <50% for an emergency = reference guide only and can be adjusted Respiratory according to clinical judgement) RESEARCH REVIEW ™ Prednisone regimen Making Education Easy (for severe asthma prednisone 40 mg/day for 5 days or In this issue: Race to find COVID-19 Welcome Issue 172 – 2020 Thank you for the feedback on the COVID-19to issue issue. 172 In of this Respiratory autumn issue, weResearch are sticking Review. with the topic of respiratory infection; treatments however, we will mainly focus on research around pneumonia and highlight only four articles related to COVID-19. Reliable and ™ Respiratoryfrequently updated information on COVID-19 is available from: NZ Ministry of Health, the 40 mg/day until definite improvement, then 20 mg/day for the COVID-19 vaccine development collection of articles focussed on COVID-19, the JAMA Network COVID-19 collection and the CEBM Oxford COVID-19 Evidence Service (The Centre of Evidence-Based Medicine site from Oxford University) – very user-friendly and relevant to clinical practice. RESEARCH Coronaviruses in REVIEWAlternatively you may with to read WHO, the N Engl J Med Coronavirus immunosuppressed patients In October 2019, ‘Lessons of a pandemic’ publishedIssue in 1919. 172 – 2020 Some of the questionsAmerican it addresses Thoracic follow. Society guidelines on the ‘Diagnosis and treatment of adults with CAP’ were published. same number of days) Correlation of chest CT and Question 1: Making Education Easy In adults with CAP (community-acquired pneumonia), should gram stain and culture of lower respiratory PCR testing in COVID-19 secretions be obtained at the time of diagnosis? – No in the community, and yes in the hospital setting. Question to2: issue 172 of Respiratory Research Review. Anti-influenza immune plasmaWelcome In adults with CAP, should blood cultures be obtained at the time of diagnosis? No, unless in severe pneumonia, Thank you for the feedback on the COVID-19or when issue. expecting In this resistantautumn issue, organisms. we are sticking withWHO the, the topic N Englof respiratory J Med Coronavirus infection; In this issue: however, we will mainlyQuestion focus on research3: around pneumonia and highlight only four articles related to COVID-19. Reliable and for severe influenza A In adults with CAP, should Legionella and pneumococcal urinary antigen testing be performed at the time of Race to find COVID-19 frequently updated information on COVID-19diagnosis? is available from: NZ Ministry of Health, the Azithromycin reduces collection of articles focussed on COVID-19, the JAMANo. Network COVID-19 collection and the CEBM Oxford COVID-19 Evidence Question 4: Additional instructions treatments Service (The Centre of Evidence-Based‘LessonsIn Medicine adults of awith pandemic’site CAP, from should Oxford published aUniversity) respiratory in 1919. – verysample user-friendly be tested andfor influenza relevant tovirus clinical at the practice. time of diagnosis? Yes rhinovirus-induced airwayAlternatively you may with to read the time of high influenza activity in the community. AmericanQuestion Thoracic 6: Society guidelines on the ‘Diagnosis and treatment of adults with CAP’ were published. COVID-19 vaccineinflammation development In October 2019, Should a clinical prediction rule for prognosis plus clinical judgment versus clinical judgment alone be used to Some of the questions it addresses determinefollow. inpatient versus outpatient treatment location for adults with CAP? Yes , during Coronaviruses in Severity Index) or the CURB-65 tool. Bacteriophages improve Question 1: In adults with CAP (community-acquired pneumonia), should gram stain and culture of lower respiratory (avoidance of provoking factors such as aspirin/NSAIDs, option of secretionsQuestion be obtained8: at the time of diagnosis? – No in the community, and yes in the hospital setting. immunosuppressedoutcomes patients in experimental In the outpatient setting, which antibiotics are recommended for empirical treatment, consider ofthe CAP PSI (Pneumoniain adults? In adults with CAP,Amoxycillin. should blood cultures be obtained at the time of diagnosis? No, unless in severe pneumonia, pneumonia Question 2: Question 9: In patients with comorbidities, co-amoxiclav (amoxicillin/clavulanic acid) and a macrolide. Correlation of chest CT and or when expecting In resistant the inpatient organisms. setting, which antibiotic regimens are recommended for empirical treatment of CAP in adults PCR testing Novel in COVID-19 intranasal vaccine Question 3: In adults with CAP,without should risk Legionella factors for and MRSA pneumococcal and Pseudomonas urinary antigenaeruginosa testing? be performed at the ,time during of diagnosis?Question No10:. increasing ICS dose through increasing frequency up to 4 x daily In the inpatient setting, should patients with suspected aspiration pneumonia receive additional anaerobic against RSV β-lactam and a macrolide. Anti-influenza immune plasma Question 4: In adults with CAP,coverage should beyond a respiratory standard sample empirical be tested treatment for influenza