Comparing airways clearance techniques in chronic obstructive pulmonary disease and bronchiectasis: positive expiratory pressure or temporary positive expiratory pressure? a retrospective study

Comparing airways clearance techniques in chronic obstructive pulmonary disease and bronchiectasis positive expiratory pressure or temporary positive expiratory pressure? A retrospective study ARTICLE[.]

pul-https://www.journals.elsevier.com/brazilian-journal-of-physical-therapy

ORIGINAL RESEARCH

Francesco D’Abroscaa , b , ∗, Barbara Garabellia , c, Gloria Savioa, Agnese Barisona,

Lorenzo Appendinia, Luis V.F Oliveirad, Paola Baiardie, Bruno Balbia

aDivisione di Pneumologia Riabilitativa, Fondazione Salvatore Maugeri, I.R.C.C.S., Centro Medico di Veruno, Veruno, NO, Italy

bFondazione IRCCS Ca’ Granda - Ospedale Maggiore Policlinico Milano, Milano, MI, Italy

cNEMO Center - Centro Clinico NEMO, Ospedale Niguarda Cà Granda, Milano, Milano, MI, Italy

dPrograma de Pós-Graduac ¸ão em Ciências da Reabilitac ¸ão, Universidade Nove de Julho (UNINOVE), São Paulo, SP, Brazil

eDirezione Scientifica Centrale, Fondazione Salvatore Maugeri, I.R.C.C.S., Pavia, PV, Italy

Received1June2015;receivedinrevisedform28October2015;accepted29March2016

KEYWORDS

Pulmonary

rehabilitation;

Airwayclearance

techniques;

Chronicbronchitis;

TPEP;

COPD;

Bronchiectasis

Abstract

Background: Airwayclearancetechniquesincludepositiveexpiratorypressure,commonlyused

inourclinicalpractice,andarecentlyintroducedtemporarypositiveexpiratorypressuredevice calledUNIKO®.Itisunclearwhichoneprovidesthebestbenefittopatients

Objectives: The aimof thisobservational4-year study was to retrospectivelycompare the efficacy of andspecificindications for temporary positive expiratorypressure compared to positiveexpiratorypressureinastandardrehabilitationprogram

Method: We retrospectively collecteddata from 162subjects (107 males,mean age70±9 years,97withprimarydiagnosisofchronicobstructivepulmonarydisease,65with bronchiec-tasis),51treatedwithtemporarypositiveexpiratorypressureand111withpositiveexpiratory pressure

Results:Subjectsshowedsignificantimprovementinratioofpartialpressurearterialoxygen andfractionofinspiredoxygen(p<0.001),forcedvitalcapacity,forcedexpiratoryvolumeinone second,peakexpiratoryflow,arterialoxygensaturation,andpartialpressurearterialoxygen with no significantdifference between positive expiratory pressure andtemporary positive

Italy.

http://dx.doi.org/10.1016/j.bjpt.2016.12.001

1413-3555/© 2017 Associac ¸˜ ao Brasileira de Pesquisa e P´ os-Graduac ¸˜ ao em Fisioterapia Published by Elsevier Editora Ltda All rights reserved.

pul-expiratorypressuregroupsapartfromforcedexpiratoryflow,whichincreasedonlyinthe pos-itiveexpiratorypressuregroup.Evaluatingspecificsubgroups,temporarypositiveexpiratory pressurewasmoreeffectivethanpositiveexpiratorypressureinimprovinggastransferin sub-jectswithemphysemaandinthoseonoxygentherapy,astheeffectivesupplementoxygenflow decreasedsignificantly(p=0.034and0.046respectivelyfortemporarypositiveexpiratory pres-surevs.positiveexpiratorypressure).Insubjectsonmechanicalventilation,positiveexpiratory pressurewassuperiortotemporarypositiveexpiratorypressureinincreasingforcedexpiratory flow(p=0.018)

Conclusion:Thephysiologicalparametersofbothgroupsimprovedsignificantlyandsimilarly Subgroup analysis suggests thattemporary positive expiratory pressure couldprovide some advantagetosubjectswithemphysemaandthoseonoxygentherapy,whilepositiveexpiratory pressurewouldbenefitpatientsonmechanicalventilation.Randomizedclinicaltrialsare nec-essarytoconfirmourpreliminaryresultsindicatingthatdifferentsubgroups/phenotypescan benefitmorefromonetypeoftreatment

