JOURNAL OF THE ROYAL SOCIETY OF MEDICINE Supplement No. 38 Volume 93 2000

Physiotherapy in cystic fibrosis

SAmmaniPrasadMCSP Esta-Lee Tannenbaum MCSP Christine Mikelsons MCSP

J R Soc Med 2000;93(Suppl. 38):27–36 SECTION OF PAEDIATRICS & CHILD HEALTH, 23 NOVEMBER 1999

INTRODUCTION Box 1 Airway clearance techniques Major advances over the past 15 years in the management of cystic fibrosis (CF) have resulted in dramatic improvements Active cycle of techniques (ACBT) in longevity and quality of life for many patients. However, Autogenic drainage (AD) respiratory dysfunction remains responsible for much of the Conventional chest physiotherapy (CCPT) morbidity and mortality associated with the disorder. Exercise Physiotherapy has long played an important role in the High frequency chest wall oscillation (HFCWO) respiratory management of the disease and has had to adapt Intrapulmonary percussive ventilation (IPV) to the changes in disease pattern from infancy to adulthood. Oscillatory positive expiratory pressure devices: The role of the physiotherapist is not limited to airway Flutter RC Cornet1 clearance but also includes encouragement and advice on Positive expiratory pressure (PEP) exercise, posture and mobility, inhalation therapy and, in High-pressure PEP (H PEP) the later stages of the disease process, non-invasive respiratory support. It is generally felt that the use of chest physiotherapy in as effective as chest physiotherapy in terms of sputum 3–6 CF has lacked good scientific basis and the current call for clearance and short-term lung function . evidence-based medicine requires physiotherapists to More recent data provides strong evidence to suggest scrutinize their practice closely. A series of systematic that pulmonary infection and inflammation occur at a very reviews of the existing data on airway clearance techniques early stage in the disease process, even before the onset of 7–9 in CF is currently being undertaken by the Cochrane CF respiratory signs . Such pathophysiological evidence group and the results of these are awaited with interest. At supports the theoretical assumption that early intervention the present time many questions regarding the long term (not necessarily physiotherapy) might be of value. Ethical efficacy and application of the various airway clearance concerns regarding withdrawal of such a well-established regimens remain unanswered. treatment probably mean that a randomized controlled trial of treatment versus no treatment even in an asymptomatic group of patients is now unlikely. Most studies therefore IS DOING SOMETHING ALWAYS BETTER THAN attempt to compare the efficacy of two or more different DOING NOTHING? treatment techniques. Daily airway clearance regimens are time consuming and burdensome, hence the significant and well-documented WHICH AIRWAY CLEARANCE TECHNIQUE? problems with adherence. Scientifically proven justification Traditionally, chest physiotherapy constituted a passive of therapy might serve not only to persuade patients and treatment—usually a combination of and carers of the value of a routine which often does not offer percussion in gravity assisted positions—administered to immediate or obvious benefit, but also reassure therapists the patient by an assistant. With improved longevity and that their practice is worthwhile. Examination of the emphasis placed on enabling patients to lead active and current literature reveals few studies which evaluate independent lifestyles, several airway clearance techniques treatment versus no treatment, although a 3 week period (ACT) have been developed (Box 1). These all aim to without treatment has been reported to have detrimental promote self-administration of treatment and yet to be 1 effects on lung function . In another study no demonstrable effective and efficient. benefit from either chest physiotherapy or inhalation alone was reported2. Some authors report coughing alone to be Conventional chest physiotherapy

Respiratory Unit, Great Ormond Street Hospital For Children, Great Ormond The traditional modality of chest physiotherapy described Street, London WC1N 3JH and The London Chest Hospital, Bonner Road, above is often referred to as conventional chest physio- London E2 9JX, UK therapy (CCPT). Nowadays it also includes breathing Correspondence to: S Ammani Prasad exercises and forced expiratory manoeuvres and is often 27 JOURNAL OF THE ROYAL SOCIETY OF MEDICINE Supplement No. 38 Volume 93 2000

performed without assistance using self-applied or Autogenic drainage mechanical percussion. Autogenic drainage (AD) consists of a three-phase breathing Many studies use CCPT as the comparison for one of the regimen in which clearance is facilitated by the ‘newer’ techniques. Most of these comparative studies adjustment of the tidal breath toward low, mid and high conclude equal efficacy between techniques. However, lung volumes depending on the localization of the mucus Reisman et al. in a 3-year prospective study reported (whether peripheral or central). The aims of AD are to conventional therapy (postural drainage and percussion with achieve as high an expiratory flow as possible whilst keeping the addition of forced expiration) to be superior to the the resistance to flow to a minimum. This prevents airway forced expiratory technique alone10. The group not using collapse and helps the mucus to travel the furthest distance conventional therapy showed a significantly greater decline over a longer expiration25. Studies have indicated that AD is in forced expiratory volume in 1 s (FEV1) and forced as effective as CCPT26,27, the Flutter28 and ACBT23.Itis expiration 25%–75% (FEF25–75). also reported to be advantageous in the presence of airway Postural drainage as an additional individual component hyper-reactivity29,30. of chest physiotherapy has been reported as beneficial11–13. Another study found postural drainage combined with the Exercise forced expiration technique (FET) had no advantage over positive expiratory pressure (PEP) and FET in terms of Early studies of exercise as a method of airway clearance 14 suggested it could replace other forms of chest tracheobronchial clearance . The physiological principle of 31,32 postural drainage uses gravity to assist mobilization of physiotherapy . However, more recent data suggests that though certainly beneficial it should be complementary secretions to the central airways. Lannefors et al. reported 33–35 maximal clearance from the dependent lung region during to other techniques . Investigation of the type of postural drainage for the right middle lobe using exercise most beneficial in facilitating airway clearance has scintigraphic imaging and inhaled radiolabelled particles, not been undertaken. Some authors have, however, questioned the effectiveness of cycle ergometry compared hypothesizing that gravity is not the only factor influencing 15,36 mucus clearance during postural drainage15. with other forms of aerobic exercise .

