Neutrophils in chronic inflammatory airway diseases: can we target them and how?

Many lung diseases, such as severe asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), bronchiectasis and infiltrative pulmonary diseases are associated with chronic neutrophilic inflammation. These diseases are common, can be severe and, together, represent a major economic burden and worldwide public health challenge. In addition to chronic handicap, these diseases also feature recurrent episodes of acute worsening of inflammatory symptoms, known as exacerbations, a leading cause for progressive lung impairment. Prevention and prompt management of exacerbations is strongly recommended since they often influence disease prognosis. In COPD 1, the high number of neutrophils recruited to the lungs is known to positively correlate with the thickness of the sputum 2; to account, in large part, for the poor response to corticosteroid treatment 3; and to associate with poorer prognosis 4. Recruited neutrophils have been shown to infiltrate the airway epithelium and submucosal glands 2 from the proximal to the distal part of the airway tree. Activation of lung neutrophils leads to the release of granule proteins, including human neutrophil elastase (HNE) and myeloperoxidase (MPO) 5. HNE and MPO contribute to the bronchial inflammation and to structural changes such as peribronchiolar fibrosis and emphysema 6, 7. None of the currently available therapies has any effect on the release and/or pathological activity of these cytotoxic …