It is believed that in
patients with asthma, the airway narrowing induced by allergen exposure may in
itself be a sufficient stimulus in airway remodeling. Christopher Grainge, PhD,
of University of Southampton School of Medicine, United Kingdom, and colleagues
evaluated airway structural changes in response to the challenges before, and
four days after, the challenge protocol. Forty-eight asthma patients underwent
three inhalation challenges with a single agent at 48-hour intervals.
The two active challenges
were taken-- with either a dust-mite allergen (which causes bronchoconstriction
and eosinophilic inflammation) or methacholine (which causes
bronchoconstriction but no eosinophilic inflammation). The other two control
challenges were either saline alone, or albuterol, followed by methacholine
(neither of which causes bronchoconstriction). Bronchial biopsy specimens were
obtained before and 4 days after completion of the challenges.
The biopsies revealed that dust mite allergen
and methacholine produced similar amount of bronchoconstriction, while an
eosinophilic airway inflammation occurred only in subjects who received
Nevertheless, both the methacholine and allergen groups had significant
airway remodeling as compared to the control groups.
Asthmatic airway remodeling has been
attributed to the effects of eosinophilic inflammation. However, this recent
study strongly indicates that compressive mechanical forces associated with
bronchoconstriction may have an independent effect in promoting remodeling.
The authors reported that,
"Since repeated epithelial stress may lead to remodeling, the prevention of
bronchoconstriction itself should be an important aim of asthma management.
Especially in patients with severe asthma which is not controlled by inhaled
glucocorticoids, the addition of "sustained and safe broncho-protection"
may help in preventing the long-term effects of airway remodeling".
As a concluding note,
authors stated that "This inhaled challenge study supports the hypothesis that
bronchoconstriction contributes to asthmatic airway remodeling, independent of
the effects of eosinophilic inflammation."
The findings from the
study have implications for the better management
of asthma as so far airway remodeling has been associated with a decline in
lung function and the loss of bronchodilator reversibility.