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]

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 per 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%

Step 1 Therapy:

• Preferred treatment:
  • Short-acting inhaled β2-agonist PRN

Mild Persistent Asthma

Symptoms per day	Symptoms per 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%

Step 2 Therapy:

• Preferred treatment:
  • Low-dose inhaled corticosteroid combined with a short-acting inhaled β2-agonist PRN
• Alternative therapies include:
  • Either cromolyn or nedocromil, or Theophylline, or montelukast, or zafirlukast combined with a short-acting inhaled β2-agonist PRN

Moderate Persistent Asthma

Symptoms per day	Symptoms per 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%

Step 3 Therapy:

• Preferred treatment:

• Medium-dose inhaled corticosteroid combined with a short-acting inhaled β2-agonists PRN, OR
• Low-dose inhaled corticosteroid along with either inhaled long-acting β2-agonists or sustained-release theophylline for nocturnal symptoms combined with a short-acting inhaled β2-agonists PRN

• Alternative therapies include:
  • Low-dose of inhaled steroid combined with long-acting bronchodilators (either inhaled long-acting β2-agonists or sustained-release theophylline) combined with a short-acting inhaled β2-agonists PRN

Severe Persistent Asthma

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

Step 4 Therapy:

• Preferred treatment:
  • Medium-dose inhaled corticosteroid combined with inhaled long-acting β2-agonists
• Alternative therapies include:
  • Medium-dose inhaled corticosteroid combined with long-acting bronchodilators (such as inhaled β2-agonists or sustained-release theophylline used alone or in combination) combined with a short-acting inhaled β2-agonists PRN

Step 5 Therapy:

• Preferred treatment:
  • High-dose inhaled corticosteroid combined with inhaled long-acting β2-agonists and omalizumab in patients who have allergies

Step 6 Therapy:

• Preferred treatment:
  • High-dose inhaled corticosteroid combined with oral corticosteroids, inhaled long-acting β2-agonists, and omalizumab in patients who have allergies

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.