Thorax 1995;50:165-169

Chest physiotherapy in cystic fibrosis: acomparative study of autogenic drainage andthe active cycle of breathing techniques withpostural drainage

S Miller, D 0 Hall, C B Clayton, R Nelson

AbstractBackground - Autogenic drainage hasbeen suggested as an alternative methodof chest physiotherapy in patients withcystic fibrosis. In this study autogenicdrainage was compared with the activecycle of breathing techniques (ACBT) to-gether with postural drainage.Methods - Eighteen patients with cysticfibrosis took part in a randomised two-daycrossover trial. There were two sessions ofone method ofphysiotherapy on each day,either autogenic drainage or ACBT. Thestudy days were one week apart. On eachday the patients were monitored for sixhours. Mucus movement was quantifiedby a radioaerosol technique. Airway clear-ance was studied qualitatively usingxenon-133 scintigraphic studies at the startand end ofeach day. Expectorated sputumwas collected during and for one hour aftereach session ofphysiotherapy. Pulmonaryfunctions tests were performed before andafter each session. Oxygen saturation(Sao,) and heart rate were measured be-fore, during, and after each session.Results - Autogenic drainage clearedmucus from the lungs faster than ACBTover the whole day. Both methods im-proved ventilation, as assessed by thexenon-133 ventilation studies. No overalldifferences were found in the pulmonaryfunction test results, but more patients hadan improved forced expiratory flow from25% to 75% with autogenic drainage, whilemore showed an improved forced vital ca-pacity with ACBT. No differences werefound in sputum weight and heart rate,nor in mean Sao, over the series, but fourpatients desaturated during ACBT.Conclusions - Autogenic drainage wasfound to be as good as ACBT at clearingmucus in patients with cystic fibrosis andis therefore an effective method of homephysiotherapy. Patients with cystic fib-rosis should be assessed as to whichmethod suits them best.(Thorax 1995;5O:165-169)

Keywords: cystic fibrosis, autogenic drainage, activecycle of breathing techniques, physiotherapy.

Chest physiotherapy in the treatment of cysticfibrosis is long established.' The conventionaltreatment for many years was postural drainage

with percussion. Thompson and Thompson in1968 developed the forced expiration techniqueto improve the efficiency of secretion removal.6Pryor et al explained the mechanism of thistechnique using Mead's concept of the equalpressure point7 8 and studied this method com-bined with postural drainage in patients withcystic fibrosis.9 Since the early 1980s mostcystic fibrosis centres in Britain have taught thisform ofhome management for chest clearance.The name of the method has recently beenchanged to the active cycle of breathing tech-niques (ACBT).

In recent years new methods of chest clear-ance have been developed,'0 among which arepositive expiratory pressure mask therapy(PEP)," high pressure PEP,'2 and autogenicdrainage.'3Autogenic drainage was developed by

Chevaillier in Belgium. This technique aims toreach the highest possible airflow in the differ-ent generations of bronchi to move secretionsand does not involve any forced expiration.There has been little research into the effectsofautogenic drainage in comparision with othermethods,'1'7 and none comparing it withACBT.

In chest physiotherapy it has become clearthat judging a method by the amount ofsputumexpectorated is not always correct. Mucusclearance of radiolabelled aerosol gives a pic-ture of where mucus is in the lungs, if it ismoving from a particular area, and whetherthere is any effect on the more peripheral air-ways. Scintigraphic studies have shown thatmucus may be swallowed during and aftertreatment as it is visible in the stomach, sug-gesting that measurement of the amount ofsputum expectorated can be misleading.'8-20 Itwas therefore decided to compare these twomethods using lung scintigraphy.

MethodsThe study was carried out to determine whetherautogenic drainage, a technique carried out atonly 17% of centres in the UK, was as effectivein clearing lung mucus as ACBT, the standardmethod used at 96% of centres.'0 The studyalso looked for differences between the meth-ods, particularly in the clearance of central andperipheral airways.

