Clinical Transplantation. 2021;00:e14315.  | 1 of 10https://doi.org/10.1111/ctr.14315

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1  |  INTRODUC TION

Primary graft dysfunction (PGD) after lung transplantation is a form of acute lung injury occurring immediately post- operatively and associated with increased mortality.1 PGD is characterized by hypoxia and radiographic findings of bilateral infiltrates consistent

with pulmonary edema. While its imaging features on chest ra-diography typically resolve around 10 days post- transplant, PGD has been shown to negatively impact recipients in the long term.2- 4 Survival in patients who develop PGD is impaired compared to those who do not and this difference is most distinct in patients who have grade 3 PGD (PGD3), defined as severe reduction in the

Received:21January2021  | Revised:9March2021  | Accepted:5April2021DOI: 10.1111/ctr.14315

O R I G I N A L A R T I C L E

Atelectasis in primary graft dysfunction survivors after lung transplantation

David Li1  | Jonathan Abele2 | Justin Weinkauf1 | Ali Kapasi1 | Alim Hirji1  | Rhea Varughese1 | Jayan Nagendran3 | Dale Lien1 | Karen Doucette1 | Kieran Halloran1

©2021JohnWiley&SonsA/S.PublishedbyJohnWiley&SonsLtd

1DepartmentofMedicine,UniversityofAlberta,Edmonton,AB,Canada2Department of Radiology and Diagnostic Imaging,UniversityofAlberta,Edmonton,AB,Canada3DepartmentofSurgery,UniversityofAlberta,Edmonton,AB,Canada

CorrespondenceKieranHalloran,1135083rdStreet,CSB3-114,Edmonton,AB,T6G2G3Canada.Email:kieran.halloran@ualberta.ca

Funding informationThisstudywassupportedbyagrantfromtheAlbertaTransplantInstitute.

AbstractBackground: Primary graft dysfunction (PGD) is an important contributor to early mortality in lung transplant recipients and is associated with impaired lung function. The radiographic sequelae of PGD on computed tomography (CT) have not beencharacterized.Methods: Westudiedadultdoublelungtransplantrecipientsfrom2010to2016forwhomprotocol3-monthpost-transplantCTscanswereavailable.WeassessedCTsfor changes including pleural effusions, ground glass opacification, atelectasis, cen-trilobular nodularity, consolidation, interlobular septal thickening, air trapping andfibrosis, and their relationship to prior post- transplant PGD, future lung function, post-transplantbaselinelungallograftdysfunction(BLAD),andchroniclungallograftdysfunction(CLAD).Results: Of 237 patients studied, 50 (21%) developed grade 3 PGD (PGD3) at 48 or 72h.PGD3wasassociatedwithincreasedinterlobularseptalthickening(p=.0389)and atelectasis (p = .0001) at 3 months, but only atelectasis remained associated after correctionformultipletesting.Atelectasisseveritywasassociatedwith lowerpeakforcedexpiratoryvolumein1s(FEV1)andincreasedriskofBLAD(p = .0014) but not withfutureCLADonset(p=.7789).Conclusions: Severe PGD was associated with atelectasis on 3- month post- transplant CTinourcohort.AtelectasisonroutineCTmaybeanintermediaryidentifiablestagebetween PGD and future poor lung function.

K E Y W O R D Satelectasis, lung transplantation, primary graft dysfunction

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partial pressure of oxygen (PaO2) to fraction of inspired oxygen (FiO2) ratio of <200 mmHg, at the 48 or 72 h time point.5 Survivors tend to demonstrate abnormalities in multiple functional domains, most notably in lung function and particularly with respect to ei-ther peak forcedexpiratory volume (FEV1) or FEV1at one-yearpost- transplant.6-8Thecausesoftheseabnormalitiesarenotwell-established and in particular, there has been little exploration of potential structural or imaging changes in PGD survivors or their prognostic implications.

Protocolizedhigh resolution computed tomography (CT) scansof the lungs can potentially offer greater insight into lung struc-tural and parenchymal abnormalities post- transplant compared with chest radiography, including those associated with PGD.9 We as-sessedabnormalitiesonCTlungscansdoneroutinelyat3-monthspost- transplant and their association with long- term lung function. WehypothesizedthatCTabnormalitieswouldbemorefrequentinPGD survivors and would predict lower lung function at 1 year.

