Guideline sources The following summarized guidelines for the evaluation and management of asthma are prepared by our editorial team based on guidelines from the Global Initiative for Asthma (GINA 2022), the European Respiratory Society (ERS 2022; 2021; 2017; 2012), the American Thoracic Society (ATS 2021), the British Thoracic Society (BTS 2020), the National Heart, Lung, and Blood Institute (NHLBI 2020), the American Heart Association (AHA 2020), the American College of Chest Physicians (ACCP 2020), the British Thoracic Society (BTS/SIGN 2019), the Canadian Thoracic Society (CTS 2017; 2012), the Infectious Diseases Society of America (IDSA 2016), and the European Respiratory Society (ERS/ATS 2014). 1 2 3 4 5 6 7 8 9 10 12 13 14 15 16 Calculator Calculator Calculator Asthma Control Test ACT Pediatric Asthma Severity Score PRAM sco https://web.pathway.md/diseases/recoid4eeyMVLDPrX 1/26 6/23/23, 3:13 AM Asthma Pathway Guidelines 1. Screening and diagnosis Indications for screening: obtain questionnaire-based identification for surveillance of asthma in all workers at risk of developing work-related asthma. A Show 5 more Diagnostic criteria: As per ERS 2022 guidelines, avoid combining fraction exhaled nitric oxide, blood eosinophils, and serum IgE results to make a diagnosis of asthma. D As per GINA 2022 guidelines, diagnose asthma in adult, adolescent, and pediatric (aged 6-11 years) patients based on characteristic respiratory symptoms and evidence of variable expiratory airflow limitation: Situation Guidance > 1 type of respiratory symptom Wheeze, shortness of breath, chest tightness, and cough Symptoms occurring variably over time and vary in intensity Symptoms often worse at night or on waking Symptoms often triggered by exercise, laughter, allergens, cold air Symptoms often appear or worsen with viral infections Reduced FEV in 1 second/FVC compared with the LLN (> 0.75-0.80 in adults, > 0.90 in children) at a time when FEV in 1 second is reduced Documented expiratory airflow limitation Positive bronchodilator responsiveness test Documented excessive variability in lung function ( 1 of the following) Excessive variability in twice-daily peak expiratory flow over 2 weeks Significant increase in lung function after 4 weeks of anti-inflammatory treatment Positive exercise challenge test Positive bronchial challenge test (usually only for adults) https://web.pathway.md/diseases/recoid4eeyMVLDPrX 2/26 6/23/23, 3:13 AM Asthma Pathway Excessive variation in lung function between visits. As per CTS 2017 guidelines, confirm the diagnosis of asthma based on history and objective measures of lung function in patients old enough to reliably undergo pulmonary function tests. E Show 4 more 2. Classification and risk stratification Severity definitions: define severe asthma as asthma remaining uncontrolled despite optimized treatment with high-dose ICS-long-acting -agonist, or requiring high-dose ICS-long-acting - agonist to prevent it from becoming uncontrolled. Distinguish severe asthma from asthma that is difficult to treat due to inadequate or inappropriate treatment, or persistent problems with adherence or comorbidities, such as chronic rhinosinusitis or obesity. Show 2 more 3. Diagnostic investigations Initial assessment: As per GINA 2022 guidelines, assess symptom control, future risk of adverse outcomes, and treatment issues in adult, adolescent, and pediatric (aged 6-11 years) patients presenting with asthma: assess symptom control over the last 4 weeks identify any other risk factors for exacerbations, persistent airflow limitation, or side-effects measure lung function at diagnosis/initiation of treatment, 3-6 months after starting controller treatment, then periodically (at least once every 1-2 years), but more often in at-risk patients and patients with severe asthma document the patient's current treatment step watch inhaler technique, assess adherence and side-effects check that the patient has a written asthma action plan ask about the patient's attitudes and goals for their asthma and medications assess comorbidities contributing to symptoms and poor quality of life, and sometimes to poor asthma control (such as rhinitis, rhinosinusitis, GERD, obesity, obstructive sleep apnea, depression, and anxiety). As per SIGN 2019 guidelines, obtain a structured clinical assessment to assess the initial probability of asthma based on: history of recurrent episodes of symptoms, ideally corroborated by variable peak flows when symptomatic and asymptomatic symptoms of wheeze, cough, breathlessness, and chest tightness varying over time https://web.pathway.md/diseases/recoid4eeyMVLDPrX 3/26 6/23/23, 3:13 AM Asthma Pathway recorded observation of wheeze heard by a healthcare professional personal/family history of other atopic conditions (atopic