PATIENTSEighteen patients (10 men) aged 11-32 years

PhysiotherapyDepartmentS Miller

Medical PhysicsDepartmentD 0 HallC B Clayton

PaediatricDepartmentR Nelson

Royal VictoriaInfirmary,Newcastle upon TyneNE1 4LP, UK

Reprint requests to:Dr D 0 Hall.Received 12 April 1994Returned to authors18 May 1994Revised version received1 September 1994Accepted for publication8 November 1994

165

on 26 April 2019 by guest. P

rotected by copyright.http://thorax.bm

j.com/

Thorax: first published as 10.1136/thx.50.2.165 on 1 F

ebruary 1995. Dow

nloaded from

Miller, Hall, Clayton, Nelson

with cystic fibrosis were studied. Shwachman-Kulczycki scores,21 modified with the Chrispin-Norman score,22 were between 34 and 87. Allpatients were clinically stable at the time ofthe study and were not receiving intravenousantibiotics. A lower age limit of 11 years wasset because of the high degree of patientcooperation necessary. Informed consent, asapproved by the hospital ethics committee,was obtained from all patients. ARSAC(Administration of Radioactive SubstancesAdvisory Committee) approval was also ob-tained for the use of radioactive preparations.The patients were tested before the study for

reversibility to a bronchodilator. If there was apositive response patients received a nebulisedbronchodilator before each session of physio-therapy; if there was no response they receivednebulised saline.Each patient was studied over two days one

week apart to prevent any carry over effect. Oneach day the patient performed two sessions ofphysiotherapy- morning and afternoon. Theywere all fully trained in both methods, but allhad used ACBT for many years before learningautogenic drainage. Patients were asked to beregular with their home physiotherapy in theweek leading up to the trial and in the inter-vening period.

PHYSIOTHERAPY TECHNIQUESBefore physiotherapy the patients inhaled apretreatment nebuliser of salbutamol or saline,depending on established reversibility studies.Volumes of 4 ml were nebulised (2 5 ml sal-butamol and 1-5 ml saline, or 4 ml saline) in aMedicaid system 22 nebuliser with a mouth-piece powered by a Medicaid CR60 com-pressor. This took approximately eight minutes.In accordance with established practice, on theday ACBT was performed the patients wereasked to breath normally, while on the dayautogenic drainage was performed they didautogenic drainage breathing exercises duringinhalation. A 30 minute treatment session thenfollowed. On each day there was a morningand an afternoon session consisting of eightminutes inhalation through the nebuliser and30 minutes of chest clearance per session. Forthe purposes of the study we standardised thepostural drainage positions so that as much ofthe lungs as possible would be treated on theACBT days for comparison with autogenicdrainage which is a whole lung treatment. Wedo not recommend that these same posturaldrainage positions should be adhered to as arigid regimen for all patients.On the day ACBT was performed, postural

drainage was performed on a Chesham frame.In the morning session postural drainage po-sitions were adopted to drain the posteriorlower lobes, anterior lower lobes, left lowerlobes, and right lower lobes, and in the after-noon the left middle lobe, right middle lobe,anterior upper lobe, and apical upper lobe.Each position was held for seven and a halfminutes. In each postural drainage position theACBT was performed several times, com-mencing with tidal volume breathing with the

lower chest (breathing control) for ap-proximately six breaths, followed by 3-4 deepinspirations offull capacity, then another periodof breathing control. Finally, the patient per-formed one or two forced expirations (huffs)from mid to low lung volume. If secretionswere felt to be high enough in the proximalairways a huff was performed at a higher lungvolume. Patients were encouraged to coughand expectorate only if the secretions were highenough. After the huffs and/or cough a furtherperiod of gentle lower chest breathing controlwas performed, and the cycle repeated. Self-clapping was performed on a limited basis dur-ing the deep inspiration phase.On the day autogenic drainage was per-

formed the patient's position for the treatmentwas sitting or supine. The posture, if sitting,was upright with the neck slightly extended; iflying it was flat with the arms away from thebody and the thorax unrestricted.The patient began by performing dia-

phragmatic breathing at a low lung volume.Inspiration was slow with a pause of threeseconds, and expiration was done as a sigh withan open glottis and with as high a velocity aspossible but no forced expiration. During thislow lung volume breathing, expiration was en-couraged down to the expiratory reserve vol-ume. When the patient felt secretions to bemoving, the volume of inspiration becamedeeper and the expiration did not go down asfar as the expiratory reserve volume. As thesecretions moved up the bronchial tree to thelarge airways the patient performed higher lungvolume breathing, tidal volume to inspiratoryreserve volume. Only when the secretions werefelt to be as high as possible did expectorationoccur. The patients were taught to suppressthe cough to allow this. The cycle of breathingexercises was repeated throughout the 30 min-ute morning and afternoon treatment sessions.