©2017Associac¸˜ BrasileiradePesquisaeP´os-Graduac¸˜ emFisioterapia.PublishedbyElsevier EditoraLtda.Allrightsreserved

Introduction

Patients with chronic hypersecretion (CH) of

tracheo-bronchialmucus representa challenging clinicalproblem

CHis asocially disablingcondition causing a high

suscep-tibilitytoairway infectionandfrequent, difficult-to-treat

acuteexacerbationswithasignificantimpactonprognosis,

qualityof life,and use of health care resources,

particu-larlyinsubjectswithseverelyimpairedrespiratoryfunction

and/orchronicrespiratoryfailure(CRF).1 -5

Airway clearance techniques (ACTs), commonly

per-formedbyrespiratoryphysiotherapists,areintendedtoaid

secretion mobilizationand expectoration and to mitigate

complicationsassociatedwithsecretionretention.6Thereis

alackofevidenceonthesuperiorityofanyparticularACTor

deviceandtheguidelinesdonotsupporttheirroutineuse

inthese subjects,6 most ofwhom have chronic bronchitis

(CB),chronicobstructivepulmonarydisease(COPD),and/or

bronchiectasis,evenduringanacuteexacerbation.7

Never-theless,ACTsstillremainachallengingoptionofpulmonary

rehabilitation(PR)programs.8,9

ACTs consist of a variety of approaches, such as

forced exhalation, manual compression, and/or vibration

of the thorax, and positive expiratory pressure (PEP)

breathing.10,11 Three main clinical indications for PEP are

described:toincreaselungvolumes,i.e.,functionalresidual

capacity (FRC) and tidal volume (VT), to reduce

hyper-inflation, and to improve airway clearance.12 One of the

best-knownmethodstogenerateincreasedPEPistobreathe

througharesistancedevice,suchasaPEPmask

More recently, the mechanical generation of low-level

PEPduringthemainpartofexpiration(temporarypositive

expiratorypressure, TPEP)hasbeen proposed toenhance

airwayclearance.A recentrandomizedclinical trial

com-paring the addition of TPEP to usual care13 showed an

improvementin thelevel ofdyspnea andof some

physio-logicalparametersintheTPEPgroup

Theaimofthisretrospectivestudywastoanalyzedata

fromour clinical experience over a 4-year period

involv-ingACTsaspartof acomprehensive PRprogram,in order

tocomparethephysiologicaloutcomes(i.e.,gasexchanges

and lung volumes)of twogroups of patients treatedwith PEPmaskandTPEPrespectively.Wealsosoughttoidentify specificindicationsfordifferentACTsindifferent subpopu-lationsofsubjectswithCH

Method

Wechosetoanalyzedatacollectedover4yearsfrom162

CHpatientsadmittedtotheDepartmentofPulmonary Reha-bilitation in theSalvatore MaugeriFoundation Institute of Veruno (NO), Italy, withprimary diagnosis of CB/COPDor bronchiectasis,sincetheseconditionsarecharacterizedby symptoms(suchaschronicandprogressivedyspnea,cough, andaugmentedsputumproduction14)andonthebasisofthe presenceofCHasclinicallydefinedbyanabundantvolume

ofdailysputum(>30mL/die).15Allpatientshadclinicalsigns andsymptomsofCH,e.g.,ahistoryoffrequent exacerba-tions,hospitalizations,andfrequentuseofantibiotics.On admission, subjectsconsented tothe use of theirclinical dataforscientificpurposes.Thestudywasapprovedbythe InternalReviewBoardattheVerunoMedicalCenter,Veruno (NO),Italy

Atthetimeofadmission,CBwasdefinedbythepresence

ofcoughandsputumforatleast3monthsoftheyearfortwo consecutiveyears.COPDpatientswerestagedandtreated accordingtoGlobalInitiativefor ChronicObstructiveLung Diseases(GOLD)criteria.14Diagnosesofbronchiectasisand emphysema were confirmed by high-resolution computed tomography (HRCT) of the chest.16 Subjects with severe and/or unstable comorbidities (i.e., severe concomitant cardiovascular or neoplastic disease), which might have limitedor impeded theexecution ofACTs,wereexcluded fromanalysis