dermatitis, allergic rhinitis) no symptoms/signs suggesting alternative diagnoses. B Pulmonary function testing: As per ERS 2022 guidelines: Obtain spirometry as part of the diagnostic work-up in adult patients with suspected asthma. B Avoid recording peak expiratory flow variability as the primary test to make a diagnosis of asthma. D As per GINA 2022 guidelines, obtain pulmonary function testing at diagnosis of asthma or initiation of treatment to assess. B Bronchial challenge testing: As per SIGN 2019 guidelines: Consider obtaining bronchial challenge testing in adult patients with no evidence of airflow obstruction on initial assessment and inconclusive results on other objective tests where asthma remains a possibility. C Obtain bronchial challenge testing to identify eosinophilic inflammation in adult and pediatric patients with an intermediate probability of asthma and normal spirometry results. B As per ERS 2012 guidelines, obtain specific bronchial challenge testing if the diagnosis of occupational asthma is not clear, the cause of occupational asthma is new, or it is necessary for the management of the individual worker. B Show 2 more FeNO testing: As per ERS 2022 guidelines, consider measuring fractional exhaled nitric oxide as part of the diagnostic work-up in adult patients with suspected asthma. C As per ATS 2021 guidelines, consider obtaining fractional exhaled nitric oxide measurement in addition to usual care in patients with asthma considered for treatment. C As per NHLBI 2020 guidelines, consider obtaining fractional exhaled nitric oxide measurement as an adjunct to the evaluation process of 5 years old patients, if the diagnosis of asthma is uncertain based on history, clinical findings, clinical course, and spirometry, including bronchodilator responsiveness testing, or if spirometry cannot be performed. C Show 2 more As per CTS 2017 guidelines: Obtain measurement of fractional exhaled nitric oxide levels where available to help characterize the phenotype in patients with confirmed severe asthma. E Insufficient evidence to support the use of fractional exhaled nitric oxide levels to predict response or responders to omalizumab or anti-IL-5 therapies. I Complete blood count: https://web.pathway.md/diseases/recoid4eeyMVLDPrX 4/26 6/23/23, 3:13 AM Asthma Pathway As per ERS 2022 guidelines, avoid measuring blood eosinophil count to make a diagnosis of asthma. D As per CTS 2017 guidelines: Obtain peripheral eosinophil count to help characterize the phenotype in patients with confirmed severe asthma. E Recognize that blood eosinophil counts may help to identify patients that will experience fewer exacerbations with anti-IL-5 therapies or omalizumab. E Serum immunoglobulin E: As per ERS 2022 guidelines, avoid measuring total serum IgE to make a diagnosis of asthma. D As per CTS 2017 guidelines: Obtain measurement of total serum IgE levels to help characterize the phenotype in patients with confirmed severe asthma. E Recognize that serum IgE does not predict response to anti-IL-5 therapies or omalizumab. E Sputum eosinophils: Obtain sputum eosinophils where available to help characterize the phenotype in patients with confirmed severe asthma. E Recognize that sputum eosinophils may help in identifying responders to anti-IL-5 therapies but not in identifying responders to macrolides. E Plethysmography: avoid measuring specific airway conductance and residual volume/total lung capacity by whole-body plethysmography to make a diagnosis of asthma. D Chest CT: consider obtaining HRCT in adult and pediatric patients with severe asthma only when the presentation is atypical. C Screening for occupational exposure: As per GINA 2022 guidelines, elicit work history and other exposures in all patients with adult- onset asthma. A As per ERS 2012 guidelines, ask adult patients with new, recurrent, or deteriorating symptoms of asthma, COPD, or rhinitis about their job, the materials with which they work, and whether they improve when away from work. A Show 4 more Screening for atopy: assess previous records of skin-prick tests, blood eosinophilia ( 4%), or elevated levels of allergen-specific IgE to corroborate a history of atopic status. Do not obtain these tests routinely as a diagnostic test for asthma. B Screening for food allergy: ask patients with asthma about symptoms associated with any specific foods. B Screening for COPD: assess smokers/former smokers (> 10 pack-year history) for COPD or overlapping features of asthma and COPD (asthma-COPD overlap). B Screening for alpha-1 antitrypsin deficiency: https://web.pathway.md/diseases/recoid4eeyMVLDPrX 5/26 6/23/23, 3:13 AM Asthma Pathway As per ERS 2017 guidelines, test for AAT deficiency in all patients with adult-onset asthma. E As per Alpha-1 2012 guidelines, avoid obtaining targeted testing