MEASUREMENTSA xenon-133 gas ventilation study was carriedout at the start of the day. First breath, equi-librium, and washout pictures were recordedby a gamma camera (Siemens ZLC 7500)linked to a nuclear medicine computer system(Bartec System 3). These images were assessedby a radiologist experienced in both cystic fib-rosis and scintigraphy to confirm that the pa-tient's condition was essentially the same onboth days, and to group the patients into mild,moderate, and severe disease according to thepattern ofxenon distribution in the lungs. Fromthe tenth patient onwards the ventilation studywas repeated at the end of both days to lookfor changes in lung ventilation due to the treat-ment.23Pulmonary function tests were carried out

using a spirometer (Vitalograph Alpha) whichwas calibrated daily. Vital capacity (VC), forcedvital capacity (FVC), forced expiratory volumein one second (FEVy), peak expiratory flow(PEF), and forced expiratory flow from 25-75% (FEF2,75) were recorded at the beginningof the day and before and after each sessionof chest clearance. Oxygen saturation levels

166

on 26 April 2019 by guest. P

rotected by copyright.http://thorax.bm

j.com/

Thorax: first published as 10.1136/thx.50.2.165 on 1 F

ebruary 1995. Dow

nloaded from

Chest physiotherapy in cystic fibrosis

(Sao2) and heart rate were recorded duringeach treatment session using a Nellcor pulseoximeter, and resting levels were recorded be-fore and after.

After the ventilation study, pulmonary func-tion tests, Sao2, and heart rate recordings hadbeen performed, the patient inhaled humanserum albumin aerosol labelled with tech-netium-99m (Solco Venticoll supplied by Inc-star). A Medicaid System 22 Optimist nebuliserpowered by a Medicaid CR60 air compressordelivered the aerosol. The aerosol particles hada mass median diameter of 0 9 ,um and a geo-metric standard deviation of 1-4 jm.24The patients inhaled the aerosol via a mouth-

piece while wearing a noseclip and sitting up-right. They were asked to breath normally and,approximately every 10 breaths, to breath inslowly and deeply and hold their breath forthree seconds.25 The inhalation time was 20minutes. At the start of each session a staticposterior image of the distribution of the radio-labelled aerosol in the lungs was acquired for150 seconds on the gamma camera with thepatient sitting. Dynamic images were takenduring the physiotherapy. Further static pos-terior images were recorded immediately afterthe end of each session and about one hourlater (the exact time varied according to cameraavailability).The static images were corrected for back-

ground and radioactive decay, and regions ofinterest were drawn over the right and left lungsto measure retained activity. The equilibriumventilation images were used to draw the lungoutlines and to designate a central and peri-pheral lung region. Using a single compartmentmodel, clearance was assumed to be ex-

ponential. A value of percentage change perhour was calculated for each region using a leastsquares fit to the log ofthe counts, corrected forradioactivity decay. The time of the first viewwas taken to be time zero. For each patient theproportional difference between the rates ofchange on the two days was calculated.Sputum was collected in a preweighed pot

during the nebuliser and treatment period. Itwas weighed immediately after treatment. Spu-tum was then collected for a further hour andweighed again.A visual analogue score to assess patient

preference between autogenic drainage andACBT was performed at the end of the secondday. Patients were also asked to give two reasons

for their preference.

DATA ANALYSISThe study was analysed using the method out-lined by Hills and Armitage for a two periodcrossover clinical trial.26 Carry over betweenthe two study periods was tested for but foundnot to be significant. Differences between thetwo methods were tested using the paired ttest.

ResultsOXYGEN SATURATION LEVELSThere was no difference in mean Sao, between

the methods over the study days. However,four patients with moderate to severe diseasedesaturated during the morningACBT session,and one of these patients also desaturated inthe afternoon ACBT session. No patientsdesaturated during any autogenic drainagesession.

HEART RATEThe change in heart rate from the value meas-ured just before treatment to the average valueduring and immediately after treatment wascalculated for each patient. The results werenot clinically significant.

PATIENT PREFERENCENine patients preferred autogenic drainage,eight preferred ACBT, and one patient had nopreference.

PULMONARY FUNCTION TESTSTaken overall, pulmonary function testsshowed no significant difference between thetwo methods. However, more patients had animproved FEF25,- on autogenic drainage thanon ACBT, while the converse was true for FVC(table 1).