Subjectswereclassifiedasbeingonoxygentherapy(OT)

if on continuous oxygen treatment (24h) or only during sleep and/or exercise They were classified as being on nocturnal positive pressuremechanical ventilation (MV) if prescribedbytheattendingphysician.COPDexacerbation

pul-Inpatients at the department of pulmonary rehabilitation

2006 – 2009 (n=3770)

Excluded (n=1718)

− Diagnosis different from CB/COPD and bronchiectasis

Assessed for eligibility (n=2,052)

− CB/COPD (n=1731)

− Bronchiectasis (n=321)

Excluded (n=1890)

− No treatment with ACT/PEP and/or severe/unstable condi-tions (n=1789)

− Unavailable pre/post treatment data (n=98)

− Other reasons (n=3)

Analyzed patients (n=162)

− CB/COPD n=97

− Bronchiectasis n=65

Treated with PEP (n=111)

Treated with T-PEP (n=51)

Figure 1 Flowdiagramofthepatientsincludedinthestudy

andbronchiectasisexacerbationweredefinedaccordingto

existingguidelines.14,15,17 Inaddition,subjects includedin

thisanalysisunderwentACTswithPEP-maskorTPEP(Fig.1)

Treatments

Subjects were selected and underwent a comprehensive

PRprogram inaccordancewiththeexistingATS/ERSJoint

Statementon Pulmonary Rehabilitation,1 individually

tail-ored and designed, taking into account disabilities and

tolerance to exercise All patients performed two daily

training sessions on a cycle ergometer or treadmill and

unsupported upper limb exercises, graded as the subject

progressedintheprogram.SubjectswithCRFwereprovided

withambulatoryoxygenasneededduringtrainingsessions

The needfor ACTswasdefinedbythe physiotherapists,in

agreementwiththephysicianincharge,basedonsymptoms

andsignsofexcessiveand/orretainedsecretions

TPEPwasapprovedin2005bytheMinistryofHealthasa

therapeuticdeviceforairwayclearance.In2006,the

phys-icaltherapistsofourDepartmentwereadequatelytrained

todeliverTPEPtreatmentasanalternativetoPEP-mask.At thattime,theywere notawareofthesubsequent collec-tionofdata,soallocationtoPEP-maskor TPEPtreatment wasbasedonpatientpreference,includingcomfortdyspnea andcollaborationduringthefirstACTtrial.Basedona ret-rospectiveanalysisofthedatacollectedbetween2006and

2009,weexcludedpatientswithsevereorunstablediseases, withoutCB/COPDorbronchiectasis,nottreatedwithACTs,

ormissing pre-or post-treatment.Atotal of162 patients withCHusingPEP(n=111)or TPEP(n=51)wereincluded foranalysis(Fig.1)

Patients using PEP-mask performed two 15-min daily cycles They were instructed to reach and maintain the highestmid-expiratorypressuretolerated between10and

20cmH2O (fixed by a manometer weekly) breathing at slightlyincreasedVT,butnottouseforceattheendofthe expiration.Aboutevery2min,theyperformedaforced expi-ratorytechnique(FET)maneuver,huffing,and/orcoughing withouttheresistor.12

PatientsusingTPEP performed two15-min daily treat-ments with UNIKO (Medical Products Research, Legnano, Italy) They were asked to blow through a mouthpiece

pul-keepingTPEPactiveaslongaspossibleforeverybreathand

tocough asneeded or at least every3 -5min Both

tech-niqueswereadministeredinthesittingpositionwithelbows

restingona hardsurfaceinfrontofthem Sideeffectsor

adverse eventsassociated withtreatmentswererecorded

bythephysiotherapistsincharge

OnlydatafromsubjectswhounderwentACTsforatleast

10 days within the in-hospital rehabilitation period were

considered.ACTswerestoppedattheendof PRprogram,

correspondingtodischargefromtheDepartment

Physiological parameters, i.e., data from spirometry and

arterialbloodgasanalysis,measuredbothat baselineand

atdischargewereconsideredasprimaryendpointsbasedon

previousdataonthetreatmentofCHinseverepatients.18

Dyspnea,othersymptoms,andcharacteristicsofsecretions

werenotcollectedinastandardizedwayatthattimeand

thuswerenotconsideredinouranalysis

Respiratoryfunctionwasassessedusingstandard

spirom-etry(6200 Auto box Pulmonary Function Laboratory,

Sen-sormedics,YorbaLinda, CA,USA) Resultswereexpressed

asabsolute valuesand percentageof their predicted

val-ueswhenindicated.Arterialoxygensaturation (SaO2)was

monitoredduringtreatmentsforsafetyprocedures

Arterialbloodgases(ABGs)weredeterminedinaradial

arterybloodsample,withthepatientinrestingcondition,

breathingroom air or oxygen at the prescribedflow rate

(fractionof inspired oxygen - FiO2).Both spirometryand

ABGanalysis(ABL analyzer, Radiometer,Copenhagen, DK)

