EFFECTS OF SPUTUM OSCILLATIONS AND RHDNASE IN-VITRO - A COMBINED APPROACH TO TREAT CYSTIC-FIBROSIS LUNG-DISEASE

Mucolytic treatment with rhDNase is part of the current therapy for cy stic fibrosis (CF) lung disease. The Flutter(R) valve, a device for en hancing airway mucus clearance, has recently been approved for use in CF patients. Exhalation through the Flutter(R) valve leads to oscillat ions of expiratory airflow, improving mucus viscoelasticity and stimul ating clearance. The goal of our in vitro study was to evaluate the in dividual and combined effects of Flutter(R) valve oscillations and rhD Nase treatment on the viscoelastic (rheological) properties of CF sput um. Sputum specimens were collected from 19 CF patients and subjected to the following protocols: 1) baseline sample with no treatment appli ed; 2) application of oscillations generated by airflow through the Fl utter(R) valve; 3) incubation at 37 degrees C for 30 min with 10% vol/ wt rhDNase (Pulmozyme(R)) to achieve a final concentration of 2.5 mu g /mL (similar to 100 nM); 4) combination of Flutter(R) valve oscillatio ns and 10% vol/wt normal saline (0.9% NaCl); 5) combination of Flutter (R) valve oscillations and 10% vol/wt rhDNase at 2.5 mu g/mL final con centration. For each protocol, the mucus rigidity index (log G at 1 r ad/s) was measured at baseline and at 30 min. Values are presented as mean +/-SEM. The cough clearability index (CCl) was computed from meas urements of mucus viscoelasticity, based on relationships established in model studies. Flutter(R) 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 mu g/mL) alone, althou gh we have previously shown (Pediatr. Pulmonol. 1995; 20:78) that both of these treatments reduce sputum spinnability, which is more sensiti ve to molecular weight reduction. In comparison to individual treatmen ts, combined treatment with Flutter(R) 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, 1 998; 26:250-255. (C) 1998 Wiley-Liss, Inc.