Acapella versus usual airway clearance during acute exacerbation in bronchiectasis: a randomized crossover trial

Chronic Respiratory Disease 2007; 4: 67 74 http://crd.sagepub.com ORIGINAL PAPER Acapella versus usual airway clearance during acute exacerbation in bronchiectasis: a randomized crossover trial JE Patterson, O Hewitt, L Kent, I Bradbury, JS Elborn and JM Bradley Regional Respiratory Centre, Belfast City Hospital, Belfast, Northern Ireland Devices such as the Acapella may facilitate independent airway clearance, however, few clinical trials have investigated the efficacy of Acapella. The aim of this study was to compare the effectiveness of Acapella to usual airway clearance in adults during an acute exacerbation of bronchiectasis requiring oral antibiotic therapy. Twenty patients with bronchiectasis and an acute exacerbation requiring oral antibiotic therapy were recruited into a randomized crossover trial. Patients were allocated to one of two groups determined by concealed computer generated randomization. Group 1 (n 10): airway clearance session using Acapella at home twice daily during oral antibiotic therapy. Group 2 (n 10): usual airway clearance sessions at home during oral antibiotic therapy. Patients recorded duration of each treatment session, volume of sputum produced and perception of breathlessness. An independent assessor performed outcome measures of spirometric lung function, pulse oximetry and breathlessness at the beginning and end of the study period. The mean volume of sputum expectorated during Acapella sessions was greater than for usual airway clearance sessions although this difference was not significant 2.61 ml (95% CI-1.62 to 6.84). Mean duration of Acapella sessions was greater than usual airway clearance sessions and approached significance. There were no significant between group differences in changes in lung function. This study demonstrates that the Acapella device may offer an acceptable, user-friendly method of airway clearance in patients with bronchiectasis. Chronic Respiratory Disease 2007; 4: 67 74 Key words: Acapella ; airway clearance techniques; bronchiectasis Introduction Respiratory exacerbations are characterized by increased cough and increased sputum production with changes in viscosity making expectoration difficult. 1, 2 Daily airway clearance to remove secretions is important in the management of bronchiectasis and during exacerbations more intensive airway clearance may be required. Moderate and severe exacerbations are treated with intravenous (IV) antibiotics often in an inpatient setting and with an intensive care package typically including one to two daily supervised airway clearance sessions. 1 Mild exacerbations are treated at home with a 10 14-day course of oral antibiotics. 1 Adherence to airway clearance during an exacerbation is important in order to clear the increased sputum load. Correspondence: Judy M Bradley, Reader in Physiotherapy, Health and Rehabilitation Sciences Research Institute, School of Health Sciences, University of Ulster, Northern Ireland; and Regional Respiratory Centre, Belfast City Hospital, Lisburn Road, Belfast, BT9 7AB, Northern Ireland. E-mail: jm.bradley@ulster.ac.uk It has been proposed that adherence with selfmanaged therapy is generally improved with userfriendly devices. 1 A recent UK survey showed that the active cycle of breathing techniques (ACBT) is the most frequently used airway clearance technique (ACT) in patients with bronchiectasis. 3 However, a number of devices (eg, positive expiratory pressure, Flutter, Acapella ) have also been used in the management of these patients. 3 6 Evidence of the effectiveness of ACTs in patients with bronchiectasis is limited and focuses on five randomized controlled trials (RCTs), only three of which exclusively involve patients with bronchiectasis. A long-term RCT showed the Flutter (Scandipharm, Birmingham, Alabama) device to be as effective as ACBT in 17 patients with bronchiectasis; a single intervention randomized crossover trial showed ACBT to be more effective than an inspiratory muscle training technique device in 20 patients with bronchiectasis; and a single intervention randomized crossover trial showed the Acapella (Smiths Medical, formerly DHD Healthcare, Wampsville, New York, CE approved) 2007 SAGE Publications 10.1177/1479972306075483

