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Cough and Airway Responses to Direct and Indirect Challenges: An Integrative Review
Maria Korovina1,2, Nicolle J Domnik1,2,3, M Diane Lougheed1,2,3
1Ms. Korovina, Prof. Domnik, and Dr. Lougheed are affiliated with Division of Respirology, Department of Medicine, Queen's University, Kingston, Ontario, Canada.
Respiratory Care
|May 4, 2026
Summary
Chronic cough can be the sole symptom of asthma. New research explores cough variant asthma and a related condition, COUGH, using indirect challenges to differentiate these airway disease phenotypes.
Area of Science:
- Pulmonology
- Allergy and Immunology
- Respiratory Medicine
Background:
- Classic asthma presents with wheezing, dyspnea, chest tightness, and/or cough.
- Cough can be the primary or sole symptom, known as cough variant asthma.
- Diagnosing and managing cough in asthma is challenging due to complex physiology.
Purpose of the Study:
- To explore pathophysiological distinctions between classic asthma, cough variant asthma, and COUGH.
- To investigate the utility of indirect inhalation challenges in differentiating these airway phenotypes.
- To highlight opportunities for insight using impulse oscillometry and bronchodilation/bronchoprotection measurements.
Main Methods:
- Review of previous studies on methacholine (MCh) challenges.
- Emphasis on indirect inhalation challenges: mannitol, hypertonic saline, and eucapneic voluntary hyperventilation.
- Examination of impulse oscillometry and deep inspiration effects.
Main Results:
- Cough variant asthma excludes normal airway sensitivity to MCh.
- COUGH involves normal airway sensitivity but exhibits small airway obstruction, dynamic hyperinflation, and gas trapping.
- Indirect challenges may offer greater specificity for asthma diagnosis and phenotype differentiation.
Conclusions:
- COUGH may represent a distinct airway disease phenotype.
- Indirect inhalation challenges and impulse oscillometry can provide further insight into asthma-related phenotypes.
- Differentiating these phenotypes is crucial for accurate diagnosis and management.
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