METHODS: Sputum from 294 asthmatic subjects from the Severe Asthma Research Program (SARP) were analyzed. Eosinophils were enumerated on homogenized sputum cytospins. MCs were quantified by qPCR for tryptase. Subjects were classified as MC and Eos ‘Hi’ or ‘Lo’ using the sputum tryptase median and eosinophil count of 2%. Cell phenotypes were analyzed individually and by MC/Eos Hi/Hi, Hi/Lo, Lo/Hi and Lo/Lo with respect to baseline spirometry and exacerbations at baseline and year 1 and 2 of follow-up.
RESULTS: While MCHi and EosHi asthmatics had lower FEV1%predicted than MCLo and EosLo asthma (p<0.001, p=0.007, respectively), the MCHi/EosHi asthmatics had the lowest FEV1%p of all MC/Eos subgroups (overall p<0.0001) and lower than MCHi or EosHi groups. By sputum MC or Eos alone, there was a tendency for more exacerbations in the Hi phenotypes, however, the MCHi/EosHi subgroup had more exacerbations at baseline (overall p=0.0015), and at both year 1 and 2 (each p<0.006) than any other subgroup.
CONCLUSIONS: Compared to SARP subjects without increases in both sputum MCs and eosinophils, those with both MC and eosinophil elevations had lower lung function and more exacerbations at baseline and year 1 and 2 of follow-up. This suggests that MCs and eosinophilic inflammation are separate but overlapping pathologic processes that combine to worsen asthma outcomes.