68 device to be as effective as ACBT in 20 patients with bronchiectasis. 4,5,7 No previous studies have investigated airway clearance during exacerbations. The Acapella is a small hand-held device, which combines PEP and high-frequency oscillation therapy. The manufacturers suggest that Acapella may offer a beneficial alternative to other ACTs as it requires less therapist time, is self performed, can be used in any postural drainage position and is suitable to patients with a wide range of pulmonary function. No clinical trials have investigated the efficacy of Acapella during a pulmonary exacerbation requiring oral antibiotic therapy. The aim of this study was to compare the efficacy of Acapella with usual airway clearance in adults during an acute exacerbation of bronchiectasis requiring oral antibiotics. Methods The local ethics committee approved the study and written informed consent was obtained from all participants. Study design Patients were allocated to one of two groups determined by computer generated randomization performed by a clinician not involved in the trial. Codes for randomization were held in sealed envelopes and were unopened until the patient agreed to participate in the study. Group 1 (n 10) were required to perform airway clearance at home twice daily during oral antibiotic therapy using the Acapella device. Group 2 (n 10) were required to perform their usual airway clearance sessions at home during oral antibiotic therapy. Outcome measures were performed pre and post airway clearance session on day one and end day antibiotics (days 10 14) by an independent assessor (OH) blinded to group allocation. All patients were provided with a patient diary, 28 sputum containers (two for each day) calibrated with a scale measuring 0 20 ml and a Borg scale for perception of breathlessness. Methods Twenty adult patients with bronchiectasis (diagnosis by CT scan) were recruited from a specialist respiratory clinic at the Belfast City Hospital, Northern Ireland between January and August 2004. No suitable data was available to carry out a sample size calculation. Patients were studied during an acute exacerbation. As there are no criteria available to define an acute exacerbation in patients with bronchiectasis criteria developed in CF were used. An acute exacerbation was defined as the presence of four out of 12 symptoms of a respiratory exacerbation, and requiring a course of oral antibiotics. 8 Antibiotics were prescribed by a physician with expertise in bronchiectasis. Nineteen patients reported an increase in sputum volume or a change in sputum colour prior to inclusion in the trial. Exclusion criterions were: complications that would affect their ability to perform airway clearance such as pulmonary embolisms or haemoptysis; pulmonary infection requiring IV antibiotics; or inpatient admission. Both groups received a 30-minute training/assessment session on day one of their course of antibiotics with a physiotherapist (JP). The Group 1 patients training/assessment session included: determination of two postural drainage positions by auscultation; selection of the correct Acapella device (green Acapella for patients able to sustain an expiratory flow of greater than 15 L/M for at least three seconds and blue Acapella for patients with an expiratory flow of less than 15 L/M); determination of the correct Acapella settings; training on its use; and instruction to use the device for a maximum of 15 minutes in each postural drainage position or until patient could no longer tolerate treatment. The Group 2 patients training/ assessment involved review of their usual airway clearance regimen including: technique used, positioning, duration and frequency of treatments. Acapella Acapella consists of a counterweighted plug and metal strip attached to a lever, and a magnet. Airflow oscillations are created by the breaking and reforming of a magnetic attraction by the plug as it intermittently occludes air passing through the device. The device incorporates an adjustable frequency/resistance dial which adjusts the proximity of the magnet to the metal strip, thereby adjusting expiratory pressure, and amplitude and frequency of oscillations. The initial training session and subsequent treatment sessions were conducted as recommended by the manufacturer s of Acapella. During the initial training session patients were taught to exhale through the device (with the frequency/resistance dial set at minimum setting) in a three to four-second timeframe. If exhalation was too slow or too fast patients were encouraged to exhale more or less forcefully. A manometer was then included in the circuit and the frequency/resistance dial increased until the expiratory pressure reading was maintained between 10 and 20 cmh 2 O. Acapella was performed in the two predetermined postural drainage Chronic Respiratory Disease

