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. Chest physiotherapy in cystic fibrosis: improved tolerance with nasal pressure support ventilation. Low-flow oxygen and bilevel ventilatory support: effects on ventilation during sleep in cystic fibrosis. Non-invasive ventilation assists chest physiotherapy in adults with acute exacerbations of cystic fibrosis. Nocturnal ventilatory support in patients with cystic fibrosis: comparison with supplemental oxygen. Randomised placebo controlled trial of non-invasive ventilation for hypercapnia in cystic fibrosis.
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. Chest physiotherapy (CPT) is an integral part of the treatment of patients with cystic fibrosis (CF). CPT imposes additional respiratory work that may carry a risk of respiratory muscle fatigue. Inspiratory pressure support ventilation (PSV) is a new mode of ventilatory assistance designed to maintain a constant preset positive airway pressure during spontaneous inspiration with the goal of decreasing the patient's inspiratory work. The aim of our study was 1) to evaluate respiratory muscle fatigue and oxygen desaturation during CPT and 2) to determine whether noninvasive PSV can relieve these potential adverse effects of CPT.
                Sixteen CF patients in stable condition with a mean age of 13 +/- 4 years participated to the study. For CPT, we used the forced expiratory technique (FET), which consisted of one or more slow active expirations starting near the total lung capacity (TLC) and ending near the residual volume. After each expiration, the child was asked to perform a slow, nonmaximal, diaphragmatic inspiration. After one to four forced breathing cycles, the child was asked to cough and to expectorate. A typical 20-minute CPT session consisted of 10 to 15 FET maneuvers separated by rest periods of 10 to 20 breathing cycles each. During the study, each patient received two CPT sessions in random order on two different days, at the same time of day, with the same physiotherapist. During one of these two sessions, PSV was provided throughout the session (PSV session) via a nasal mask using the pressure support generator ARM25 designed for acute patients (TAEMA, Antony, France). The control session was performed with no nasal mask or PSV. Both CPT sessions were performed without supplemental oxygen. Lung function and maximal inspiratory pressures (PImax) and expiratory pressures (PEmax) were recorded before and after each CPT session.
                Mean lung function parameters were comparable before the PSV and the control sessions. Baseline pulse oximetry (SpO2) was significantly correlated with the baseline vital capacity (% predicted) and forced expiratory volume in 1 second (FEV1) (% predicted). PSV was associated with an increase in tidal volume (Vt) from 0.42 +/- 0.01 liters to 1.0 +/- 0.02 liters. Respiratory rate was significantly lower during PSV. SpO2 between the FET maneuvers was significantly higher during PSV as compared with the control session. SpO2 decreases after FET were significantly larger during the control session (nadir: 91.8 +/- 0. 7%) than during the PSV session (93.8 +/- 0.6%). Maximal pressures decreased during the control session (from 71.9 +/- 6.1 to 60.9 +/- 5.3 cmH2O, and from 85.3 +/- 7.9 to 77.5 +/- 4.8 cmH2O, for PImax and PEmax, respectively) and increased during the PSV session (from 71.6 +/- 8.6 to 83.9 +/- 8.7 cmH2O, and from 80.4 +/- 7.8 to 88.0 +/- 7.4 cmH2O, for PImax and PEmax, respectively). The decrease in PEmax was significantly correlated with the severity of bronchial obstruction as evaluated based on baseline FEV1 (% predicted). Forced expiratory flows did not change after either CPT session. The amount of sputum expectorated was similar for the two CPT sessions (5.3 +/- 5.3 g vs 4.6 +/- 4.8 g after the control and PSV session, respectively; NS). Fifteen patients felt less tired after the PSV session. Ten patients reported that expectoration was easier with PSV, whereas 4 did not note any difference; 2 patients did not expectorate. Nine patients expressed a marked and 5 a small preference for PSV, and 2 patients had no preference. The physiotherapists found it easier to perform CPT with PSV in 14 patients and did not perceive any difference in 2 patients.
                Our study in CF children shows that respiratory muscle performance, as evaluated based on various parameters, decreased after CPT and that significant falls in oxygen saturation occurred after the FET maneuvers despite the quiet breathing periods between each FET cycle. These unwanted effects of CPT were We measured ventilation in all sleep stages in patients with cystic fibrosis (CF) and moderate to severe lung disease, and compared the effects of low-flow oxygen (LFO2) and bilevel ventilatory support (BVS) on ventilation and gas exchange during sleep. Thirteen subjects, age 26 +/- 5.9 yr (mean +/- 1 SD), body mass index (BMI) 20 +/- 3 kg/m2, FEV1 32 +/- 11% predicted, underwent three sleep studies breathing, in random order, room air (RA), LFO2, and BVS +/- O2 with recording of oxyhemoglobin saturation (SpO2) (%) and transcutaneous carbon dioxide (TcCO2) (mm Hg). During RA and LFO2 studies, patients wore a nasal mask with a baseline continuous positive airway pressure (CPAP) of 4 to 5 cm H2O. Minute ventilation (V I) was measured using a pneumotachograph in the circuit and was not different between wake and non-rapid eye movement (NREM) sleep on any night. However, V I was reduced on the RA and LFO2 nights from awake to rapid eye movement (REM) (p < 0.01) and from NREM to REM (p < 0.01). On the BVS night there was no significant difference in V I between NREM and REM sleep. Both BVS and LFO2 improved nocturnal SpO2, especially during REM sleep (p < 0.05). The rise in TcCO2 seen with REM sleep with both RA and LFO2 was attenuated with BVS (p < 0.05). We conclude that BVS leads to improvements in alveolar ventilation during sleep in this patient group. Chest physiotherapy is essential to the management of cystic fibrosis (CF). However, respiratory muscle fatigue and oxygen desaturation during treatment have been reported. The aim of this study was to determine whether non-invasive ventilation (NIV) during chest physiotherapy could prevent these adverse effects in adults with exacerbations of CF.
