Abstract
Asthma is a chronic inflammatory airway disease resulting in airflow
obstruction, which in part can become irreversible to conventional
therapies, defining the concept of airway remodeling. The introduction
of biologics in severe asthma has led in some patients to the complete
normalization of previously considered irreversible airflow obstruction.
This highlights the need to distinguish a “fixed” bronchial
obstruction due to structural changes unresponsive to current therapies,
from a “reversible” one as demonstrated by lung function normalization
during biological therapies not previously obtained even with high dose
systemic glucocorticoids. The mechanisms by which exposure to
environmental factors initiates the inflammatory responses that trigger
airway remodeling are still incompletely understood. Alarmins represent
tissue-derived cytokines that initiate immunologic events leading to
inflammatory airway remodeling. Biological therapies can improve airflow
obstruction by addressing these airway inflammatory changes. In
addition, biologics might prevent and possibly even revert “fixed”
remodeling due to structural changes. Hence, it appears clinically
important to separate the therapeutic effects (early and late) of
biologics as a new paradigm to evaluate the effects of these drugs and
future treatments on airway remodeling in severe asthma.