2  |  MATERIAL S AND METHODS

2.1  |  Population

We studied all adult patients who underwent double lung trans-plant in the University of Alberta Lung Transplant Program fromJanuary2010toDecember2016forwhom3-monthCTchestscanswere available. We excluded all single lung, heart- lung, and living lobar lung transplant recipients, as well as patients without suffi-cient data to grade for PGD post- transplant. Individual consent was waived given the retrospective design and inclusion of deceased pa-tients.ThestudywasapprovedbytheUniversityofAlbertaHumanResearchEthicsBoard(Pro00070542).

2.2  |  PGD grading

The primary risk factor was the development of grade 3 PGD at48-or72-hpost-transplant,definedasper the2016 InternationalSocietyforHeartandLungTransplantation(ISHLT)consensuscrite-ria as bilateral lung edema on post- operative chest X- ray according to the interpreting radiologist and PaO2/FiO2 <200 mmHg.10 Thisis accepted as the PGD severity and timing most associated with mortalityrisk.5 Patients who were switched to nasal cannula or ven-tilator oxygen at an FIO2oflessthan0.3weregradedatsubsequenttimepoints as grade 1 PGD if edema is present on chest X- ray and grade0PGDifnoedemaispresent.ThefullISHLTgradingschemeisdepictedinTable1.

2.3  |  Chest computed tomography abnormalities

TheprimaryoutcomewasthepresenceofabnormalitiesonroutineCTofthechestasnotedbythestudy'sinterpretingradiologist–all

sub-specialists in thoracic radiology – including pleural effusion,groundglassopacification(GGO),centrilobularnodularity(CLN),in-terlobularseptalthickening(ILS),atelectasis,consolidation,fibrosis,and air trapping. Grading of radiographic abnormalities was done according to the number of involved lobes for each of consolida-tion,atelectasis,CLN,GGO,andILS.Airtrappingandfibrosisweregraded as present or absent, and pleural effusions were graded and rankedasnone,trace,small,mediumorlargeaswellasbilateralorunilateral.

2.4  |  Allograft microbiology on routine 3- month bronchoscopy

We assessed microbiology on bronchoalveolar lavage on 3- month bronchoscopy. Findings were refined to a list of clinically relevant organisms based on consensus between a lung transplant physician and a transplant infectious disease physician. Both were blindedto all other patient data including PGD status and long- term lung function.

2.5  |  Long term lung function

WereviewedFEV1valuesoverall recordedpost-transplantmeas-urements. We analyzed long- term lung function both continuously as well as in terms of the presence or absence of baseline lung allo-graftdysfunction(BLAD),definedasfailuretoachieveanFEV1andforced vital capacity >80% predicted on two consecutive occasions >3weeksapart.11 We designated chronic lung allograft dysfunction (CLAD)asdeclineinFEV1to<80%ofestablishedbaselineinliters,aswellasgradesandphenotypesinaccordancewiththe2019ISHLTconsensusstatement.OurCLADanalysisdescribedbelowfocusedonthetimetoonsetofCLADgrade1orhigher.12

2.6  |  Statistics

We compared continuous variables using t- tests or Wilcoxon ranksumtestsdependingonnormality,andbinaryorcategoricalvariables using Fisher's exact tests or Pearson chi-square tests.Ranked ordinal variables were compared via Cochran Armitage

TA B L E 1 2016Internationalsocietyforheartandlungtransplantation primary graft dysfunction and severity grading scheme

GradePulmonary edema on chest x- ray

PaO2/FiO2 ratio

PGD grade 0 No Any

PGD grade 1 Yes >300

PGD grade 2 Yes 200- 300

PGD grade 3 Yes <200

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trendtesting.WeappliedBonferronicorrectionformultipletest-ing on the eight CT-abnormality outcomes of interest, resultingin a p- value significance threshold of p= .00625fortheprimaryoutcomesofinterest.Althoughconservative,thiswasjustifiedbythe high sensitivity of Cochrane Armitage trend testing. To ac-count for potential confounders in baseline characteristics, we ran adjusted ordinal regression models for the association between PGD3andatelectasisrank. Inoursecondaryanalysis,weusedamultivariable linear regression to model the impact of radiographic abnormalitieson1-yearFEV1, controlling for historyof grade3PGD. We also used logistic and proportional hazards regression modelling to measure the association between atelectasis and the presenceofBLADorfutureriskofdeath-censoredgrade1CLADonset,respectively.AllanalyseswereperformedonJMPversion12software(SASInstitute,Inc).

