Effects of sputum oscillations and rhDNase in vitro: A combined approach to treat cystic fibrosis lung disease

Abstract

Mucolytic treatment with rhDNase is part of the current therapy for cystic fibrosis (CF) lung disease. The Flutter® valve, a device for enhancing airway mucus clearance, has recently been approved for use in CF patients. Exhalation through the Flutter® valve leads to oscillations of expiratory airflow, improving mucus viscoelasticity and stimulating clearance. The goal of our in vitro study was to evaluate the individual and combined effects of Flutter® valve oscillations and rhDNase treatment on the viscoelastic (rheological) properties of CF sputum. Sputum specimens were collected from 19 CF patients and subjected to the following protocols: (1) baseline sample with no treatment applied; (2) application of oscillations generated by airflow through the Flutter® valve; (3) incubation at 37°C for 30 min with 10% vol/wt rhDNase (Pulmozyme®) to achieve a final concentration of 2.5 μg/mL (∼100 nM); (4) combination of Flutter® valve oscillations and 10% vol/wt normal saline (0.9% NaCl); (5) combination of Flutter® valve oscillations and 10% vol/wt rhDNase at 2.5 μg/mL final concentration. For each protocol, the mucus rigidity index (log G* at 1 rad/s) was measured at baseline and at 30 min. Values are presented as mean ±SEM. The cough clearability index (CCI) was computed from measurements of mucus viscoelasticity, based on relationships established in model studies. Flutter® valve treatment alone did not result in a significant reduction in the rigidity of CF sputum (2.24 ± 0.13 vs. 2.11 ± 0.13, P = 0.19), nor did rhDNase (2.5 μg/mL) alone, although we have previously shown (Pediatr. Pulmonol. 1995; 20:78) that both of these treatments reduce sputum spinnability, which is more sensitive to molecular weight reduction. In comparison to individual treatments, combined treatment with Flutter® valve oscillations and rhDNase significantly reduced the mucus rigidity to 1.85 ± 0.19 from 2.24 ± 0.13 (P < 0.001), consequently increasing the predicted clearability of the sputum (from 1.09 ± 0.26 to 1.83 ± 0.48, P = 0.012). These in vitro results suggest that a combination of biochemical treatment (e.g., DNase) and mechanical oscillation may have a better therapeutic potential for mucus clearance in CF lung disease. Pediatr Pulmonol. 1998; 26:250–255. © 1998 Wiley‐Liss, Inc.

Tracheobronchial mucus viscoelasticity during environmental challenge in horses with recurrent airway obstruction

“…This change of log 0.5 represents a 3-fold increase of viscoelasticity on a linear scale. Furthermore, log G* Fig 2: A) viscoelasticity at 10 radian/s on a logarithmic scale (log G*; d y n / c m 2 ), B) mucociliary clearability index (MCI) and C) cough clearability index (CCI) of mucus samples in RAO-affected (principal g roup) and control horses (control group) before (0) and after e n v i ronmental challenge (6, 24 and 48 h) values of 3 and more are in the range found in human patients suffering from severe airway obstruction caused by cystic fibrosis (Dasgupta et al 1998). The ratio of viscosity/elasticity did not differ between controls and RAO-horses and was not affected significantly by stabling and hay challenge.…”

Oscillating Positive Expiratory Pressure on Respiratory Resistance in Chronic Obstructive Pulmonary Disease With a Small Amount of Secretion

“…After 30 min of flutter oscillation, studies have reported a decrease in the rigidity factor of mucus samples and mucus viscosity, but no change in mucociliary transport and cough. 19 – 21 However, after 4 weeks of treatment with flutter there was an increase in the mucociliary and cough clearance indices and an increase in the in vitro mucus cough transport. 22 , 23 A Cochrane review concluded that there is no clear evidence whether oscillation was a more or less effective intervention overall than other forms of physiotherapy in cystic fibrosis patients.…”

Chest physiotherapy improves lung aeration in hypersecretive critically ill patients: a pilot randomized physiological study

“…Various mechanisms of action have been proposed for HFCWO: (1) augmentation of the expiratory flow, which increases the annular flow of mucus towards the oropharynx when exceeding by more than 10% the inspiratory peak flow [ 16 – 18 ]; (2) improvement of mucus rheological (spinnability and viscoelastic) properties [ 19 , 20 ]; (3) increase of ciliary motility by reflected stimulation of vagus nerve, in particular when the applied oscillations range between 11 and 15 Hz [ 21 ]; and (4) enhancement of the gas-liquid transport [ 16 , 22 ]. Recent findings showed that HFCWO, when compared to conventional physiotherapy, improves the amount of aerated lung regions and oxygenation of intubated patients in intensive care unit (ICU) [ 23 , 24 ].…”