RC-Cornet verbessert den Effekt einer Inhalationstherapie mit Ipratropiumbromid (Atrovent ) bei COPD-Patienten

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1 RC-Cornet verbessert den Effekt einer Inhalationstherapie mit Ipratropiumbromid (Atrovent ) bei COPD-Patienten U. H. Cegla, H.-J. Jost, A. Harten, T. Weber Pneumologisches Forschungsinstitut am Herz-Jesu-Krankenhaus, Dernbach Pneumologie 2001; 55: Seite Translation RC-Cornet improves the Efficacy of Inhalation Therapy with Ipratropiumbromide (Atrovent ) in COPD-Patients Introduction Therapy of COPD patients, especially in advanced stages, is often an unsatisfying and thankless procedure. The therapeutic problems involved in treatment of COPD patients are due on the one hand to the fact that the obstruction itself is conditioned by changes in the bronchial tree that respond to medication (contraction of the smooth musculature, increased mucus production, reduced mucociliary clearance). On the other hand, further factors contributing to the obstruction include a number of dysfunctions that do not respond to drug therapy such as reduced elastic retractivity of pulmonary tissue and relaxation of the tracheal membrane. These latter disturbances result in a mechanical obstruction of the respiratory tract in forced expiration and in coughing [1, 2], which can be improved by physiotherapeutic measures. Drug therapy of COPD is set out in national and international recommendations [3, 4]. In the area of physiotherapy, the various approaches range from coughing to breathing techniques and apparatus-based methods the efficacy of which was not evaluated until recently [15]. We demonstrated in earlier studies that respiratory physiotherapy with the RC-Cornet (an oscillating PEP system, see below) makes expectoration of mucus easier, reduces dyspnoea and improves pulmonary function parameters [15]. Summary: Christensen et al. demonstrated in 1993 an increased efficacy of inhaled beta-2 agonists with PEP (positive expiratory pressure) in asthma [14], we asked ourselves whether oscillating PEP improves the "efficacy" of ipratropium bromide in COPD patients. If it were, inhalation with parallel coupling of physiotherapy would represent a simplification and time savings for therapy of this patient collective. Method Study design 1 In a randomized crossover study we investigated 35 patients with COPD (Tab. 1) and tracheobronchial instability (check-valve in flow-volume curve and trapped air in the body plethysmography resistance loop) in a stabilized phase (no infection). The patients were examined on 2 successive days before and 2 strokes of salbutamol with an autohaler (Salbulair ) as well as subsequently inhalation of 750 µg of ipratropium bromide (Atrovent solution) in 3 ml of

2 n = women, 25 men Tab. 1 Patient demographic data Age (Y) 65 ± 10 Height (cm) 170 ± 8 Weight (kg) 75 ± 12 Vital capacity (VC) 2.4 ± 0.61 (65.6 ± 13.9% of standard)* Forced expiratory volume (FEV1) 1.15 ± 0.4 l/s (47.1 ± 15.8% of standard)* Airway resistance (Raw) 0.73 ± 0.29 kpa/l/s Residual volume (RV) 4.03 ± Smoking behaviour * EGKS 1993 Non-smokers for at least the last 5 years (acc. to personal responses) 0.9% NaCl solution using a Pari Inhaler Boy and LCplus atomizer. The patients were randomized into 2 groups, A and B. Both groups inhaled according to the same scheme, with the difference that in group A an RC-Cornet in position 1 was integrated in the expiratory branch of the Pari atomizer with a special connector, whereas group B breathed in and out conventionally with the Pari. All of the patients were non-smokers. Previous therapy (retard theophylline, beta-2 sympathomimetica inhalation and parasympathicolytic dosed aerosols and 7.5 mg prednisolone equivalent on average) was retained. Following early morning intake of their long-term medication, the patients were measured at about 10 a.m. in the pulmonary function laboratory (airway resistance in the body plethysmograph 1, residual volume, vital capacity and forced expiratory volume). Fig. 1 Schematic drawing of the inhalation system: The RC-Cornet is connected to the mouthpiece of the Pari device by means of a special adapter. RC-Cornet The RC-Cornet is a physiotherapeutic device that produces a "combined PEP" when the patient blows into it, i.e. it builds up a continuous positive pressure of about 20 cm head of water when blown into with additional pressure oscillations of about 5 cm head of water depending on how strongly the patient blows (Figs. 1-3). Three pressure oscillation frequencies are superimposed (see Fig. 2): A low frequency at about 20 Hz, a middle frequency at 80 Hz and a high frequency pressure oscillation of 300 Hz. Further details were published in this journal one year ago [6]. Fig. 2 Registration of the pressure (lower curve) and airflow changes with the RC-Cornet, one DIV 20 ms, one DIV in the pressure curve 20 H 2 0, one DIV in the airflow curve 45 l/min, (green = pressure, yellow = flow). The pressure and airflow oscillations generated by expiration through the RC-Cornet are imparted to the bronchial tree by way of the mouthpiece, causing calibre fluctuations in the bronchi and thus helping to prevent respiratory tract collapse. The statistical evaluation of the results was done with the program Statistica from Statsoft, Version 6, 2001 edition, Statsoft Inc., Tulsa, Oklahoma, USA. 1 Bodyscope from Ganshorn Elektronik, Niederlauer 2