wereperformedaccordingtoexistingguidelines.19

Descriptive statistics were calculated for all variables;

means and standard deviations or frequencies and

per-centages were reported according to the quantitative or

qualitative nature of the variables, respectively Baseline

characteristics were comparedusing unpaired Student’s t

testorchi-squaretest,asappropriate.Repeatedmeasures

analysisofvariancewithonefactor(TPEPvs.PEP)wasused

totest differences between pre- and post-assessments in

theTPEPandPEPgroups.Astatisticallysignificant

interac-tiontermwasinterpretedasasignificantdifferencein

pre-andpost-effectbetweentwotechniques.Thesame

analy-siswasappliedtoassessdifferencesinsubgroupsidentified

accordingtoclinicallyrelevantvariables(emphysema,OT,

MV)

Results

Thebaselinedemographic,clinical,andphysiological

char-acteristicsof allsubjectsandcomparisonbetween groups

(TPEPvs.PEPmask)areshowninTable1.Mostofthemwere

male(66%),meanage70years(range35 -89),andcurrent

orformersmokers;60%hadaprimarydiagnosisofCB/COPD

and40%hadbronchiectasis

Thesamplewascomposedofsubjectswithmoderateto severe lung disease Alarge proportion(92/162) of them wereCRFrequiringOTand/orMV.Subjectsshowedawide rangeoflungfunctionvalues.Overall,thestudypopulation wascharacterizedbyasignificantimpairmentofspirometric parameters(forcedvitalcapacity -FVC%predicted69(21), forcedexpiratoryvolumeinonesecond -FEV1%predicted

51(23)).AhighernumberofpatientsweretreatedwithPEP mask(111subjects,68%)thanwithTPEP(51subjects).Inthe majorityofcases(67%),bothtreatmentswereperformedfor

atleast15days

ComparingthePEPmaskandTPEPgroupsatbaseline,no significant differences emergedinany of theparameters, exceptahigherproportionofsubjectswithanacute exacer-bationtreatedwithTPEP(p=0.037,Table1).Nostatistical differencewasfoundinlungfunctiondataatbaselineandin theproportionofsubjectswithCRFbetweengroups.During treatments,weobservednomajorsideeffectsoradverse event,apartfromoccasionaldizzinessdueto hyperventila-tioninbothgroups

ACT Subjects as a whole

After ACT treatment, we observed significant improve-ments in most physiological measures both in the TPEP and PEP mask groups (Table 2) Almost all ventilatory parametersimprovedsignificantlyinbothgroups,i.e.,FVC andFVC%,FEV1 andFEV1%predicted,andpeakexpiratory flow and PEF% predicted Most gas exchange parameters (SaO2, partial pressure arterial oxygen (PaO2), and ratio

ofpartialpressurearterialoxygenandfractionofinspired oxygen (PaO2/FiO2)) were also greatly improved in both ACTgroups, while partialpressurearterial carbondioxide (PaCO2)remainedunchanged

Comparingthemagnitudeofthechangesobservedafter thetwotypesoftreatment(TPEPvs.PEP),therewereno significant differencesapart fromborderline FEF25 -75% and FEF50%improvementsinthePEPmaskgroup(Table2)

Subject subgroups

Thelargenumberofsubjectsevaluatedinthepresentstudy enabledustoperformanalysesinsubgroupstodetectany specificeffectsofeitherofthetwoACTs.Wecomparedthe changesobservedaftertreatmentsinthetwogroupsofACT stratifyingthesubjectsaccordingtothecategoriesreported

inTable1 Therewerenodifferencesbetweentheeffectsof treat-mentwithPEPmaskorTPEPintermsofprimarydiagnosis (bronchiectasisvs.CB/COPD),smokinghistory,presenceor absence ofan acuteexacerbation,or levelof FEV1% pre-dicted(>vs.<50%).Furthermore,treatmentswereequally effective in both treatment groups irrespective of their duration (< or >15 days), suggesting that 10 days of ACT (i.e., theshortest lengthof treatment allowed) are suffi-cienttoyieldapositiveeffectonclinicalandphysiological parametersregardlessofthemethodused

interesting differences between the two groups The need for supplemental oxygen before and after differed

pul-Table 1 Characteristicsofthestudiedpopulation

T-PEP(n=51) PEP(n=111) TOTAL(n=162)

