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.