69 positions. The components of the Acapella treatment included: breathing control, 10 breaths through the Acapella device inhaling to three-quarter maximum breathing capacity, two to three-second breath hold, active exhalation to function residual capacity (FRC), and cough or forced expiration (huff) in a set cycle. Usual airway clearance Usual was defined as the ACT currently used by the patient. In some patients usual airway clearance may potentially have been no airway clearance. A number of outcome measures were recorded in this study however sputum volume/weight were chosen to be the primary outcome. Patients were instructed to keep a record of duration of all treatment sessions, volume of sputum produced during treatment sessions and perception of breathlessness and to administer their medication (short-acting bronchodilaters, long-acting bronchodilaters and steroids, where applicable) at least one-hour pretreatment. Patients were contacted once per week and encouraged to comply with their airway clearance regimen and complete the diary. Outcome measures performed pre- and post airway clearance session on day one and end day antibiotics included: spirometric measures of lung function (Micro Lab, 3500 UK); pulse oximetry (Nellcor Puritan Bennett NPB 40); Borg breathlessness score; and 15-count breathlessness score. 9 The independent assessor also administered a short interview based symptoms questionnaire prior to airway clearance on day one and end day antibiotics (days 10 14) addressing patient perceived changes during the previous week in: sputum volume and colour, cough, exercise tolerance, dysponea, fatigue, sinus discharge and appetite. Number of coughs was recorded during airway clearance sessions on day one and final day antibiotics by a physiotherapist (JP). Assessments were conducted at approximately the same time on both days. At end day antibiotics the randomization code was broken after completion of all other outcome measures. This facilitated the independent assessor to administer a short questionnaire to all patients in Group 1 (Acapella group) determining preference of Acapella with their previous technique (Appendix 1). A further questionnaire was administered to these patients one month following completion of study to determine continued use of Acapella (Appendix 1). Analysis Statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS version 11.0). The t-test for independent samples was used to compare sputum volumes and duration of treatment sessions. The t-test for paired samples was used to compare pre- and posttreatment outcome measures within each group. Analysis of covariance was used to compare between group pretreatment day 1 and pretreatment end antibiotic day lung function; between group day 1 and end antibiotic day cough counts and between group day 1 and end antibiotic day sputum volume. The Mann Whitney test was used to compare mean rank day 1 and end antibiotic day symptoms questionnaire. A P-value of 0.05 was considered statistically significant. Results All 20 patients completed the study (Figure 1). Demographic details as well as information on infecting organisms and antibiotics received are outlined in Table 1. There was no difference in baseline age or lung function between the groups. Two patients in Group 1 and one patient in Group 2 received a 10-day course of antibiotics, the remaining patients received a 14-day course of antibiotics. Oral antibiotics were prescribed according to sputum sensitivity results at their previous visit to the clinic and the likely current infecting organisms. Antibiotics were not changed in any patients during the course of the study. Of the seven patients who cultured organisms in their baseline sputum, the infecting organism (Haemophilis influenzae) was eradicated in four patients (Table 1). In one patient Pseudomonas aeruginosa was not eradicated; in one patient infected at baseline with Streptoccocus pneumoniae and H. influenzae only the S. pneumoniae was eradicated; and in one patient although the baseline infecting organisms (S. pneumoniae and H. influenzae) were eradicated P. aeruginosa was isolated at the end of antibiotics. Usual airway clearance regimens conducted by patients prior to the study included ACBT (n 14), autogenic drainage (n 2), PEP (n 2), Flutter (n 1) and no airway clearance (n 1) and usual mean daily duration of airway clearance was [mean (SD)] 22.87 (16.30) minutes. Usual airway clearance regimens conducted by patients in Group 2 were: ACBT (n 9) and PEP (n 1). All patients in Group 1 and eight patients in Group 2 performed two airway clearance sessions per day (morning and evening); two patients in Group 2 performed one airway clearance session per day (morning). The mean volume of sputum expectorated during Acapella sessions was greater than for usual airway clearance sessions although this difference was not significant 2.61 ml (95% CI-1.62 to 6.84) (Table 2). There were no significant between group differences in http://crd.sagepub.com