Demographic data

Gender

Smoking history

Diagnosis

Main diagnosis

Additional diagnoses/conditions

Nocturnalmechanicalventilationa 11(22%) 19(17%) 30(19%)

Days of ACT

Data expressed as mean (SD) orn(%) COPD, chronic obstructive pulmonary disease; OT, oxygen therapy; MV, nocturnal positive pressure mechanical ventilation; FEV 1 , forced expiratory volume in one second % predicted; FVC, forced vital capacity % predicted; FEF 25 -75% and FEF 50% , forced expiratory flows at 25 -75% and at 50% of FEV 1 ; PEF, peak expiratory flow % predicted; SaO 2 , arterial oxygen saturation; PaO 2 , partial pressure arterial oxygen; PaCO 2 , partial pressure arterial carbon dioxide; PaO 2 /FiO 2 , ratio of partial pressure arterial oxygen and fraction of inspired oxygen.

a 14 patients were on both OT and MV.

b 10 -15 days.

* p= 0.037 comparing T-PEP with PEP group.

significantlyinTPEPsubjects(reduced)comparedtothose

treated with PEP mask (increased, p=0.034, Fig 2A) In

addition, the FiO2 at which the patients were breathing

differed significantly between the PEP and TPEP groups

(p=0.031,notshown).Inthiscontext,in theTPEPgroup,

oxygen supplementation was reduced in the majority of

subjectswithemphysema,andonesubjectdiscontinuedit

completely.InthePEPgroup,manysubjectsincreasedthe

oxygensupplementation,andthreeofthemwhowerenoton

oxygenatbaselinestartedtouseit.PaCO2diminishedonly

in the TPEP group, while it increased in subjects treated

withPEPmask(p=0.02,notshown)

Asshown inTable1,themajority ofoursubjectswere

onOTand/orMV.Datareferringonlytoallthoseon oxygen

dimin-ishedsignificantlyintheTPEPgroup comparedtothePEP mask group (p=0.046, Fig 2B) In addition, in the TPEP group,the FiO2 diminishedin themajority of subjects on

OT whereas it increased in the PEP group (p=0.038, not shown),andsixsubjectswhowerenotonoxygenstartedto useit

In subjects on MV, PEP mask was superior to TPEP in increasing FEF50 and FEF50%, TPEP treatment was associ-atedwithFEF50% reductionsand PEPmask treatment with

pul-Table 2 Mainresultsintheoverallstudygroup

TPEPgroup Prevs

post

PEPgroup Prevs

post

TPEPvs

PEP

comparison Mean(SD) Mean(SD) Mean(SD) Mean(SD)

FVC(L) 2.06(0.66) 2.18(0.66) <0.001 2.03(0.57) 2.21(0.70) <0.001 NS

FVC% 69.44(21.95) 73.73(21.93) 0.015 71.15(19.02) 74.78(23.72) 0.015 NS

FEV1(L/s) 1.16(0.53) 1.21(0.54) <0.001 1.16(0.44) 1.27(0.52) <0.001 NS

FEV1% 50.00(23.46) 52.22(23.97) <0.001 53.11(21.59) 58.41(24.10) <0.001 NS

FEV1/FVC 56.07(13.39) 55.02(12.64) NS 57.79(14.10) 58.54(15.33) NS NS

FEF25 -75% 22.31(20.1) 22.22(17.31) NS 25.83(20.09) 30.80(25.73) NS 0.05

FEF50% 21.84(21.74) 21.39(18.94) NS 25.28(21.51) 29.85(26.73) NS 0.046 FEF75% 22.48(16.03) 23.75(17.28) NS 28.11(23.06) 31.95(26.33) NS NS