SPUTUM WEIGHTSSputum was collected and weighed during andfor up to one hour after each physiotherapysession. The average weight in one day was 23(range 2-105) g. The mean (SE) differencebetween autogenic drainage and ACBT wasnot significant (-0 4 (1 -8) g). No correlationwas found with the results of radiolabelledaerosol clearance, in agreement with reports inthe literature.'9

VENTILATION STUDIESUsing the intitial '33Xe ventilation study, lungcondition was found to be mildly affected insix cases, moderately affected in seven, andseverely affected in five patients. The as-sessments did not change between study days.The last nine patients (three mild, three mod-erate, and three severe) had repeat ventilationstudies performed at the end of the day. Moreuniform or more widely distributed xenon gason first breath or increased washout rate wereregarded as improvements. Examples of twopairs of first breath studies from the start and

Table 1 Number of tests out of 36 (18 morning and 18afternoon) which showed an improvement of >10%,>15%, and >20% for forced expiratory flow from 25% to75% (FEF25-75) and forced vital capacity (FVC)

Percentageimprovement FEF25-75 FVC

Autogenic AutogenicACBT drainage ACBT drainage

>10% 10 17 17 15>15% 8 11 11 10>20% 7 9 8 4

ACBT =active cycle of breathing techniques.

167

on 26 April 2019 by guest. P

rotected by copyright.http://thorax.bm

j.com/

Thorax: first published as 10.1136/thx.50.2.165 on 1 F

ebruary 1995. Dow

nloaded from

Miller, Hall, Clayton, Nelson

A

B

First breath studies from the start (left) and end (right) of the day. (A) Patient withmoderate disease, showing improvement at the end of the day. (B) Patient with severedisease, showing no improvement.

end of the day are shown in the figure. Darkareas show the presence of xenon gas. The firstpatient (A) had moderate lung disease andshowed improvement at the end of the day.The second patient (B) had severe lung diseaseand showed no improvement.

All three of the moderate patients, and oneeach of the mild and severe patients, showedimprovements for both methods of physio-therapy on first breath, while the other fourshowed no improvement. On washout, sixcleared faster and three cleared slower on auto-genic drainage, while with ACBT four clearedfaster, three slower, and two did not change.

CLEARANCE OF RADIOLABELLED AEROSOLThe clearance rates and the proportionaldifferences between the two methods over thewhole day are given, grouped according to lungregion for all patients and disease severity forthe whole lungs (table 2). Clearance rates werefaster with autogenic drainage than withACBTfor whole lung and central lung regions, but

Table 2 Average clearance rates for autogenic drainage and ACBT over the whole dayfor all 18 patients grouped according to lung region, and for the whole lungs groupedaccording to disease severity, and proportional differences in rates

n Mean (SD) Mean (SD) Mean (SE) pclearance clearance proportionalrate with rate with differenceACBT AD(%/hour) (%l/hour)

Lung regionWhole lung 18 3-2(1-4) 3-9(1-4) 0 22(0 09) <0 05Central 18 2-9(1-3) 3-6(1-4) 0-25(0-10) <0 05Peripheral 18 4-7(2-0) 5 5(2-2) 0-19(0-12) NS

Disease severityMild 6 2-7(1-2) 3 8(2 0) 0-35(0-19) NSModerate 7 2-8(1-0) 3-3(0 3) 0-21(0-13) NSSevere 5 4-3(1-5) 4-7(1-3) 0-10(0-23) NS

Proportional difference is expressed as (1/n)12(AD - ACBT)/(AD + ACBT), where AD andACBT are the rates of clearance for individual patients, and n is the number of patients in eachgroup. ACBT= active cycle of breathing techniques; AD = autogenic drainage.

not significantly different for the lung periphery.Dividing the patients according to disease se-verity makes the number in each group verysmall and therefore impossible to analyse stat-istically. However, any differences are mostapparent in the mild and moderate categories.The dynamic images were not used in the

quantitative analysis. Inspection of these im-ages showed activity appearing in the stomach,but no major shifts of activity between regionsof the lungs.