for CAP? virus No at. the time of diagnosis? Yes Questionthe time of 12: high influenza activity in the community. for severe influenza A In the inpatient setting, should adults with CAP be treated with corticosteroids?, consider the NoPSI. (Pneumonia Broad-spectrum antibiotic use Question 13: Question 6: Should a clinical In adultsprediction with rule CAP for who prognosis test positive plus clinicalfor influenza, judgment should versus the clinicaltreatment judgment regimen alone include be usedantiviral to therapy? Yes and outcomes in CAP determine inpatient versus outpatient treatment location for adults with CAP? Yes Azithromycin reduces Question 14: when symptoms worsen with 4 stage plan, etc.) Severity Index) In or adults the CURB-65 with CAP tool. who test positive for influenza, should the treatment regimen include antibacterial therapy? rhinovirus-induced Comorbidities airway and outcomes in Yes . Question 8:Question In the outpatient15: setting, which antibiotics are recommended for empirical treatment of CAP in adults? inflammationadults with pleural infections Amoxycillin. In Inoutpatient patients withand comorbidities,inpatient adults co-amoxiclav with CAP who (amoxicillin/clavulanic are improving, what is acid)the appropriate and a macrolide duration. of antibiotic. treatment? Until clinical stability and not less thanβ-lactam 5 days. and a macrolide. Question 9:Question In the 16:inpatient setting, which antibiotic regimens are recommended for empirical treatment of CAP in adults Bacteriophages improve without risk In factors adults for with MRSA CAP andwho Pseudomonas are improving, aeruginosa should follow-up? chest imaging be obtained? No, at-risk patient should undergo lung cancer screening. outcomes in experimental In the inpatient setting, should patients with suspected aspiration pneumonia receive additional anaerobic QuestionDina 10: Goodman and colleagues summarise in Lancet Respir Med on the ‘Challenges in the diagnosis of paediatric pneumonia in pneumoniaAbbreviations used in this issue coverage beyond standard empirical treatment for CAP? No. . ARDS = acute respiratory distress syndrome intervention field trials: recommendations from a pneumonia field trial working group’. At a time when the world is in lockdown, Questionand 12: we In are the mindful inpatient of setting, the mortality should data, adults it withis sobering CAP be totreated remind with ourselves corticosteroids? that pneumonia No. is the cause of death in 13–16% NovelCAP = community-acquiredintranasal vaccine pneumonia Questionof 13:children In adults younger with than CAP 5who years, test withpositive an annualfor influenza, mortality should rate the of 700,000–900,000.treatment regimen include Finally, antiviral we have therapy? a great Yes review on the COVID-19against =RSV 2019 novel coronavirus disease ‘Pathophysiological role of respiratory dysbiosis in hospital-acquired pneumonia’, which reminds us of emerging treatment HIV = human immunodeficiency virus Question 14: In adults with CAP who test positive for influenza, should the treatment regimen include antibacterial therapy? alternatives to. antibiotics, including a so-called ‘normal community transplant therapy’. MRSA = methicillin-resistant Yes Broad-spectrum antibioticStaphylococcus use aureus Thank you again for the feedback, and we hope you enjoy the selection of articles. RSV = respiratory syncytial virus Question 15: In outpatient and inpatient adults with CAP who are improving, what is the appropriate duration of antibiotic and outcomes in CAP Kind regards,treatment? Until clinical stability and not less than 5 days. 1 Professor Lutz Beckert Adapted from Beasley R et al., 2020 Question 16: In adults with CAP who are improving, should follow-up chest imaging be obtained? No, at-risk patient should Comorbidities and outcomes in [email protected] lung cancer screening. adults with pleural infections Dina Goodman and colleagues summarise in Lancet Respir Med on the ‘Challenges in the diagnosis of paediatric pneumonia in intervention field trials: recommendations from a pneumonia field trial working group’. At a time when the world is in lockdown, and we are mindful of the mortality data, it is sobering to remind ourselves that pneumonia is the cause of death in 13–16% of children younger than 5 years, with an annual mortality rate of 700,000–900,000. Finally, we have a great review on the Abbreviations used in this issue ‘Pathophysiological role of respiratory dysbiosis in hospital-acquired pneumonia’, which reminds us of emerging treatment ARDS = acute respiratory distress syndrome alternatives to antibiotics, including a so-called ‘normal community transplant therapy’. CAP = community-acquired pneumonia Thank you again for the feedback, and we hope you enjoy the selection of articles. COVID-19 = 2019 novel coronavirus disease Kind regards, HIV = human immunodeficiency virus Professor Lutz Beckert MRSA = methicillin-resistant Staphylococcus aureus [email protected] www.researchreview.co.nz RSV = respiratory syncytial virus a RESEARCH REVIEW™ publication