for AAT deficiency in patients with asthma. D Screening for GERD: Consider suspecting GERD as a possible cause of a dry cough in patients with confirmed asthma, but do not obtain screening for GERD in patients with uncontrolled asthma. B Do not offer anti-reflux therapy in patients with poorly controlled asthma unless symptomatic GERD presents. D 4. Diagnostic procedures Bronchoalveolar lavage: consider performing bronchial challenge testing in secondary care to confirm a diagnosis of asthma in adult patients, if the diagnosis was not previously established in primary care. C 5. Medical management Treatment guidance: As per GINA 2022 guidelines, offer sputum-guided treatment in adult patients with moderate or severe asthma managed in (or referred to) centers experienced in this technique. A Show 2 more As per ERS 2014 guidelines, consider using sputum eosinophil counts, obtained in centers experienced in using this technique, in addition to clinical criteria to guide treatment in adult patients with severe asthma. C Show 2 more Stepwise management: Use the following track as the preferred stepwise approach to the management of asthma in adult and adolescent patients, with as-needed low-dose ICS-formoterol as the preferred reliever in all steps: Situation Guidance Offer as-needed low-dose ICS-formoterol B Steps 1-2. Symptoms < 4-5 days per week Offer low-dose maintenance ICS-formoterol A Step 3. Symptoms most days, or waking with asthma 1 per week Offer medium-dose maintenance ICS- formoterol B ; consider administering a short course of oral corticosteroids in Step 4. Daily symptoms, or waking with asthma 1 per week, and low lung function https://web.pathway.md/diseases/recoid4eeyMVLDPrX 6/26 6/23/23, 3:13 AM Asthma Pathway patients presenting with severely uncontrolled asthma A Offer add-on LAMAs Step 5. Refer for assessment of phenotype Consider offering high-dose maintenance ICS-formoterol Offer anti-IgE, anti-interleukin 5/5 receptor, anti-interleukin 4, and anti-thymic stromal lymphopoietin therapies A Use the following track as the alternative stepwise approach to the management of asthma in adult and adolescent patients, with an as-needed short-acting -agonist as the alternative reliever in all steps: Situation Guidance Offer ICS whenever short-acting -agonist is taken B Step 1. Symptoms < 2 days per month Offer low-dose maintenance ICSs A Step 2. Symptoms 2 days per month, but < 4-5 days per week Offer low-dose maintenance ICS-long-acting -agonist A Step 3. Symptoms most days, or waking with asthma 1 per week Offer medium/high-dose maintenance ICS- long-acting -agonist B ; consider administering a short course of oral corticosteroids in patients presenting with severely uncontrolled asthma A Step 4. Daily symptoms, or waking with asthma 1 per week, and low lung function Offer add-on LAMAs Step 5. Refer for assessment of phenotype Consider offering high-dose maintenance ICS-long-acting -agonist Offer anti-IgE, anti-interleukin 5/5 receptor, anti-interleukin 4, and anti-thymic stromal lymphopoietin therapies A Adjustment of treatment (assessment): review patients with asthma regularly, ideally 1-3 months after starting treatment and every 3-12 months thereafter, and within 1 week after an exacerbation, B to monitor symptom control, risk factors and occurrence of exacerbations, as well as to document the response to any treatment changes. https://web.pathway.md/diseases/recoid4eeyMVLDPrX 7/26 6/23/23, 3:13 AM Asthma Pathway Adjustment of treatment (stepping up): Step up treatment with the following adjustment options when asthma remains uncontrolled despite good adherence and inhaler technique: Situation Guidance Adjusting the number of as-needed doses of ICS-formoterol from day to day according to symptoms (by the patient), if the reliever inhaler is budesonide-formoterol or beclometasone-formoterol (with or without maintenance ICS-formoterol) Day-to-day adjustment Increasing the dose of maintenance ICS for 1-2 weeks (by the patient according to the written asthma action plan or by the healthcare provider), for example, during viral infections or seasonal allergen exposure Short-term step up (for 1-2 weeks) Increasing the low dose of maintenance ICS to medium when the symptoms are confirmed to be due to asthma, inhaler technique and adherence are satisfactory, and modifiable risk factors such as smoking have been addressed. Reduce the dose to the previous level if there is no response after 2-3 months, and consider offering alternative treatments or referring to a specialist center. Sustained step up (for at least 2-3 months) Adjustment of treatment (stepping down): consider stepping down treatment once asthma symptoms are well controlled and lung function has been stable for 3 months. C Show 4 more Landmark trials: SYGMA 2 In patients with