High-frequency chest wall oscillation Active cycle of breathing techniques The application of high-frequency chest wall oscillation The active cycle of breathing techniques (ACBT) is a (HFCWO) through a range of oscillatory frequencies flexible regimen comprising breathing control, thoracic between 5 and 15 Hz is said to enhance mucus clearance expansion exercises and the FET, frequently combined with and alter the viscoelastic properties of secretions. Such gravity assisted positioning. Increasing lung volume during thoracic expansion allows air to get behind distal secretions via collateral ventilatory channels. During a forced expiratory manoeuvre compression and narrowing occurs within the airways at a point dependent on lung volume (the equal pressure point). This is shifted distally as a forced expiration is continued to low lung volume thereby mobilizing peripheral secretions. This technique has been reported to be an effective and efficient means of airway clearance16,17, with documented improvements in lung function18 and no detrimental effect on oxygen saturation19. In comparative studies the ACBT has been found to be advantageous when compared with CCPT17, Flutter20,21 and PEP22. When compared with the technique of autogenic drainage (AD) Miller et al., reported no differences in efficacy although ACBT was associated with desaturation in some cases23. There was, however, no significant overall difference in saturation between the two techniques. A more recent comparison of the Flutter and forced expiration with the ACBT reported no significant differences between the treatments for sputum weight, lung Figure 1 The ThAIRapy vest, provides high frequency chest wall 28 function tests or oxygen saturation24. oscillation via an air pulse generator attached to the vest JOURNAL OF THE ROYAL SOCIETY OF MEDICINE Supplement No. 38 Volume 93 2000

37,38 47 systems include the Hayek oscillatory and the Increased sputum clearance , improvements in FEV1, ThAIRapy vest in which a thoracic vest is rapidly inflated forced vital capacity (FVC)46,48 and a reduction in the and deflated by an air-pulse generator, creating chest wall viscoelasticity of secretions28,49 with use of this device have oscillation (Figure 1). Treatment is often accompanied by been documented. Whilst short-term comparative studies the inhalation of nebulized 0.9% saline. report equal efficacy between the Flutter and other airway Improvements in lung function39,40, a reduction in clearance techniques44,50–52, a longer-term study of 40 sputum viscosity41 and enhanced mucus clearance39,42 have patients over a 1-year period has reported it to be less been reported with this modality. Arens et al. reported it to effective than PEP in terms of decline in FEV1 and be equally effective as conventional chest physiotherapy in a frequency of exacerbations53. group of 50 CF patients during an acute pulmonary exacerbation40. RC Cornet1111 Based on a similar physiological principle as the Flutter, the Intrapulmonary percussive ventilation Cornet is a relatively new oscillatory device. It consists of a mouthpiece, hose, curved tube and sound damper Intrapulmonary percussive ventilation (IPV) aims to deliver (Figure 2). Expiration through the device creates an aerosol inhalation whilst simultaneously applying positive increasing pressure within the hose until sufficient to cause pressure oscillations to the airway, to provide intra- the hose end to catapult open, thus releasing the pressure pulmonary percussion at 6 to 14 Hz and a positive end and allowing air to flow through the device. This cycle expiratory pressure of 2 to 8 cmH2O. Small bursts of room continues throughout exhalation, producing an oscillatory air along with a side stream of nebulized solution (using the PEP. The pressure and flow rate can be adjusted by rotating jet Venturi principle) are delivered via a mouthpiece with the mouthpiece in the tube. The Cornet has been reported an aerosol delivery rate of approximately 1 mL/min. No to reduce sputum cohesiveness54. In a comparative study of significant differences were noted in studies comparing IPV the two devices, the Cornet is reported to have advantages 46 or Flutter in a small single intervention study . The same over the Flutter in terms of being position independent and study also documented significant but inconsistent improve- providing a more constant pressure and flow rate ments with both oscillatory devices. Other documented throughout expiration55, but further studies of efficacy are benefits of IPV include alterations in sputum viscosity and necessary. cost effectiveness37. Positive expiratory pressure Oscillatory PEP The application of a positive expiratory pressure (PEP) Flutter between 10–20 cmH2O via a facemask or mouthpiece has The Flutter is a small pipe-shaped, hand-held device been reported to increase regional lung volume, reduce the generating an oscillatory positive pressure during expira- volume of trapped gas, limit compression of compliant tion. Altering the inclination of the device from the airways and promote ventilation through collateral channels horizontal can regulate the frequency of oscillation. The thereby enhancing the peripheral secretions56–58. Many resulting vibratory effect combined with PEP is said to short-term studies document this technique to be an maintain airway patency and enhance mucus clearance. acceptable and effective alternative to CCPT59–62.A

Figure 2 (a) The RC Cornet1.(b) Schematic diagram of the RC Cornet11 29 JOURNAL OF THE ROYAL SOCIETY OF MEDICINE Supplement No. 38 Volume 93 2000