70 Figure 1 Flow diagram of the progress of patients through trial. Table 1 Demographic details: information of infecting organisms and antibiotics received Gender 10 M: 10 F FEV 1 % predicted Mean (SD) FEV 1 64.70 (21.13) Age (years) Mean (SD) 61.1 (10.9) Infecting organisms Pseudomonas aeruginosa n 1 Haemophilis influenzae n 6 Commensals only n 13 Streptoccocus pneumoniae n 2 Antibiotics Ciprofloxacin n 14 Co Amoxiclav n 4 Doxycycline n 1 Co-trimoxazole n 1 Table 2 Between group differences in mean session volume of sputum expectorated and mean session duration Mean Acapella Usual Rx difference Rx Mean (SD) Mean (SD) (95% CI) P-value Sputum 5.83 3.22 2.61ml 0.31 volume (4.96) (3.99) (95% CI-1.62 (Rx sessions) to 6.84) (ml) Duration 15.37 11.35 4.02 0.06 (Rx sessions) (2.73) (5.58) ( 0.22 to 8.26) (minutes) day one and final day (days 10 14) sputum volume [mean difference 1.16 ml (95% CI 2.36 to 0.04)]. The mean daily volume of sputum expectorated fluctuated over the period of antibiotic therapy although a greater amount of sputum was expectorated during Acapell. The mean duration of Acapella sessions was greater than of usual airway clearance sessions and approached significance [mean difference 4.02 minutes (95% CI 0.22 to 8.26) P 0.06] (Table 2). No significant differences were found between preand posttreatment lung function, SpO 2 or breathlessness for either group at day one or final day of antibiotics (days 10 14) indicating neither Acapella nor usual airway clearance increased airway obstruction or desaturation. There were no significant between group differences in change in pretreatment day one and pretreatment final day lung function: VC [mean difference 0.02 L (95% CI 0.21 to 0.17)], FVC [mean difference 0.16 L (95% CI 0.36 to 0.05)], FEV 1 [mean difference 0.09 L (95% CI 0.22 to 0.03)], PEF [mean difference 22.78 L/min (95% CI 34.08 to 79.64)] (Table 3). There were no significant between group differences in day one and final day cough counts. There were no significant between group differences in patient perception of changes in: sputum volume or colour; cough; exercise tolerance; dyspnoea; or fatigue between beginning and end of study period. Patient Chronic Respiratory Disease

71 Figure 2 Mean daily sputum volumes. Table 3 Between group differences in changes in pretreatment day one and pretreatment final day lung function perception of changes in sinus discharge and appetite between beginning and end of study period were improved in the Acapella group and approached significance (Table 4). No patients in either group reported any side effects from their airway clearance treatment. Seven patients in group one preferred Acapella to their usual airway clearance used previous to the study, one patient had no preference and two patients preferred their usual airway clearance. One month post study, seven patients were using Acapella every day, two patients were using Acapella three to four times a week and one patient was not using Acapella at all. Discussion Mean difference (95% CI) P-value FEV 1 (L) 0.09 0.13 ( 0.22 to 0.03) FVC (L) 0.16 0.12 ( 0.36 to 0.05) VC (L) 0.02 0.84 0.21 to 0.07) PEF (L/min) 22.78 0.41 ( 34.08 to 79.64) This study demonstrates that the Acapella device offers an alternative acceptable method of clearance Table 4 Between group differences in changes in day one and final day respiratory symptoms Acapella Rx Mean Usual Rx Significance rank Mean rank of mean difference difference difference Sputum volume 10.65 10.35 0.91 Sputum colour 12.10 8.90 0.19 Intensity of cough 10.55 10.45 0.97 Frequency of cough 9.95 11.05 0.67 Exercise tolerance 8.75 12.25 0.17 Fatigue 10.00 11.00 0.69 Sinus discharge 12.90 8.10 0.06 Appetite 12.65 8.35 0.08 to usual airway clearance in patients with bronchiectasis and an acute exacerbation of their condition requiring treatment with oral antibiotics. The most common usual airway clearance techniques in this group of patients prior to the study were ACBT, autogenic drainage and PEP. This trial contributes to the limited evidence base for airway clearance in bronchiectasis: first, it investigates the efficacy of a new airway clearance device, Acapella, and second, it provides unique data regarding daily changes in sputum output during an oral antibiotic treatment in patients with bronchiectasis. The Acapella device creates PEP and oscillatory vibrations of the air within the airways by resisting and intermittently occluding expiratory air flow through the device. It has been proposed that PEP therapy creates a positive back pressure during expiration that splints open the peripheral airways, temporarily http://crd.sagepub.com

72 increasing lung volume and allowing air to move behind the obstructed lung segments through collateral ventilation pathways. 10, 11 The device generates oscillations of between zero and 30 Hertz during expiration, which further facilitates the mobilization of secretions. Expiratory flow moves secretions into the central airways where they are expectorated following cough or huff. A clinical short-term study compared Acapella with ACBT in patients with stable bronchiectasis and showed the techniques to be equally as effective. 5 A laboratory study compared Acapella with an established oscillatory PEP device, the Flutter. 