Table 2.
Clinical Phenotypes and Proposed Endotypes of Eosinophilic and Noneosinophilic Asthma
| Phenotype | Clinical Characteristics | Biomarkers | Lung Physiology | Targeted Treatments | Possible Mechanism (Endotype) |
|---|---|---|---|---|---|
| Early-onset, allergic asthma | Childhood onset, allergen triggers, allergic rhinitis | Aeroallergen-specific IgE, elevated total IgE, elevated FeNO | Bronchospasm with allergen exposure | ICS, anti-IgE, inhibition of IL-4/13 pathways | IgE-mediated Th2/T2 inflammation |
| Early onset, obesity exacerbated | Obesity, childhood onset, allergy | Allergen-specific IgE, eosinophilia | Airway hyperresponsiveness | Weight loss | Eosinophil recruitment, airway remodeling |
| Aspirin-exacerbated respiratory disease | Adult onset, severe asthma, nasal polyposis | Eosinophils, leukotrienes | Bronchospasm with aspirin/NSAID exposure | Aspirin desensitization, leukotriene inhibitors, systemic steroids | Eicosanoids |
| Allergic bronchopulmonary mycosis | Adult onset, severe asthma, pronounced mucus production | High IgE, eosinophils in blood and sputum, specific IgE to mold | Fixed airflow obstruction can develop with bronchiectasis and/or fibrosis | Systemic steroids, antifungals, anti-IgE | Fungal colonization with Th2/T2 and mixed responses |
| Asthma-predictive index-positive preschool wheezer | >3 episodes of wheeze per year, 1 major or 2 minor atopy characteristics | Eosinophils, aeroallergen-specific IgE | Potential increased risk of loss of lung function | ICS | Th2/T2 inflammation, eicosanoids |
| Severe late onset hypereosinophilic | Adult onset, severe exacerbations, less atopic | Eosinophils in blood and sputum, sinusitis | Variably steroid-sensitive obstruction | Systemic or inhaled steroids, anti–IL-5 agents | ILC2 activation; dual-positive Th2/Th17 inflammation |
| Exacerbation prone | Frequent exacerbations, sinusitis, GERD | Eosinophils in blood | Lower lung function | Antieosinophil | Eosinophil-driven inflammation |
| Exercise-induced asthma | Symptoms develop with or after exercise, more so in cold, dry air | Some aeroallergen-specific IgE, variable eosinophils in blood and sputum | Bronchospasm with sustained exercise | ICS, systemic steroids, leukotriene antagonists, reduction of exercise intensity | Th2/T2 in some, but not clear in others |
| Neutrophilic | Adult onset, variable severity | Elevated neutrophils in blood and sputum | Reduced lung function, less bronchodilator reversibility | Steroids are variably effective; antibiotics | Lack of Th2/T2 inflammation; Th17, infection, inflammasome |
| Obesity induced | Adult onset predominantly female, very symptomatic | Lack of Th2 biomarkers, IL-6, leptin | Variable restriction, bronchial hyperreactivity | Weight loss, lower-fat diet, antioxidants | IL-6, oxidative stress pathways |
| Paucigranulocytic | Mild and severe | Lack of airway inflammation | Fixed airflow obstruction, bronchial hyperreactivity | Antimuscarinics, β2 antagonists, bronchial thermoplasty | Airway remodeling, increased smooth muscle tone, thickened basement membrane |
| Asthma with smoking | Current or former tobacco smoke exposure, worse quality of life and more symptoms, corticosteroid insensitivity | Less eosinophilic, more neutrophilic | Fixed airflow obstruction | Smoking cessation, steroids, antimuscarinic antagonists | Epithelial dysfunction, altered histone deacetylase |
Definition of abbreviations: FeNO = fraction of exhaled nitric oxide; GERD = gastroesophageal reflux disease; ICS = inhaled corticosteroids; ILC2 = innate lymphoid cells type 2; NSAID = nonsteroidal antiinflammatory drug; T2 = type 2; Th2 = T-helper type 2 cell; Th17 = T-helper type 17 cell.