DiscussionSome workers have found falls in Sao, due topostural drainage and percussion in patientswith cystic fibrosis.," while others have notfound such a fall when breathing control restsare included.27 In our results falls in Sao2 werefound during ACBT with postural drainagedespite our inclusion of breathing control, butthese did not show in the mean Sao2 resultswhich may explain some of the disagreementin the literature.The patients who preferred autogenic drain-

age to ACBT (nine of 18) tended to be thosewith better concentration who were generallymore compliant with treatment. The con-centration needed to perform autogenic drain-age is an important factor in deciding whetherto advise autogenic drainage as a method ofchoice. The time taken to learn autogenicdrainage is much longer than the time neededto learn ACBT. In general, younger patientsmay lack the necessary concentration.Pulmonary function tests were performed

initially before the inhalation of radiolabelledaerosol, and then after physiotherapy. It wasnoted that pulmonary function decreased byan excessive amount after the morning sessionsin two of the first three patients. Therefore,from the fourth patient onwards the pulmonaryfunction tests were repeated after inhalation ofthe aerosol. This showed an adverse effectin a further seven patients, probably due tobronchoconstriction. This effect rapidly dis-appeared but we felt that, where this occurred,pulmonary function tests after physiotherapywere worse than they would have been other-wise. This should be noted for further researchusing inhaled radiolabelled aerosols since theremay be an adverse effect on deposition.

Repeat ventilation studies showed two typesof change. Improvements in first breath imagesshowed areas of the lungs which had beencleared ofmucus or where bronchoconstrictionhad decreased. Conversely, new deficits showedeither that mucus had moved into an areaof the lung or that bronchoconstriction wasaffecting that area. The changes in washoutrates indicated whether airflow and lung com-pliance had got better or worse.De Cesare et al23 studied nine patients with

cystic fibrosis using krypton-81m ventilationstudies (equivalent to 133Xe first breath studies)and found no improvements in three patientswith mild disease, improvements in threepatients with severe disease, and changes in-dependent of treatment for three patients withmoderate disease. We cannot say whether the

168

on 26 April 2019 by guest. P

rotected by copyright.http://thorax.bm

j.com/

Thorax: first published as 10.1136/thx.50.2.165 on 1 F

ebruary 1995. Dow

nloaded from

Chest physiotherapy in cystic fibrosis

changes found in our study were independent

of treatment, although we were looking for

definite improvements in regional ventilation

rather than simply changes. The one patient in

our study assessed as mild on first breath, and

who showed improvements, expectorated more

than 50 g of mucus during each day. The im-

provement in the ventilation in this case was

increased uniformity of gas distribution rather

than the clearance of blocked areas.

The ventilation studies indicated that both

methods of physiotherapy are effective at clear-

ing lung obstruction caused by mucus.

Aerosol deposition in severe disease is pre-

dominantly in the central airways, whereas for

mild disease there is better peripheral de-

position. The information gained about clear-

ance is more reliable when deposition is good

than when it is poor. As a consequence, pro-

portional differences in clearance are likely to

be more reliable for central lung regions, for

the whole lungs, and for patients with mild

disease.In conclusion, the results showed increased

rates of clearance of mucus on the days when

autogenic drainage was performed. There was

no overall difference in sputum weights. Both

methods proved able to clear lung obstructions,

shown by scintigraphic ventilation studies. Pul-

monary function tests showed no overall

difference between the methods, but showed

that autogenic drainage improved FEV25 15

more often than ACBT, while the converse was

true for FVC. The patients were found to

have similar oxygen saturation levels for both

methods, but the ACBT caused desaturation

in some cases. Heart rate changes were not

clinically significant. Overall, patients liked

both methods equally.

We are grateful to Dr R Lee, consultant radiologist,

J Matthews, medical statistician, for their invaluable

and help during this study. We would also like to

clinical medical physics technologists, the physiotherapy

partment, and particularly the patients who participated,

their time and energy. The Optimist nebulisers were

by MedicAid.

1 Cochrane GM, Webber BA, Clarke SW. Effects

on pulmonary function. BMJ 1977;2:1181.

2 Feldman J, Traver GA, Tuassig LM. Maximal

flows after postural drainage. Am Rev Respir Dis119:239-45.

3 Levison HL, Godfrey S. Pulmonary aspects of cystic

In: Mangos JA, Talamo RC, eds. Cystic fibrosis, projections

into the future. New York: Stratton, 1976:3-24.4 Lorin MI, Denning CR. Evaluation of postural drainage by

measurement of sputum volume and consistency. Am JPhys Med 1971;50:215-9.

5 Maxwell M, Redmond A. Comparative trial of manual andmechanical percussion techniques with gravity assistedbronchial drainage in patients with cystic fibrosis. ArchDis Child 1979;54:542-4.