12 The devices were compared in terms of PEP, oscillatory pressure amplitude and frequency over a clinically relevant range of flows produced from a compressed oxygen source. The study demonstrated that Acapella had similar performance characteristics to the Flutter but produced more stable air flow oscillations at the highest and lowest flow settings tested. 12 Acapella may therefore be suitable for patients with a wider range of lung function and can also be used in any postural drainage position. No previous studies have investigated airway clearance in patients with an acute exacerbation of bronchiectasis. In this study there were no between group differences in any parameters of lung function. This is usual in mild exacerbations such as these. In a study of severe exacerbations treated with intravenous antibiotics only small non-significant improvements in FEV 1 was described. 13 Lung function has been traditionally used as the primary outcome measure in airway clearance studies. This is based on the assumption that retention of sputum reduces airway diameter and contributes to airflow obstruction. However, Van der Schans postulates that although measurement of lung function is important in airway clearance studies to evaluate possible side effects, lung function is neither sensitive nor specific enough to detect clinically important changes in sputum transport. 14 The use of alternative outcome measures that relate closely to the overall objective of airway clearance, that is to improve muco-ciliary transport, may therefore be more relevant. For example, the use of inhaled radioactive aerosols may more accurately quantify changes in muco-ciliary transport. However, these cannot be performed easily and in general it has been shown that improvement in sputum transport as quantified by inhaled radioactive aerosols was associated with an improvement in sputum transport quantified by volume of expectorated sputum. 14 Sputum volume was recorded as the primary outcome measure in this trial for two reasons. Sputum volume provides information which establishes the short term clinical efficacy and safety of this new airway clearance adjunct. Only when short term efficacy and safety become established as in this trial, should the effect on relevant endpoint (or endpoints) be investigated. Furthermore, despite controversy surrounding the use of outcome measures relating to sputum load, amount of sputum expectorated is an outcome measure of key importance to patients. In this trial sputum volume was used in preference to sputum weight as patients were involved in the trial concurrently and therefore it was not feasible to provide individual patients with weighing scales. Previous studies have suggested that sputum volume and weight are comparable and that each gram of sputum is considered to have a volume equivalent to 1 ml. 15 Van der Schans highlights that an important but often overlooked aspect of sputum expectoration is the subjective experience of the patient. This is important as one of the potential effects of airway clearance is to make sputum clearance more efficient for the patient. 14 This study shows that patients perceived changes in sputum volume and other symptoms related to the potential effects of airway clearance improve irrespective of group allocation, and the between group differences do not reach significance. In this study the main daily sputum volume expectorated using Acapella showed an overall decrease from day one through to day 14 with the greatest percentage decrease from baseline at final day antibiotics. The daily sputum volume expectorated using usual airway clearance fluctuated throughout the antibiotic period with the mean percentage change from baseline almost zero at final day antibiotics. A limitation of this study was the reliance on patient self-reported outcome measures. However, every effort was taken to minimize errors, for example, calibrated containers were provided to measure sputum and patients were contacted weekly to encourage adherence and the completion of the patient diary which were completed daily by all patients in the study. In summary sputum clearance was greater in the group of patients in this study who incorporated the Acapella device into their regimen spending a greater period of time performing airway clearance. Many patients prefer to use user-friendly devices to facilitate airway clearance and follow-up evaluation suggested the Acapella device may facilitate long term adherence to regular airway clearance. This study demonstrates the Acapella device may offer a user-friendly alternative to usual methods of airway clearance. Chronic Respiratory Disease