                Twenty six patients of mean (SD) age 27 (6) years and forced expiratory volume in 1 second (FEV1) 34 (12)% predicted completed a randomised crossover trial comparing standard treatment (active cycle of breathing technique, ACBT) with ACBT + NIV. Respiratory muscle strength (PImax, PEmax), spirometric parameters, and dyspnoea were measured before and after treatment. Pulse oximetry (SpO2) was recorded during treatment. Sputum production during treatment and 4 and 24 hours after treatment was evaluated.
                There was a significant reduction in PImax following standard treatment that was correlated with baseline PImax (r=0.73, p<0.001). PImax was maintained following NIV (mean difference from standard treatment 9.04 cm H2O, 95% confidence interval (CI) 4.25 to 13.83 cm H2O, p=0.006). A significant increase in PEmax was observed following the NIV session (8.04 cm H2O, 95% CI 0.61 to 15.46 cm H2O, p=0.02). The proportion of treatment time with SpO2 < or =90% was correlated with FEV1 (r=-0.65, p<0.001). NIV improved mean SpO2 (p<0.001) and reduced dyspnoea (p=0.02). There were no differences in FEV1, forced vital capacity (FVC) or sputum weight, but FEF(25-75) increased following NIV (p=0.006).
                Reduced inspiratory muscle strength and oxygen desaturation during chest physiotherapy are associated with inspiratory muscle weakness and severity of lung disease in adults with exacerbations of CF. Addition of NIV improves inspiratory muscle function, oxygen saturation and small airway function and reduces dyspnoea. Progressive deterioration of lung function in cystic fibrosis (CF) patients may lead to significant hypoxaemia and hypercapnia, especially during sleep. The effects of bi-level noninvasive positive pressure nasal mask ventilation (NIPPV) on respiration and sleep were compared to those of low-flow oxygen therapy in six CF patients (mean +/- SD age 22.3 +/- 4.7 yrs, with severe lung disease (forced expiratory volume in one second (FEV1) 29.4 +/- 3.4% predicted). Compared to the control night, NIPPV and oxygen therapy significantly improved overall night-time oxygen saturation during both rapid eye movement (REM) and non-rapid eye movement (NREM) sleep stages. However, significant increases in transcutaneous CO2 tension occurred during oxygen therapy, while NIPPV markedly improved alveolar ventilation during all sleep states. Sleep architecture and arousals remained unchanged during NIPPV and oxygen therapy treatment nights. We conclude that noninvasive positive pressure ventilation improves sleep-related hypoxaemia and hypercapnia in severe cystic fibrosis patients without affecting sleep. The long-term compliance and benefits of noninvasive positive pressure ventilation remain unclear. The clinical benefits of domiciliary non-invasive positive pressure ventilation (NIV) have not been established in cystic fibrosis (CF). We studied the effects of nocturnal NIV on quality of life (QoL), functional and physiological outcomes in CF subjects with awake hypercapnia (arterial carbon dioxide pressure PaCO2>45 mm Hg).
                In a randomised, placebo controlled, crossover study, eight subjects with CF, mean (SD) age 37 (8) years, body mass index 21.1 (2.6) kg/m2, forced expiratory volume in 1 s 35 (8)% predicted and PaCO2 52 (4) mm Hg received 6 weeks of nocturnal (1) air (placebo), (2) oxygen and (3) NIV. The primary outcome measures were CF specific QoL, daytime sleepiness and exertional dyspnoea. Secondary outcome measures were awake and asleep gas exchange, sleep architecture, lung function and peak exercise capacity.
                Compared with air, NIV improved the chest symptom score in the CF QoL Questionnaire (mean difference 10; 95% CI 5 to 16; p = 0.002) and the transitional dyspnoea index score (mean difference 3.1; 95% CI 1.2-5.0; p = 0.01). It reduced maximum nocturnal pressure of transcutaneous CO2 (PtcCO2 mean difference -17 mm Hg; 95% CI -7 to -28 mm Hg; p = 0.005) and increased exercise performance on the Modified Shuttle Test (mean difference 83 m; 95% CI 21 to 144 m; p = 0.02). NIV did not improve sleep architecture, lung function or awake PaCO2.
                6 weeks of nocturnal NIV improves chest symptoms, exertional dyspnoea, nocturnal hypoventilation and peak exercise capacity in adult patients with stable CF with awake hypercapnia. Further studies are required to determine whether or not NIV can improve survival.
Non-invasive ventilation may be a useful adjunct to other airway clearance techniques, particularly in people with cystic fibrosis who have difficulty expectorating sputum. Non-invasive ventilation, used in addition to oxygen, may improve gas exchange during sleep to a greater extent than oxygen therapy alone in moderate to severe disease. These benefits of non-invasive ventilation have largely been demonstrated in single treatment sessions with small numbers of participants. The impact of this therapy on pulmonary exacerbations and disease progression remain unclear. There is a need for long-term randomised controlled trials which are adequately powered to determine the clinical effects of non-invasive ventilation in cystic fibrosis airway clearance and exercise.