Effects of a community-based pulmonary rehabilitation programme during acute exacerbations of chronic obstructive pulmonary disease - a quasi-experimental pilot study

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Pleasecitethisarticleinpressas:MachadoA,etal.Pulmonol.2019.https://doi.org/10.1016/j.pulmoe.2019.05.004

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PULMOE-1373; No.ofPages12

Pulmonol.2019;xxx(xx):xxx---xxx

www.journalpulmonology.org

ORIGINAL

ARTICLE

Effects

of

a

community-based

pulmonary

rehabilitation

programme

during

acute

exacerbations

of

chronic

obstructive

pulmonary

disease

---

A

quasi-experimental

pilot

study

夽

A. Machado

a_,b

_,

_A.

_Oliveira

a_,b

_,

_C.

_Valente

c

_,

_C.

_Burtin

d

_,

_A.

_Marques

a_,b_,_∗

a_Lab_3R_---_Respiratory_Research_and_{Rehabilitation}_Laboratory,_School_of_Health_Sciences,_University_of_Aveiro,_Aveiro,_Portugal b_Institute_of_Biomedicine_(iBiMED),_University_of_Aveiro,_Aveiro,_Portugal

c_Pulmonology_Department,_Centro_Hospitalar_do_Baixo_Vouga,_Aveiro,_Portugal d_Faculty_of_{Rehabilitation}_Sciences,_Hasselt_University,_Diepenbeek,_Belgium

Received12February2019;accepted3May2019

KEYWORDS Pulmonarydisease; Chronicobstructive; Diseaseprogression; Communityhealth services; Rehabilitation Abstract

Background: Pulmonaryrehabilitation(PR)isacornerstoneinterventionforthemanagement ofpatientswithstablechronicobstructivepulmonarydisease(COPD).However,itsrole dur-ingacuteexacerbations(AECOPD)iscontroversialsincemoststudieshavebeenconductedin hospitalisedpatients, whenmorethan80%ofAECOPDaremanagedonanoutpatientbasis. Thisquasi-experimentalpilotstudyassessedtheeffectsofacommunity-basedPRprogramme duringmild-to-moderateAECOPD.

Methods:Outpatientswererecruitedfromhospitalsandallocatedtoexperimental(EG)or con-trol(CG)groups.EGreceivedstandardmedicationplus3-weeksofPR.TheCGreceivedstandard medication.Dyspnoea(mMRC),quadricepsmusclestrength(QMS),functionality(5-repetition sit-to-standtest)andimpactofthedisease(COPDassessmenttest(CAT))wereassessedwithin 48hofthe AECOPD onsetandafter PR. Symptomsofdyspnoeaand fatigue(mBorg), heart andrespiratory(RR)ratesandperipheraloxygensaturation(SpO2)wereassessedatrestand

monitoredinallPRsessions.Needforhospitalisationwasmonitoredduringthe3-weeks.

Results:Twelvepatients(69_±7years,FEV152±27pp)intheEGandelevenintheCG(66±9

years,FEV155±22pp)wereenrolled.TheEGpresentedsigniﬁcantimprovementsonQMS(Pre

21.0vs.Post25.0,p=0.012),CAT(Pre23.0vs.Post14.5,p=0.008),symptomsofdyspnoeaat rest(Pre3.0vs.Post1.0,p=0.008),SpO2(Pre94.0vs.Post96.0,p=0.031)andRR(Pre24.0

vs.Post20.5,p=0.004).NosigniﬁcantimprovementswerefoundintheCG.

夽 _Previous_{presentations:}_Part_of_this_work_was_presented_at_the_28th_European_Respiratory_Society_{International}_Congress_as_a_poster discussion.

∗_{Corresponding}_author.

E-mailaddress:[email protected](A.Marques).

https://doi.org/10.1016/j.pulmoe.2019.05.004

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Conclusion:AddingPR to themanagement ofmild-to-moderateAECOPD seems toresultin improvementsonparametersusuallyassociatedwithanincreasedriskofre-exacerbationand poorprognosis.Randomisedstudieswithlargersamplesareneededtoconﬁrmtheseresults. © 2019 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Introduction

The trajectory of chronic obstructive pulmonary disease (COPD)isfrequentlypunctuatedbyexacerbations,deﬁned asepisodesofacuteworseningofrespiratorysymptomsthat resultinadditionaltherapy.1,2_Acute_{exacerbations}_of_COPD

(AECOPD)account for more than 70% of all COPD-related costs3 _and _are _mainly _responsible _for _patients’ _clinical

deterioration.1 _It _is _known _that _AECOPD _result _in

signiﬁ-cantdeclineinmusclestrength,functionalcapacityandlung function, which further impairs patients’ health-related qualityoflife(HRQoL)andincreasestheirsusceptibilityto moreexacerbations,hospitalisationsanddeath.1,2,4,5

There-fore, treatment goals for patients with AECOPD are to minimisethenegativeimpactoftheseeventsandprevent theirrecurrence.1