PEF(L/s) 3.46(1.56) 3.63(1.42) NS 3.31(1.22) 3.88(2.59) NS NS

PEF% 52.39(23.33) 54.45(20.25) 0.006 51.26(18.43) 56.32(20.59) 0.006 NS

SaO2% 93.06(3.92) 94.31(2.28) <0.001 92.75(3.41) 94.45(1.98) <0.001 NS

PaO2(mmHg) 64.7(13.99) 71.09(13.76) <0.001 65.24(9.67) 71.46(11.85) <0.001 NS

PaCO2(mmHg) 43.96(9.32) 44.01(7.90) NS 43.77(9.72) 43.67(10.94) NS NS

PaO2/FiO2% 274.21(73.17) 305.94(83.78) <0.001 289.33(56.34) 311.99(70.42) <0.001 NS

FVC (FVC%), forced vital capacity (% predicted); FEV1 (FEV1%), forced expiratory volume in one second (% predicted); FEF25 -75(%), FEF50(%), FEF75(%), forced expiratory flows at 25 -75%, 50% and 75% of FEV1(% predicted respectively); PEF (PEF%), peak expiratory flow (% predicted); SaO2, arterial oxygen saturation; PaO2, partial pressure arterial oxygen; PaCO2, partial pressure arterial carbon dioxide; FiO2, fraction of inspired oxygen; PaO2/FiO2, ratio of partial pressure arterial oxygen and fraction of inspired oxygen.

4

Panel - A

Panel - B

O2

B

∗

2

1

0

4

3

O2

2

1

0

Figure 2 (PanelA)MeansandstandarddeviationsofoxygensupplementinsubjectswithemphysemaintheTPEPgroup(A)and PEPgroup(B).*p=0.034,comparisonbetweenintergroupchanges.(PanelB)Meansandstandarddeviationsofoxygensupplement

insubjects on oxygentherapy (OT) inthe TPEP group (A) andthe PEP group (B) *p=0.046,comparison between intergroup changes.O2suppl,oxygensupplementisexpressedinL/min,litersperminute;TPEPpre,baselinevalueintheTPEPgroup;TPEPpost, post-treatmentvalueintheTPEPgroup;PEPpre,baselinevalueinthePEPgroup;PEPpost,baselinevalueinthePEPgroup

pul-TPEPpre TPEPpost PEPpre PEPpost

100

80

60

40

20

0

∗

Figure 3 MeansandstandarddeviationsofFEF50%, percent

ofpredictedforcedexpiratoryflowat50%ofvitalcapacity,in

subjectsonmechanicalventilationintheTPEPgroup(A)and

thePEPgroup(B).TPEPpre,baselinevalueintheTPEPgroup;

TPEPpost,post-treatmentvalueintheTPEPgroup;PEPpre,

base-linevalueinthePEPgroup;PEPpost,baselinevalueinthePEP

group.*p=0.018,comparisonbetweenintergroupchanges

itsincrease(p=0.018,Fig.3).Asimilarbutnotstatistically

significanttrendwasobservedinthesamesubjectsforthe

changesinFEF25 -75%andFEF25 -75%

Finally,in subjectswithout CRF(neitheronOTnorMV)

we observed statistically significant differences in PaO2

(p=0.0024)andPaO2/FiO2(p=0.021)betweengroups.TPEP

group showed a greater improvement of both PaO2 and

PaO2/FiO2.Ofnote,inthissubgroupofpatients,baselines

PaO2valueswereratherlow(<70mmHg)

