Abstract
Background: Abnormal wound repair is implicated in asthma pathogenesis.
The nose is the point of first contact with the environment, yet wound
repair ability of the nasal epithelium has received little attention. We
sought to determine the impact of atopy and asthma on wound healing of
nasal epithelium. Methods: Primary nasal epithelial cells harvested from
adult volunteers classified into mutually exclusive groups [healthy
(H), atopic non-asthmatic (ANA), non-atopic asthmatic (NAA) and atopic
asthmatic (AA)] were grown into well-differentiated epithelium at the
air-liquid interface. The ability of the epithelium to heal a mechanical
wound was determined under various conditions. Results: Wound healing
rate (%/hour) was slowest in ANA (2.9±1.8, vs 4.3±1.9 in H, p=0.02).
Healing rates of AA (3.8±1.0) and NAA (4.1±1.1) were not different from
H. Exogenous IL-13 slowed healing (2.2±1.1 vs 4.0±1.3,
p<0.002) across all subject groups (p<0.001).
However, blocking endogenous IL-13 had no effect on wound healing
(p=0.68). Blocking endogenous EGF markedly slowed wound healing (0.6±0.4
vs 4.1±1.9, p=0.006), whereas adding exogenous EGF had no effect
(p=0.58). Wound healing was significantly faster (4.4±1.0 vs 3.4±0.9,
p=0.013) in subjects (6 AA, 9 NAA) who took regular inhaled
corticosteroids prior to cell harvesting. Infecting epithelial cultures
with RSV 6 days prior to wounding slowed healing in all groups
(p<0.001). Prior inhaled steroids also improved wound healing
following RSV infection (P<0.001). Conclusion: Nasal
epithelium from atopic adults heal wounds more slowly. Inhaled
corticosteroids taken in vivo prior to harvest influence their responses
in vitro, improving wound healing.