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Specific allergy issues Management of acute severe asthma

Allergens such as house dust mites, pollens or Acute asthma management is based on the objective measurement of severity, administering treatment appropriate pet dander are the most likely allergic triggers for for the degree of severity, repeatedly reassessing the response to treatment, and assessing the need for referral asthma.1 to hospital and/or hospital admission.1 The 2020 NZ Adolescent and Adult Asthma Guidelines include a practical Testing for allergen-specific IgE to aero-allergens algorithm for the management of acute severe asthma (Figure 7).1 should be considered in patients with allergic asthma.1 Allergen immunotherapy (approved for use in NZ but not funded) can be considered in patients with asthma and rhinitis who have evidence of allergy to house dust mites and/or pollens. All patients with ASSESS SEVERITY food-related anaphylaxis should be referred to an immunologist/allergist.1

MILD/MODERATE: SEVERE: LIFE THREATENING: FEV OR PEF >50% FEV OR PEF 30-50% FEV OR PEF <30% Asthma in Māori and 1 1 1 Give 6 x 100 μg salbutamol Give 6 x 100 μg salbutamol via Give continuous salbutamol via nebulisation, ipratropium bromide Pacific people IMMEDIATELY via MDI and spacer MDI and spacer or salbutamol 2.5 mg via nebulisation, 500 μg via nebulisation, IV prednisone 40 mg, oxygen if hydrocortisone 100 mg or prednisone Māori and Pacific people are disproportionately required to keep sats >92% 40 mg, oxygen if required to keep sats affected by severe asthma, exhibiting over 3-fold >92%.If anaphylaxis is present give higher rates of asthma-related hospitalisations and IM adrenaline higher mortality rates than NZ Europeans and other ethnic groups.2,22 Furthermore, a concerning ARRANGE URGENT TRANSFER TO inequality is seen across the socio-economic HOSPITAL BY AMBULANCE spectrum, with 3-fold higher rates of respiratory- REASSESS All patients will require hospital related hospitalisations in those living in the most admission deprived versus the least deprived areas.2 This may be partly due tobarriers to health literacy (knowing about REFER TO ICU/HDU illness and when to seek primary care treatment) among lower socio-economic groups and highlights the importance of patient education in primary care 23 FEV or PEF FEV or PEF Give salbutamol 2.5 mg via settings. Effective education in essential for optimal 1 1 FEV1 or PEF <50% >70% 50-70% Give 6 x 100 μg salbutamol via nebulisation, frequency determined asthma management and care must be taken to Consider oral Give prednisone MDI and spacer, or salbutamol by response, up to continously; IV explain and deliver health information in a way that prednisone 40 mg if 2.5 mg via nebulisation, up to hydrocortisone 100 mg 6 hourly or 23,24 15-60 MIN 40 mg, if not not given 3 times over 1st hour prednisone 40 mg daily, ipratropium is understandable to the patient and their family. bromide 500 μg via nebulisation up given above above. Repeat Ipratropium bromide 6 x 20 μg salbutamol to hourly; consider IV magnesium via MDI and spacer, or 500 μg sulphate 1.2-2.0 g over 20 min; 6 x 100 μg via via nebulisation, oxygen if oxygen if required to keep sats TAKE-HOME MESSAGE: Patient MDI and spacer required to keep sats 92-96% DISCHARGE 92-96%. Investigations include ABG, education is key to effective asthma Once CXR, U & E management. Make time for patient pre-discharge asthma education. Make sure the patient conditions are met* understands what good asthma control looks like and how they can achieve it. Consider triaging Māori and Pacific REASSESS asthma patients as being at high risk of asthma exacerbations in view of their greater burden of disease. Multifaceted STABLE UNSTABLE No signs of severe Signs of severe

interventions may be required. asthma and FEV1 or asthma or FEV1 or PEF >70% PEF <50-70% 1-2 HRS Asthma in pregnancy DISCHARGE ADMIT The risks to the mother and baby of poor asthma Once pre-discharge control in pregnancy outweigh the theoretical risks conditions are met* with asthma medications.1,7