Discussion

By evaluatingtwogroups of subjectswithCHinthe

com-mon clinical scenario, included in a standard PR program

and treated withdifferent ACTs, we found improvements

inthePaO2/FiO2ratioandinmanyimportantphysiological

parameters.Furthermore,ourdatashowthatTPEPperforms

aswell asis the most commonly used PEP mask Finally,

subgroup analyses indicate that TPEP and PEP could

per-formdifferentlyindifferentconditions,suggestingthatan

accurateselectionofACTs,notexclusivelytailoredto

indi-vidualpreferenceorcomfort,iswarrantedtoobtainabetter

performance

A previous report on the experimental use of TPEP

showed improvements in symptoms, static and dynamic

lungvolumes,andasignificantandprogressivereductionin

mucusproductionandinperceivedbronchialencumbrance

in chronic respiratory diseases, including COPD, asthma,

andcysticfibrosis,andinthepreparationofCOPDpatients

for major abdominal surgery.20 Based on those

prelimi-nary findings suggesting an effect on the distribution of

lung ventilation with significant improvements in ABGs, a

multi-center randomized controlled trial was designed.13

The ‘‘UNIKO Project’’ showed that TPEP in combination

withmanuallyassistedACT,namelyELTGOL21 -23(Expiration

lung function andsymptomsin subjects withCHand

pro-motes a faster recovery fromsymptoms duringtreatment

comparedtoELTGOLalone.Inthatstudy,therewereno sig-nificantdifferencesinABGvaluesbetweenthetwogroups Our analysis, performed on subjects admitted to the Pneumology Department of a rehabilitation center and conventionallytreated witha comprehensive PR program includingACTtechniques, confirms previous experimental results.Inparticular,itconfirmsthatsuchanapproachcan produce significant improvements in respiratory function andABGsinamixedpopulationof patients.However,our findingsandpreviousobservations18areincontrastwiththe

‘‘UNIKOProject’’ reportstatingthat theadditionofTPEP didnotproduceanychangeinABGs

There are a number of differences between our study andthe‘‘UNIKOProject’’thatmayexplainthedifferences

intheresultsobserved.ThestudybyVenturellietal.13had

anumberofexclusioncriteriaasitenrolledonlysubjects

instableconditions,excludingthosewithacute exacerba-tionoronMV.Infact,ABGvaluesatthebeginningoftheir treatmentswerenormal,sofindingsignificantchangesafter treatmentwouldhavebeenveryunlikely.Despitethis,their TPEPgroupstillshowedabettertrendinashorter period

oftreatment

In thepresent study,we evaluated alargernumber of subjectsina‘‘real-life’’clinicalscenario.Theywere con-secutivesubjectswithCB/COPDorbronchiectasisasprimary diagnosis and history of CH who were enrolled in a PR programincludingACT.Thus,weincludedasignificant per-centageofsubjectswithacuteexacerbationsandthoseon

OTand/orMV (39,47,and 19%,respectively).In addition

toourcomparison,wedifferentiatedthetwotypesofACT (TPEPvs.PEP),whileVenturellietal.13addedTPEPto con-ventionaltreatment

Ourresultsshowthatonaveragebothgroupshadequally improved physiological parameters such as lung volumes, flows,andABGvalues.BothPEP-maskand TPEPare clas-sified as PEP methods aimed to favor the mobilization

of secretions in the lung by ‘‘stenting’’ the airways The mechanismandeffectsofPEParewidelydescribedinthe literature PEP increases intrathoracic pressure and FRC, withimprovement incollateralventilation.24 The applica-tionofa15cmH2OPEPtemporarilyincreasesVT,reducing respiratoryfrequency,25andbothinspiratoryandexpiratory muscleactivity.26Inaddition,atemporaryincreaseinFRC, relatedwith increasing PEP has been shown.27 This leads

to changes in breathing pattern, with decreased expira-toryflows,increasedexpiratorytime,andasmallerexhaled volume.28PEPpressureshigherthan10cmH2Oarerequired

toopentheairways.12

Withthisinmind,it seemsdifficulttounderstand how

apressureaslittleas1cmH2O,suchasthatgeneratedby TPEPwhenmeasuredatthemouth,couldbeaseffectiveas thePEPmask Otherfactorsprobablyplayarole.Infact,

intheTPEPdevice,thereisapressuresensorthatdetects exhalation,activatingacompressor thatblows airagainst theexpiratory flow.The resistancedelivery timedepends

ontheabilityofthesubjecttosustainacertainflowaslong

aspossible.Aforcedexhalationwillgenerateapeakof expi-ratoryflowcausingasuddendropinpressure(thatleadsto

acollapseoftheperipheralairways).Thebestperformance

isobtainedwhentheexpiratoryflowisalittlehigherthan duringquietbreathing,almostreachingresidualvolumeand achievingthesamegoalasthatofotherclassicalACTssuch

