Please systematically extract the recommendations from each original asthma guideline, organized section by section.

Systematic Extraction of Asthma Guideline Recommendations by Section

NAEPP 2020 Focused Updates 1

Methodology Framework

• First use of GRADE methodology by NAEPP to provide transparency in decision-making
• Strict conflict of interest standards following Institute of Medicine recommendations
• External input sought from NAEPP Coordinating Committee, public, and federal agencies
• Recommendations combine certainty of evidence with patient values/preferences and weigh benefits versus harms

Scope and Limitations

• Six priority topics updated (biologic agents deliberately excluded due to rapidly evolving evidence)
• Not a complete revision of EPR-3
• Important aspects not covered: asthma education, inhaler technique, assessment tools for control/adherence
• Most recommendations downgraded to conditional due to inconsistencies in study results, risk of bias, or absence of standardized outcome measures

Implementation Features

• New Implementation Guidance section added for each topic to aid providers in patient discussions
• Emphasis on standardized and validated outcome measures from Asthma Outcomes Workshop (2012)

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European Respiratory Society Pediatric Guidelines (Ages 5-16) 2

Core Diagnostic Principles

• Diagnosis requires at least two abnormal objective test results (strong recommendation)
• Trials of treatment where symptom improvement alone confirms diagnosis are NOT recommended
• No single abnormal test is sufficient to make the diagnosis

First-Line Diagnostic Tests

1. Spirometry (first-line)
2. Bronchodilator reversibility (BDR) (first-line)
3. FeNO measurement (first-line)

Diagnostic Algorithm Structure

Initial Spirometry Assessment:

• Abnormal spirometry (FEV1 or FEV1/FVC < LLN and/or <80% predicted):

  • Perform BDR testing
  • BDR positive (≥12% AND/OR ≥200 mL): Asthma confirmed
  • BDR negative (<12% AND/OR <200 mL): Perform FeNO measurement

• Normal spirometry (FEV1 and FEV1/FVC ≥LLN and/or ≥80% predicted):

  • Perform FeNO measurement
  • FeNO ≥25 ppb: Asthma confirmed
  • FeNO <25 ppb: Consider PEFR variability testing or challenge testing

Secondary Diagnostic Tests

• PEFR variability ≥12%: Supports diagnosis
• Positive challenge test: Supports diagnosis
• Watchful waiting with repeat testing can be considered in children with normal spirometry, especially when symptomatic

Treatment Trial Approach

• If FeNO ≥25 ppb but spirometry normal and BDR negative: Consider asthma treatment, review after 4-8 weeks
• Repeat spirometry after treatment trial:
  • If spirometry improved AND symptoms improved AND BDR positive: Asthma confirmed
  • If BDR negative: Refer for specialist opinion

Age Applicability

• Algorithm valid across entire 5-16 year age range (no separate stratification for 5-11 vs 12-16 years)

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Chinese Guidelines for Asthma Prevention and Management (2024 Edition) 3

Diagnostic Recommendations

Recommendation 1: Bronchial provocation test should be considered when FEV1 ≥70% predicted (excluding respiratory infections within past 4 weeks) (1, D)

Recommendation 2: When clinical symptoms suggest asthma but bronchial provocation test unavailable or doesn't meet criteria, avoid relying on cutoff value alone to exclude asthma; initiate presumptive diagnostic pathway (1, D)

Recommendation 3: Diagnostic anti-inflammatory therapy may be initiated if ANY of following met:

• Positive PEF-based bronchodilation test (≥20% increase from baseline) when spirometry unavailable
• FEV1 variability ≥12% AND absolute change ≥200 ml between two prior tests
• Small airway dysfunction (2 of 3 parameters ≤65% predicted: MEF25, MEF50, MMEF) OR FEV1 improvement ≥10% with FeNO ≥35 ppb in bronchodilation test when baseline FEV1 ≥80% predicted (1, C)

Disease Classification and Monitoring

Recommendation 4: "Clinical remission" defined as: ≥1 year symptom-free, no exacerbations, normal/near-normal lung function, no need for oral corticosteroids after biologic or other anti-asthma therapy (1, D)

Recommendation 5: Classify asthma severity based on treatment steps required to achieve control rather than pre-treatment status (1, D)

Recommendation 6: Type 2 airway inflammation characterized by elevated blood/sputum eosinophils, and/or FeNO, and/or atopy or elevated total IgE. Non-type 2 inflammation identified only after excluding confounders (infections, medications) (1, D)