longitudinal study of 40 patients over 1 year has reported attempt to evaluate the relatively short-term efficacy of 63 long-term benefits for FEV1 and FVC . airway clearance techniques. Often, however, the results of comparative studies are contradictory. Some report specific High-pressure PEP advantages of one modality over another, whilst others fail to reproduce similar results. Confusion in the existing High-pressure PEP is a modification of the above technique literature might be explained in terms of study design, which utilizes forced expiratory manoeuvres through the protocol and methodology. PEP mask. Such a manoeuvre produces a constant The majority of studies are of short-term duration, expiratory flow (with expiratory pressures ranging from ranging from the evaluation of response to a single 40–100 cmH O) whilst the force generated by the 2 treatment to 3–4 day cross over trials (Figure 3). Such respiratory muscles balances the resistance offered by the study designs are easy to undertake, and minimize device. As the respiratory muscles encounter a mechanical confounding variables. Whilst some valuable information disadvantage at low lung volume, flow falls as does the might be gained, relating to treatment safety and short-term resistance offered by the mask. An equal pressure point physiological effects, the results of such studies are difficult develops but relatively late in expiration and at a point to extrapolate to the longer term. Yet it is the long-term further downstream. Avoiding airway collapse and enhan- effects of daily treatment on clinical well being and quality cing expiratory flow is said to facilitate airway clearance and of life which are important. Longitudinal studies, whilst the recruitment of obstructed and atelectatic lung units fraught with the difficulties of recruitment, adherence and enables evacuation of trapped gas. confounding variables, give more valuable information on Beneficial effects of this technique include an increase in these more pertinent outcomes. mucus clearance64,65, reduction in hyperinflation and Descriptions of treatment protocols for the same improvements in lung function30,65. Concerns have been technique vary widely in the literature. Standardization of expressed regarding the potential risk of high airway treatment regimens, whilst necessary in terms of scientific pressures with regard to pneumothorax and haemoptysis. evaluation, may not be a true reflection of everyday The safety of the technique has been documented with a practice. It could be argued that although the experimental reported incidence of one spontaneous pneumothorax and environment of longitudinal studies is difficult to control, one case of severe haemoptysis in 3866 patient treatment these may, in fact, better reflect every-day clinical months66. practice. Most studies evaluate and compare the effect of two or more interventions on outcome measures such WHY IS THE EXISTING LITERATURE CONFUSING? as sputum weight/volume or lung function67. Only a few Currently, the choice of an airway clearance technique is to studies are of sufficient duration to evaluate the impact of some extent led by geographical therapeutic trends and an intervention on measures of long-term clinical status, therapists’ personal experiences rather than robust long such as frequency of exacerbation, requirement of term scientific data. Several comparative studies exist which antibiotics, or the impact of daily treatment on quality of life10,39,53,63. In the majority of studies subject numbers are relatively small (Figure 4). These studies may, therefore, not be of sufficient power to demonstrate differences. The recruit- ment of sufficient numbers from any one CF clinic often poses practical problems, and multicentre trials are likely to be required. Population samples from different centres may also vary significantly in terms of general clinical status and approach to management. They could, therefore, poten- tially demonstrate different responses to the same technique. Overall there appears to be no conclusive evidence to promote any single technique. One could, of course, question the validity of such a question in a complex and variable disorder which spans many years of life. It is more reasonable to assume that an individual might respond differently to any one technique or another at various stages

Figure 3 Duration of study in 50 randomly selected studies of of the disease, depending on their clinical status, age and 30 airway clearance techniques in cystic fibrosis social circumstance at the time. JOURNAL OF THE ROYAL SOCIETY OF MEDICINE Supplement No. 38 Volume 93 2000

Multicentre trials are currently underway to evaluate the efficacy of these devices.

RESPIRATORY SUPPORT TECHNIQUES—WHAT ROLE DO THEY PLAY? Respiratory support techniques such as intermittent positive-pressure breathing (IPPB), continuous positive- airway pressure (CPAP), and non-invasive positive-pressure ventilation (NIPPV) are each described in the literature as fulfilling a useful function in the treatment of patients with CF during acute bronchopulmonary exacerbation70–73. The use of these techniques is usually only considered when other methods of airway clearance have become ineffective despite optimization of oxygen therapy and humidifica- tion74. Careful assessment will indicate which modality is most appropriate, and any contraindications (e.g. undrained Figure 4 Subject numbers in 50 randomly selected studies of pneumothorax, hypotension, large bullae, severe haem- airway clearance techniques in cystic fibrosis optysis) to applying positive-pressure should, of course, be excluded. The use of CPAP as an adjunct to physiotherapy has been shown to decrease the work of breathing and increase WHAT IS THE ROLE OF INHALATION THERAPY IN functional residual capacity75 and could be used to re- RELATION TO AIRWAY CLEARANCE TECHNIQUES? expand atelectatic areas of lung76. It may also be useful in Aerosol therapy plays an essential role in the treatment of patients with rib fractures, resulting from steroid therapy, chronically infected CF airways providing topical delivery of where an increase in tidal volume would cause pain73. the drug. Correct inhalation techniques in conjunction with CPAP is not appropriate for use in terminally ill patients or physiotherapy may improve drug deposition thereby those with significant carbon dioxide retention, as there is optimizing clinical efficacy. It is also suggested that no increase in tidal volume or respiratory rate. Caution inhalation of nebulized medication in positions other than should always be exercised to ensure that CPAP is used sitting might further improve drug deposition by using the appropriately and careful monitoring undertaken. The concept of regional ventilation68. system should be adequately humidified in high-volume It is becoming increasingly popular to combine sputum producing patients77. inhalation therapy with ACT, e.g. AD, PEP or Flutter. The increasingly widespread use of NIPPV has to some However, there is no scientific evidence to suggest that this extent led to a decline in the use of IPPB. However, IPPB methodology is more effective. In vitro studies, however, do still has a role in those suffering from respiratory muscle suggest that simultaneous therapy with oscillation and fatigue due to sputum retention and in the terminal stages DNase can effectively reduce the viscoelasticity of of the disease73. IPPB in such circumstances can optimize mucus49,69. sputum clearance with minimal effort from the patient by The timing and order in which the drug is taken is reducing the work of breathing and increasing tidal necessary to ensure maximum benefit (i.e. bronchodilators volume78. Furthermore, it may be a useful alternative to and mucolytics taken prior to therapy whilst antibiotics and NIPPV when a more intensive intervention is considered inhaled steroids should be administered after airway inappropriate. clearance). Other factors such as cleaning and maintenance NIPPV has been shown to be useful in the treatment of of compressor and nebulizer systems, the degree of lung type II respiratory failure in a wide variety of diseases disease and inhalation technique may also influence the including chronic obstructive pulmonary disease79. How- result of nebulization therapy. Inhalation therapy as part of ever, few studies evaluate its use in patients with CF. Piper physiotherapy may reduce the overall time spent on et al. reported successful treatment of a small number of treatment and provide additional therapeutic benefit. patients with end-stage CF in type II respiratory failure71. However, further studies are required to prove the efficacy These patients were discharged home using NIPPV. Its use as of such regimens. New delivery devices such as the adaptive a bridge to transplantation has also been documented70,80. aerosol system deliver medication on inspiration only, However, the major dilemma for many clinicians using aiming to shorten inhalation time yet optimize delivery. NIPPV in the terminal stages of the disease lies in the ethical 31 JOURNAL OF THE ROYAL SOCIETY OF MEDICINE Supplement No. 38 Volume 93 2000

issue of prolonging life at all costs versus clinical benefit and effective analgesia is essential as pain itself can cause quality of life. sputum retention and respiratory failure.

