What is the management of type 2 inflammation in asthma?

From the Guidelines

The management of type 2 inflammation in asthma involves targeted biologic therapies and anti-inflammatory medications, with a focus on controlling type-2 airway inflammation as a key treatment target, as proposed by recent research 1.

Key Considerations

• Type 2 inflammation in asthma is characterized by elevated blood eosinophils, increased FeNO, or allergic features, and is a key driver of eosinophilic inflammation, mucus hypersecretion, and airway hyperresponsiveness.
• Biologics, such as anti-IgE therapy (omalizumab), anti-IL5 therapies (mepolizumab, benralizumab), anti-IL5R (benralizumab), and anti-IL4R (dupilumab), are the cornerstone of treatment for patients with moderate to severe asthma and evidence of type 2 inflammation.
• Inhaled corticosteroids remain fundamental, with medium to high doses often required, and adding a long-acting beta-agonist (LABA) like salmeterol or formoterol provides synergistic effects.
• Treatment selection should be guided by biomarkers, specific inflammatory patterns, and clinical phenotype, with regular monitoring of symptom control, exacerbation frequency, and lung function to assess response, as suggested by recent studies 1.

Treatment Options

• Anti-IgE therapy (omalizumab, 150-375mg subcutaneously every 2-4 weeks)
• Anti-IL5 therapies (mepolizumab 100mg subcutaneously monthly, benralizumab 30mg subcutaneously every 4-8 weeks)
• Anti-IL5R (benralizumab)
• Anti-IL4R (dupilumab 200-300mg subcutaneously every 2 weeks)
• Inhaled corticosteroids (fluticasone 250-500mcg twice daily or equivalent)
• Long-acting beta-agonist (LABA) like salmeterol or formoterol
• Leukotriene modifiers (montelukast 10mg daily) for patients with aspirin-exacerbated respiratory disease.

Monitoring and Assessment

• Regular monitoring of symptom control, exacerbation frequency, and lung function to assess response to treatment.
• Biomarkers, such as blood eosinophils and FeNO, should be used to guide treatment selection and adjust therapy as needed, as proposed by recent research 1.

From the FDA Drug Label

Inflammation driven by IL-4 and IL-13 is an important component in the pathogenesis of asthma, AD, CRSwNP, EoE, PN, and COPD. Dupilumab inhibits IL-4 signaling via the Type I receptor and both IL-4 and IL-13 signaling through the Type II receptor Blocking IL-4Rα with dupilumab inhibits IL-4 and IL-13 cytokine-induced inflammatory responses, including the release of proinflammatory cytokines, chemokines, nitric oxide, and IgE.

Type 2 inflammation in asthma refers to the inflammation driven by IL-4 and IL-13, which are key components in the pathogenesis of asthma.

• The management of type 2 inflammation in asthma involves inhibiting IL-4 and IL-13 signaling, which can be achieved with dupilumab, a human monoclonal antibody that binds to the IL-4Rα subunit.
• Dupilumab treatment decreases biomarkers of inflammation, including fractional exhaled nitric oxide (FeNO) and circulating concentrations of eotaxin-3, total IgE, allergen-specific IgE, TARC, and periostin. 2

From the Research

Definition of Type 2 Inflammation in Asthma

• Type 2 (T2) inflammation is a characteristic feature of asthma, driven by T-helper 2 (Th2) immune responses and the production of interleukins (ILs) such as IL-4, IL-5, and IL-13 3, 4, 5.
• T2 inflammation is associated with the presence of eosinophils, IgE, and mucin in the airways, leading to symptoms such as wheezing, coughing, and shortness of breath 6, 7.

Management of Type 2 Inflammation in Asthma

• Biological therapies have been developed to target T2-inflammation in asthma, including monoclonal antibodies and soluble receptors that inhibit Th2 cytokines such as IL-4, IL-5, and IL-13 3, 4.
• Biomarkers such as fractional exhaled nitric oxide (FeNO), serum IgE, and blood and sputum eosinophils can be used to diagnose and monitor T2 inflammation in asthma, and to predict response to treatment 6.
• Targeted biologics have shown efficacy in reducing T2 inflammation and improving symptoms in patients with asthma, particularly those with high levels of Th2 cytokines and eosinophils 5, 6.
• Personalized treatment approaches using targeted biologics and biomarkers may help to improve outcomes for patients with asthma and T2 inflammation 6.

Subphenotypes of Asthma

• Asthma can be divided into distinct molecular phenotypes defined by the degree of T2 inflammation, including "Th2-high" and "Th2-low" subphenotypes 7.
• Th2-high asthma is characterized by high expression of IL-13-inducible genes, eosinophilia, and responsiveness to inhaled corticosteroids, while Th2-low asthma is indistinguishable from healthy controls 7.
• Understanding the molecular mechanisms underlying these subphenotypes may help to develop more effective treatments for patients with asthma and T2 inflammation 5, 7.