Effect of Hypertonic Saline on Lung Function as Add-on Treatment in People With Cystic Fibrosis Receiving Dornase Alfa: A Cystic Fibrosis Foundation Patient Registry Analysis.

BACKGROUND: Introduction of novel therapies for cystic fibrosis (CF) raises the question of whether traditional treatments can be withdrawn. Nebulized hypertonic saline (HS) potentially could be discontinued in patients receiving dornase alfa (DA). RESEARCH QUESTION: In the era before modulators, did people with CF who are F508del homozygous (CFF508del) and who received DA and HS have better preserved lung function than those treated with DA only? STUDY DESIGN AND METHODS: Retrospective analysis of the Cystic Fibrosis Foundation Patient Registry data (2006-2014). Among 13,406 CFF508del with data for at least 2 consecutive years, 1,241 CFF508del had spirometry results and were treated with DA for 1 to 5 years without DA or HS during the preceding (baseline) year. Absolute FEV1 % predicted change while receiving DA and HS, relative to treatment with DA only, was the main outcome. A marginal structural model was applied to assess the effect of 1 to 5 years of HS treatment while controlling for time-dependent confounding. RESULTS: Of 1,241 CFF508del, 619 patients (median baseline age, 14.6 years; interquartile range, 6-53 years) received DA only and 622 patients (median baseline age, 14.55 years; interquartile range, 6-48.1 years) were treated with DA and HS for 1 to 5 years. After 1 year, patients receiving DA and HS showed FEV1 % predicted that averaged 6.60% lower than that in patients treated with DA only (95% CI, -8.54% to -4.66%; P < .001). Lower lung function in the former relative to the latter persisted throughout follow-up, highlighting confounding by indication. After accounting for baseline age, sex, race, DA use duration, baseline and previous year's FEV1 % predicted, and time-varying clinical characteristics, patients treated with DA and HS for 1 to 5 years were similar to those treated with DA only regarding FEV1 % predicted (year 1: mean FEV1 % predicted change, +0.53% [95% CI, -0.66% to +1.71%; P = .38]; year 5: mean FEV1 % predicted change, -1.82% [95% CI, -4.01% to +0.36%; P = .10]). INTERPRETATION: In the era before modulators, CFF508del showed no significant difference in lung function when nebulized HS was added to DA for 1 to 5 years.

Intrapleural administration of DNase alone for pleural empyema.

INTRODUCTION: Pleural empyema is a severe complication of various diseases. The essential is the inserting a drain into the pleural cavity and evacuation of the pus. Sometimes the pus is very thick and its evacuation and re-expansion of the lung is very difficult. METHODS: We report a group of 10 patients with intrapleural administration of Pulmozyme (dornase alpha) in dosages of either 2.5 mg once or on two separate occasions. All of the patients had a chest tube inserted into the pleural cavity. Measurement of viscosity was done before and after the instillation of the dornase alpha. RESULTS: In six patients dornase alfa was introduced into the pleural cavity once. Three of them received this on the 4th whilst the rest were treated with the agent on the 6th day. Four patients received the dornase alpha twice because of the small amount of drainage fluid after the previous instillation. Five patients were discharged from hospital with complete re-expansion of their lungs. Two patients were qualified for a surgical operation since the lung was trapped and did not re-expand. Three patients had to be discharged with a drain as a result of incomplete re-expansion of the lung. In all the patients the density of the pus after administering the dornase alpha decreased and the amount of the pus drainage increased. CONCLUSIONS: Dornase alpha may be used in some patients with pleural empyema with good results.

Successful treatment of atelectasis with Dornase alpha in a patient with congenital muscular dystrophy.

