Inhaled medication and inhalation devices for lung disease in patients with cystic fibrosis: A European consensus

Abstract

In cystic fibrosis inhalation of drugs for the treatment of CF related lung disease has been proven to be highly effective. Consequently, an increasing number of drugs and devices have been developed for CF lung disease or are currently under development. In this European consensus document we review the current status of inhaled medication in CF, including the mechanisms of action of the various drugs, their modes of administration and indications, their effects on lung function, exacerbation rates, survival and quality of life, as well as side effects. Specifically we address antibiotics, mucolytics/mucous mobilizers, anti-inflammatory drugs, bronchodilators and combinations of solutions. Additionally, we review the current knowledge on devices for inhalation therapy with regard to optimal particle sizes and characteristics of wet nebulisers, dry powder and metered dose inhalers. Finally, we address the subject of testing new devices before market introduction.

Cystic fibrosis, atopy, asthma and ABPA

“…24,25 Likewise, the role of bronchodilator responsiveness in patients with CF is not well defined and several studies report important limitations. 26,27 CF patients often show a degree of bronchodilator responsiveness whether they have CF asthma or not. 28,29 Bronchial hyperresponsiveness (BHR) is a typical finding in, but not exclusive to, asthma and even though it is also found in many CF patients, especially those with poorer lung function, the underlying mechanism is still debatable.…”

Einführung des deutschlandweiten Neugeborenenscreenings für Mukoviszidose

“…Dornase alfa ist eine rekombinante DNAse, die inhaliert über einen mukolytischen Effekt die Viskoelastizität des Schleims reduziert. Effekte sind Lungenfunktionsverbesserung und Reduzierung von Exazerbationen [21,40]. Pulmonale Exazerbationen werden in Anwesenheit von pathogenen Bakterien antibiotisch behandelt, um sowohl eine akute Verbesserung herbeizuführen als auch mittelfristig Lungenfunktionsverlust und Bronchiektasen zu vermeiden [41,42].…”

Bronchial Hyperreactivity Related to Inhalation Therapy in Cystic Fibrosis Patients

“…Bronchodilator therapy may increase mucociliary transport, decrease inflammatory damage to the airways, increase exercise tolerance and decrease dyspnea [8,36,37]. Response to short-acting inhaled bronchodilators is variable over time and between patients; [8,17,19,22,24] approximately 50 to 60% of the patients show an improvement of up to 15% in forced expiratory volume in one second (FEV1), 30% of patients show no change and a further 10 to 20% deteriorate with lower FEV1 values after inhalation of a bronchodilator [17].…”

“…Since the human enzyme DNase I was cloned and sequenced in 1990, [42] rhDNase has become the most widely used treatment to reduce sputum viscosity [5,43] rhDNase digests polymeric extracellular DNA, thereby reducing the viscoelasticity of CF sputum and increasing mucociliary transport [36,42]. Long-term use of rhDNase reduces the frequency of pulmonary exacerbations and delays decline in pulmonary function [6,44,45].…”

“…However, CF patients are particularly vulnerable to respiratory infections [3] Dense plaques of mucus become adherent to the epithelial surface from which bacteria cannot be cleared normally [1,3]. While Haemophilus influenzae and Staphylococcus aureus may predominate early in life, approximately 15-30% of children with CF 2-5 years of age and 65-80% of young adults aged 25-34 years are chronically infected with Pseudomonas aeruginosa (Pa) [3,36,[70][71][72]. The association between chronic colonization with Pa and worsening pulmonary function is well known [7].…”