Pulmonaryrehabilitation(PR)isawell-established inter-ventionforthemanagementofpatientswithstableCOPD.1,6

Ithasbeen shown to:(i)improveexercise capacity, func-tional capacity, muscle strength and HRQoL; (ii) reduce symptoms,hospitalisationsandunscheduledhealthcare vis-its;and (iii) enhance self-management and self-efﬁcacy.6

Giventhesebeneﬁtsitwouldseemreasonabletoconsider PRasamanagementstrategyforAECOPD.7_However,

stud-ies assessing the role of PR during AECOPD have shown controversialresults;1,8_this_is_probably_related_to_the

set-tings in which the PR programmes have been conducted and the disease severity of patients included. Most stud-ies have been conducted in hospitalised patients,3,9 _who

present more severe exacerbations and/or more severe underlying disease than those managed on an outpatient setting.1 _Although _it _is _recognised_that _more _than _80% _of

allAECOPDaremanagedonanoutpatientbasis,1_only_a_few

studies have conducted PR programmes on an outpatient setting.10---13 _{Additionally,} _those_studies _did_not _start _their

interventionat theonsetof theAECOPDbut shortlyafter theAECOPD,10,11_included _patients_with_AECOPD_who_have

previouslybeenhospitalised,12,13_and_have_found_signiﬁcant

results in differentoutcomes (e.g., exercisecapacity,10,12

HRQoL,10---12 _and _{re-exacerbations}13_). _Thus, _the _potential

role of PR programmes during AECOPD in patients man-agedonan outpatientbasisisnot yetclariﬁed. Moreover, outpatientbasisincludescommunity-basedPR(i.e.,PR pro-grammesnearbypatients’homes),whichmaybeapromising approachtoovercomingtheshortcomingsofpooraccessand transporttoPR,especiallyinpatientswithAECOPD,buthas hardlybeeninvestigated.14,15

Therefore, this pilot study aimed to explore the fea-sibility of conducting a community-based PR programme duringAECOPDandassessitseffectsonpatients’symptoms,

muscle strength, functionality, impact of the disease, peripheraloxygensaturationandhospitalizations.

Methods

Ethics

Approval for this study was obtained from the ethics committees of the Administrac¸ão Regional de Saúde do Centro, I.P. (3NOV’2016:64/2016), Centro Hospitalar do Baixo Vouga(22MAR’2017:777638),HospitalPedro Hispano (17FEB’2017:10/CE/JAS) andHospital Distrital daFigueira daFoz(18JUL’2017)andfromtheNationalDataProtection Committee (8828/2016). Written informed consents were obtainedfromallparticipantsbeforeanydatacollection. Studydesignandparticipants

A quasi-experimental study was conductedin outpatients withAECOPDrecruitedfromthreemainhospitalsbetween November2016andDecember2017.Inclusioncriteriawere diagnosis ofAECOPD accordingtothe GlobalInitiativefor ChronicObstructiveLungDisease(GOLD)criteria.1_Exclusion

criteriawere:(i)hospitalisation;(ii)presenceofsevere co-existingcardiac,respiratory,neurological,musculoskeletal, orsignsofpsychiatricimpairments;(iii)currentneoplasiaor immunologicaldiseaseand(v)anytherapeuticintervention inadditiontostandardofcare.Eligiblepatientswere iden-tiﬁedbypulmonologistsandcontactedbytheresearchers, who explainedthe purposeof thestudy andasked about their willingness to participate.An appointmentwith the researchers wasscheduled within48h of thediagnosis of AECOPDwiththoseinterestedinparticipating.Duetothe exploratorynatureofthisstudyandthecontroversyaround theefﬁcacyandsafetyofconductingPRduringAECOPD,2_we

feltthatrandomisingpatientswasnotsuitable.16_Like_other

studies,17---19 _patients_were _given_the_choice _of_treatment.

ParticipantswhoacceptedenrolmentinthePRprogramme wereassignedtotheexperimentalgroup(EG),the remain-ingparticipants,whoacceptedparticipationinthestudybut didnotwanttobeenrolledinthePRprogramme,composed thecontrolgroup(CG).

Samplesize

According to the recommendations for adequate sample sizes toconductpilotstudies, twelveparticipantsineach groupwouldbeneededtoconductthisstudy.20_However,_as

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Community-basedpulmonaryrehabilitationduringexacerbationsofCOPD 3

arearound30---35%,21 _sixteen _patients_in _each_group _were

aimedtoberecruited. Intervention

The interventionconsisted ofstandard medicaltreatment for the CG (i.e., pharmacotherapy) and standard medi-caltreatment plus acommunity-based PR programmefor the EG. The community-based PR programme was per-formed twicea weekfor 3 weeks.22,23 _The _mean_duration

of each session was 60min and included breathing con-trol and airway clearance techniques, thoracic expansion andmobilityexercises,exercisetrainingand psychoeduca-tionalsupport.3,24,25_Exercise_training_was_set_at_an_intensity

of60---80%ofpatients’maximumestimatedheartrateand symptomsofdyspnoeaandperceivedexertionwere main-tainedbetween4and6atthemodiﬁedBorgscale(mBorg). Psychoeducationalsupportwasperformedusingﬂyersand verbaldiscussions.25,26 _A_{multidisciplinary} _team_was

avail-able toprovide additional support. Sessionswere held at theSchoolofHealthSciences,UniversityofAveiro(ESSUA) orat patients’homebyaphysiotherapistwithexperience in respiratory interventions. Adetailed description of the interventionprotocolcanbefoundinFig.1.