References 1. Silverman E, Ebright L, Kwiatkowski M, Cullina J. Current management of bronchiectasis: review and 3 case studies. Lung 2003; 32: 59 64. 2. Evans DJ, Greenstone M. Long-term antibiotics in the management of non-cf bronchiectasis do they improve outcome? Respir Med 2003; 97: 851 858. 3. O Neill B, Bradley JM, McCardle N, MacMahon J. The current physiotherapy management of patients with bronchiectasis: a UK survey. Int J Clin Pract 2002; 56: 34 35. 4. Thompson CS, Harrison S, Ashley J, Day K, Smith DL. Randomised crossover study of the Flutter device and the active cycle of breathing technique in non-cystic fibrosis bronchiectasis. Thorax 2002; 57: 446 448. 5. Patterson JE, Bradley JM, Hewitt O, Bradbury I, Elborn JS. Airway clearance in bronchiectasis: a randomized crossover trial of active cycle of breathing techniques (ACBT) versus Acapella. Respiration 2005; 72: 239 242. 6. Pryor JA. Physical therapy for adults with bronchiectasis. Clin Pulm Med 2004; 11: 201 209. 7. Patterson JE, Bradley JM, Elborn JS. : a randomized crossover trial of active cycle of breathing techniques (incorporating postural drainage and vibration) versus test of incremental respiratory endurance. Chron Respir Dis 2004; 1: 127 130. 8. Ramsey BW, Pepe M, Williams WJ. Pulmonary exacerbation (PE): How do we define it? Pediatr Pulmonol 1994; 9 (Suppl): 77 78. 9. Prasad SA, Randall SD, Balfour-Lynn IM. Fifteen-count breathlessness score: an objective measure for children. Pediatr Pulmonol 2000; 30: 56 62. 10. Falk M, Andersen JB. Positive expiratory presseure (PEP) mask. In Pryor JA ed. Respiratory care. Churchill Livingstone, 1991: 51 63. 11. Falk M, Kelstrup M, Andersen JB, Kinoshita T, Falk P, Stovring S, Gothgen I. Improving the ketchup bottle method with positive expiratory pressure, PEP, in cystic fibrosis. Eur J Respir Dis 1984; 65: 423 432. 12. Volsko TA, DiFore JM, Chatburn RL. Performance comparison of two oscillating positive expiratory pressure devices: Acapella versus Flutter. Respir Care 2003; 48: 124 130. 13. Watt AP, Brown V, Courtney J et al. Neutrophil apoptosis, proinflammatory mediators and cell counts in bronchiectasis. Thorax 59: 23 26. 14. Van der Schans CP, Postma DS, Koeter GH, Rubin BK. Physiotherapy and bronchial mucus transport. Euro Respir J 1999; 13: 1477 1486. 15. Wilson MJB, Martin DE. Quantitative sputum culture as a means of excluding false positive reports in the routine microbiology laboratory. J Clin Path 1972; 25: 697 700. Appendix 1 Preference questionnaire Part 1 Which of the following treatment techniques would you prefer: Acapella to your normal airway clearance regimen which you used prior to this study Go to part 2 your normal airway clearance regimen to Acapella Go to part 3 no preference Go to part 4 Part 2 Can you think of any reasons why you preferred Acapella to your normal airway clearance regimen, which you used prior to this study? I will now read a list of reasons, which some people who have used Acapella, have given as to why they have preferred this method of airway clearance. I will pause after each item long enough for you to tell me if you agree, disagree or don t know. The reasons are: Increased sputum expectoration with Acapella Shorter treatment time with Acapella Less effort required during airway clearance with Acapella Decreased feeling of breathlessness with Acapella Part 3 Can you think of any reasons why you preferred your normal airway clearance regimen, which you used prior to this study to Acapella? I will now read a list of reasons, which some people who have used Acapella, have given as to why they have preferred their normal airway clearance regimen. I will pause after each item long enough for you to tell me if you agree, disagree or don t know. The reasons are: Increased sputum expectoration with your normal airway clearance regime Shorter treatment time with your normal airway clearance regime Less effort required during airway clearance with your normal airway clearance regimen Decreased feeling of breathlessness with your normal airway clearance regimen 73 http://crd.sagepub.com

74 Part 4 Can you think of any reasons why you had no preference between your normal airway clearance regimen, which you used prior to this study to Acapella? I will now read a list of reasons, which some people who have used Acapella, have given as to why they had no preference between Acapella and their normal airway clearance regimen. I will pause after each item long enough for you to tell me if you agree, disagree or don t know. The reasons are: Similar sputum expectoration with both Acapella and your normal airway clearance regimen Similar treatment time with both Acapella and your normal airway clearance regimen Similar effort required during both Acapella and your normal airway clearance regimen Similar feelings of breathlessness with Acapella and your normal airway clearance regimen One-month post study questionnaire Telephone interview 1. How often have you used Acapella since completing the trial? (a) every day (b) three to four times a week (c) once a week (d) not at all 2. How often have you used your normal airway clearance since completing the trial? (a) every day (b) three to four times a week (c) once a week (d) not at all Chronic Respiratory Disease