1. Introduction
Impaired mucociliary clearance characterizes lung disease in cystic fibrosis (CF). In CF patients, the alteration of the cystic fibrosis transmembrane conductance regulator (CFTR) results in defects of the electrolytes transport, which then cause increased water reabsorption across respiratory epithelia1,2. This may induce dehydration of the airways’ surface liquid which may prevent normal mucus clearance. In the airways, alterations of the ionic transport lead to the production of thick secretions with obstruction of the glandular ducts and progressive epithelial damage. In pediatric CF patients, recurrent bacterial infections and chronic colonisations induce persistent inflammatory response, progressive fibrosis with loss of lung parenchyma function3,4.
Purulent pulmonary secretions of individuals with cystic fibrosis contain very high concentrations of extracellular DNA released by degenerating leukocytes that accumulate in response to these infections5.
Cystic fibrosis is characterized by a progressive decline in lung function over the patient’s lifetime and by a chronic inflammation in the pulmonary tissues. The cycle of chronic obstruction, infection, and inflammation ultimately contributes to the occurrence of respiratory failure, which accounts for more than 80% of mortality in patients with CF6. Therefore, most patients require mucoactive agents and additional therapeutics that target downstream manifestations of the disease.
Strategies to enhance sputum clearance are a major therapeutic aim in CF and treatment with dornase alfa has been widely accepted to be of benefit7. Hydrolyzing the DNA in CF patients’ mucus and reducing sputum viscoelasticity, this mucoactive agent is effective in reducing the decline in lung function and decreasing the number of pulmonary exacerbations8.
Despite the inclusion of dornase alfa in the recommended therapies for CF, databases managed by the main Cystic Fibrosis Societies show that significant differences exist between countries in its prescription for CF treatment in current clinical practice.
In the United States, according to the Cystic Fibrosis Foundation (CFF) Patient Registry, dornase alfa was used by the vast majority of individuals with CF (87%) in 20179. These use rates of dornase alfa are much higher than those observed in the same period of time in European countries. Italy, Spain, Sweden and some eastern countries, are among countries with the lowest use of this mucoactive agent in Europe. Indeed, the most recent Patient Registry Annual data report of the European Cystic Fibrosis Society (ECFS) shows that in 2017 the use rates of dornase alfa, seen in all CF patients, were 33% in Italy and 62% in United Kingdom10.
Considering the current scenario of dornase alfa use in different geographic areas, the aim of this multicenter work was to investigate the level of consensus among specialists from Italian CF Centers on appropriateness of therapeutic use of dornase alfa for CF patients. Indeed, the evidence of how the Italian CF experts are dealing with the use of dornase alfa may contribute to expand the global discussion within the international scientific community on factors that influence the prescription of mucolytic agents in CF clinical practice.
Therefore, our final goal was to promote the most appropriate use of dornase alfa to improve lung function and long-term outcomes in people with CF, in alignment with recommendations of the international pulmonary guidelines.