3  |  RESULTS

3.1  |  Baseline characteristics

Atotalof316patientsunderwent transplantduring the indicatedtimeframe, 23 of whom were excluded on the basis of non- double lung transplant, 14 for death prior to three months and 42 for miss-ing data (n = 3 insufficient data to grade for PGD, n=39no3-monthCT),forafinalcohortof237patients(Figure1).Baselinecharacter-isticsandpost-operativeoutcomesaresummarizedinTables2and3. 50 patients (21%) developed grade 3 PGD at 48 or 72 h. Patients whodeveloped grade3PGDhadhigher bodymass indices (BMI)at the time of transplant (27 vs. 25, p=.0150)andweremorelikelytohavereceivedanon-Caucasiandonor.PGD3patientshadmorecomplex post- transplant courses with longer ventilation times as well as intensive care unit and hospital lengths of stay. Other base-line characteristics were similar.

3.2  |  Radiographic abnormalities on 3- month CT scans

Sample images of the noted abnormalities are provided in Figure 2. The extent of CT abnormalities stratified by PGD3 status is il-lustratedinFigure3andsummarizedinSupplementaryTableS1.Grade 3 PGDwas associatedwithmore frequent and/orwidelydistributed interlobular septal thickening (p = .0389) and atelec-tasis (p < .0001) at three months. Increasing PGD grades (0- 3) correlated with increasing frequency and severity of atelectasis(Figure 4, p = .0003). Fibrosis was also increased in PGD3 survivors, but therewerevery fewcases.Therewasnonotabledifferencein the presence or extent of pleural effusion, consolidation, cen-trilobular nodularity, ground glass opacification, and air trapping. After Bonferroni correction formultiple testing, only atelectasisremained significantly associated with a history of severe PGD.

3.3  |  Atelectasis on 3- month CT scans

Given the strong association observed between PGD3 and atelec-tasis, we elected to study this in more detail. First, we studied rela-tionships between atelectasis and other radiographic findings and noted a strong association with the presence and extent of pleural effusions (p < .0001). Other relationships among the radiographic findingsaredepictedinSupplementaryTableS2.

Given the observed discrepancies between the cohorts with andwithoutthePGD3riskfactorintermsofBMIanddonoreth-nicity(Table2),weranmultivariableordinalregressionmodelsforthe outcome of extent of atelectasis involvement, including PGD3 andeitherBMI≥30kg/m2ordonorethnicity.Adjustmentforei-ther of these factors did not affect the association between PGD3 andatelectasis(BMI-adjustedp = .0003, donor ethnicity- adjusted p < .0001). We were also concerned about the effects of donor- recipient size discrepancies given this could feasibly result in atel-ectasis,howeveramodeladjustedforpTLCratiodidnotaltertheassociation between PGD3 and atelectasis extent (p=.0002).Thesame held true when the logistic models were adjusted for dis-crepancies in baseline characteristics when patients were strati-fiedbyatelectasisvs.none(seeSupplementaryTableS3)includinga recipient sex- adjusted model, p = .0003; a pulmonary diagnosis- adjusted model, p = .0014; and a recipient bridging- adjusted model [ventilation or ECMO], p = .0006. PGD3 remained significantly

F I G U R E 1 Studycohort

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associated with atelectasis (p = .0297) in amultivariable ordinalregression model, adjusted for all observed baseline discrep-ancies (recipient gender, BMI, pulmonary diagnosis, bridging

status, donor ethnicity and donor-recipient pTLC ratio). Finally,toensureatelectasison3-monthCTscanwasnotanartifactofpost- transplant weight gain during this time period and extrinsic

TA B L E 2 Baselinecharacteristicsstratifiedbygrade3primarygraftdysfunctionstatus

Characteristic Overall (n = 237) Grade 3 PGD (n = 50) No Grade 3 PGD (n = 187) p- value

Ageinyears,mean 54 (12) 55(9) 54 (13) .639

Female sex 87 (37) 21 (42) 66(35) .411

Bodymassindex,mean 25 (4.7) 27 (4.3) 25 (4.7) .015

Diagnosis

Obstructive lung disease 93(39) 15 (30) 78 (42) .093

Interstitial lung disease 101 (43) 25 (50) 76(40)

Bronchiectasis 25 (11) 4 (8) 21 (11)

Pulmonary vascular disease 10 (4) 5 (10) 5 (3)

Other 58(3) 1 (2) 7 (4)

Recipient bridging

Ventilated 19(8) 5 (10) 14 (7) .098

ECMO 8 (3) 4 (8) 4 (2)

None 210(89) 41 (82) 169(90)

CMVmismatch 45(19) 10 (20) 35(19) .841

Crossmatchpositive 28 (12) 6(12) 22 (12) 1.000

Intraoperative support

CPB 179(76) 44 (88) 135 (72) .054

ECMO 28 (12) 4 (8) 24 (13)

