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Independent factors contributing to the daytime and nighttime asthmatic cough refractory to inhaled corticosteroids

Kanemitsu Y1,2, Matsumoto H1, Oguma T1, Nagasaki T1, Ito I1, Izuhara Y1, Tajiri T1, Iwata T1, Mishima M1, Niimi A2

1Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
2Department of Respiratory Medicine, Allergy and Clinical Immunology, Graduate School of Medical Sciences, Nagoya City University, Aichi, Japan

J Investig Allergol Clin Immunol 2019; Vol. 29(1)
doi: 10.18176/jiaci.0281

Background: Cough is a common feature of asthma, which is often resistant to inhaled corticosteroids (ICS). The pathophysiology involved in such refractoriness may be different between the daytime and nighttime asthmatic cough. We sought to identify factors contributing to the daytime and nighttime asthmatic cough refractory to ICS treatment.
Methods: Sixty-seven patients with asthma solely or predominantly presenting with chronic cough were prospectively enrolled from April 2012 to December 2014. At baseline and 12 weeks after ICS treatment, capsaicin cough threshold (C2, C5) and methacholine airway sensitivity and reactivity were examined. Cough visual analogue scales (VAS) and numeric scores were used to evaluate daytime and nighttime cough symptoms separately. The Japanese version of Leicester Cough Questionnaire was also completed. When either cough VAS or numeric scores showed an improvement of ≥50% or ≥2 points, patients were considered responders to ICS treatment.
Results: Fifty-five patients were eligible for evaluation. Subjective cough indices significantly improved at 12 weeks after ICS treatment (p < 0.001). Multivariate analysis revealed that lower C2 significantly contributed to the residual daytime cough (p = 0.04). Meanwhile, methacholine hyperreactivity and lower IgE levels were predictors of the nighttime residual cough (p = 0.002, and p = 0.03, respectively).
Conclusions: Heightened cough sensitivity is an independent factor of the daytime asthmatic cough refractory to ICS. In contrast, airway reactivity and less-allergic nature contribute to the nighttime cough refractory to ICS.

Key words: Asthmatic cough, Cough sensitivity, Airway reactivity, IgE, Inhaled corticosteroids