Recommendation 7: Patients with dyspnea/chest tightness after routine therapy with normalized lung function, eosinophils, and FeNO should undergo psychosocial assessment (anxiety/depression scales) and comorbidity evaluation (1, D)

Recommendation 8: Provocative dose causing 20% FEV1 decrease may reflect airway hyperresponsiveness and be used in disease monitoring/therapeutic evaluation (2, D)

Recommendation 9: Induced sputum eosinophil is gold standard biomarker for airway inflammation assessment, phenotype classification, corticosteroid response prediction, and exacerbation risk assessment (1, A)

Recommendation 10: Peripheral blood eosinophil ≥150/μl identifies eosinophil phenotype or type 2 inflammatory endotype; key biomarker to predict/evaluate biologic responses (1, C)

Treatment Safety and Principles

Recommendation 11: Long-term ICS at recommended clinical doses is safe. Prolonged high-dose ICS may cause: osteoporosis, HPA axis suppression, increased pneumonia risk (1, D)

Recommendation 12: For severe asthma adults, low-dose OCS (≤7.5 mg/day prednisone equivalent) as last choice (1, D)

Recommendation 13: ICS-LABA demonstrates synergistic effects, achieving efficacy equivalent to or better than doubling ICS dose; improves adherence, reduces high-dose ICS adverse effects; particularly recommended for moderate-to-severe asthma (1, A)

Recommendation 14: Triple combination inhalers prescribed to improve symptoms, lung function, reduce exacerbations when uncontrolled on medium/high-dose ICS-LABA (1, A)

Recommendation 15: Subcutaneous immunotherapy in adults may reduce required ICS dosage, improve quality of life and lung function (2, B)

Recommendation 16: For HDM-sensitized adolescents/adults with FEV1 >70% predicted, HDM sublingual immunotherapy may be added to reduce symptoms and ICS dose if symptoms persist despite low-to-medium-dose ICS-containing therapy (2, B)

Stepwise Treatment Approach

Recommendation 17 (Step 1): As-needed low-dose ICS-formoterol for patients with occasional transient daytime symptoms (<2 times/month, lasting hours), no nocturnal symptoms, no exacerbation risk, FEV1 >80% predicted (1, A)

Recommendation 18 (Step 2): As-needed low-dose ICS-formoterol recommended; significantly reduces moderate-to-severe exacerbations by comparison with SABA alone (1, A)

Recommendation 19 (Step 4+): Patients with persistent symptoms/exacerbations despite correct technique and adherence to Step 4 treatment should be referred to asthma specialists (1, D)

Recommendation 20 (Follow-up): Schedule visits every 2-4 weeks after initial therapy, then every 1-3 months if responding. Regular training in correct inhaler technique essential (1, B)

Risk Stratification

Recommendation 21: Risk factors for asthma-related death include:

• History requiring intubation/mechanical ventilation
• Hospitalization/emergency visit for exacerbation in past year
• Currently use or recent cessation of OCS
• No current ICS use
• SABA overuse (>1 canister salbutamol/month)
• Psychiatric illness/psychosocial problems including sedative use
• Poor adherence
• Confirmed food allergy history
• Comorbidities: pneumonia, diabetes, arrhythmias (1, D)

Acute Exacerbation Management

Recommendation 22: In early mild-to-moderate exacerbations, when budesonide-formoterol used as anti-inflammatory reliever, take 1-2 additional inhalations (160/4.5 μg strength); daily dose should not exceed 8 inhalations (1, D)

Severe Asthma Definition and Management

Recommendation 23: Severe asthma defined as: uncontrolled despite 3+ months continuous standardized medium/high-dose ICS-LABA, treated comorbidities, avoided environmental stimuli, OR worsening after stepping down (1, D)

Recommendation 24: Severe type 2 asthma treated with biologic therapy; good responders can prioritize decreasing/stopping maintenance OCS but should not completely stop ICS-LABA (1, A)

Recommendation 25: Adult patients with persistent symptoms despite step 5 treatment: add-on low-dose azithromycin (250-500 mg/day, three times weekly, 26-48 weeks) may reduce exacerbations (2, A)

Recommendation 26: Bronchial thermoplasty indicated for adults with uncontrolled asthma despite optimized treatment and specialist referral, or when targeted biologic therapy unavailable/inappropriate (2, A)

Specific Asthma Phenotypes

Recommendation 27 (CVA): Treatment principles same as typical asthma; most respond to ICS or ICS-LABA. ICS-LABA recommended as first choice for >8 weeks (1, B)

Recommendation 28 (CVA): For CVA with poor response and severe airway inflammation, consider adding leukotriene receptor antagonist or short-term OCS (10-20 mg/d, 3-5 days) (2, D)