Urinary incontinence COMPLICATIONS OF —WHAT CAN PHYSIOTHERAPY DO? Stress incontinence is an infrequently raised but a distressing The current median survival of CF patients born today is and socially embarrassing problem for women, with a predicted to be 40 years compared with 15–18 years for reported incidence of 8.5% between the ages of 15 and 65 those born between 1968 and 197081,82. Improved years86. In an unpublished survey of 188 respiratory longevity carries with it the possibility of developing medicine inpatients, 63% reported urinary and 13% faecal complications which perhaps have not been encountered incontinence, 83% of whom had not sought help for the previously and the emergence of problems such as stress problem87. Another study reported a 35% occasional and incontinence and those posed by pregnancy present a new 24% regular incidence of incontinence88. Physical activity challenge. and forced expiratory manoeuvres, particularly coughing, are likely to exacerbate the problem. It is important that this is not overlooked. Modification of the physiotherapy Haemoptysis regimen and pelvic floor exercises may help to alleviate Significant haemoptysis is infrequent in childhood but symptoms. Referral to a specialist physiotherapist might occurs in approximately 7% of older patients with CF83.It also be appropriate. is described as severe if more than 200 ml is expectorated over a 24-h period and such cases may require bronchial Pregnancy artery embolization. More usually haemoptysis can be Although not a complication in itself pregnancy often poses managed conservatively. However, it is advisable to problems, particularly in its later stages when the discontinue airway clearance techniques whilst there is a diaphragm is displaced and its movement restricted due significant amount of fresh bleeding. Adequate humidifi- to the gravid uterus. The resulting fall in functional residual cation should be given during this period to promote capacity may result in airway closure at the lung bases and expectoration with minimal effort. Physiotherapy should be retention of secretions. It is important that chest re-instated as soon as possible to prevent old blood causing physiotherapy is continued throughout pregnancy. Assis- problems with atelectasis and sputum retention73. It has tance and advice should be offered on coping with been suggested that nebulized bronchodilators can exacer- breathlessness and modifications or changes in technique bate bleeding, as they may cause systemic and pulmonary may be necessary as pregnancy progresses. There may also be vascular vasodilatation84. In some circumstances it may be a place for the use of NIPPV in cases where the patient is so appropriate to use IPPB to promote maximal chest severely compromised that type II respiratory failure is clearance with minimal effort73. precipitated89.

Pneumothorax ARE TRADITIONAL METHODS BEING ABANDONED? Although a relatively infrequent complication, the incidence Most centres advocate that a daily regimen of postural of pneumothorax rises with age85. The management of drainage and percussion be instigated as soon as the small pneumothoraces is usually conservative, with careful diagnosis of CF is confirmed. One of the most challenging monitoring and the use of inspired oxygen to promote questions remains: does a child who is generally healthy and reabsorption. Physiotherapy for chest clearance may asymptomatic really need to undergo once or twice a daily continue with caution as long as there is no evidence to postural drainage and percussion? The burden imposed on suggest that treatment is increasing the air leak. Larger patients and carers from such demanding and time pneumothoraces are usually managed with intercostal consuming treatments can lead to poor adherence and drainage in the first instance, though persistent or recurrent strain on family relationships90. leaks often require surgical intervention. Physiotherapy Whilst surmising that treatment is beneficial in the long should be discontinued in the presence of a large term, even in the absence of clinical signs and symptoms, pneumothorax until an intercostal chest drain has been there is no evidence to suggest that postural drainage and sited. Once intercostal drainage is effective, or if surgical percussion is the optimal method of airway clearance. intervention has been undertaken, physiotherapy should Several centres use alternative methods to these traditional focus on maintaining effective sputum clearance to prevent techniques in newly diagnosed infants and small children. atelectasis and lobar collapse due to obstructive secretions. These include periods of intense but varied physical activity91, 32 Inspired oxygen should be adequately humidified and PEP either via mask or mouthpiece, and AD. Few centres JOURNAL OF THE ROYAL SOCIETY OF MEDICINE Supplement No. 38 Volume 93 2000 have reported the longitudinal outcomes of these cohorts. exercise testing should only be conducted with adequate However, Constantini et al. compared PEP applied via safety precautions (resuscitation equipment and personnel facemask with postural drainage in 14 children during the trained in resuscitation). Simpler incremental tests include