Background

Airway neuroplasticity and neurogenic inflammation are part of asthma pathogenesis. To date, few articles have explored these phenomena in human asthma and, to our knowledge, quantitative studies assessing fatal asthma (FA) lungs have never been performed.

Methods

We used lungs obtained from FA cases autopsied at Sao Paulo University Academic Hospital, compared to tissue obtained from individuals that died to non-pulmonary causes. By immunohistochemistry, we quantified peripheral nerves using PGP 9.5, as a pan-neuronal marker, CGRP as a sensory marker, and double stained sections with PGP 9.5 and tryptase/ Congo red dye for mast cell and eosinophil identification, respectively. We quantified eosinophils and mast cells surrounding nerve bundles within radial distance of 50µm from the outer border of the epineurium, and the positive area fraction of PGP 9.5 and CGRP neurons around the large airways.

Results

12 lung samples from FA (41.7% male; 50.5 median years) and 10 from controls (60.0% male; 58.5 median years) were included. We found increased neuronal area in the airway wall of FA individuals (FC=3.0; p<0.0001), and increased CGRP expression in nerve bundles of FA (FC=1.9; p=0.0090). There was a significant increase in mast cells (FC=3.3; p<0.0001) and eosinophils (FC=19.9; p<0.0001) surrounding nerve bundles in FA, with several cells touching the nerve sheath. Positive significant correlations were found between total PGP area with mast cells (Spearman r = 0.57; p<0.01) and eosinophils (Spearman r = 0.74; p<0.01).

Conclusion

We showed, for the first time that, in the airways of FA patients, there is an increased total and sensorial neuronal density and perineural eosinophilic/mast cell inflammation.