Mucus clearance and lung function in cystic fibrosis with hypertonic saline. Effects of the flutter device on pulmonary function studies among pediatric cystic fibrosis patients. Chest physiotherapy in cystic fibrosis: a comparative study of autogenic drainage and the active cycle of breathing techniques with postural drainage. The effect of inhaled mannitol on bronchial mucus clearance in cystic fibrosis patients: a pilot study. Effect of positive expiratory pressure breathing in patients with cystic fibrosis. Reappraisal of continuous positive airway pressure therapy in acute cardiogenic pulmonary edema. Short-term results and long-term follow-up. Chest physiotherapy with positive airway pressure: a pilot study of short-term effects on sputum clearance in patients with cystic fibrosis and severe airway obstruction. Comparison of high-frequency chest wall oscillation and oscillating positive expiratory pressure in the home management of cystic fibrosis: a pilot study. Flutter valve improves respiratory mechanics and sputum production in patients with bronchiectasis. Short-term recombinant human DNase in bronchiectasis. Effect on clinical state and in vitro sputum transportability. Short-term comparative study of high frequency chest wall oscillation and European airway clearance techniques in patients with cystic fibrosis.
Abnormal homeostasis of the volume of airway surface liquid in patients with cystic fibrosis is thought to produce defects in mucus clearance and airway defense. Through osmotic forces, hypertonic saline may increase the volume of airway surface liquid, restore mucus clearance, and improve lung function.
                A total of 24 patients with cystic fibrosis were randomly assigned to receive treatment with inhaled hypertonic saline (5 ml of 7 percent sodium chloride) four times daily with or without pretreatment with amiloride. Mucus clearance and lung function were measured during 14-day baseline and treatment periods.
                Long-term inhalation of hypertonic saline without pretreatment with amiloride (i.e., with placebo pretreatment) resulted in a sustained (> or =8 hours) increase in 1-hour rates of mucus clearance, as compared with those with amiloride pretreatment (14.0+/-2.0 vs. 7.0+/-1.5 percent, respectively; P=0.02) and increased 24-hour rates of mucus clearance over baseline. Furthermore, inhalation of hypertonic saline with placebo improved the forced expiratory volume in one second (FEV1) between the baseline period and the treatment period (mean difference, 6.62 percent; 95 percent confidence interval, 1.6 to 11.7; P=0.02), whereas hypertonic saline with amiloride did not improve FEV1 (mean difference, 2.9 percent; 95 percent confidence interval, -2.2 to 8.0; P=0.23). Forced vital capacity (FVC), the forced expiratory flow between 25 and 75 percent of FVC (FEF25-75), and respiratory symptoms also significantly improved in patients treated with hypertonic saline and placebo, whereas the residual volume as a proportion of total lung capacity (RV:TLC) did not change in either group. A comparison of the changes in lung function in the two groups showed no significant difference. In vitro data suggested that sustained hydration of airway surfaces was responsible for the sustained improvement in mucus clearance, whereas inhibition of osmotically driven water transport by amiloride accounted for the observed loss of clinical benefit.
                In patients with cystic fibrosis, inhalation of hypertonic saline produced a sustained acceleration of mucus clearance and improved lung function. This treatment may protect the lung from insults that reduce mucus clearance and produce lung disease.
                Copyright 2006 Massachusetts Medical Society. Previous studies have shown that the Scandipharm Flutter airway clearance device has increased the ability of cystic fibrosis patients to expectorate mucus. Studies that show the effects of the Flutter on pulmonary function among the pediatric cystic fibrosis patients are limited. Thus, we embarked on a study to assess the device's effectiveness.
                The long-term effect of the Flutter on pulmonary function tests (PFTs) was studied and compared with other airway clearance techniques, such as chest physiotherapy (CPT) and Vital Signs, Inc. 9000 PEP positive expiratory pressure (PEP) therapy for cystic fibrosis patients of five to 17 years of age with mild to moderate disease. Of the 15 patients who qualified, six completed the study. The patients were evaluated using PFTs and a respiratory assessment at the beginning and end of each new therapy. Duration of each therapy was one month.
                No respiratory assessment parameters changed between the therapies studied. All patients who used the Flutter preferred it over the other two therapies. The patients stated they felt better clinically, were able to expectorate mucus more easily, and felt more in control of their therapies. Paired t-test statistical analysis from the PFT data indicated no significant changes in forced expiratory volume in the first second of expiration (FEV1), forced expiratory flow from 25 percent to 75 percent of the loop (FEF25-75), airway resistance (Raw), or specific airway conductance (sGaw) among the three therapies studied.