A 28-year-old neuromuscular patient chronically treated with nocturnal noninvasive ventilation developed pulmonary lobar atelectasis and daytime hypoxemia. Twenty four-hour 5L/min oxygen was begun, while mechanical cough assist aids were applied for seven days. In the following three days, treatment with nebulized Dornase alpha (rhDNase) b.i.d. was tested, without any significant improvement. On 11 and 13th days rhDNase was instilled by flexible bronchoscopy. A rapid resolution of the atelectasis was observed with relief of hypoxemia, without significant side effects. On day 16 the patient was discharged without oxygen requirements. In non-intubated neuromuscular patients with atelectasis who do not respond successfully to non-invasive treatments intrabronchial instillation of rhDNase may safely help to improve airway clearance.

Efecto de la rhDNasa sobre la obstrucción bronquial irreversible en adultos con asma grave / Effect of rhDNase on irreversible bronchial obstruction in severe adult asthma

Introducción: En algunos pacientes asmáticos la obstrucción de las vías aéreas no puede ser revertida por tratamiento broncodilatador y/o corticosteroideo. Esta obstrucción irreversible se ha atribuido a la remodelación de las vías aéreas, pero otros mecanismos, como el taponamiento mucoso, no se han explorado. Objetivo: Evaluar si la rhDNasa, enzima ampliamente usada para fluidificar el moco respiratorio en la fibrosis quística, mejora las variables espirométricas y la calidad de vida de pacientes con asma grave. Pacientes y métodos: Diez pacientes adultos (6 mujeres) con asma grave, dependientes de corticosteroides, recibieron nebulizaciones diarias de 2.5 mg de rhDNasa durante 14-28 días. Se realizaron espirometrías por lo menos cada semana, evaluando la capacidad vital forzada (FVC), el volumen espiratorio forzado al primer segundo (FEV1, la relación FEV1/ FVC y el flujo espiratorio máximo (PEF). Los cambios espirométricos se evaluaron mediante análisis de regresión. Se aplicó un cuestionario de calidad de vida antes y al final del tratamiento. Resultados: Las variables espirométricas no cambiaron en la mayoría de los pacientes. Sin embargo, al menos un paciente tuvo mejoría de la función pulmonar, de acuerdo con las pendientes ascendentes estadísticamente significativas en la FVC, el FEV1 y la relación FEV1/FVC. Aunque otros sujetos también tuvieron cambios ascendentes (2 pacientes) o descendentes (2 pacientes) de las pendientes, éstos sólo ocurrieron en una de las variables espirométricas. Como grupo, los pacientes mostraron tendencia a la mejoría en la calidad de vida. Conclusiones: Aunque la rhDNasa no modifica la obstrucción bronquial irreversible en la gran mayoría de los pacientes con asma grave, una pequeña proporción de ellos podría obtener algún efecto benéfico.

Background: In some asthma patients airway obstruction can not be reverted by bronchodilator and/ or corticosteroid treatment. This irreversible obstruction has been attributed to the remodeling process of airways, but other mechanisms such as mucus plugging have not been explored. Objective: To evaluate if rhDNase, an enzyme extensively used to fluidize the mucus in cystic fibrosis, improves spirometric variables and quality of life of asthmatic patients. Patients and methods: Ten adult patients (6 females) with severe corticosteroid-dependent asthma received daily nebulizations of 2.5 mg rhDNase during 14-28 days. Spirometries were performed at least at weekly intervals to evaluate the forced vital capacity (FVC), forced expiratory flow at the first second (FEV1, the FEV1/FVC ratio and peak expiratory flow (PEF). Changes in spirometric variables were assessed by regression analysis. An asthma quality of life questionnaire was applied before and at the end of treatment. Results: Spirometric variables did not change in most patients. However, pulmonary function improved in one patient, according to the statistically significant ascending slopes in FVC, FEV1 and FEV1/FVC. Although other subjects also had ascending (2 patients) or descending (2 patients) slopes, these changes only occurred in one spirometric variable. As a group, there was a trend for improvement in quality of life. Conclusions: Although rhDNase does not modify the irreversible bronchial obstruction in most patients with severe asthma, a small proportion of them might obtain some beneficial effect.