Alpha-1-antitrypsin inhalation reduces airway inflammation in cystic fibrosis patients

¹ Lung Research Group, Children's Hospital, Ludwig-Maximilians-University, Munich, Germany
² Bayer Healthcare - Biological Products, Q 30, Leverkusen, Germany

^* To whom correspondence should be addressed. E-mail: matthias.griese{at}med.uni-muenchen.de.

	Abstract

Airways of cystic fibrosis (CF) patients are characterized by neutrophils that release high amounts of elastase, overwhelming the local antiprotease shield. Inhalation of ₁-antitrypsin (AAT) may restore the protease-antiprotease dysbalance and attenuate airway inflammation in CF airways.

To assess the best deposition region for inhaled AAT by two different inhalation strategies. To examine the effect of four weeks AAT inhalation on lung function, protease-antiprotease balance and airway inflammation in CF patients.

In a prospective, randomized study, 52 CF patients received a daily deposition of 25 mg AAT by inhalation for four weeks targeting their peripheral or bronchial compartment. Levels of elastase activity, AAT, pro-inflammatory cytokines, neutrophils, IgG fragments and Pseudomonas numbers were assessed in induced sputum before and after the inhalation period.

Inhalation of AAT increased AAT levels and decreased elastase activity levels, neutrophils, pro-inflammatory cytokines and numbers of Pseudomonas, but had no effect on lung function. No difference was found between the peripheral and bronchial inhalation mode.

Although no effect on lung function was observed, the clear reduction of airway inflammation after AAT treatment may precede pulmonary structural changes. The AAT deposition region may play a minor role for AAT inhalation in CF patients.

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