Recommendation 29 (Fungal sensitization): Antifungal drugs can reduce airway inflammation and systemic corticosteroid dose by minimizing fungal colonization/burden (1, D)

Recommendation 30 (Fungal sensitization): Anti-IgE, anti-IL-5, anti-IL-5Rα, anti-IL-4Rα monoclonal antibodies can reduce exacerbations, improve control/lung function/quality of life (1, B)

Recommendation 31 (AIA): Most effective prevention is avoiding reapplication; desensitization therapy considered for patients requiring high-dose ICS, failed conventional nasal treatment, or require aspirin for other diseases (2, B)

Recommendation 32 (Severe asthma with CRSwNP): May benefit from anti-IgE, anti-IL-5, anti-IL-5Rα, anti-IL-4Rα monoclonal antibodies (1, B)

Recommendation 33 (ACO): Consider ACO diagnosis in asthma patients with: persistent airflow limitation (FEV1/FVC <70% post-bronchodilator), noxious gas/substance exposure (smoking ≥10 pack-years), emphysema on HRCT, decreased diffusion capacity after 3-6 months standardized treatment (1, D)

Patient-Centered Care

Recommendation 34: When developing control goals, consider health care system, medication availability, cultural differences, and personal preferences (1, D)

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GINA 2021 Strategy Report 4

Core Principle Changes

• Asthma in adults/adolescents should NOT be treated solely with SABA due to risks of SABA-only treatment and SABA overuse
• Evidence for benefit of ICS across all severity levels

Treatment Track Structure

Track 1 (Preferred):

• Low-dose ICS-formoterol as reliever at ALL steps
• Steps 1-2 (mild asthma): As-needed only
• Steps 3-5: Daily maintenance ICS-formoterol (MART)

Track 2 (Alternative):

• As-needed SABA across all steps
• Plus regular ICS (Step 2) or ICS-LABA (Steps 3-5)

Evidence Base for Mild Asthma

• Large trials show as-needed ICS-formoterol reduces severe exacerbations by ≥60% compared with SABA alone in mild asthma
• Similar exacerbation, symptom, lung function, and inflammatory outcomes as daily ICS plus as-needed SABA

Step 5 Add-On Therapies (Moderate-to-Severe Asthma)

• Long-acting muscarinic antagonists (LAMA)
• Azithromycin
• Biologic therapies for severe asthma

Pediatric Updates (Ages 6-11)

• New treatment options added at Steps 3-4

Universal Principles Across All Ages/Severity

• Regular personalized assessment
• Treatment of modifiable risk factors
• Self-management education
• Skills training
• Appropriate medication adjustment
• Regular review essential to optimize outcomes

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ERS/ATS Severe Asthma Guidelines (2020) 5

Biologic Therapy Recommendations

Recommendation 1: Suggest using anti-IL-5 and anti-IL-5Rα for severe uncontrolled adult eosinophilic asthma phenotypes

Recommendation 2: Suggest blood eosinophil cut-point ≥150 μL⁻¹ to guide anti-IL-5 initiation in adult severe asthma

Recommendation 3: Suggest specific cut-offs for anti-IgE therapy in adolescents/adults:

• Eosinophil ≥260 μL⁻¹
• FeNO ≥19.5 ppb
• These identify patients with greatest likelihood of response

Recommendation 6: Suggest using anti-IL-4/13 for:

• Adult patients with severe eosinophilic asthma
• Severe corticosteroid-dependent asthma regardless of blood eosinophil levels

Add-On Therapy Recommendations

Recommendation 4: Suggest inhaled tiotropium for adolescents/adults with severe uncontrolled asthma despite GINA step 4-5 or NAEPP step 5 therapies

Recommendation 5: Suggest trial of chronic macrolide therapy to reduce exacerbations in persistently symptomatic/uncontrolled patients on GINA step 5 or NAEPP step 5 therapies, irrespective of asthma phenotype

Methodology

• GRADE approach used
• Comprehensive evidence syntheses including meta-analyses
• Evidence profiles summarized
• Recommendations formulated by multidisciplinary Task Force
• Balance of desirable/undesirable consequences, quality of evidence, feasibility, and acceptability considered

Future Considerations

• Recommendations should be reconsidered as new evidence becomes available

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New Zealand Asthma Guidelines (2020) 6