3 Tab. 2 Attenuation of drop in airway resistance in both groups Airway resistance with RC-Cornet without RC-Cornet (kpa/l/s) Start 0.73 ± ± nd stroke 0.62 ± ± 0.25 inhalation 0.47 ± ± 0.23 Wilcoxon test for associated random samples: p < Tab. 3 Vital capacity increase curve Vital capacity (VC) with RC-Cornet without RC-Cornet Fig. 3 Illustration of the oscillating tube valve system in the RC-Cornet ; observe the 2-chamber system that alternately fills and empties, maintaining a continuous positive pressure and generating pressure and flow oscillations on top of this pressure during the filling and emptying phases in this PEP. Start 2.38 ± ± nd stroke 2.47 ± ± 0.65 inhalation 2.65 ± ± 0.72 Wilcoxon test for associated random samples: p < Tab. 4 Forced expiratory volume increase curve Forced expiratory volume (1s) with RC-Cornet without RC-Cornet (l/s) Results Statistical evaluation of the drop in airway resistance in the two groups revealed that in group A, who had expired through the oscillating PEP system, the drop in resistance compared to sole inhalation inhalation was greater to a statistically significant degree (p < ) (Tab. 2). Vital capacity also rose more in group A to a statistically significant degree following ipratropium bromide inhalation than in group B (Tab. 3). Forced expiratory volume showed an increase in the oscillating PEP therapy group that was greater to a statistically significant degree than in the normal ipratropium bromide inhalation group (Tab. 4). In residual volume, a tendency to a decrease is seen in the oscillating PEP group, although statistical significance was not attained (Tab. 5). As the airway resistances for the individual patients show, individual differences in response to beta-2 sympathomimetics and ipratropium bromide were considerable (Figs. 4 and 5). 3 Start 1.15 ± ± nd stroke 1.24 ± ± 0.46 inhalation 1.34 ± ± 0.55 Wilcoxon test for associated random samples: p < Tab. 5 Attenuation of drop in residual volume in both groups Residualvolume (l) with RC-Cornet without RC-Cornet Start 4.05 ± ± nd stroke 3.98 ± ± 1.04 inhalation 3.90 ± ± 1.11 Wilcoxon test for associated random samples: p <

4 placebo-controlled, prospective study involving 90 patients with COPD in 1997 we demonstrated that treatment with the RC-Cornet in the starting position (e.g. set for continuous positive pressure and additive pressure oscillations) in the sense of the combined PEP, significantly reduced a massively raised residual volume. After such therapy, sputum was also expectorated more readily and frustrated expectorant coughing was reduced, so that patients felt "better" under this physiotherapy [5]. Individual patient Baseline value after salbutamol after ipratropium bromide Fig. 4 Changes in airway resistance before and after salbutamol and after ipratropium bromide inhalation without RC-Cornet (all 35 individual patients are shown). Individual patient Baseline value after salbutamol after ipratropium bromide Fig. 5 Changes in airway resistance before and after salbutamol and after ipratropium bromide inhalation with RC-Cornet in the expiratory branch (35 individual patients are shown in the same order as in Fig. 4). Further studies have shown that a positive effect of physiotherapy is pronounced in COPD patients when it is done with "combined PEP" [10]. The continuous positive pressure open collaterals in the bronchial and bronchiole areas so that air once again gets behind regions that have collapsed or contain bronchial mucus, thus also contributing to a decrease in hyperdistension (reduction of residual volume) [7, 8]. The dyspnoea-reducing effect of the oscillating PEP system is, besides the reduction of the central respiratory position, also caused by the oscillations generated by the device in the mouth, throat and thorax. As demonstrated in studies by Homma et al., a dyspnoea-reducing effect on the thorax is achieved in particular with midfrequency oscillations between 80 and 120 Hz [11, 12]. These oscillation frequencies simulate a higher rate of respiratory airflow to the sensors of the thoracic ligament and musculature apparatus and the sensors of the bronchial tree, which is experienced as decreased dyspnoea. According to initial studies, integrating the RC-Cornet in the expiratory branch of the atomizer results in an improved deposition of the inhaled agent in the bronchial tree [13], which would also explain the increased bronchodilatation in pharmacological terms. Besides the improvement of bronchospasmolysis, the combination of inhalation from a nozzled atomizer with parallel physiotherapy shortens the amount of time required for this "therapy" in COPD patients. Discussion This study demonstrated that pulmonary function improvement following inhalation through an RC-Cornet integrated in the expiratory branch of the atomizer was significantly enhanced in COPD patients. COPD involves various different pathological changes in the bronchi, which can be categorized as reversible (responsive to drug treatment) components of bronchial obstruction, and a primarily "drug-refractory" component that can be improved by physiotherapy [9]. In a 4

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