For practical purposes, the FEV and PEF are considered interchangeable when expressed as % predicted for the purpose of TAKE-HOME MESSAGE: The NZ 1 assessment of acute asthma severity. Adolescent and Adult Asthma Guidelines

recommend that SABAs, ICS and ICS/ ABG = arterial blood gas; CXR = chest x-ray; FEV1 = forced expiratory volume in one second; HDU = high dependency unit; ICU = intensive LABAs should be used as normal during care unit; IM = intramuscular; IV = intravenous; MDI = metered-dose inhaler; PEF = peak expiratory flow; sats = oxygen saturations; U & E = urea and electrolytes pregnancy. During severe attacks, oral *Please refer to the full NZ Adolescent and Adult Asthma Guidelines for a list of pre-discharge considerations steroids should be used as normal and patients should be treated in hospital. Figure 7. NZ Adolescent and Adult Asthma Guideline’s algorithm for the management of acute severe asthma.1

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For most patients, initial treatment with a SABA via a spacer and oral steroids is likely to be sufficient.1 Reserve nebulised SABA for those with severe asthma who The use of SABAs via a spacer is not only as effective as do not respond to initial inhaled therapy. Magnesium sulphate is the preferred IV nebulisation in severe asthma attacks, but also reduces the risk bronchodilator in life-threatening asthma. The criteria for referring a patient with a of aerosolisation, an important consideration in the COVID-19 severe asthma attack to hospital are outlined in Table 5.1 pandemic era. There is insufficient evidence to recommend the use of budesonide/formoterol by health professionals in the 1 Table 5. Criteria for referral to hospital and/or hospital admission setting of a severe attack, and for this reason SABAs are preferred • Any feature of life-threatening asthma in this situation. • Any feature of severe attack persisting after initial treatment • Other considerations suggest admission appropriate: KEY TAKE-HOME MESSAGES: - Living alone/socially isolated - Psychosocial problems • SABA reliever as sole therapy is no longer recommended in the - Physical disability or learning difficulties long-term management of adolescents and adults with asthma - Previous near fatal or brittle asthma • The use of a single 2-in-1 ICS/fast-acting LABA (budesonide/ - Exacerbation despite adequate dose oral steroids formoterol) inhaler as reliever therapy is recommended across - Presentation at night the spectrum of asthma severity, either as monotherapy - Pregnancy (no maintenance) in mild patients, or together with regular scheduled budesonide/formoterol (also known as SMART: single inhaler maintenance and reliever therapy) in moderate TAKE-HOME MESSAGE: Always maintain your position as the and severe patients patient’s advocate and refer to hospital if appropriate. The amount If prescribers are to practice evidence-based medicine they of SABA used in the 12 to 24 hours prior to presentation is a • need to be familiar with AIR therapy and how to implement this useful marker of likely need for hospital admission, as is a lack of regimen in clinical practice response to initial bronchodilator treatment and/or a requirement for repeat doses. • Add-on treatments such as LAMAs and monoclonal antibody therapies represent important management approaches to those patients with chronic severe difficult-to-treat asthma

USEFUL RESOURCES: • The identification and treatment of ‘treatable traits’ represent an important clinical approach to patients with poor respiratory https://www.asthmafoundation.org.nz health despite standard treatment. https://ginasthma.org

