Asthma and Severe Asthma

The answer first

Asthma is a heterogeneous inflammatory disease of the airways defined by a history of variable respiratory symptoms (wheeze, shortness of breath, chest tightness, cough) that fluctuate in time and intensity, together with variable expiratory airflow limitation. Two facts must land before anything else: ^[1]

1. Every patient with asthma needs an inhaled corticosteroid (ICS)-containing regimen. Since 2019, GINA has abolished short-acting beta-agonist (SABA) monotherapy — it does not suppress the underlying inflammation and it costs lives. The minimum therapy is as-needed low-dose ICS-formoterol (an anti-inflammatory reliever); most patients need regular daily ICS or ICS-LABA.
2. Severe asthma is rare. Roughly 3-8% of adults with asthma have severe disease — yet most patients labelled "severe" in clinic actually have uncontrolled asthma driven by non-adherence, poor inhaler technique, untreated comorbidities or an alternative diagnosis. The first job when a patient is referred for "severe asthma" is to prove the diagnosis, exclude mimics, and fix the basics before reaching for a biologic. ^[1]

The condition sits on a Type 2 (T2) inflammation axis in most patients: an eosinophilic, IgE-mediated, corticosteroid-responsive pathway driven by interleukin (IL)-4, IL-5 and IL-13. A minority have non-eosinophilic (neutrophilic) disease that responds poorly to steroids and is managed very differently. Phenotyping — by blood eosinophils and fractional exhaled nitric oxide (FeNO) — is now central to choosing between a biologic and predicting the response. ^[1]

---

References10ShowHide

1. [1]Beasley R, Holliday M, Reddel HK, et al. Controlled Trial of Budesonide-Formoterol as Needed for Mild Asthma N Engl J Med, 2019.PMID 31112386
2. [2]Kerstjens HA, Engel M, Dahl R, et al. Tiotropium in asthma poorly controlled with standard combination therapy N Engl J Med, 2012.PMID 22938706
3. [3]Humbert M, Beasley R, Ayres J, et al. Benefits of omalizumab as add-on therapy in patients with severe persistent asthma who are inadequately controlled despite best available therapy (GINA 2002 step 4 treatment): INNOVATE Allergy, 2005.PMID 15679715
4. [4]Pavord ID, Korn S, Howarth P, et al. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial Lancet, 2012.PMID 22901886
5. [5]Ortega HG, Liu MC, Pavord ID, et al. Mepolizumab treatment in patients with severe eosinophilic asthma N Engl J Med, 2014.PMID 25199059
6. [6]Bleecker ER, FitzGerald JM, Chanez P, et al. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting β(2)-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial Lancet, 2016.PMID 27609408
7. [7]Nair P, Wenzel S, Rabe KF, et al. Oral Glucocorticoid-Sparing Effect of Benralizumab in Severe Asthma N Engl J Med, 2017.PMID 28530840
8. [8]Castro M, Corren J, Pavord ID, et al. Dupilumab Efficacy and Safety in Moderate-to-Severe Uncontrolled Asthma N Engl J Med, 2018.PMID 29782217
9. [9]Rabe KF, Nair P, Brusselle G, et al. Efficacy and Safety of Dupilumab in Glucocorticoid-Dependent Severe Asthma N Engl J Med, 2018.PMID 29782224
10. [10]Kew KM, Kirtchuk L, Michell CI Intravenous magnesium sulfate for treating adults with acute asthma in the emergency department Cochrane Database Syst Rev, 2014.PMID 24865567