first year of life and found both to be equally effective92. the modified shuttle test104 and progressive cycle A further question currently debated is that of the effect ergometery to a symptom limited maximum. Non- of postural drainage on gastroesophageal reflux (GOR). incremental field tests such as the 3-min step test105 or There is as yet no consensus on this issue, with studies walking tests106,107 also provide useful information on reporting differing patterns of GOR, albeit in various functional exercise tolerance. populations93–95. One study has documented an increase in episodes of GOR in newly diagnosed infants whose CONCLUSION treatment included a head down tip. Follow up of these infants at 1 and 2 years reported poorer X-ray scores and There is as yet no scientifically proven ‘gold standard’ clinical status compared with a non-tipped group96.97. airway clearance technique for patients with CF. Thera- These results have led some centres to alter their practice peutic programmes should be tailored to individual need by omitting the routine use of head down tipped positions according to age, social circumstance and clinical status. from treatment regimens in newly diagnosed infants. The Rather than attempting to find the best technique, future conflicts in the existing data in other patient groups serves studies should aim to evaluate the various treatment to highlight the necessity for age and symptom appropriate modalities over the longer term in order to provide treatment. important information on long-term efficacy, quality of life and the impact of the treatment related burden on patients and carers. SHOULD MORE EMPHASIS BE PLACED ON PHYSICAL ACTIVITY? Acknowledgments The benefits of exercise in the CF population have been The help and support of the physio- well documented following short-term exercise training therapy departments and cystic fibrosis units at Great programmes in patients with a wide range of disease Ormond Street and the London Chest Hospitals has been severity98–100 and this topic has been extensively greatly appreciated. Particular thanks to Eleanor Main, reviewed101. Whilst questions remain regarding the long- Dr Robert Dinwiddie, Glenda Esmond and Dr Duncan term benefits of exercise in terms of morbidity and Empey for all their advice. mortality, the short-term benefits would indicate that exercise should be recommended in all patients. Many REFERENCES patients enjoy physical activity and include exercise as part 1 Desmond KJ, Schwenk WF, Thomas E, Beaudry PH, Coates AL. of their normal lifestyle. Some patients, however, benefit Immediate and long-term effects of chest physiotherapy in patients with from help in formulating an appropriate exercise cystic fibrosis. J Paediatr 1983;103:538–42 programme—this should probably include a combination 2 Maayan C, Bar Yishay E, Yacobi T, Marcus, Y, Katznelson D, Yahav Y, of strength training and aerobic activity to improve et al. Immediate effect of various treatments on lung function in infants with cystic fibrosis. Respiration 1989;55:144–5 endurance102. Equally, not all patients enjoy exercise and 3 Rossman CM, Waldes R, Sampson D, Newhouse MT. Effect of chest insistence on the inclusion of it in the care routine may in physiotherapy on the removal of mucus in patients with cystic fibrosis. some circumstances be burdensome rather than valuable. Am Rev Respir Dis 1982;126:131–5 4 de Boeck C, Zinman R. Cough versus chest physiotherapy. A comparison of the acute effects on pulmonary function in patients Exercise testing with cystic fibrosis. Am Rev Respir Dis 1984;129:182–4 The assessment of exercise tolerance is useful in evaluating 5 Zinman R. Cough versus chest physiotherapy. A comparison of the acute effects on pulmonary function in patients with cystic fibrosis. Am the impact of the disease on an individual’s everyday Rev Respir Dis 1984;129:182–4 function. It also allows safe and effective exercise 6 Bain J, Bishop J, Olinsky A. Evaluation of directed coughing in cystic recommendations and is useful in evaluating therapeutic fibrosis. Br J Dis Chest 1988;82:138–48 interventions. The choice of exercise test should reflect the 7 Konstan MW, Hilliard KA, Norvell TM, Berger M. Broncho-alveolar lavage findings in cystic fibrosis with stable, clinically mild lung disease information required and will, of course, depend on the suggest ongoing infection and inflammation. Am J Respir Crit Care Med facilities available. The progressive maximal test with 1994;150:448–54 respiratory gas analysis using a cycle or treadmill remains 8 Armstrong DS, Grimwood K, Carzino R, Carlin JB, Olinski A, Phelan the gold standard. However, this test requires specialist PD. Lower respiratory tract infection and inflammation in infants with BMJ laboratory equipment, is time consuming, expensive and newly diagnosed cystic fibrosis. 1995;310:1571–2 9 Khan TZ, Wagener JS, Bost T, Martinez J, Accurso FJ, Riches DN. may not be a true reflection of usual activity patterns, Early pulmonary inflammation in infants with cystic fibrosis. Am J Respir particularly in children103. Maximal tests are stressful and Crit Care 1995;151:1075–82 33 JOURNAL OF THE ROYAL SOCIETY OF MEDICINE Supplement No. 38 Volume 93 2000