mild asthma and were eligible for treatment with regular ICSs, budesonide and formoterol were noninferior to budesonide maintenance with respect to the percentage of patients achieving an improvement in ACQ-5 score. Bateman ED et al. N Engl J Med. 2018 May 17. Management of modifiable risk factors: Address potentially modifiable risk factors to reduce exacerbations in patients with asthma: Situation Guidance https://web.pathway.md/diseases/recoid4eeyMVLDPrX 8/26 6/23/23, 3:13 AM Asthma Pathway Ensure an ICS-containing controller is prescribed A ; prefer a maintenance and reliever therapy with ICS-formoterol to reduce the risk of severe exacerbations A ; provide a written action plan appropriate for the patient's health literacy A ; obtain more frequent monitoring than in low-risk patients A ; check inhaler technique and adherence frequently A ; identify any modifiable risk factors B Any patient with 1 risk factors for exacerbations, including poor symptom control Prefer ICS-formoterol maintenance and reliever regimen to reduce the risk of severe exacerbations A ; consider stepping up treatment if no modifiable risk factors present A ; identify any avoidable triggers for exacerbations B 1 severe exacerbation in last year Encourage smoking cessation by patient/family Exposure to tobacco smoke Provide counseling and resources A ; consider offering higher-dose of ICSs if asthma is poorly controlled B Consider offering a trial of high-dose ICSs for 3 months B ; consider administering oral corticosteroids for 2 weeks, taking short- and long-term risks into account B ; exclude other lung diseases, such as COPD B ; refer for expert advice if there is no improvement B Low FEV in 1 second, especially if < 60% of predicted Offer weight reduction strategies B ; distinguish asthma symptoms from symptoms due to deconditioning, mechanical restriction, and/or sleep apnea B Obesity Obtain mental health assessment Major psychological problems Help the patient to distinguish between symptoms of anxiety and asthma Counsel about the management of panic attacks B Identify the most cost-effective ICS-based regimen B Major socioeconomic problems https://web.pathway.md/diseases/recoid4eeyMVLDPrX 9/26 6/23/23, 3:13 AM Asthma Pathway Confirmed food allergy Advise appropriate food avoidance Prescribe injectable epinephrine A Advise a trial of simple avoidance strategies, taking the cost into account B ; consider stepping up controller treatment B ; consider adding subcutaneous immunotherapy in symptomatic adult house dust mite-sensitive patients with allergic rhinitis despite ICSs, provided FEV in 1 second is > 70% of predicted B Allergen exposure if sensitized Increase ICS dose independent of the level of symptom control A Sputum eosinophilia Management of exacerbation, self-management: Include the following short-term self- management strategies for worsening asthma in the written asthma action plan: low-dose ICS-formoterol as reliever: increase the frequency of as-needed ICS-formoterol A short-acting -agonist as reliever: increase the frequency of short-acting -agonist use; add spacer for pressurized metered-dose inhaler A maintenance and reliever ICS-formoterol: continue maintenance ICS-formoterol and increase reliever ICS-formoterol as needed A maintenance ICS with short-acting -agonist as reliever: increase ICS dose 4 times in adult and adolescent patients B maintenance ICS-formoterol with short-acting -agonist as reliever: increase maintenance ICS- formoterol dose 4 times B maintenance ICS plus other long-acting -blocker with short-acting -agonist as reliever: step up to higher dose formulation of ICS plus other long-acting -agonist B ; consider adding a separate ICS inhaler to increase ICS dose 4 times in adult patients B addition of oral corticosteroids: add oral corticosteroids for severe exacerbations, such as peak expiratory flow or FEV in 1 second < 60% personal best or predicted, or not responding to treatment > 48 hours, preferably with morning dosing A administer prednisolone 40-50 mg/day, usually for 5-7 days in adult patients, and 1-2 mg/kg/day, maximum 40 mg, usually for 3-5 days in pediatric patients aged 6-11 years B do not taper if administered for < 2 weeks B Landmark trials: FAST In adult and adolescent patients with asthma who were receiving ICSs, with or without add-on therapy, and who had at least one exacerbation in the previous 12 months, quadrupling was superior to non-quadrupling with respect to use of systemic corticosteroids. McKeever T et al. N Engl J Med. 2018 Mar 8. https://web.pathway.md/diseases/recoid4eeyMVLDPrX 10/26 6/23/23, 3:13 AM Asthma Pathway Management of exacerbation, primary care setting (evaluation): Elicit brief focused history, perform a relevant physical examination, and obtain objective measurements, concurrently