Sputum analysis reveals eosinophilic inflammation in difficult-to-control asthma patients with low blood eosinophils and FENO

<b>Introduction:</b> Blood eosinophils and fraction of exhaled nitric oxide (FENO) are inflammatory biomarkers used to identify type 2 airway inflammation which has therapeutic consequences, particularly in severe asthma. Sputum induction and analysis, though an elaborative procedure, may reveal eosinophilic inflammation not detected by these biomarkers. <b>Aim:</b> To investigate the presence of sputum eosinophilia in difficult-to-control asthma patients with low levels of blood eosinophils and/or FENO. <b>Method:</b> 270 adults with uncontrolled asthma (GINA 4-5) referred to our severe asthma centre were included. As part of the total assessment, blood eosinophils, FENO, and sputum eosinophils were measured. Cut-off values were defined for low levels of blood eosinophils (&lt;0.150x10^9/l) and FENO (&lt;25ppb). Sputum eosinophilia was defined as ≥2% eosinophils in induced sputum sample. <b>Results:</b> 166/270 patients had adequate sputum samples. 32% of the 66 patients with low blood eosinophils showed sputum eosinophilia. Of the 70 patients with low FENO 33% had sputum eosinophilia. Remarkably, 8/40 patients with low levels of blood eosinophils as well as FENO showed sputum eosinophils ≥2% (range 2-34%). In the subgroup of 46 patients on daily oral corticosteroids 44% had sputum eosinophilia (range 3.0-22.6%) despite blood eosinophils &lt;0.150x10^9/l. <b>Conclusion:</b> This study shows that a substantial proportion of difficult-to-control asthma patients have sputum eosinophilia without elevated blood eosinophils or FENO. This warns against diagnosing non-eosinophilic or type 2 low asthma, and thus excluding biological treatment, based solely on low levels of blood eosinophils and FENO.