Outcomemeasures

Sociodemographic (age, gender), anthropometric (height, weight,body mass index--- BMI)and general clinical data (smokinghabits,numberofexacerbationsinthepastyear, medicationusedinthestableandexacerbatedperiodofthe disease,long-termoxygen,non-invasiveventilation, comor-biditiesandphysicalactivitylevels)werecollectedwithin 48h of the AECOPD onset. The severity of comorbid dis-easeswas recordedand scored according tothe Charlson ComorbidityIndex(CCI):27_mild_(CCI_scores_of_1---2),

moder-ate(CCIscoresof3---4)andsevere(CCIscores≥5).Physical activitylevel wasassessedwiththe briefphysicalactivity assessment tool.28,29 _{Additionally,} _severity_of _airﬂow

limi-tationwasclassiﬁedbased onthe mostrecent spirometry fromthepatients’clinicalnotes,performedwhentheywere stable.1_Patients’_clinical_notes_were_checked_for_any_need

ofhospitalisationand/orunscheduledhealthcareutilisation duringthe3weeksofintervention.

Outcomesassessedbeforeandafterthe3weeksof inter-ventionweredyspnoeaduringactivities,quadricepsmuscle strength, functionality and impact of the disease. Symp-toms of dyspnoea and fatigue at rest, peripheral oxygen saturation(SpO2)andvitalsigns(i.e.,respiratoryandheart rates)wereassessedbeforeandaftertheinterventionand also monitored in all PR sessions. All assessments were conductedbyatrainedphysiotherapistfollowingthe stan-dardisedorderdescribed.

Dyspnoea and fatigue were assessed by asking partici-pants to rate their perceived levels of these symptoms on the mBorg.30,31 _The _MCID _established _for _dyspnoea

symptoms in the mBorg is of 0.9 units for patients with AECOPDreceivingpharmacologicaltreatment.32 _Symptoms

of dyspnoea and fatigue, SpO2 and vital signs (to ensure patients’securityduringtheintervention7_),_were_assessed

at rest whilst participants were sitting andresting for at

least10min. Respiratoryrate wasassessed during 60s by directobservationofthechestwall.33_Heart_rate_and_SpO

2 were collected with a pulse oximeter (Pulsox 300i, Kon-ica Minolta, Tokyo, Japan). In AECOPD, a SpO2<90% has beenshowntohavehighsensitivityandspecificitytodetect both hypoxaemia (sensitivity=83.9%, specificity=88.9%) and hypercapnia (sensitivity=71.3%, specificity=76%),9,34

andhasbeenpositivelycorrelatedwitharterialoxygen sat-uration(r=0.91;p<0.001).9

Dyspnoea during activities was assessed with the modiﬁed BritishMedical ResearchCouncil dyspnoea ques-tionnaire(mMRC).35_This_is_a_simple,_valid_and_widely_used

instrumenttocharacterisetheimpactofdyspnoeaonthe dailyactivitiesofpatientswithCOPDthatrelateswellwith othermeasuresofhealthstatusandpredictsmortalityrisk.1

Variationsof0.6unitshavebeenrecentlyindicatedasthe minimalclinicallyimportantdifference(MCID)forpatients withAECOPDafterpharmacologicaltreatment.32

Quadricepsmusclestrengthwasmeasured onthe dom-inantsideduringanisometriccontractionwithahandheld dynamometer (microFET2, Hoggan Health, The best Salt Lake City, Utah).36 _This _is _an _important _outcome _since

quadriceps muscle strength is an independent predictor of mortality in COPD37 _and _is _usually _decreased _during

AECOPD.38

Functionalitywasassessedwiththeﬁve-repetition sit-to-standtest(5-STS)accordingtotheprotocolofJonesetal.39

AMCIDof1.7shasbeenestablishedforpatientswithstable COPDafterPR.39_According_to_the_authors_best_knowledge,

thereisnoMCIDestablishedforAECOPD.