                This study has shown no significant change in respiratory assessment parameters or pulmonary function. Further studies involving multicenter trials are warranted to evaluate the effects of the Flutter on pulmonary function. BACKGROUND--Autogenic drainage has been suggested as an alternative method of chest physiotherapy in patients with cystic fibrosis. In this study autogenic drainage was compared with the active cycle of breathing techniques (ACBT) together with postural drainage. METHODS--Eighteen patients with cystic fibrosis took part in a randomised two-day crossover trial. There were two sessions of one method of physiotherapy on each day, either autogenic drainage or ACBT. The study days were one week apart. On each day the patients were monitored for six hours. Mucus movement was quantified by a radioaerosol technique. Airway clearance was studied qualitatively using xenon-133 scintigraphic studies at the start and end of each day. Expectorated sputum was collected during and for one hour after each session of physiotherapy. Pulmonary functions tests were performed before and after each session. Oxygen saturation (SaO2) and heart rate were measured before, during, and after each session. RESULTS--Autogenic drainage cleared mucus from the lungs faster than ACBT over the whole day. Both methods improved ventilation, as assessed by the xenon-133 ventilation studies. No overall differences were found in the pulmonary function test results, but more patients had an improved forced expiratory flow from 25% to 75% with autogenic drainage, while more showed an improved forced vital capacity with ACBT. No differences were found in sputum weight and heart rate, nor in mean SaO2 over the series, but four patients desaturated during ACBT. CONCLUSIONS--Autogenic drainage was found to be as good as ACBT at clearing mucus in patients with cystic fibrosis and is therefore an effective method of home physiotherapy. Patients with cystic fibrosis should be assessed as to which method suits them best. It has been postulated that hypertonic saline (HS) might impair the antimicrobial effects of defensins within the airways. Alternative non-ionic osmotic agents such as mannitol may thus be preferable to HS in promoting bronchial mucus clearance (BMC) in patients with cystic fibrosis (CF). This study reports the effect of inhalation of another osmotic agent, dry powder Mannitol (300 mg), compared with its control (empty capsules plus matched voluntary cough) and a 6% solution of HS on BMC in 12 patients with cystic fibrosis (CF). Mucus clearance was measured using a radioaerosol/gamma camera technique. Post-intervention clearance was measured for 60 min, followed by cough clearance for 30 min. Neither mannitol nor HS improved BMC during the actual intervention period compared with their respective controls. However during the post-intervention measurement there was a significant improvement in BMC for both the mannitol (8.7+/-3.3% versus 2.8+/-0.7%) and HS (10.0+/-2.3% versus 3.5+/-0.8%). There was also a significant improvement in cough clearance with the Mannitol (9.7+/-2.4%) compared with its control (2.5+/-0.8%). Despite premedication with a bronchodilator, a small fall in forced expiratory volume in one second (FEV1) was seen immediately after administration of both the mannitol (7.3+/-2.5%) and HS (5.8+/-1.2%). Values of FEV1 returned to baseline by the end of the study. Inhaled mannitol is a potential mucoactive agent in cystic fibrosis patients. Further studies are required to establish the optimal dose and the long-term effectiveness of mannitol. The effect of positive expiratory pressure breathing, alone and in combination with coughing, was investigated in eight patients with cystic fibrosis. Functional residual capacity and total lung capacity was measured with a body plethysmograph before, during, and immediately after breathing with expiratory pressure of 5 and 15 cm H2O, and after a coughing period. The positive expiratory pressure breathing was carried out five times for two minutes with a two minute interval between each period. Mucus transport was measured in a peripheral lung region and over the whole lung by a radioactive aerosol tracer technique. Clearance measurements were carried out continuously during positive expiratory pressure breathing and during a control period. Two minutes' breathing with an expiratory pressure of 5 and 15 cm H2O caused an increase in mean (SEM) functional residual capacity from 2.6 (0.1) to 3.6 (0.3) and 4.4 (0.5) 1 and an increase in total lung capacity from 5.1 (0.2) to 5.9 (0.3) and 6.9 (0.4) 1. Lung volumes were higher during breathing with an expiratory pressure of 15 cm H2O than with 5 cm H2O; both returned to baseline values immediately after positive expiratory pressure breathing. Spontaneous mucus clearance and mucus clearance by coughing were not influenced by positive expiratory pressure breathing at either expiratory pressure. Thus in patients with cystic fibrosis positive expiratory pressure breathing increases lung volumes in relation to the expiratory pressure imposed; these changes in lung volume did not, however, lead to an improvement of mucus transport. To investigate whether serial incremental continuous positive airway pressure (CPAP) has any short-term or long-term advantages over face-mask oxygen therapy by way of intrapulmonary shunt reduction, 100 patients admitted to the coronary care unit for the treatment of acute cardiogenic pulmonary edema were studied. All patients received Swan-Ganz