6 Thompson B, Thompson HT. Forced expiration exercisesin asthma and their effect on FEV,. NZJPhysiother 1968;3:19-21.

7 PryorJA, Webber BA, Hodson ME, BattenJC. Evaluation ofthe forced expiration technique as an adjunct to posturaldrainage in the treatment of cystic fibrosis. BMJ 1979;2:417-8.

8 Mead J, Turner JM, Macklem PT, Little JB. Significanceof the relationship between lung recoil and maximumexpiratory flow. Appl Physiol 1967;22:95-108.

9 PryorJA, Webber BA. An evaluation of the forced expiratorytechnique as an adjunct to postural drainage. Physio-therapy 1979;65:304-7.

10 Prasad SA. Current concepts in physiotherapy. JR Soc Med1993;86(Suppl 20):23-9.

11 Falk M, Kelstrup M, Anderson JB, Kinoshita T, Falk P,StovringS, et al. Improving the ketchup bottle methodwith positive expiratory pressure PEP in cystic fibrosis.Eur3 _RespirDis 1984;65:423-32.

12 Oberwaldner B, Evans JC, Zach MS. Forced expirationsagainst a variable resistance: a new chest physiotherapymethod in cystic fibrosis. PediatrPulmonol 1986;2:358-67.

13 Schoni MH. Autogenic drainage: a modern approach tophysiotherapy in cystic fibrosis. J R Soc Med 1989;82(Suppl 16):32-7.

14 Chevaillier J. Autogenic drainage (AD). In: Lawson D, ed.Cystic fibrosis: horizons. Chichester: John Wiley, 1984:235.

15 McIlwaine M, Davidson AGF, Wong LTK, Pirie GE, Nak-ielna EM. Comparison of positive expiratory pressureand autogenic drainage with conventional percussion anddrainage therapy in the treatment of cystic fibrosis. AsiaPacific Congress Series, 10th International Cystic FibrosisCongress, Sydney. Excerpta Medica, 1988:120.

16 Mcllwaine PM, Wong LTK, Pirie GE, Davidson AGF.Long term comparative trial of conventional percussionand drainage versus autogenic drainage in cystic fibrosis.XIth International CF Congress Book of Abstracts, Dublin1992:Allied Health Professionals No. 32 (abstract).

17 Pfleger A,Theissl B, Oberwaldner B, Zach MS. Self ad-ministered chest physiotherapy in cystic fibrosis: a com-parative study of high pressure PEP and autogenicdrainage. Lung 1992;170:323-30.

18 Rossman CM, Waldes R, Sampson D, Newhouse MT.Effect of chest physiotherapy on the removal of mucusin patients with cystic fibrosis. Am Rev Respir Dis 1982;126:131-5.

19 Mortensen J, Falk M, Groth S, Jensen C.The effects ofpostural drainage and positive expiratory pressure physio-therapy on tracheobronchial clearance in cystic fibrosis.Chest 1991;100:1350-7.

20 Isawa T, Teshima T, Hirano T, Ebina A, Motomiya M,Konno K. Lung clearance mechanisms in obstructiveairways disease. J Nucl Med 1984;25:447-54.

21 Shwachman H, Kulczycki LL. Long-term study of onehundred and five patients with cystic fibrosis. Am J DisChild 1968;96:6-15.

22 Chrispin AR, Norman AP.The systematic evaluation of thechest radiograph in cystic fibrosis. Pediatr Radiol 1974;2:101-6.

23 De Cesare JA, Babchyck BM, Colten HR, Treves S. Radio-nuclide assessment of the effects of chest physical therapyon ventilation in cystic fibrosis. Phys Ther 1982;62:820-5.

24O'Doherty MJ, Miller RF. Aerosols for therapy and diag-nosis. EurJNucl Med 1993;20:1201- 13.

25 Clarke SW, Pavia D. Aerosols and the lungs. London: But-terworths, 1984:49-70.

26 Hills M, Armitage P. The two-period cross-over clinicaltrial. Br J Clin Pharmacol 1979;8:7-20.

27 Pryor JA, Webber BA, Hodson ME. Effects of chest physio-therapy on oxygen saturation in patients with cystic fib-rosis. Thorax 1990;45:77.

tK94-187

169

on 26 April 2019 by guest. P

rotected by copyright.http://thorax.bm

j.com/

Thorax: first published as 10.1136/thx.50.2.165 on 1 F

ebruary 1995. Dow

nloaded from