with the prompt initiation of therapy, in patients with asthma exacerbation presenting to primary care: Situation Guidance Timing of onset and cause (if known) of the present exacerbation History Severity of asthma symptoms, including any limiting exercise or disturbing sleep Any symptoms of anaphylaxis Any risk factors for asthma-related death All current reliever and controller medications, including doses and devices prescribed, adherence pattern, any recent dose changes, and response to current therapy Signs of exacerbation severity and vital signs (level of consciousness, temperature, HR, respiratory rate, BP, ability to complete sentences, use of accessory muscles, wheeze) Physical examination Complicating factors (such as anaphylaxis, pneumonia, pneumothorax) Signs of alternative conditions explaining acute breathlessness (such as cardiac failure, inducible laryngeal obstruction, inhaled foreign body, or pulmonary embolism) Pulse oximetry (saturation levels < 90% in signal the need for aggressive therapy in pediatric and adult patients) Objective measurements Peak expiratory flow in > 5 years old patients. Management of exacerbation, primary care setting (oxygen therapy): Administer oxygen therapy titrated against pulse oximetry (if available) to maintain oxygen saturation at 93-95% (94-98% for pediatric patients aged 6-11 years). A Do not withhold oxygen if oximetry is not available, instead monitor patients for deterioration, somnolence, or fatigue because of the risk of hypercapnia and respiratory failure. https://web.pathway.md/diseases/recoid4eeyMVLDPrX 11/26 6/23/23, 3:13 AM Asthma Pathway Management of exacerbation, primary care setting (SABA): Administer inhaled short-acting -agonists up to 4-10 puffs every 20 minutes for the first hour to achieve rapid reversal of airflow limitation in patients with mild-to-moderate exacerbations. A Do not administer additional short-acting -agonists if there is a good response to initial treatment, such as peak expiratory flow > 60-80% of predicted or personal best for 3-4 hours. Recognize that delivery of short-acting -agonists via a pressurized-metered dose inhaler and spacer or a dry-powdered inhaler leads to a similar improvement in lung function as delivery via nebulizer, A although the most cost-effective route of delivery is pressurized-metered dose inhaler and spacer. Management of exacerbation, primary care setting (oral corticosteroids): administer oral corticosteroids (prednisolone 1 mg/kg/day or equivalent up to a maximum of 50 mg/day, usually for 5-7 days in adult patients, and 1-2 mg/kg/day up to a maximum of 40 mg/day, usually for 3-5 days in pediatric patients aged 6-11 years), especially if the patient is deteriorating, or had already increased reliever and controller doses before the presentation. B Management of exacerbation, primary care setting (inhaled corticosteroids): counsel patients already prescribed controller medication about increasing the dose for the next 2-4 weeks. Initiate regular ICS-containing therapy in patients not currently taking controller medication. Management of exacerbation, primary care setting (antibiotics): do not use antibiotics routinely in the treatment of acute asthma exacerbations unless there is strong evidence of lung infection (such as fever and purulent sputum, or radiographic evidence of pneumonia). Management of exacerbation, primary care setting (monitoring and discharge): Obtain close monitoring during exacerbation treatment, and titrate treatment according to the response. Transfer patients immediately to an acute care facility when presenting with signs of a severe or life-threatening exacerbation not responding to treatment or continuing to deteriorate. Include as-needed reliever medication (low dose ICSs-formoterol or short-acting -agonists), a short course of oral corticosteroids, and regular controller treatment in the discharge medications. Do not prescribe short-acting -agonist-only treatment. Review inhaler technique and adherence before discharge. Advise patients to use their reliever inhaler only as-needed, rather than routinely. Schedule a follow-up appointment for 2-7 days later, depending on the clinical and social context. Management of exacerbation, emergency department setting (evaluation): obtain pulmonary function testing in patients with asthma exacerbation presenting to the emergency department. Document peak expiratory flow or FEV in 1 second, if possible and without unduly delaying treatment, before initiating treatment. Monitor lung function at 1 hour and at intervals until a clear response to treatment has occurred or a plateau is reached. Show 3 more Management of exacerbation, emergency department setting (SABA): https://web.pathway.md/diseases/recoid4eeyMVLDPrX 12/26 6/23/23, 3:13 AM Asthma Pathway Administer