catheterization. Hemodynamic and pulmonary function parameters were recorded over the next 6 h, and the patients were followed until hospital discharge. All survivors received regular follow-up at 1-month intervals in the outpatient clinic. During the first-stage investigation period (3 h) PaO2 in the CPAP group showed a significant increase, whereas the intrapulmonary shunt and alveolar-arterial oxygen tension gradient (P[A-a]O2) was significantly reduced (p < 0.005). The CPAP group had significantly lower rate-pressure product and higher stroke volume index compared with the control group. The therapeutic failure rate over 6 h was 24% in the CPAP group and 50% in the control group (p < 0.01). The CPAP group had a significantly lower incidence of tracheal intubation and ventilator therapy than the control group; however, there was no significant difference in short-term mortality and hospital stay between the two groups. In conclusion, although study size was not large enough to demonstrate a difference in mortality, CPAP therapy resulted in physiologic cardiovascular and pulmonary function improvement and significantly reduced the need for intubation; however, it did not decrease mortality in patients with acute cardiogenic pulmonary edema, and a much larger study is needed to investigate this possibility. The periodic administration of positive airway pressure combined with directed cough could aid mucus clearance in patients with cystic fibrosis (CF) and severe airway obstruction.
                To compare the short-term effect of positive expiratory pressure (PEP) physiotherapy via mask (mask PEP), continuous positive airway pressure (CPAP), and noninvasive positive-pressure ventilation (NPPV) physiotherapies on amount of sputum collected.
                Directed cough was standardized for each patient and used as the control treatment. We studied 17 patients with CF (mean +/- SD age 28 +/- 7 y) and severe airway obstruction (forced expiratory volume in the first second 25 +/- 6% of predicted) admitted for pulmonary exacerbation. Mask PEP, CPAP, NPPV, and the control treatment (directed cough) were administered in a random sequence. Each patient received each treatment twice a day (in 70-min sessions) for 2 consecutive days. We measured the wet and dry weight of sputum collected and the number of directed and spontaneous coughs during each session. Spirometry and pulse oximetry were conducted before and after each session. For mask PEP, CPAP, and NPPV, each patient gave a subjective score for the efficacy and tolerability of the treatment, compared to the control treatment.
                There was no statistically significant difference in the dry weight of sputum collected: mask PEP 0.9 +/- 0.6 g, CPAP 0.8 +/- 0.4 g, NPPV 0.9 +/- 0.6 g, control treatment 1.0 +/- 0.8 g. There was a statistically significant difference in the wet weight of sputum collected: mask PEP 15.8 +/- 5.5 g, CPAP 13.7 +/- 5.5 g, NPPV 13.2 +/- 5.0 g, control treatment 14.0 +/- 5.0 g (p < 0.05), but that difference became nonsignificant when we took into account the number of spontaneous coughs. There were no statistically significant changes in the spirometry and pulse-oximetry values. The patients' subjective efficacy scores were similar for mask PEP, CPAP, and NPPV. Less fatigue was reported after NPPV and CPAP than after mask PEP.
                There were no differences in sputum clearance or pulmonary-function measures between mask PEP and short-term administration of either CPAP or NPPV combined with directed cough. After mask PEP these patients felt more tired than after CPAP or NPPV secretion-clearance therapy. Enhanced airway clearance is thought to result in better-maintained pulmonary function in cystic fibrosis (CF). Postural drainage, percussion, and vibration (PDPV) have been the primary airway clearance technique (ACT) employed in CF for over 40 years. Two new airway clearance modalities are high-frequency chest wall oscillation (HFCWO) and oscillating positive expiratory pressure (OPEP). This pilot study was undertaken to evaluate the efficacy of these techniques during home use, assess patient satisfaction with them as compared to PDPV, and assess the feasibility of performing a definitive comparative trial. The prospective, randomized, multicenter crossover trial was conducted at three urban academic CF Care Centers. Twenty-nine CF patients, 9-39 years of age, participated. Subjects performed 4 weeks each of HFCWO and OPEP following 2-week lead-in/washout periods. Spirometry, lung volumes, National Institutes of Health and Petty Scores, and a satisfaction survey were performed at baseline and after each treatment period. An ACT preference survey was completed at the conclusion of the study. Twenty-four subjects completed both therapies. There were no statistically significant differences between therapies for spirometry, lung volumes, or clinical scores. No significant safety issues arose during the study period. Compliance between therapies was similar. Significant differences among therapies existed in patient satisfaction. Given a choice of therapy, 50% of subjects chose HFCWO, 37% OPEP, and 13% PDPV. This study suggests that HFCWO and OPEP are safe and as effective as patients' routine therapies when used for airway clearance in a home setting. Patient satisfaction and preference differ among ACTs and should be considered when prescribing home therapy. A definitive, multi-center, comparative study evaluating long-term efficacy of these techniques is feasible.
