Mast cells are a hallmark of airway hyperresponsiveness or airway allergy. While they also have protective functions, mast cells play a critical role in the pathophysiology of asthma. Histamines, leukotrienes and cytokines released by activation of the mast cells cause bronchoconstriction, secretion of mucus and swelling of the airway mucosa resulting in acute asthma symptoms.¹ However, Kjarsgaard et al noted in a study that “their sub-mucosal location and lack of trans-luminal migration makes it challenging to enumerate in sputum”.²

They carried out a study to evaluate activity of mast cells in patients with moderate to severe asthma. For this they collected sputum samples from 98 asthma patients and 18 healthy persons who had no diagnosed respiratory disease and had never smoked to measure the tryptase levels by ELISA in cell-free supernatant, which were correlated with cells in the sputum. Based on the cut-off level of 0.66ng/ml, 49 patients were categorized as having high serum tryptase and an equal number of them as having low tryptase.

Patients with high sputum tryptase levels tended to be older and have poor lung function. They had lower total cell count and elevated eosinophils (%) in the sputum. When asthmatic patients were categorized according to the airway inflammatory cell types, majority (36.7%) of those with high tryptase levels had an eosinophilic airway inflammation; 28% had neutrophilic, 20% had mixed granulocytic, while 14.3% had paucigranulocytic sputum with normal cell counts. When asthma patients and healthy individuals were compared, the absolute detectable tryptase levels were significantly higher in the eosinophilic (sputum eosinophil≥3%) and the paucigranulocytic (sputum eosinophil<3%) sputum. Nine patients experienced saline induced bronchoconstriction with decline in FEV1 ≥15%. Of these, five patients with paucigranulocytic and two with mixed granulocytic sputum had tryptase levels above the cut-off (mean 1.2 ng/mL).

These findings show tryptase levels as indicators of mast cell activity and demonstrate a correlation between tryptase levels in the sputum of patients with eosinophilic and mixed granulocytic airway inflammation with enhanced hyperresponsiveness of the airways, including those with normal sputum cell counts.

References

1. Bradding P. Mast cell regulation of airway smooth muscle function in asthma. Eur Respir J. 2007 29: 827-830; DOI: 10.1183/09031936.00017707.
2. Kjarsgaard M, et al. Sputum tryptase in patients with moderate to severe asthma. Am J Respir Crit Care Med 2023;207:A1301. https://doi.org/10.1164/ajrccm-conference.2023.207.1_MeetingAbstracts.A1301.