frequent inhaled short-acting -agonists in patients presenting with acute asthma. Recognize that the most cost-effective and efficient delivery is by pressurized metered-dose inhalers with a spacer. A Insufficient evidence to support the routine use of IV -2 agonists in patients with severe asthma exacerbations. I Management of exacerbation, emergency department setting (systemic corticosteroids): administer systemic corticosteroids in acute care settings to speed resolution of exacerbations and prevent relapses in all adult, adolescent, and pediatric (6-11 years of age) patients with asthma exacerbation, except for the mildest exacerbations. A Show 2 more Management of exacerbation, emergency department setting (inhaled corticosteroids): Administer high-dose ICSs within the first hour of presentation to the emergency department to reduce the need for hospitalization in patients not receiving systemic corticosteroids. A Consider administering ICSs, with or without concomitant systemic corticosteroids, within the first hours of presentation to the emergency department to reduce the risk of hospital admission and the need for systemic corticosteroids in pediatric patients. C Management of exacerbation, emergency department setting (oxygen therapy): administer controlled low-flow oxygen therapy (by nasal cannulae or mask) using pulse oximetry to maintain saturation at 93-95% in patients with severe exacerbations (94-98% in pediatric patients aged 6- 11 years). B Show 3 more Management of exacerbation, emergency department setting (other treatments): consider administering ipratropium in addition to short-acting -agonists for the management of moderate- to-severe exacerbations in the emergency department, to reduce hospitalizations in adult, B adolescent, and pediatric patients C and to improve peak expiratory flow and FEV in 1 second in adolescent and adult patients. B Show 2 more Management of exacerbation, emergency department setting (monitoring and discharge): on discharge home: Prescribe ongoing ICS-containing treatment since the occurrence of a severe exacerbation is a risk factor for future exacerbations , and ICS-containing medications significantly reduce the risk of asthma-related death or hospitalization (Evidence A). short-acting -agonist- only treatment of asthma is no longer recommended. For short-term outcomes such as relapse requiring admission, symptoms, and quality of life, a systematic review found no significant differences when ICSs were added to systemic corticosteroids after discharge. There was some evidence, however, that post-discharge ICSs were as effective as systemic corticosteroids for milder exacerbations, but the confidence limits were wide. (Evidence B). Cost may be a significant factor for patients in the use of high-dose ICSs, and further studies are required to establish their role. B Allergen immunotherapy: As per GINA 2022 guidelines: https://web.pathway.md/diseases/recoid4eeyMVLDPrX 13/26 6/23/23, 3:13 AM Asthma Pathway Consider offering subcutaneous immunotherapy in adult patients with allergic rhinitis and sensitized to house dust mite, with persisting asthma symptoms despite low-to-medium-dose ICS-containing therapy, provided FEV in 1 second is > 70% of predicted. C Weigh potential benefits of subcutaneous immunotherapy against the risk of adverse effects and the inconvenience and cost of the prolonged course of therapy, including the minimum half-hour wait required after each injection. B As per NHLBI 2020 guidelines: Consider offering subcutaneous immunotherapy as an adjunct treatment to standard pharmacotherapy in 5 years old patients with mild-to-moderate allergic asthma controlled at the initiation, build-up, and maintenance phases of immunotherapy. C Avoid using sublingual immunotherapy in patients with persistent allergic asthma. D Long-term macrolides: As per GINA 2022 guidelines, consider offering add-on azithromycin (3 times per week, for at least 6 months) after specialist referral in adult patients with persistent symptomatic asthma despite high dose ICSs-long-term -agonists. Assess sputum for atypical mycobacteria and obtain an ECG for long QTc before initiation (and reassess after a month on treatment), taking into account the risk of increasing antimicrobial resistance. C As per BTS 2020 guidelines: Consider offering oral macrolide therapy for a minimum of 6-12 months to reduce exacerbation frequency in adult (50-70 years) patients with ongoing symptoms despite > 80% adherence to high-dose ICSs (> 800 g/day) and at least one exacerbation requiring oral corticosteroids in the past year. C Do not offer oral macrolide therapy as a way to reduce oral corticosteroid dose, recognizing that in some patients this may result as a consequence of a reduction in exacerbations or symptoms. D Landmark trials: AMAZES In patients with uncontrolled persistent asthma on medium-to-high dose ICS plus a long- acting bronchodilator, oral azithromycin was superior to placebo with respect to total asthma exacerbations. Gibson PG et al. Lancet. 