Impact of the disease was measured with the COPD assessmenttest(CAT).CATisoneofthekeyoutcome mea-suresrecommendedby the GOLD1 _to_assess _patients _with

COPD,and is alsothe outcome measure presenting more robustmeasurementpropertiesduringAECOPD.9_A_MCID_of

2pointsforpatientswithAECOPDreceivingpharmacological treatmenthasbeenestablished.40

Dataanalysis

StatisticalanalyseswereperformedusingIBMSPSSStatistics version24.0(IBMCorporation,Armonk,NY,USA)andplots createdusingGraphPadPrismversion5.01(GraphPad Soft-ware,Inc.,LaJolla,CA,USA).Thelevelofsigniﬁcancewas setat0.05.

Descriptivestatisticswereusedtodescribethesample. The normality of the data was explored with the Shapiro---Wilk test. Then, independent t tests, Mann---WhitneyUtestsandchi-squared testswereusedto compare sociodemographic, anthropometric and general clinical characteristics between groups (i.e., EG vs. CG). Thedifferencesbetweenpre-andpost-intervention assess-ments,pergroup,werepooledforeachoutcomemeasure andMann---WhitneyUtests wereusedtocompare groups. Comparisons between pre- and post-intervention assess-ments within each group were performed with Wilcoxon signed-ranktests.

Wheneverpossible,thenumberandpercentageof parti-cipants in each group that improved abovethe MCID was determined and compared with chi-squared tests. Data

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First week

Techniques/components First session Second session

Psychoeducational support Education on relaxation and dyspnoea relief

positions (10 min) Clarification of doubts of the 1 st _session

Breathing retraining Breathing control (10-15 cycles)

Pursed-lips breathing (apnoea for 3-5s, 8 cycles)

Breathing control (10-15 cycles) Deep breathing exercises (5-10 cycles) Pursed-lips breathing (apnoea for 3-5s, 6 cycles) Slow inspiratory and

expiratory techniques*

EDIC and ELTGOL (apnoea for 3-5s, 10 repetitions)

EDIC and ELTGOL (apnoea for 5s, 8 repetitions)

Active cycle of breathing techniques*

Teachingof part of this technique(huffing and cough)

Original cycles (3-5 repetitions)

Warm up (5 min) Circumduction of upper limbs Flexion and extension of the trunk

Circumduction of upper limbs Lateral flexion of the trunk

Thoracic mobility and expansion exercises (2x10 each exercise)

Proprioceptive neuromuscular facilitation diagonal

Rotation of the trunk

Proprioceptive neuromuscular facilitation diagonal (progression 1)

Rotation of the trunk (progression 1)

Flexibility/stretch exercises (2-3x30s each exercise)

Lateral flexors of the neck Abductors of upper limbs Adductors of upper limbs

Lateral flexors of the neck (progression 1) Abductors of upper limbs (progression 1) Adductors of upper limbs (progression 1) Psychoeducational support

(flyers)

Breathing control Dyspnoea relief

Airway clearance techniques

Respiratory system

Lower respiratory tract infections

Second week

Techniques/components Third session Fourth session

Psychoeducational support Breathing retraining

Clarification of doubts of the 2nd_session Breathing control (10-15 cycles) Deep breathing exercises (5 cycles) Pursed-lips breathing plus PEP technique performed with a mechanical device (apnoea for 5s, 5 cycles)

EDIC and ELTGOL plus PEP technique performed with a mechanical device (apnoea for 5s, 8 repetitions)

Clarification of doubts of the 3rd _session Breathing control (10-15 cycles) Deep breathing exercises (5 cycles) Pursed-lips breathing plus PEP technique performed with a mechanical device (apnoea for 5s, 5 cycles)

Slow inspiratory and expiratory techniques*

Active cycle of breathing techniques*

Original cycles (3-5 repetitions) Original cycles (3-5 repetitions)

Warm up (5 min) Circumduction of upper limbs (progression 1) Lateral flexion of the trunk (progression 1)

Circumduction of upper limbs (progression 1) Lateral flexion of the trunk (progression 2) Step in place

Thoracic mobility and expansion exercises and muscle strength (2x10 each exercise) Aerobic training

Flexion and extension of upper limbs (strengthening)

Rotation of the trunk (progression 2)

Squats

Cycling or Step (interval) or Walking (5 min)

Elbow extensors Lateral flexors of the trunk Upper limb flexors

Knee extensors Posterior chain muscles

Abductors and Adductors of upper limbs Psychoeducational support

(flyers)

Exercise Nutrition

Figure1 Interventionprotocolforthe3-weekcommunity-basedpulmonaryrehabilitationprogramme. AdaptedfromMarquesetal.25

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Third week

Techniques/components Fifth session Sixth session

Psychoeducational support Breathing retraining

Clarification of doubts of the 4th_session Deep breathing exercises (5 cycles) Pursed-lips breathing plus PEP technique performed with a mechanical device (apnoea for 5s, 5 cycles)

Original cycles (3-5 repetitions)

Clarification of doubts of the 5th_session Deep breathing exercises (5 cycles) Pursed-lips breathing plus PEP technique performed with a mechanical device (apnoea for 5s, 5 cycles)