Major Changes from Previous Version

1. Combined adolescent and adult recommendations in single document (age 12+)

2. Avoid SABA-only treatment in long-term asthma management

3. Budesonide/formoterol reliever preferred to SABA reliever across asthma severity spectrum:

   • With or without maintenance budesonide/formoterol
   • With or without maintenance ICS or ICS/LABA

4. Introduction of "Anti-Inflammatory Reliever (AIR)" terminology:

   • Describes budesonide/formoterol as reliever medication
   • With or without maintenance budesonide/formoterol therapy
   • Encompasses and extends previous SMART approach

5. Two stepwise management algorithms included

6. Clinical allergy section added

7. LAMA therapy role in severe asthma addressed

8. Biologic therapy guidance:

   • Omalizumab role in severe allergic asthma
   • Mepolizumab role in severe eosinophilic asthma

9. Educational materials appendix detailed

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ERS/ATS Severe Asthma Definition and Evaluation Guidelines (2014) 7

Severe Asthma Definition

Severe asthma requires treatment with:

• High-dose inhaled corticosteroids PLUS second controller and/or systemic corticosteroids to prevent becoming "uncontrolled"
• OR remains "uncontrolled" despite this therapy

Prerequisites:

• Diagnosis of asthma confirmed
• Comorbidities addressed

Phenotype Recognition

• Severe asthma is heterogeneous consisting of phenotypes such as eosinophilic asthma
• Specific phenotyping necessary for targeted therapy

Specific Treatment Recommendations

Biomarker-Guided Therapy:

• Use of sputum eosinophil count to guide therapy
• Use of exhaled nitric oxide to guide therapy

Pharmacologic Interventions:

• Anti-IgE antibody
• Methotrexate
• Macrolide antibiotics
• Antifungal agents

Procedural Intervention:

• Bronchial thermoplasty

Future Direction

• Coordinated research efforts for improved phenotyping
• Goal: safe and effective biomarker-driven approaches to severe asthma therapy

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GINA 2026 Strategy Report 8

Core Principles

Central Approach:

• Personalized, iterative care based on Assess-Adjust-Review cycle
• Focus on symptom control AND reduction of future risk (severe exacerbations, persistent airflow limitation, treatment-related harm)

Diagnostic Emphasis:

• Objective confirmation of diagnosis wherever possible

Regular Assessment Components:

• Lung function
• Inhaler technique
• Adherence
• Multimorbidity
• Risk factors (including Type-2 biomarkers)
• Patient goals and preferences

Universal Treatment Principles

Strong Recommendations:

• All adults, adolescents, children and most preschoolers with asthma should receive ICS-containing treatment
• Recommends AGAINST SABA-only treatment

Adult/Adolescent Treatment

Track 1 (Preferred):

• Low-dose ICS-formoterol as anti-inflammatory reliever (AIR)
• Either as-needed-only (AIR-only) OR as maintenance-and-reliever therapy (MART)
• Preferred because: substantial reduction in severe exacerbations compared with SABA-based regimens AND simplicity

Pediatric Treatment

• Age-specific treatment pathways
• Emphasize ICS-containing therapy
• Focus on exacerbation prevention

Difficult-to-Treat and Severe Asthma

Structured Guidance Includes:

• Diagnostic verification
• Optimization of modifiable factors
• Inflammatory phenotyping
• Biologic therapy selection
• Systemic corticosteroid stewardship (as for all patients)

Acute Exacerbation Management

• Incorporates long-term preventive treatment
• Post-discharge reassessment of management
• Action plan review

Key 2026 Updates

1. Expanded AIR options for adults and children
2. Revised guidance on severe asthma and biologic treatment selection
3. Substantial updates to acute asthma management

Integration Approach

• Evidence-based management with shared decision-making
• Self-management education
• Implementation strategies
• Global advocacy to reduce preventable asthma morbidity and mortality

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BTS/NICE/SIGN UK Guideline (2024) Comparison with GINA 9

Diagnostic Approach Differences

BTS/NICE/SIGN:

• Emphasis on markers of eosinophilic inflammation as initial key diagnostic tests

GINA:

• Emphasis on tests of reversible airflow limitation

Common Ground:

• Both acknowledge no one "gold-standard" test
• IPCRG "jigsaw puzzle" approach to diagnosis particularly useful where limited/delayed test access

Treatment Approach Convergence

Strong Economic Evidence Supports:

• Single anti-inflammatory-reliever (AIR) therapy as cornerstone of asthma management (age 12+)
• Maintenance and Reliever (MART) therapies as cornerstone of asthma management (age 12+)

Geographic Applicability

• BTS/NICE/SIGN represents major shift in UK asthma diagnosis and management
• Launched November 2024