pul-asautogenicdrainageandELTGOL.22,29 Anotherdifference

betweenthetwoACTsisthat,withthePEPmask,theflowis

variableandeffort-dependent,24,30,31whiletheTPEPdevice

givesfeedbackandguidesthesubjecttoadaptinspiration

andexpirationtoreachthegoal.Furthermore,while

blow-ingintothemouthpiece,anoscillationisclearlyperceived

while resistance is active, due to the reciprocating

com-pressor.High-frequencyoscillations arethoughttohave a

mucolyticeffectonbronchialsecretions,32andthisfeature

couldplay some rolein explaining themechanism of this

technique

OperationaldifferencesbetweenPEPmaskandTPEPmay

alsoaccountforthedifferencesfoundbetweentheeffects

obtainedbythetwoACTtechniquesinourstudy.Subgroup

analysisgave some preliminary indications Subjects with

emphysemashowedareducedneedforoxygen(O2)supply,

FiO2,andPaCO2.Theabovedata,combinedwiththegeneral

reductionin theneed for O2 in OTsubjects andwiththe

increaseinPaO2inthosewithoutCRF,seemstoindicatethat

TPEP may facilitate gas exchange During TPEP, very low

pressuresare appliedtotheairways, making unlikelyany

directrecruitmenteffectorchangesinsurfactantactivities

and/orproductionasseenwithPEPsystems.30

We speculate thatbreathing pattern andthe effective

mucus clearance achieved by the increase in gas -liquid

interaction33duringsustainedexpiratoryflowcouldexplain

gas-exchange improvements It would also be interesting

toinvestigate if any post-treatment change is present in

respiratorypatternandmechanicsorinairwayresistance

Infact, TPEPforcespatients tobreathe ina regularway,

withopen glottis,for the entiretreatment time,andthis

‘‘training’’couldhavecontributedtoimprovetheabilityto

controlbreathinginsubjectswithemphysema.26,34

We observed a statistically significant difference

between groups when evaluating subjects onMV only for

the forced expiratory flows (FEF50%) The interpretation

of this findingis difficult particularlybecause volumes or

gasexchange parametersdidnot differbetween subjects

on MV We might speculate that MV, providing positive

pressureinsidetheairways,canovercometheTPEPeffects

onFEF.Onthecontrary,theadministrationofahigherPEP

withFET maneuvers could have enhanced mid-expiratory

flows.Clearly,furtheranalysesareneededtoconfirmthis

hypothesis

Comfortisanotherimportantfactorwetakeintoaccount

whenallocatingpatientstodifferenttreatments.Notably,

many of the subjects treated with TPEP were already

PEP-maskusers at home and found thenew device more

comfortableandsimpletouse,sincelesseffortisrequired

comparedtothePEP mask withthesame subjective

per-ceptionofefficacy.Thisfeedbackwasimportant,prompting

usto continue investigations and, asunderlined by many

authors,10,11,35 -38itmightimproveadherencetothe

treat-ment

The majorlimitation of the study is the retrospective

design and other sources of bias such as the consequent

lackofrandomizationandintention-to-treatanalysis.Thus,

cautionshouldbeappliedwheninterpretingtheresultsof

thisstudy.Moreover,futurerandomizedcontrolledtrialsare

warrantedtoconfirmtheresultsofthisstudy

Otherlimitationsincludethelackofdataonthevolume

andcharacteristicsofsputum,symptomsandhealth-related

qualityof life, not systematicallyavailable in theclinical documentationforallpatientsincluded.Furthermore, allo-cation to one or other treatment group may have been affected by thepatient’s perception andcompliance dur-ingthefirstassessment.TPEPrequireslesseffortthanPEP

tobeactivated:thismightexplaininpartwhyagreater pro-portionofsubjectswithanacuteexacerbationwereinthe TPEP group, though nosignificant differences werefound betweentheeffectsoftreatmentinrelationtothepresence

ofanacutecondition

Nevertheless, no other differences in baseline param-eters were found between groups Furthermore, the PEP mask isawell-established techniquethatphysiotherapists andpatientsarefamiliarwith,whileatthattime,TPEPhad justbeenintroducedintoclinicalpractice,afactthat prob-ablywasthecauseofthesmallernumberofsubjectstreated withthisnewertechnique

Conclusions

Inconclusion,ourdatashowedthat,inmostsubjectswith

CHin current clinicalpractice,TPEP yieldssimilarresults

to the PEP mask Both groups significantly and similarly improved physiological parameters, but subgroup analysis suggeststhatTPEPcouldprovide someadvantagesto sub-jects with emphysema or those on OT, while PEP would

bemoreadvantageousinpatientsonMV TPEPaddedtoa standardPRprogramappliedinsubjectswithCHappearsto

beasafeandwell-acceptedACTandavalidalternativeto PEP.Weneedfurtherprospective,highqualityrandomized controlled trials to confirm preliminary results indicating thatdifferentsubgroups/phenotypescanbenefitmorefrom oneortheothertypeoftreatment

Conflicts of interest

Theauthorsdeclarenoconflictofinterest

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