A link between severe asthma and fungi has long been known, but the fundamental basis of this relationship remains unclear. We have shown that fungal proteases induce asthma-like disease in mice by cleaving fibrinogen to create fibrinogen cleavage products that signal through Toll-like receptor 4. Fibrinogen cleavage in asthma is also seen, suggesting that fibrinogen is essential to the asthmatic response. To further define the importance of fibrinogen cleavage in asthma, we investigated the sputum of patients with severe asthma to determine if fibrin is present, and its physiological significance.
Spontaneously produced sputum samples were obtained from 41 severe asthmatic patients. Insoluble material from sputum was cultured for fungi. Four samples were also treated with the fibrin-degrading protease plasmin. Western blot analysis for the D-dimer antigen was then performed.
92.7% of sputa were positive for fungal growth. All samples contained insoluble matter which was solubilized following treatment with plasmin. All samples were positive for the D-dimer antigen.
• Using our new culture technique, fungi can be reliably cultured from the vast majority of sputum samples from asthmatics.
• Fibrin may universally exist in the sputum of severe asthmatics as insoluble aggregates.
• Fibrin complexes produced in the airways may trap fungi to facilitate their clearance as part of an elaborate antifungal defense mechanism.
• Our findings add to the growing body of literature that supports airway surface mycotic infection as a contributing factor in severe asthma.
• We also provide further evidence of activation of the coagulation cascade in asthma.
- AAAAI 2014 (70th)