10 Reisman JJ, Rivington Law B, Corey M, Marcotte J, Wannamaker E, cystic fibrosis [Abstract] In: Proceedings of the Tenth International Cystical Harcourt D. Role of conventional physiotherapy in cystic fibrosis. J Fibrosis Congress, Sydney. Hong Kong: Excerpta Medica Asia, 1998:R(d)3 Pediatr 1988;113:632–6 30 Pfleger A, Theissl B, Qberwaldner B, Zach MS. Self-administered 11 Sutton PP, Parker RA, Webber BA, et al. Assessment of the forced chest physiotherapy in cystic fibrosis: a comparative study of high- expiration technique, postural drainage and directed coughing in chest pressure PEP and autogenic drainage. Lung 1992;170:323–30 physiotherapy. Eur J Respir Dis 1983;64:62–8 31 Zach M, Oberwaldner B, Hausler F. Cystic fibrosis: physical exercise 12 Parker RA, Webber BA, Sutton PP. Evaluation of three individual versus chest physiotherapy. Arch Dis Child 1982;57:587–9 components of a postural drainage programme [Abstract 2.13]. In: 32 Andreasson B, Jonson B, Komfalt R, Nordmark E, Sandstrom S. Long- Course Proceedings of Ninth International Cystic Fibrosis Conference. term effects of physical exercise on working capacity and pulmonary Brighton: ICF Congress, 1984 function in cystic fibrosis. Acta Paediatr Scand 1987;76:70–5 13 Verboon JM, Bakker W, Sterk PJ. The value of the forced expiration 33 Sahl W, Bilton D, Dodd M, Webb AK. Effect of exercise and technique with and without postural drainage in adults with cystic physiotherapy in aiding sputum clearance in adults with cystic fibrosis. fibrosis. Eur J Respir Dis 1986;69:169–74 Thorax 1989;44:1006–8 14 Mortensen J, Falk M, Groth S, Jensen C. The effects of postural 34 Bilton D, Dodd ME, Abbot JV, Webb AK. The benefits of exercise drainage and positive expiratory pressure physiotherapy on combined with physiotherapy in the treatment of adults with cystic tracheobronchial clearance in cystic fibrosis. Chest 1991;100:1350–7 fibrosis. Respir Med 1992;86:507–11 15 Lannefors L, Wollmer P. Mucus clearance with three chest 35 Baldwin DR, Hill AL, Peckham KG, Knox AJ. Effect of addition of physiotherapy regimes in cystic fibrosis: a comparison between exercise to chest physiotherapy on sputum expectoration and lung postural drainage, PEP and physical exercise. Eur Respir J function in adults with cystic fibrosis. Respir Med 1994;88:49–53 1992;5:748–53 36 Falk M, Kelstrup M, Anderson JB, Pederson SS, Rossing I, Dirksen H. 16 Pryor JA, Webber BA. Evaluation of the forced expiration technique Pep treatment or physical exercise. Effects on secretions expectorated as an adjunct to postural drainage in treatment of cystic fibrosis. BMJ and indices of central and peripheral airway function [Abstract]. In: 1979;2:417–18 Proceedings of the Tenth International Cystic Fibrosis Congress, Sydney. Hong 17 Wilson GE, Baldwin AL, Walshaw MJ. A comparison of traditional Kong: Excerpta Medica Asia, 1988: A(o)1 chest physiotherapy with the active cycle of breathing in patients with 37 Scherer TA, Barandun J, Martinez E, Wanner A, Rubin EM. Effect of chronic supperative lung disease. Eur Respir J 1985;8(suppl 19):S171 high-frequency oral airway and chest wall oscillation and conventional 18 Webber BA, Hofmeyr JL, Morgan MDL, Hodson ME. Effects of chest on expectoration in patients with stable cystic postural drainage, incorporating the forced expiratory technique, on fibrosis. Chest 1998;113:1019–27 pulmonary function in cystic fibrosis. Br J Dis Chest 1986;80:353–9 38 Phillips GE, Pike S, Jaffe A, Bush A. Comparison of the active cycle of 19 Pryor JA, Webber B, Hodson ME. Effect of chest physiotherapy on breathing techniques and external high frequency oscillation with a oxygen saturation in patients with cystic fibrosis. Thorax 1990;45:77 cuirass for clearance of secretions in children with cystic fibrosis. Respir 20 Lyons E, Chatham K, Campbell IA, Prescott RJ. Evaluation of the Crit Care Med 1999;159:A687 flutter VRP1 device in young adults with cystic fibrosis. Med Sci Res 39 Warwick WJ, Hansen LG. The long term effect of high frequency 1993;21:101–2 compression therapy on pulmonary complications of cystic fibrosis. 21 Pryor JA, Webber BA, Hodson ME, Warner JO. The flutter VRP1 as Pediatr Pulmonol 1991;11:265–71 an adjunct to chest physiotherapy in cystic fibrosis. Respir Med 1994;88: 40 Arens R, Gozal D, Omlin KJ. Comparison of high frequency chest 677–81 compression and conventional chest physiotherapy in hospitalized 22 Hofmeyer JL, Webber BA, Hodson ME. Evaluation of positive patients with cystic fibrosis. Am J Respir Crit Care Med 1994;50:1154–7 expiratory pressure as an adjunct of chest physiotherapy in the 41 Majaesic CM, Montgomery M, Jones R, King M. Reduction in sputum treatment of cystic fibrosis. Thorax 1986;41:951–4 viscosity using high frequency chest compression (HFCC) compared to 23 Miller S, Hall DO, Clayton CB, Nelson R. Chest physiotherapy in conventional chest physiotherapy (CCP). Pediatr Pulmonol cystic fibrosis; a comparative study of autogenic drainage and the active 1996;22(suppl 13):A308 cycle of breathing techniques with postural drainage. Thorax 42 Kluft J, Beker L, Castagnino M, Gaiser J, Chaney H, Fink RJ. A 1995;50:165–9 comparison of bronchial drainage treatments in cystic fibrosis. Pediatr 24 Pike SE, Machin AC, Dix KJ, Pryor JA, Hodson ME. Comparison of Pulmonol 1996;22:271–4 flutter VRP1 and forced expirations with active cycle of breathing 43 Natale JE, Pfeifle J, Homnick DN. Comparison of intrapulmonary techniques in subjects with cystic fibrosis. Netherlands J Med percussive ventilation and chest physiotherapy. A pilot study in 1999;54:A125 patients with cystic fibrosis. Chest 1994;105:1789–93 25 Schoni MH. Autogenic drainage—a modern approach to chest 44 Homnick DN, White F, de Castro C. Comparison of effects of an physiotherapy in cystic fibrosis. J R Soc Med 1989;82(suppl 16):32–7 intrapulmonary percussive ventilator to standard aerosol and chest 26 Davidson AGF, Wong LTK, Pirie GE, McIlwaine PM. Long-term physiotherapy in treatment of cystic fibrosis. Pediatr Pulmonol 1995;20: comparative trial of conventional percussion and drainage 50–5 physiotherapy versus autogenic drainage in cystic fibrosis. Pediatr 45 Wolkerstorfer A, Gotz M. Physiotherapy in cystic fibrosis— Pumonol 1992;14(suppl 8):A235 intrapulmonary percussive ventilation versus positive expiratory 27 Giles DR, Wagener IS, Accurso F, Butler-Simon N. Short-term pressure. Pediatr Pulm 1995;20(suppl 12):A267 effects of postural drainage with clapping vs autogenic drainage on 46 Newhouse MD, White RRT, Marks MD, Homnick DN. The oxygen saturation and sputum recovery in patients with cystic fibrosis. intrapulmonary percussive ventilator and Flutter device compared to Chest 1995;108:952–4 standard chest physiotherapy in patients with cystic fibrosis. Clin Pediatr 28 App EM, Kieselman R, Reinhardt D, Lindeman H, Dasgupta B, King 1998;37:427–32 M, et al. Sputum rheology changes in cystic fibrosis lung disease 47 Konstan MW, Stern RC, Doershuk CF. Efficacy of the Flutter device following two different types of physiotherapy—VRP1 (flutter) versus for airway mucus clearance in patients with cystic fibrosis. J Pediatr autogenic drainage. Chest 1998;114:171–7 1994;124:689–93 29 McIlwaine PM, Davidson AGF, Wong LTK, Pirie GE, Nakielna FM. 48 Althaus P, Bovay F, Cao P, Escoffey AM, Ruiz N, Montulet F, et al. Comparison of positive expiratory pressure and autogenic drainage The bronchial hygiene assisted by the flutter VRP1 [Abstract 118]. In: 34 with conventional percussion and drainage therapy in the treatment of Congress Proceedings 16th European Working Group for CF, Prague 1989 JOURNAL OF THE ROYAL SOCIETY OF MEDICINE Supplement No. 38 Volume 93 2000

