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Obesity and aspirin intolerance are risk factors for difficult-to-treat asthma in Japanese non-atopic women


Correspondence: Yuma Fukutomi, Clinical Research Center for Allergy and Rheumatology, Sagamihara National Hospital, 18-1 Sakuradai, Minami-ku, Sagamihara, Kanagawa 252-0392, Japan. E-mail:



Asthma is a clinical syndrome characterized by variabilities in disease expression and severity. The pathophysiological mechanism underlying anti-asthma treatment resistance is also assumed to be different between disease phenotypes.


To elucidate the effect of gender and atopic phenotype on the relationship between clinical factors and the risk of treatment resistance.


We compared outpatients with difficult-to-treat asthma (DTA; n = 486) in a tertiary hospital for allergic diseases in central Japan with those with controlled severe asthma (n = 621) with respect to clinical factors including body mass index (BMI) and aspirin intolerance using multivariate logistic regression analysis stratified by gender and atopic phenotype.


When analysis was performed on the entire study populations, obesity (BMI ≥ 30 kg/m2; adjusted odds ratio (OR) 1.92; 95% confidence interval (95% CI: 1.07–3.43) and aspirin intolerance (OR: 2.56, 95% CI: 1.44–4.57) were found to be the significant risk factors for DTA. However, after the stratification by gender and atopic phenotype, the association between obesity and DTA was significant only in women (OR: 2.76, 95% CI: 1.31–5.78), but not in men (OR: 1.03, 95% CI: 0.38–2.81), and only in non-atopics (OR: 4.03, 95% CI: 1.15–14.08), but not in atopics (OR: 1.54, 95% CI: 0.79–3.02). The similar gender and phenotypic differences were also observed in the association between aspirin intolerance and DTA: namely, the association was significant only in women (OR: 3.96, 95% CI: 1.84–8.50), but not in men (OR: 1.19, 95% CI: 0.46–3.05); and only in non-atopics (OR: 5.49, 95% CI: 1.98–15.19), but not in atopics (OR: 1.39, 95% CI: 0.65–2.98).

Conclusions and Clinical Relevance

Significant associations of obesity and aspirin intolerance with DTA were observed only in women and in non-atopics. These findings suggest that a phenotype-specific approach is needed to treat patients with DTA.