Original cycles (3-5 repetitions) Slow inspiratory and

expiratory techniques* Active cycle of breathing techniques*

Warm up (5 min)

Circumduction of upper limbs (progression 1) Lateral flexion of the trunk (progression 2 Step in place)

Crunches

Squats

Cycling or Step (interval) or Walking (10 min)

Circumduction of upper limbs (progression 1) Lateral flexion of the trunk (progression 2) Step in place

Crunches

Lunges

Cycling or Step (interval) or Walking (20 min) Thoracic mobility and

expansion exercises and muscle strength (2x10 each exercise) Aerobic training

Upper limb abductors and adductors Knee extensors

Posterior chain muscles

Upper limb abductors and adductors Knee extensors

Posterior chain muscles “Morning stretch” Psychoeducational support

(flyers)

Smoking cessation (if applicable)

*Only applied if needed and based on pulmonary auscultation findings.

Legend: EDIC, exercise with inspiratory controlled flow; ELTGOL, total slow expiration with glottis open in lateral posture; PEP, positive expiratory pressure.

Figure1 (Continued)

are presented as mean±standard deviation or median [interquartilerange].

Results

Thirty-ﬁveoutpatientswithAECOPDwerereferredfor possi-bleinclusioninthestudy.Fromthese,threewereexcluded due to the presence of sequels from a cerebrovascular accidentthatimpairedher/hisabilitytoperformthe assess-ments(n=1),sufferingfromParkinson’sdisease(n=1)and interstitial lung disease (n=1). Thus, 32 patients were invitedtoparticipateinthestudy andallocatedtoeither the EG or CG. Threepatients in the EG (1due to incom-patibility of schedules and 2 no reason given) and six in theCG(2duetoincompatibilityofschedulesand4no rea-songiven)droppedoutofthestudy.Therefore,23patients (19males,67.3±8.0years,forcedexpiratoryvolumein1s 57.2±23.9%predicted),12intheEGand11intheCG,were included(Fig.2).

There were no signiﬁcant differences between com-pletersanddropoutsintermsofage(p=0.551)andgender (p=0.303).Participants’characteristicsaresummarisedin

Table1.Nosigniﬁcantdifferenceswereobservedbetween

groupsatbaseline(p>0.05).

AllpatientsintheEGcompletedthefullPRprogramme (i.e., 6/6 sessions, attendance=100%) and no adverse eventswerereported.

After the community-based PR programme, signiﬁcant improvements werefoundinthe EGinsymptomsof dysp-noeaatrest(Pre3[0.5;3.8]vs.Post1[0.0;2.8],p=0.008),

respiratoryrate(Pre24[20.5;27]vs.Post20.5[18;23.5], p=0.004),SpO2 (Pre 94 [89.3; 96] vs. Post96 [94.3; 96], p=0.031),quadriceps musclestrength(Pre21[19.7;27.2] vs.Post 25 [22.4; 28.8], p=0.012) and CAT score (Pre 23 [19.3; 24.8] vs. Post 14.5 [6.3; 19.5], p=0.008). No dif-ferenceswere found in the remaining outcome measures (p>0.05).TheCGdidnotpresentanysigniﬁcantdifferences aftertheintervention(Fig.3).

Inthebetweengroupscomparison,theEGshowed signif-icantimprovementswhencomparedtotheCGinrespiratory rate(EG−3.5[−4;−0.5]vs.CG2[0;4],p=0.015), quadri-cepsmusclestrength(EG3.1[1.9;7.2]vs.CG−0.5[−2.8; 1.4],p=0.021)andCAT(EG−6[−15;−4.0]vs.CG0[−8; 3],p=0.013).Noadditionaldifferenceswerefound(Fig.3). There was a signiﬁcantly higher number of patients improvingabovetheMCIDofCATintheEGthanintheCG (EG11vs.CG5,p=0.027).Nodifferenceswerefound for theremainingoutcomemeasures.

None of the patients, either in the EG or in the CG, neededtobehospitalisedormadeunscheduleduseofthe healthcareservicesduringthe3weeksofintervention.

Discussion

Thisquasi-experimentalpilotstudyshowedthat community-based PR might be effective during mild-to-moderate AECOPD.Signiﬁcantimprovementswerefoundinsymptoms, vitalsigns,quadriceps muscle strength andimpactof the disease and no adverse events were reported. However, patientswereallowedtochoosetheirgroupallocation.

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Table1 Samplecharacterisation(n=23).