2017 Aug 12. As per CTS 2017 guidelines, consider offering macrolides to reduce the frequency of exacerbations in 18 years old patients with severe asthma. E Show 3 more As per ERS 2014 guidelines, avoid using macrolide antibiotics in adult and pediatric patients with severe asthma. D Biologic therapy: https://web.pathway.md/diseases/recoid4eeyMVLDPrX 14/26 6/23/23, 3:13 AM Asthma Pathway As per GINA 2022 guidelines, offer add-on anti-IgE therapy (omalizumab) in 6 years old patients with moderate-to-severe allergic asthma uncontrolled on step 4-5 treatment. A Show 3 more As per CTS 2017 guidelines, consider offering omalizumab in 6 years old patients with severe asthma meeting the following criteria: inadequate disease control despite high-dose ICSs and at least one other controller sensitization to at least one perennial allergen serum IgE levels of 30-1,300 IU/mL (for children aged 6-11 years) or 30-700 IU/mL (for adults and adolescents aged 12 years). E Show 8 more As per ERS 2014 guidelines, consider offering a therapeutic trial of omalizumab in adult C and pediatric patients with severe allergic asthma. C Landmark trials: EXTRA In patients with inadequately controlled severe asthma who are receiving high-dose ICS and long-acting -agonists, with or without additional controller therapy, omalizumab was superior to placebo with respect to asthma exacerbations at 48 weeks. Hanania NA et al. Ann Intern Med. 2011 May 3. Oral corticosteroids: As per GINA 2022 guidelines: Offer add-on low-dose oral corticosteroids ( 7.5 mg/day prednisone equivalent) as a last resort only in selected adult patients with severe asthma with poor symptom control and/or frequent exacerbations despite good inhaler technique and adherence with step 5 treatment, and after exclusion of other contributory factors and other add-on treatments including biologics (where available and affordable). B Counsel patients about potential side effects, and assess and monitor for risk of adrenal suppression and corticosteroid-induced osteoporosis. Provide relevant lifestyle counseling and prescription of therapy for prevention of osteoporosis (where appropriate) in patients expected to be treated for 3 months. As per SIGN 2019 guidelines, offer daily oral corticosteroids (at the lowest dose providing adequate control) in selected patients not controlled on high-dose therapies. B Immunosuppressants: as per ERS 2014 guidelines, avoid using methotrexate in adult and pediatric patients with severe asthma. D 6. Nonpharmacologic interventions Smoking cessation: https://web.pathway.md/diseases/recoid4eeyMVLDPrX 15/26 6/23/23, 3:13 AM Asthma Pathway As per GINA 2022 guidelines, advise smoking cessation at every visit in smoker patients with asthma. Provide access to counseling and smoking cessation programs if available. A Show 2 more As per SIGN 2019 guidelines, counsel patients with asthma and parents/carers of pediatric patients with asthma about the dangers of smoking and second-hand tobacco smoke exposure, and advise quitting smoking. B Physical activity: encourage patients with asthma to engage in regular physical activity for its general health benefits, A including improvement in cardiopulmonary fitness as well as for a small benefit for asthma control and lung function, including with swimming in young patients with asthma. B Show 3 more Dietary modifications: advise patients with asthma to follow a diet high in fruit and vegetables for its general health benefits. A Show 2 more Weight loss: As per GINA 2022 guidelines: Include weight reduction in the treatment plan of patients with asthma and obesity. B Advise a weight reduction program combined with twice-weekly aerobic and strength exercises for symptom control in adult patients with asthma and obesity. B As per SIGN 2019 guidelines, consider offering weight-loss interventions (including dietary and exercise-based programs) to improve asthma control in adult and pediatric patients with overweight or obesity. C Breathing exercises: As per GINA 2022 guidelines, consider offering breathing exercises as an adjunct to pharmacotherapy to improve symptoms and quality of life, but not for reducing exacerbation risk or improving lung function. B As per SIGN 2019 guidelines, consider offering breathing exercise programs (including face-to- face physiotherapist-delivered methods and audiovisual programs) as an adjuvant to pharmacotherapy to improve quality of life and reduce symptoms in adult patients with asthma. B Stress management: encourage patients to identify goals and strategies to deal with emotional