Clinical use of dornase alfa is associated with a slower rate of FEV₁ decline in cystic fibrosis

Abstract

SUMMARY Objectives Randomized controlled trials of dornase alfa have shown forced expiratory volume in 1 second (FEV1) to improve in patients with cystic fibrosis (CF) but have not assessed change in the rate of lung function decline. We assessed the relationship of dornase alfa use and FEV1 decline using the Epidemiologic Study of CF (ESCF). Methodology Patients aged 8–38 years who had been enrolled in ESCF for 2 years when initially treated with dornase alfa were selected if they remained on treatment during the following 2 years. A comparator group included patients aged 8–38 who were not yet reported to have received dornase alfa. For each patient we estimated the annual rate of decline in FEV1 % predicted before and after the index using a mixed-effects model adjusted for age, gender, pulmonary exacerbations, respiratory therapies, and nutritional supplements. Results The dornase alfa group (n = 2,230) had a lower FEV1 % predicted at index and a more rapid decline during the pre-index period. The mean rate of FEV1 decline improved for the dornase alfa group; the improvement was similar in adults and children 8–17 years old but was not statistically significant in adults. The comparator group (n = 5,970) showed no change among adults and an increased rate of decline among children 8–17 years old. Conclusions The use of dornase alfa for a 2-year period is associated with a reduction in the rate of FEV1 decline. These results also demonstrate the value of using an observational study to assess the association of instituting new therapies in the clinical setting with changes in the rate of FEV1 decline in patients with CF.

Abundant DNase I-Sensitive Bacterial DNA in Healthy Porcine Lungs and Its Implications for the Lung Microbiome

“…A dramatic example is that of cystic fibrosis, where a significant proportion of mucus and mucopurulent secretions is associated with DNA (42). In this case, exogenous DNase is actually used as a therapeutic agent that results in decreased mucus viscosity and improved pulmonary function (43)(44)(45). We speculate that constant exposure to bacteria results in some constant levels of DNase-sensitive bacterial DNA in the lungs.…”

Inhaled Therapy in Children

“…Dornaz alfa DNA miktarını azaltarak aminoglikozid antibiyotiklerin etkinliğini artırmaktadır. 33 Hipertonik salin (HS): Hipertonik salin, solunum yolu yüzey sıvısının hidrasyonunu dolayısıyla da mukosiliyer klirensi artırması amacıyla geliştirilmiştir. 34 Ucuz, etkili ve güvenlidir.…”

“…Sadece balgam indüksiyonu için %3'lük, 33 fizyoterapiye yardımcı olarak ise %6-7'lik salin kullanılır. Günde 2 kez, 4-5 ml/kez kullanılır.…”

“…Bronkokonstrüksiyona yol açabileceği için, birçok merkezde, HS öncesi hastalara rutin olarak bronkodilatör verilmesi önerilmektedir. 33 İlk defa HS kullanacak hastalara, ilk doz mutlaka hastanede verilmeli, uygulama öncesinde ve sonrasında spirometri yapılmalıdır. FEV 1 'de kabul edilebilir geçici düşüşün genellikle %15 olduğu düşünülür.…”

The Prognosis of Cystic Fibrosis - A Clinician's Perspective

“…Several medications have been associated to slowing down the rate of FEV 1 decline: dornase alpha (Konstan et al, 2011), ibuprofen (Konstan et al, 1995;, azithromycin (Hansen et al, 2005) and inhaled corticosteroids (De Boeck et al, 2011). This does not mean that all patients will benefit from them.…”