Characteristics Experimentalgroup(n=12) Controlgroup

(n=11) p-Value Age,years 68.6±7.4 65.8±8.8 0.42 Gender,n(%) Male Female 10(83.3) 2(16.7) 9(81.8) 2(18.2) 1.00 BMI,kg/m2 _26.8_±_3.2 _27.6_±_5.5 _0.69 Smokingstatus,n(%) Current Former Never 1(8.3) 9(75.0) 2(16.7) 3(27.3) 6(54.5) 2(18.2) 0.60 Pack-years 26.5[2.7;57.5] 27.0[7.4;60.0] 0.75 Exacerbations/previousyear 2.0[1.0;1.8] 1.0[0.0;2.0] 0.25 FEV1,L 1.3±0.7 1.4±0.5 0.73 FEV1,%predicted 51.5±26.6 55.0±21.5 0.74 FVC,L 2.7_±0.7 2.6_±0.7 0.83 FVC,%predicted 81.6±24.6 78.5±18.5 0.73 FEV1/FVC,% 48.3±16.8 53.1±12.0 0.44 GOLDstages,n(%) I II III IV 3(25.0) 3(25.0) 4(33.3) 2(16.7) 2(18.2) 4(36.4) 3(27.3) 2(18.2) 1.00 GOLDgroups,n(%) A B C D 1(8.3) 3(25.0) 1(8.3) 7(58.3) 3(27.3) 3(27.3) 1(9.1) 4(36.4) 0.68

Briefphysicalactivityassessment tool

0.0[0.0;7.3] 0.0[0.0;0.0] 0.07

Non-invasiveventilation,n(%) 3(25.0) 2(18.2) 1.00

Long-termoxygentherapy,_n(%) 3(25.0) 2(18.2) 1.00

CCI,n(%) Mild Moderate Severe 1(8.3) 9(75.0) 2(16.7) 3(27.3) 6(54.5) 2(18.2) 0.60

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Characteristics Experimentalgroup(n=12) Controlgroup

(n=11)

p-Value

Medicationuse,n(%) Stability AECOPD

(extra) Stability AECOPD (extra) Stability 0.20 Antibiotics 1(8.3) 5(41.7) 1(9.1) 9(81.8) AECOPD 1.00 Antihistaminic 0(0.0) 2(16.7) 0(0.0) 0(0.0) Antipyretics 0(0.0) 1(8.3) 3(27.3) 2(18.2) Antitussive 0(0.0) 0(0.0) 0(0.0) 1(9.1) Bronchodilators Beta-adrenergicagonists 4(33.3) 0(0.0) 3(27.3) 0(0.0) Cholinergicantagonists 9(75.0) 0(0.0) 3(27.3) 1(9.1) Anti-inﬂammatory 5(41.7) 1(8.3) 2(18.2) 1(9.1) Xanthines 6(50.0) 0(0.0) 1(9.1) 0(0.0) Associationsofbronchodilators withcholinergicantagonists

10(83.3) 2(16.7) 5(45.5) 3(27.3) Corticosteroids 0(0.0) 2(16.7) 0(0.0) 1(9.1) Expectorants 3(25.0) 5(41.7) 1(9.1) 5(45.5) mMRCscore 2.5[1.3;3.0] 2.0[1.0;3.0] 0.84 Heartrate,bpm 76.0[74.0;95.0] 82.0[67.0;91.0] 0.85 Respiratoryrate,cpm 24.0[20.5;27.0] 20.0[18.0;24.0] 0.06 SpO2,% 94.0[89.3;96.0] 93.0[92.0;94.0] 0.46

Dyspnoeascore,mBorg 3.0[0.5;3.8] 3.0[0.0;4.0] 0.86

Fatiguescore,mBorg 3.0[0.9;6.3] 0.0[0.0;3.0] 0.09

Quadricepsmusclestrength,kgf 21.0[19.7;27.2] 18.8[17.4;20.9] 0.10

5-Repetitionsit-to-stand,s 9.4[6.9;13.0] 7.6[5.6;9.8] 0.24

CATtotalscore 23.0[19.3;24.8] 21.0[14.0;28.0] 0.89

Valuesarepresentedasmean±standarddeviationormedian[interquartilerange],unlessotherwisestated.

Legend:AECOPD,acuteexacerbationofchronicobstructivepulmonarydisease;BMI,bodymassindex;bpm,beatsperminute;CAT,COPDassessmenttest;CCI,Charlsoncomorbidity index;cpm,cyclesperminute;FVC,forcedvitalcapacity;FEV1,forcedexpiratoryvolumeinonesecond;GOLD,GlobalInitiativeforChronicObstructiveLungDisease;mBorg,modiﬁed Borgscale;mMRC,modiﬁedBritishMedicalResearchCouncilquestionnaire;SpO2,peripheraloxygensaturation.

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35 patients

3 patients excluded due to: - Sequels of cerebrovascular

accident (n=1)

- Parkinson’s disease (n=1) - Interstitial lung disease (n=1)

15 patients in Experimental group

17 patients in Control group

3 Dropouts - incompatibility of schedules (n=1) - no reason given (n=2) 6 Dropouts - incompatibility of schedules (n=2) - no reason given (n=4) 12 included patients in Experimental group

11 included patients in Control group

Figure2 Flowdiagramofparticipantsthroughthestudy.

