What is hyperactive airway disease?

Hyperreactive Airway Disease

Hyperreactive airway disease refers to a condition characterized by airways that narrow too easily or excessively in response to various stimuli, manifesting as exaggerated bronchial constriction to triggers that would not cause comparable narrowing in healthy individuals. 1, 2

Core Pathophysiology

Hyperreactive airway disease encompasses two distinct but related components that require separate consideration 3:

• Hypersensitivity: Airways respond at lower concentrations or doses of constrictor stimuli (measured as PC20 or PD20 on bronchial provocation testing) 1, 3
• Excessive airway narrowing: Airways achieve greater maximal degrees of narrowing beyond what occurs in healthy subjects, with failure to reach a plateau in the dose-response curve 4, 3

The underlying mechanisms involve airway smooth muscle dysfunction, where the muscle exhibits altered contractile behavior and increased responsiveness to acetylcholine and other bronchoconstrictors 5. This is accompanied by airway inflammation that enhances the hyperresponsive state 1.

Clinical Manifestations

Patients with hyperreactive airways typically present with 6, 2:

• Episodic wheezing, coughing, and shortness of breath that varies in intensity 6
• Symptoms triggered by: environmental allergens, irritants, cold air exposure, exercise, or viral infections 4
• Variable and reversible airflow obstruction that may resolve spontaneously or with bronchodilator therapy 6

Diagnostic Approach

Bronchial provocation testing with methacholine is the gold standard for confirming airway hyperresponsiveness 2:

• PC20 >16 mg/mL or PD20 >400 μg rules out current asthma with high sensitivity 2
• PC20 <1 mg/mL or PD20 <25 μg is highly specific (diagnostic) for asthma but insensitive 2
• Testing must use standardized 2-minute tidal breathing method with controlled nebulizer performance 2

Additional diagnostic considerations include 4:

• Spirometry demonstrating reversible airflow limitation: FEV1 improvement ≥12% and ≥200 mL after bronchodilator 7
• Peak flow variability >15% over 2 weeks supports the diagnosis 7
• Airway smooth muscle hypertrophy may be present on pathologic examination 4

Associated Conditions

Hyperreactive airways occur in multiple clinical contexts 4:

• Asthma: The prototypical hyperreactive airway disease, characterized by chronic airway inflammation and episodic reversible obstruction 6, 1
• Chronic lung disease of infancy (CLDI): Demonstrates airway hyperreactivity with bronchodilator responsiveness as early as 3 days of age 4
• Post-infectious states: Airway hyperreactivity can develop following respiratory infections, with mechanisms involving airway inflammation 4
• Nerve agent exposure: Acetylcholinesterase inhibition causes severe bronchial constriction through heightened muscarinic activity 4

Treatment Principles

Management targets both the hypersensitivity and excessive narrowing components 3:

• Bronchodilators (β-agonists, anticholinergics) address acute airway narrowing 4
• Anti-inflammatory therapy with inhaled corticosteroids reduces underlying airway inflammation and hyperresponsiveness 7
• Avoidance of triggers (allergens, irritants, cold air) prevents exacerbations 6

For acute severe bronchospasm unresponsive to standard therapy 4:

• Aerosolized albuterol 2.5 mg in 3 mL saline 4
• Ipratropium bromide 0.5 mg similarly prepared 4
• Intravenous methylprednisolone 125 mg three times daily for refractory cases 4

Important Caveats

• Airway hyperresponsiveness persists even after intensive anti-inflammatory treatment in many patients, suggesting structural airway alterations beyond reversible inflammation 4
• Hypersensitivity and excessive narrowing may have different underlying mechanisms and require distinct therapeutic approaches 3
• Pyridostigmine (acetylcholinesterase inhibitor) can cause dose-dependent airway resistance increases and should be used cautiously in patients with pre-existing hyperreactive airway disease 4
• Cold air exposure and hypoxia can trigger airway constriction in susceptible individuals 4