49 Dasgupta B, Tomkiewicz Rp, Boyd WA, Brown NE, King M. Effects 70 Hodson ME, Madden BP, Steven MH, Steven MH, Tsang VT, Yacoub of combined treatment with rhDNase and airflow oscillations on MH. Non-invasive mechanical ventilation for cystic fibrosis patients—a spinnability of cystic fibrosis sputum in vitro. Pediatr Pulmonol potential bridge to transplantation. Eur Respir J 1991;4:524–7 1995;20:78–82 71 Piper AJ, Parker S, Torzillo PJ, Sullivan CE, Bye PT. Nocturnal nasal 50 van Winden CMQ, Visser A, Hop W, Sterk J, Beckers S, de Jongste IPPV stabilizes patients with cystic fibrosis and hypercapnic respiratory JC. Effects of flutter and PEP mask physiotherapy on symptoms and failure. Chest 1992;102:846–50 lung function in children with cystic fibrosis. Eur Respir J 1998;12: 72 Pryor JA, Webber BA. Physiotherapy for cystic fibrosis—which 143–7 technique? Physiotherapy 1992;78:105–8 51 Lindemann H. Zum stelienwert der physiotheraoue nut dem VRP I- 73 Pryor JA, Webber BA. , primary ciliary dyskinesia and destin (Flutter). Pneumologie 1992;46:626–30 cystic fibrosis. In: Pryor JA, Webber BA, eds. Physiotherapy for 52 Padman R, Geouque DM, Engelhardt MT. Effects of the flutter device Respiratory and Cardiac Problems. Edinburgh: Churchill Livingstone, on pulmonary function studies among paediatric cystic fibrosis patients. 1998:463–84 Del Med J 1999;71:13–18 74 Dodd ME, Haworth CS, Webb AK. A practical approach to oxygen 53 Davidson AGF, McIlwaine M, Wong LTK, Peacock D. ‘‘Flutter versus therapy in cystic fibrosis. J R Soc Med 1998;91(suppl 34):30–9 PEP’’: A long-term comparative trial of positive expiratory pressure 75 Gherini S, Peters RM, Virgilio RW. Mechanical work on the lungs and (PEP) versus oscillating positive expiratory pressure (Flutter) work of breathing with positive end expiratory pressure and physiotherapy techniques. In: Congress Proceedings of 22nd European continuous positive airway pressure. Chest 1979;76:251–6 Cystic Fibrosis Conference, Berlin 1998 76 Bott J, Keilty S, Noone L. Intermittent positive pressure breathing—a 54 Dasgupta B, Nakamura S, App EM, King M. Comparative evaluation dying art? Physiotherapy 1992;78:656–60 of the flutter and the cornet in improving the cohesiveness of cystic fibrosis sputum. Pediatr Pulmonol 1997;24(suppl 14):A341 77 Conway JH. The effects of humidification for patients with chronic airways disease. Physiotherapy 1992;78:97–101 55 Cegla UH, Bautz M, Frode G, Werner T. Physiotherapy in patients with COAD and tracheobronchial instability—a comparison of two 78 Sukulmalchantra Y, Park SS, Williams MH. The effect of intermittent oscillating PEP systems. Pneumologie 1997;51:129–36 positive pressure breathing (IPPB) in acute respiratory failure. Am Rev Respir Dis 1965;92:885–93 56 Falk M, Kelstrup M, Andersen JB, Kinoshita T, Falk P, Stouring S, et al. Improving the ketchup bottle method with positive 79 Meecham-Jones DJ, Paul EA, Graham-Clarke C, Wedzicha JA. Nasal expiratory pressure, PEP, in cystic fibrosis. Eur J Respir Dis 1984; ventilation in acute exacerbations of chronic obstructive pulmonary 65:423–32 disease: effect of ventilator mode on arterial blood gases. Thorax 1994;49:1222–4 57 Groth S, Stafanger G, Dirksen H, Anderson JB, Falk M, Kelstrup M. Positive expiratory pressure (PEP mask) physiotherapy improves 80 Hill AT, Edenborough FP, Cayton RM, Stableforth DE. Long-term ventilation and reduces volume of trapped gas in cystic fibrosis. Bull nasal intermittent positive pressure ventilation in patients with cystic Eur Physiopath Respir 1985;21:339–43 fibrosis and hypercapnic respiratory failure (1991–1996). Respir Med 1998;92:523–6 58 van der Schans CP, van der Mark TW, de Vries G, Piers DA, Beckhuis H, Dankert-Rodse JE, etal. Effect of positive expiratory pressure 81 Dodge JA, Morison S, Lewis PA, Colest EC, Geddes D, Russel G, breathing in patients with cystic fibrosis. Thorax 1991;46:252–6 et al. Cystic fibrosis in the United Kingdom, 1968–88: incidence, population and survival. Paediatr Perinat Epidemiol 1993;7:157–66 59 Tyrell JC, Hiller EJ, Martin J. Face mask physiotherapy in cystic fibrosis. Arch Dis Child 1986;61:598–611 82 Clinical Standards Advisory Group. Cystic Fibrosis: Access for Availability of Specialist Services. London: HMSO, 1993 60 Van Asperen PP, Jackson L, Hennessy P, Brown J. Comparison of a positive expiratory pressure (PEP) mask with postural drainage in 83 Mearns M. Cystic fibrosis: the first 50 years: a review of the clinical patients with cystic fibrosis. Aus Paediatr J 1987;23:283–4 problems and their management. In: Dodge JA, Brock DJH, Widdicombe JH, eds. Cystic Fibrosis: Current Topics. Bristol: John 61 Steen HJ, Redmond AOB, O’Neil D. Evaluation of the PEP mask in Wiley, 1993 cystic fibrosis. Act Paediatrica Scand 1991;80:51–6 84 Ullah MI, Fegan O. Potential hazard of nebulised salbutamol in 62 Braggion C, Cappelletti LM, Comacchia M, Zanolla L, Mastella G. patients with haemoptysis. BMJ 1983;12:844–5 Short term effects of three chest physiotherapy regimens in patients hospitalized for pulmonary exacerbations of cystic fibrosis. Paediatr Pulm 85 Penketh ARL, Knight RK, Hodson ME, Batten JC. The management 1995;19:16–22 of pneumothorax in adults with cystic fibrosis. Thorax 1982;37:850–63 63 McIlwaine PM, Wong LT, Peacock D, Davidson AG. Long-term 86 Thomas TM, Plymat KR, Blannin J, Meade TW. Prevalence of urinary comparative trial of conventional postural drainage and percussion incontinence. BMJ 1980;281:1243–5 versus positive expiratory pressure physiotherapy in the treatment of 87 Machin A. Continence. In: Course Proceedings: Cardiorespiratory cystic fibrosis. J Pediatr 1997;131:570–4 Physiotherapy Study Day. London: The Royal Brompton Hospital, 1997 64 Oberwaldner B, Evans IC, Zach MS. Forced expirations against a 88 Cornacchia M, Zenorini A, Braagion C, Perobelli S, Cappelletti LM, variable resistance: a new chest physiotherapy method in cystic fibrosis. Mastella G. Prevalence of urinary incontinence in women with cystic Pediatr Pulmonol 1986;2:358–67 fibrosis. Netherlands J Med 1999;54:A117 65 Oberwaldner B, Theissl A, Rucker A, Zach MS. Chest physiotherapy 89 Butler JA, Restrick LJ, Esmond GM, Mikelsons C, Empey DW. in hospitalised patients with cystic fibrosis: a study of lung function Pregnancy assisted by nasal intermittent positive pressure ventilation in effects and sputum production. Eur Respir J 1991;4:152–8 a patient with cystic fibrosis. J R Soc Med 1997;90:222–3 66 Zach MS, Oberwaldner B. Effect of positive expiratory pressure 90 Bryon M. Adherence to treatment in children. In: Myers L, Midence breathing in patients with cystic fibrosis. Thorax 1992;47:66 K, eds. Adherence to Treatment in Medical Conditions. London: Harwood 67 Prasad SA, Main E. Finding evidence to support airway clearance Academic, 1998:111–89 techniques. Disability Rehab 1998;20:235–46 91 Lund Cystic Fibrosis Centre. Staying Ahead—Modern Chest Physiotherapy 68 Lannefors L. Guidelines for inhalation, practical aspects. Netherlands J [Video]. Lund: Lund CF Centre Med 1999;54:S24.5 92 Constantini D, Genoi S, Marzano MT, Brivio A, Brusa D, Guinta A. 69 App EM, Nakamura S, King M, Hamm H, Mathys H. Treatment The use of PEP mask in cystic fibrosis patients in the first year of life. Israel J Med Sci 1996;32:A192 modalities for mucociliary clearance. Netherlands J Med 1999;54:S3 35 JOURNAL OF THE ROYAL SOCIETY OF MEDICINE Supplement No. 38 Volume 93 2000