SymptomsarekeyfeaturesofCOPD41_and_have_been

con-sideredimportantoutcomesofPRduringexacerbations.3,42

Inthis study,after PR therewasa significant decreasein dyspnoealevelsat restandmostpatientsimproved above theMCIDinthemMRCandmBorg.Nevertheless, although positiveimprovements havebeen found for theEG, there werenosignificant differencesin betweengroup compar-isons,whichisprobablyrelatedwiththesmallsamplesize. Furthermore,nosignificantimprovementshavebeenfound forfatigue,possiblybecauseoftherelativelylowbaseline fatiguescoresfoundinourpatients.Theseresultsmustbe carefullyinterpretedasdyspnoeaandfatigueare multifac-torialsymptomsthatshouldbedescribedconsideredasboth patients’subjectiveperceptionandaperformance compo-nent,andthemMRCandthemBorgareunidimensionaltools thatmeasureonlya specificmomentandwereappliedat rest.43,44_Therefore,_these_instruments_might_have_failed_to

capture dyspnoea andthe overall impactof fatigue. Mul-tidimensionalanddisease-speciﬁcscalesshouldbeusedin futurestudiestoallowamultifactorialassessmentofthese symptomsandcontributetoabetterunderstandingoftheir behaviourduring aPR programmeinAECOPD.45 _Moreover,

theavailableMCIDsforthemMRCandthemBorghavebeen established for patients with AECOPD receiving standard ofcare.32 _Future_studies _exploring_MCIDs_for _patients_with

AECOPDundergoingPRareneededtobetterunderstandthe addedvalueofthisintervention.

Despitethe importance of assessing symptoms individ-ually, it is their combination that impacts on patients’ HRQoL,9,41 _hence_a _{comprehensive}_symptom _assessment _is

necessary.1 _CAT _is _a _short, _simple, _{multidimensional} _and

easytoadministerquestionnairethathasbeendevelopedto coverthemostburdensomesymptomsandlimitations per-ceivedbypatients.46 _Recent_literature_has_shown_that_CAT

isresponsive totreatment47,48_and_provides_relevant

prog-nosticinformation,49 _therefore _its_use _to_assess_PR _during

AECOPDhasbeenadvocated.9,47_In_this_study,_the_signiﬁcant

improvementsandnumberofpatientsimprovingabovethe MCIDshowthatCATissensitivetochangesandsupportsits routineuseinclinicalpractice.

Vital signs and SpO2 are measures previously used in PR programmes conducted in hospitalised patients with AECOPD and improvements, or patterns of improvement, have been reported,50---53 _suggesting _that _PR _is _a _safe

approachduringAECOPD.Thispilotstudycorroboratesthese ﬁndingsforPRimplementedinthecommunity.Noadverse eventswerereported;however,asystematicassessmentof adverse events wasnot conducted. Future studies should carefullyassessoccurrenceofadverseeventsandtheneed forunscheduledhealthcarevisitsduringandaftereach ses-sion of PR to establish effectiveness and safeness of this intervention.

Quadriceps muscle weakness is a well-known systemic consequence of COPD1 _that _affects _patients’ _HRQoL _and

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4

a

b

d

c

e

g

h

i

f

3 2 1 Experimental group Experimental group * * * * * * * * Experimental group 2.5 [1.3; 3.0] 24.0 [20.5; 27.0] _20.5 [18.0; 23.5] 3.0 [0.5; 3.8] 3.0 [0.0; 4.0] 0.0 [0.0; 3.0] 0.0 [0.0; 4.0] 0.0 [0.0; 3.0] 2.0 [0.3; 3.0] 3.0 [0.9; 6.3] 1.0 [0.0; 2.8] 21.0 [19.7; 27.2] 23.0 [19.3; 24.8] 14.5 [6.3; 19.5] 21.0 [14.0; 28.0] 23.0 [11.0; 30.0] 25.0 [22.4; 28.8] 18.8 [17.4; 20.9] 19.8 [14.1; 25.7] 7.0 [5.7; 7.9] 7.6 [5.6; 9.8] 9.3 [6.0; 14.0] 9.4 [6.9; 13.0] 20.0 [18.0; 24.0] 20.0 [18.0; 24.0] 1.5 [0.3; 1.8] 2.0 [1.0; 3.0] 2.0 [1.0; 3.0] 79.0 [73.0; 91.0] 82.0 [67.0; 91.0] 74.0 [62.3; 86.8] 76.0 [74.0; 95.0] 94.0 [89.3; 96.0] 96.0 [94.3; 96.0] [92.0; 94.0]93.0 95.0 [91.0; 96.0] Pre Post Pre Post Pre Post Pre Post Pre Post Pre Post Pre Post Pre Post Pre Post mMRC score Hear t r ate (bpm) SpO 2 (%) Respir ator y r a te (cpm)

Dyspnoea score mBorg

Quadr

iceps m

uscle strenght (kgf)

CA

T total score

5-repetition sit-to-stand (sec)

