Asthma classification

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Lakshmi Gopalakrishnan, M.B.B.S. [2] Anum Ijaz M.B.B.S., M.D.[3]

Overview

Asthma is classified into atopic and non-atopic types based on the onset of symptoms. Atopic refers to early-onset whereas non-atopic refers to late-onset. Despite the differentiation, a significant degree of overlap exists between the two types. The severity of symptoms is further classified based on the GINA severity grades into mild intermittent, mild persistent, moderate persistent and severe persistent asthma.

Classification

Based on Symptom Onset

Early-onset Asthma (Atopic, Allergic, Extrinsic)

• Early-age of onset
• Atopic individuals have an increased predisposition
• Environmental allergens play a strong role in the pathogenesis
• Positive personal and/or family history of atopic diseases such as allergic rhinitis, urticaria and eczema
• Laboratory tests may reveal increased serum IgE levels, positive skin test to specific aero-allergens and a positive bronchoprovocation test

Late-onset Asthma (Non-Atopic, Idiosyncratic, Intrinsic)

• Late-age of onset
• Non- atopic individuals have an increased predisposition
• Indoor allergens play a strong role in the pathogenesis
• Negative personal and/or family history of allergic diseases
• Laboratory tests may reveal normal serum IgE levels and a negative bronchoprovocation test

Based on GINA Severity Grade

Asthma is classified into four subgroups: mild intermittent, mild persistent, moderate persistent and severe persistent based on the Global Initiative for Asthma - GINA severity grades.

Mild Intermittent Asthma

Symptoms per day	Symptoms at night	PEF or FEV1	PEF variability
Less than once a week Brief exacerbations Asymptomatic and normal PEFR between exacerbations	Less than or equal to twice a month	≥ 80% of predicted normal	< 20%

Mild Persistent Asthma

Symptoms per day	Symptoms at night	PEF or FEV1	PEF variability
Symptoms more than twice a week but less than once a day Exacerbations may affect activity and sleep.	Greater than or equal to twice a month	≥ 80%	20-30%

Moderate Persistent Asthma

Symptoms per day	Symptoms at night	PEF or FEV1	PEF variability
Daily symptoms Exacerbations more than twice a week Exacerbations may affect activity and sleep Daily use of bronchodilators	More than once a month	60-80%	≥ 30%

Severe Persistent Asthma

Symptoms per day	Symptoms at night	PEF or FEV1	PEF variability
Continued symptoms Frequent exacerbations Limited physical activity	Frequent	≤ 60%	≥ 30%

Guidelines for Diagnosis and Management of Asthma Based On The National Heart, Blood, and Lung Institute Expert Panel Report 3 (EPR3)

Severity Components	Intermittent	Persistent Asthma
		Mild	Moderate	Severe
Symptoms	Less than 1 day/week	More than 2 days/week Not daily	Daily	Daily Throughout the day
Nocturnal Symptoms	Less than 2 times/month	3 to 4 times/month	More than 1 time/week Not every night	Every night
Interference w/ Activity	Minimal to none	Minor limitation of activity	Some limitation of activity	Severe limitation of activity
Short-Acting Beta-Agonist Use	Less than 2 days/week	More than 2 days/week but not daily Not more than once/day	Daily	Several times/day
Pulmonary Function Test	Normal FEV1 between exacerbations FEV1 > 80% predicted FEV1/FVC normal	FEV1 > 80% predicted FEV1/FVC normal	FEV1 > 60% but < 80% predicted FEV1/FVC reduced by 5%	FEV1 < 60% predicted FEV1/FVC reduced by > 5%
Recommended Treatment Strategy	STEP 1 Preferred: Short-acting beta-agonist PRN	STEP 2 Preferred: Low-dose inhaled corticosteroids Alternative: Cromolyn, Leukotriene receptor antagonist, Nedocromil, or Theophylline	STEP 3 Preferred: Either low-dose inhaled corticosteroids + long-acting beta-agonist OR Medium-dose inhaled corticosteroid Alternative: Low-dose inhaled corticosteroid + either Leukotriene receptor antagonist, Theophylline, or Zileuton	STEP 4 Preferred: Medium-dose inhaled corticosteroid + long-acting beta-agonist Alternative: Medium-dose inhaled corticosteroids + either Leukotriene receptor antagonist, Theophylline, or Zileuton STEP 5 Preferred: High-dose inhaled corticosteroids + long-acting beta-agonist Consider adding Omalizumab for patients with allergies STEP 6 Preferred: High-dose inhaled corticosteroids + long-acting beta-agonist + oral corticosteroids Consider adding Omalizumab for patients with allergies
Step down if possible and asthma is controlled for at least 3 months Step-up if needed, but first check adherence, environmental control, and comorbidities
In each step, patient education, environmental control, and management of comorbidities are important. In STEP 2 - 4, consider subcutaneous allergen immunotherapy for patients with allergic asthma
Short-acting beta-agonist as needed for symptoms. Up to 3 treatments at 20 minute intervals as needed. A short course of oral systemic corticosteroids may be needed. Use of a short-acting beta agonist for >2 days a week for symptom control indicates inadequate control and the need to step up therapy.

Severe Refractory Asthma

1. Definition

It is defined as asthma that remains uncontrolled despite treatment with high-dose inhaled corticosteroids (ICS) plus one or more additional controller therapies (such as long-acting β-agonists), in patients who are adherent to therapy, use correct inhaler technique, and receive treatment for comorbidities that may exacerbate asthma, including allergic rhinitis, chronic rhinosinusitis, and gastroesophageal reflux disease.

Patients with severe refractory asthma may experience accelerated loss of lung function and have higher mortality rates associated with exacerbations compared with individuals with milder asthma.

Epidemiology

Severe refractory asthma affects approximately 1% to 5% of patients with asthma.

Most patients with severe refractory asthma in the United States are managed exclusively in primary care, and only 50.4% see an asthma specialist within a year following an asthma exacerbation requiring emergency department or hospital care.

Type 2 (T2)–high asthma is the most common subtype, characterized by elevations in IL‑4, IL‑5, IL‑13, eosinophils, and fractional exhaled nitric oxide (FeNO). This subtype carries a higher risk of exacerbations and is more responsive to biologic therapies, though access is limited because specialists prescribe more than 90% of biologics.

2. Diagnosis

All patients with severe refractory asthma should undergo the following diagnostic evaluation:

• Pulmonary function testing (pre- and post-bronchodilator) to assess airflow obstruction, bronchodilator responsiveness, and monitor lung function decline associated with airway remodeling.

• Laboratory and biomarker testing, including complete blood count with differential to assess eosinophils, total serum IgE, and fractional exhaled nitric oxide (FeNO), available in many asthma clinics and some primary care practices.

• Environmental allergy testing using skin prick testing or allergen-specific IgE to identify sensitization to pollen, dust mites, mold, pet dander, and other allergens. These help identify allergic asthma, guide exposure reduction strategies, and determine eligibility for anti-IgE therapy (omalizumab). Allergy test interpretation should be performed by allergists, as positive predictive value may be as low as 50% unless supported by clinical history.