Combining the Mannitol Test and FeNO in the Assessment of Poorly Controlled Asthma

International guidelines recommend up-titration of anti-inflammatory treatment in asthmatic patients with poor symptom control, but patients without eosinophilic airway inflammation are less likely to benefit from this. The mannitol bronchoprovocation test and fractional exhaled nitric oxide (FeNO) are increasingly used in the diagnostic assessment of asthma, but the utility of combining these tests has not been evaluated.

The aim of this study was to determine the value of combining FeNO and the mannitol test to assess patients with asthma referred for specialist assessment because of poor symptom control.

All patients referred consecutively over a 12-month period for the assessment of asthma at the Respiratory Outpatient Clinic at Bispebjerg Hospital in Copenhagen were examined with bronchial provocation to mannitol, FeNO, and induced sputum.

Among asthmatic patients with partly controlled or uncontrolled symptoms according to Global Initiative for Asthma criteria, only 23% had sputum eosinophilia (eosinophils >2.99%). A positive mannitol test did not increase the likelihood of airway eosinophilia significantly (positive test: 32% vs negative test: 18%, P = .12). However, a positive mannitol test combined with a FeNO > 25 ppb indicated a high likelihood of airway eosinophilia (73%), compared with FeNO > 25 ppb and a negative mannitol test (29%) (P < .05). In contrast, in patients with FeNO < 25 ppb, a positive mannitol test was not associated with airway eosinophilia (sputum eosinophils > 2.99%: positive mannitol test: 0%, negative test: 11%, ns).

Combining the mannitol test and FeNO may aid in the differentiation between eosinophilic and noneosinophilic asthma in patients referred for specialist management because of poorly controlled asthma symptoms.