F

atigue score mBorg

Control group

Experimental group Control group

Control group 0 0 20 40 60 80 100 0 20 40 60 80 100 30 20 10 0 0 1 2 3 4 5 40 30 20 10 10 15 5 0 0 40 30 20 10 0 8 6 4 2 0

Figure3 Mediandifference andinterquartile range Pre/Post theintervention pergroup in: (a)the modified British Medical ResearchCouncildyspnoeaquestionnaire(mMRC);(b)heartrate(beatsperminute,bpm);(c)respiratoryrate(cyclesperminute, cpm);(d)peripheraloxygensaturation(SpO2);(e)symptomsofdyspnoeaatrestinthemodifiedBorgscale(mBorg);(f)symptoms offatigueatrestinthemodifiedBorgscale(mBorg);(g)quadricepsmusclestrength;(h)the5-repetitionsit-to-standtest(5-STS); and(i)theCOPDassessmenttest(CAT)totalscore.

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survival.54 _During _AECOPD _there _is _a _more _accentuated

decline in muscle function, resulting in long-term losses on functional capacity.55 _This _study, _similarly _to _previous

research, has shown that PR can prevent muscle dys-function by improving quadriceps muscle strength during AECOPD,13,54,56,57_thus_becoming_a_key_intervention_to

man-ageperipheralmuscleweaknessandpreventfurtherclinical decline.

It has been recognised that functionality, a vital out-come for patients’ daily life, is severely impaired during AECOPD.41,58 _In _this _study, _no _differences _were _found _in

patients’functionalityafterPR.Thisﬁndingislikelytobe duetotheceilingeffectobservedinthe5-STSandnotto theineffectivenessoftheintervention.Atbaseline,patients already presented a good functional status as they were performing the test below the cut off for risk of falling (i.e., 12s),59 _so _with_little _room _for _improvement. _Given

the importance of this outcome, further researchon the mostappropriateoutcomemeasuretoassessfunctionality inpatientswithAECOPDisneeded.

This study presents some limitations that need to be acknowledged. Firstly, patients were not randomisedand assessors were not blinded. However, efforts were made to minimise the risk of bias by ensuring that patients characteristics at baseline were similar and implement-ing a well-deﬁned assessment protocol and standardised intervention. Secondly, physical activity levels were not monitoredduringtheAECOPDanditispossiblethatpatients willingtoparticipateinthePRprogrammewerealsomore willingtobephysicallyactive.Nevertheless,baseline phys-icalactivity levelswerenodifferentbetween thegroups. Weregisteredhowever,ahigherdrop-out rateinthe con-trolgroup, probablydueto patients’lack of motivation60

and lack of perceived beneﬁt of their participation.15 _It

is known that patients who have chosen not to attend PRarealsoless likelytoparticipatein respiratory-related research61 _and,_thus,_more_likely_to_drop_out._Third,

phar-macological treatment was not standardised, but rather prescribedaccordingtopulmonologists’bestjudgementof patients’ clinical condition. Although no differences have beenfoundregardingmedicationonbaselineassessment,it mustbeacknowledgedthatdifferentcombinationsofdrugs mighthaveinfluencedpatients’recovery.Fourth,exercise capacity,which isa keyoutcome ofPR, wasnotassessed in this study due to lack of space to perform commonly used field exercise capacity tests (e.g., six-minute walk testandincrementalshuttlewalktest)atpatients’home, although aerobic training was performed. Future studies shouldexplore the effects of community-based PR during AECOPD on patients’ exercise capacity using alternative field-tests. Since informative and promising results were obtained, there is now the need to adjust the outcome measuresusedandpersonalisePRtopatients’needs,ina randomisedcontrolledtrial.

Conclusions

Community-based PR seems feasible and offers promise to provide timely and effective management of patients withmild-to-moderateAECOPD.TheadditionofPRto stan-dardofcareresulted inimprovementsinrespiratoryrate,

symptoms, quadriceps muscle strength andimpact of the disease, parameters usually associated withan increased riskofAECOPDrecurrenceandpoorprognosis,37,62,63_and_no

adverse events reported.Futureresearch shouldfocuson randomisedstudieswithlargersamplestoclarifytheroleof community-basedPRduringAECOPD.

Funding

This work was funded by Programa Operacional de Com-petitividade e Internacionalizac¸ão --- POCI, throughFundo Europeu de Desenvolvimento Regional --- FEDER (POCI-01-0145-FEDER-007628), Fundac¸ão para a Ciência e Tec-nologia (PTDC/DTP-PIC/2284/2014 and PTDC/SAU-SER/ 28806/2017) and under the project UID/BIM/04501/2013 andUID/BIM/04501/2019.

Conﬂicts

of

interest

Theauthorsreportnoconﬂictofinterest.

Acknowledgments

Theauthorswouldliketoacknowledgetheassistanceindata collectionCátiaPaixão,HélderMelroandSaraMirandaand thecollaborationinthisstudyofallpatientsandphysicians.

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