93 Button BM, Heine RG, Catto-Smith A, Phelan P, Olinski A. Postural 100 DeJong W, Kaptein AA, van der Schans CP, Mannes GP, van Aalderen drainage and gastro-oesophageal reflux in infants with cystic fibrosis. WM, Grevnick RG, et al. Quality of life in patients with cystic fibrosis. Arch Dis Child 1997;76:148–50 Pediatr Pulmonol 1997;23:95–100 94 Phillips GE, Pike SE, Rosenthal M, Bush A. Holding the baby: head 101 Webb AK, Dodd ME, Moorcroft J. Exercise and cystic fibrosis. J R Soc downwards positioning for physiotherapy does not cause gastro- Med 1995;88(suppl 25):30–6 oesophageal reflux. Eur Respir J 1998;12:954–7 102 Selvadurai HC, Van Asperen PP, Cooper PJ, Mellis CM, Blimkie CJ. 95 Wong LT, McIlwaine M, Davidson AG, Lillquist YP. Gastro- A randomised controlled study of in-hospital exercise training oesophageal reflux during chest physiotherapy: A comparison of programs in children with cystic fibrosis (CF). Pediatr Pulmonol positive expiratory pressure and postural drainage with percussion. 1999;28(suppl 19):A433 Pediatr Pulmonol 1999;28(suppl 19):A435 103 Cooper D. Rethinking exercise testing in children: a challenge. Am J 96 Button BM, Heine RG, Catto-Smith AG, Olinski A, Phelan PD, Story Respir Crit Care Med 1995;152:1154–7 I. A twelve month comparison of standard versus modified chest physiotherapy in twenty infants with cystic fibrosis. Pediatr Pulmonol 104 Bradley JM, Howard JL, Wallace ES, Elborn JS. The validity of a 1997;24(suppl 14):A338 modified shuttle test in adult cystic fibrosis. Thorax 1999;54:437–39 97 Button BM, Heine RG, Catto-Smith AG. Chest physiotherapy for 105 Balfour-Lynn IM, Prasad SA, Laverty A, Whitehead BF, Dinwiddie R. children with CF—birth to two years: issues to consider. Netherlands J A step in the right direction: assessing exercise tolerance in cystic Med 1999;54:S24.1 fibrosis. Pediatr Pulm 1998;25:278–84 98 Orenstein DM, Franklin BA, Doershuk CF, Doershuk CF, Hellerstein 106 Butland RJA, Pang J, Gross ER, Woodcock AA, Geddes DM. Two-, HK, Germann KJ, et al. Exercise conditioning and cardiopulmonary six- and 12-minute walking tests in . BMJ function in cystic fibrosis. Chest 1981;80:392–8 1982;284:1607–8 99 O’Neill PA, Dodd ME, Abbott JV, Webb AK. The benefits of exercise 107 Gulmans VA, van Veldhoven NH, de Meer K, Helders PJ. The six- and reduction of breathlessness in cystic fibrosis. Br J Dis Chest minute walking test in children with cystic fibrosis: reliability and 1987;81:62–9 validity. Pediatr Pulm 1996;22:85–9

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