                Copyright 2001 Wiley-Liss, Inc. Although the application of airway clearance techniques is considered an important component in the treatment of several obstructive pulmonary diseases, there is no scientific evidence supporting the use of Flutter Valve™ in the management of patients with bronchiectasis. Moreover, the consequences of respiratory physiotherapy techniques on respiratory mechanics have not been fully studied. Therefore, we investigated the acute, short-term effects of Flutter Valve™ on respiratory mechanics and sputum production in bronchiectatic patients. 
                EIGHT patients were evaluated in a randomized, blinded, cross-over trial. Impedance at 5 Hz (R5), resistance as a function of oscillation frequency (dR/dF), reactance at 5 Hz (X5), resonant frequency (f(0) ) and integral of reactance between 5 Hz and resonant frequency (AX) were recorded. 
                Flutter Valve™ cleared 8.4 mL more secretions than the Sham Flutter intervention (95% confidence interval [95% CI], 3.4-13.4). There was a higher percentage decrease in R5 (-11.2%; 95% CI, -4.4 to -18.2), dR/dF (-20.8%; 95% CI, -32.4 to -9) and AX (-7.8%; 95% CI, -11.9 to -3.7) under Flutter Valve™. X5 and f(0) variation did not differ between interventions. 
                 Flutter Valve™ increases sputum removal during treatment and diminishes total and peripheral airway resistance in hypersecretive patients with bronchiectasis. Impulse oscillometry is a user-friendly tool to evaluate the effects of airway clearance techniques on respiratory mechanics.
                Copyright © 2010 John Wiley & Sons, Ltd. We report a double blind placebo-controlled phase II study of the efficacy and safety of nebulized recombinant human DNase (rhDNase) administered for 14 d to adults with bronchiectasis not caused by cystic fibrosis. All were in a stable clinical state at the commencement of the study, and they received (1) rhDNase 2.5 mg twice daily, (2) rhDNase once daily, or (3) placebo (excipient only) inhalation. The outcome measures were spirometry, subjective quality of life/dyspnea, and safety. We also measured the ciliary transportability of the sputum expectorated before and after the treatment period, using the mucus-depleted bovine trachea. The drug was well tolerated, but it produced no significant change in any of the outcome variables or in sputum transportability. When the drug was incubated with bronchiectatic sputum in vitro, a fall in transportability was observed. We discuss possible explanations for the lack of a measurable benefit from rhDNase in this study population, which appears to contrast with the improvements shown in cystic fibrosis using studies of similar design. High frequency chest wall oscillation (HFCWO) is standard treatment for airway clearance in the USA and has recently been introduced in the UK and Europe. There is little published research comparing HFCWO with airway clearance techniques (ACTs) frequently used in the UK and Europe. The aim of this study was to compare the short-term effects of HFCWO with usual ACTs in patients with cystic fibrosis hospitalised with an infective pulmonary exacerbation.
                A 4-day randomised crossover design was used. Patients received either HFCWO on days 1 and 3 and usual ACTs on days 2 and 4 or vice versa. Wet weight of sputum, spirometry and oxygen saturation were measured. Perceived efficacy, comfort, incidence of urinary leakage and preference were assessed. Data were analysed by mixed model analysis.
                29 patients (72% male) of mean (SD) age 29.4 (8.4) years and mean (SD) forced expiratory volume in 1 s (FEV(1)) percentage predicted (FEV(1)%) 38 (16.7) completed the study. Significantly more sputum was expectorated during a single treatment session and over a 24 h period (mean difference 4.4 g and 6.9 g, respectively) with usual ACTs than with HFCWO (p<0.001). No statistically significant change in FEV(1)% or oxygen saturation was observed after either HFCWO or usual ACTs compared with baseline. 17 patients (55%) expressed a preference for their usual ACT.
                During both a finite treatment period and over 24 h, less sputum was cleared using HFCWO than usual ACT. HFCWO does not appear to cause any adverse physiological effects and may influence adherence.
The results of this review show that airway clearance techniques have short-term effects in the terms of increasing mucus transport. No evidence was found on which to draw conclusions concerning the long-term effects.