stress if it makes their asthma worse. B Show 2 more Vitamin D supplements: insufficient evidence to support the use of vitamin D supplements for improving disease control or reducing exacerbations in patients with asthma. I Avoidance of indoor allergens: As per GINA 2022 guidelines, do not advise routine allergen avoidance in patients with asthma. D Show 2 more https://web.pathway.md/diseases/recoid4eeyMVLDPrX 16/26 6/23/23, 3:13 AM Asthma Pathway As per NHLBI 2020 guidelines, avoid offering allergen mitigation interventions as part of routine asthma management in patients with asthma not having sensitization to specific indoor allergens or not having symptoms related to exposure to specific indoor allergens. D Show 2 more As per SIGN 2019 guidelines: Do not advise using routine physical or chemical methods of reducing house dust mite levels in the home (including acaricides, mattress covers, vacuum cleaning, heating, ventilation, freezing, washing, air filtration, and ionizers) for the management of asthma. D Do not advise using air ionizers for the treatment of asthma. D Avoidance of outdoor allergens: advise reducing exposure to outdoor allergens in sensitized patients by closing windows and doors, remaining indoors, and using air conditioning when pollen and mold counts are highest. B Avoidance of weather conditions: consider advising staying indoors in a climate-controlled environment and avoiding strenuous outdoor physical activity during unfavorable weather conditions (such as very cold weather or low humidity). Advise avoiding polluted environments during viral infections, if feasible. C Avoidance of air pollution: Advise using non-polluting heating and cooking sources, and vent sources of pollutants outdoors where possible. B Consider advising staying indoors in a climate-controlled environment and avoiding strenuous outdoor physical activity during high air pollution. Advise avoiding polluted environments during viral infections, if feasible. C Avoidance of occupational exposure: As per GINA 2022 guidelines: Identify and eliminate occupational sensitizers as soon as possible and remove any further exposure to these agents in the management of patients with occupational asthma. A Advise using non-powdered low-allergen gloves instead of powdered latex gloves to minimize latex sensitization. A As per SIGN 2019 guidelines, advise relocation away from exposure as soon as the diagnosis of work-related asthma is confirmed, ideally within 12 months of the first work-related symptoms of asthma. B As per ERS 2012 guidelines, inform patients: the risk of work-related asthma is higher in case of atopy or preexisting asthma or pre- employment sensitization B persistence of exposure to the causal agent is likely to result in a deterioration of asthma symptoms and airway obstruction B complete avoidance of exposure is associated with the highest probability of improvement, but may not lead to a complete recovery from asthma. B Show 4 more https://web.pathway.md/diseases/recoid4eeyMVLDPrX 17/26 6/23/23, 3:13 AM Asthma Pathway Avoidance of exacarbating medications: ask patients about asthma and previous reactions always before prescribing NSAIDs, and advise discontinuing them if asthma worsens. B Recognize that aspirin and NSAIDs are not generally contraindicated unless there is a history of previous reactions to these agents. A Show 3 more 7. Therapeutic procedures Bronchial thermoplasty: As per GINA 2022 guidelines, consider offering bronchial thermoplasty, if available, as step 5 in adult patients with uncontrolled asthma despite optimized therapeutic regimens and referral to an asthma specialty center. C As per NHLBI 2020 guidelines, consider offering bronchial thermoplasty in 18 years old patients with persistent asthma placing a low value on harms (short-term worsening symptoms and unknown long-term side effects) and a high value on potential benefits (improvement in quality of life, a small reduction in exacerbations). C As per CTS 2017 guidelines: Insufficient evidence regarding the precise role of bronchial thermoplasty in 18 years old patients with severe asthma. I Perform bronchial thermoplasty in highly specialized centers because of the complexity of the procedure and the occurrence of severe events, such as hospitalizations due to asthma worsening, atelectasis, and pneumonia. E As per ERS 2014 guidelines, offer bronchial thermoplasty in adult patients with severe asthma only in the context of an IRB-approved independent systematic registry or a clinical trial. B 8. Perioperative care Perioperative management: Ensure achieving good asthma control preoperatively in patients scheduled for elective surgery, especially in patients with more severe asthma, uncontrolled symptoms, exacerbation history, or persistent airflow limitation. B