REFERENCES: 1. Beasley R et al. Asthma and Respiratory Foundation NZ Adolescent and Adult Asthma Guidelines 2020: 13. Sobieraj DM et al. Association of inhaled corticosteroids and long-acting β-agonists as controller and A quick reference guide. N Z Med J. 2020;133(1517):73-99 quick relief therapy with exacerbations and symptom control in persistent asthma: A systematic review 2. Asthma and Respiratory Foundation NZ. Available from: https://www.asthmafoundation.org.nz/our-work/ and meta-analysis. JAMA 2018;319(14):1485-96 research/key-statistics (Accessed December 2020) 14. Medsafe. Symbicort® Turbuhaler® data sheet. Available from: https://www.medsafe.govt.nz/profs/ 3. Telfar Barnard L and Zhang J. The impact of respiratory disease in New Zealand 2018 update. Available Datasheet/s/Symbicortinh.pdf (Accessed December 2020) from: https://s3-ap-southeast-2.amazonaws.com/assets.asthmafoundation.org.nz/images/NZ-Impact- 15. Medsafe. DuoResp Spiromax data sheet. Available from: https://www.medsafe.govt.nz/profs/ Report-2018_FINAL.pdf (Accessed December 2020) datasheet/d/DuoRespinh.pdf (Accessed December 2020) 4. Nathan RA et al. Development of the asthma control test: a survey for assessing asthma control. J Allergy 16. Reddel H et al. GINA 2019: a fundamental change in asthma management: Treatment of asthma with Clin Immunol. 2004;113(1):59-65 short-acting bronchodilators alone is no longer recommended for adults and adolescents. Eur Respir 5. Schatz M et al. Asthma Control Test: reliability, validity, and responsiveness in patients not previously J. 2019;53(6):1901046 followed by asthma specialists. J Allergy Clin Immunol. 2006;117(3):549-56 17. Anderson DE et al. Long-acting muscarinic antagonists (LAMA) added to inhaled corticosteroids 6. Nwaru BI et al. Overuse of short-acting β 2-agonists in asthma is associated with increased risk of (ICS) versus the same dose of ICS alone for adults with asthma. Cochrane Database Syst Rev. exacerbation and mortality: a nationwide cohort study of the global SABINA programme. Eur Respir J. 2015;(8):CD011397 2020;55(4):1901872 18. Medsafe. Spiriva® Respimat® data sheet. Available from: https://www.medsafe.govt.nz/profs/ 7. 2020 GINA Report, Global Strategy for Asthma Management and Prevention. Available from: https:// Datasheet/s/Spirivarespimat.pdf (Accessed December 2020) ginasthma.org/gina-reports/ (Accessed December 2020) 19. Medsafe. XOLAIR® data sheet. Available from: https://medsafe.govt.nz/profs/Datasheet/x/Xolairinj.pdf 8. Beasley R et al. Controlled trial of budesonide-formoterol as-needed for mild asthma. N Engl J Med. (Accessed December 2020) 2019;380(21):2020-30 20. Medsafe. NUCALA data sheet. Available from: https://www.medsafe.govt.nz/profs/Datasheet/n/ 9. O’Byrne P M et al. Inhaled combined budesonide-formoterol as needed in mild asthma. N Engl J Med. nucalainj.pdf (Accessed December 2020) 2018;378(20):1865-76 21. Agusti A et al. Treatable traits: toward precision medicine of chronic airway diseases. Eur Respir J. Eur 10. Hardy J et al. Budesonide-formoterol reliever therapy versus maintenance budesonide plus terbutaline Respir J. 2016;47(2):410-419 reliever therapy in adults with mild to moderate asthma (PRACTICAL): a 52-week, open-label, 22. Telfar-Barnard L and Zhang J. The impact of respiratory disease in New Zealand: 2016 update. Available multicentre, superiority, randomised controlled trial. Lancet 2019;394(10202):919-28 from: https://www.asthmafoundation.org.nz (Accessed December 2020) 11. Bateman ED et al. As-needed budesonide-formoterol versus maintenance budesonide in mild asthma. 23. Health Partners Consulting Group 2012. Metro-Auckland Pacific Population Health Profile. Auckland: N Engl J Med. 2018;378(20):1877-87 HPCG. Available from: https://www.health.govt.nz/system/files/documents/publications/metro- 12. Rogliani P et al. SMART and as-needed therapies in mild to severe asthma: a network meta-analysis. auckland-pacific-population-health-profile-april2103.pdf (Accessed December 2020) Eur Respir J. 2020;2000625 24. BpacNZ. Asthma education in primary care. Best Practice Journal. 2015;BPJ 70. Available from: https:// bpac.org.nz/bpj/2015/september/asthma.aspx (Accessed December 2020)

This publication was commissioned by AstraZeneca Pty Ltd. The content is entirely independent and based on studies and the author’s opinion. The views expressed do not necessarily reflect the views of AstraZeneca. Please review full Product Information atwww.medsafe.govt.nz before prescribing. Treatment decisions based on these data are the full responsibility of the prescribing physician.