None 30 (13) 2 (4) 28 (15)

Induction therapy

IL2-receptorantagonists 159(67) 31(63) 128(68) .470

Anti-lymphocyteantibody 74 (31) 18 (37) 56(30)

None 3 (1) 0 (0) 3 (2)

Maintenancetherapy

Tacrolimus 218(92) 46(92) 172(92) 1.000

MMF 234(99) 49(98) 185(99) .510

Donor

Ageinyears,mean 41 (17) 45 (18) 40 (17) .055

Female sex 109(46) 26(52) 83 (44) .344

BMI,mean 25.9(5.7) 25.4 (5.0) 26.1(5.9) .419

Smoking>20packyears 30 (14) (n = 218) 8 (18) (n = 30) 22 (13) (n = 174) .335

Ischemic time in minutes, mean 345 (124) 357 (155) 342 (114) .123

Donor race

Asian 16(7) 2 (4) 14 (7) .021

Black 5 (2) 3(6) 2 (1)

Caucasian 173 (73) 31(62) 142(76)

Other 43 (18) 14 (28) 29(16)

Donor- recipient height ratio, mean 1.00 (0.03) 0.99(0.03) 1.00 (0.03) .588

Donor-recipientpTLCratio,mean 0.99(0.32) 0.87(0.65) 1.02 (0.11) .116

Donor-recipientpTLCratio>1 128 (54) 25 (50) 103 (55) .528

Note: Countsarepresentedwithpercentages;meansarepresentedwithstandarddeviationsfornormallydistributeddata;mediansarepresentedwithinterquartilerangefornon-normallydistributeddataBoldindicatesstatisticallysignificantresultsatalevelofp < 0.05.

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compression, we analyzed the relationship between the 3- month post-transplantBMIandatelectasisandfoundnoBMIdifferencesrelated to atelectasis severity (p = .324).

We considered whether post- transplant chest interventions –suchaschesttubeinsertionorsurgicaldecortication–couldbeassociatedwith post-transplant atelectasis. A total of 12 patientsrequired post-transplant chest intervention, 11 chest tube inser-tionsandonevideo-assisteddecortication.Of these12,11 (92%)were patients with some degree of atelectasis, reflecting 10% of the overall cohort of patients with atelectasis (n = 125) and consistent with the above observed association between atelectasis and post- transplant pleural effusions.

Ideally, we could assess whether these findings persisted over time,howeverourcenterdoesnotperformprotocolCTscansaside

from at the 3- month time point. We were however able to assess asubsetof58ofthe125(46%)patientswhohadatelectasison3-monthCTscanwhowentontoundergoasubsequentCTdoneforotherindicationsat1-yearpost-transplantorbeyond.Amongthese,50(86%)hadatelectasisagainnoted,improvedin24,stablein22,and progressed in 12 patients.

3.4  |  Atelectasis and microbiology on 3- month bronchoscopy

The presence of a clinically relevant bacteria (SupplementaryTable S4) or fungi on 3-month protocol bronchoscopy done con-currentlywithCTchestwasnotmorecommoninPGD3survivors

ParameterOverall (n = 237)

Grade 3 PGD (n = 50)

No Grade 3 PGD (n = 187) p- value

Intubation time in hours, median

70(29–188) 237(136–564) 48(24–112) <.001

ICUstayindays,median 7(5–14) 19(12–27) 6(4–9) <.001

Hospital stay in days, median

25(18–40) 41(27–71) 22(17–33) <.001

Diaphragm paralysisa  7 (3) 3(6) 4 (2) .165

Baselinelungallograftdysfunction (n = 233)

89(38) 26(54) 63(34) .013

Chroniclungallograftdysfunction (n = 233)

46(20) 11 (23) 35(19 .545

Note: Countsarepresentedwithpercentages;meansarepresentedwithstandarddeviationsfornormallydistributeddata;mediansarepresentedwithinterquartilerangefornon-normallydistributed data.Boldindicatesstatisticallysignificantresultsatalevelofp < 0.05.aDiaphragm paralysis as documented by ultrasonography or fluoroscopy.

TA B L E 3 Recipientpost-operativeoutcomes stratified by grade 3 primary graft dysfunction status

F I G U R E 2 Samplechestcomputedtomographyimagesofpost-transplantradiographicabnormalities.A,Pleuraleffusion.B,Consolidation.C,Atelectasis.D,Centrilobularnodularity.E,Groundglassopacification.F,Interlobularseptalthickening.G,Airtrapping(expiratory image). H, Fibrosis

(A) (B) (C) (D)

(E) (F) (G) (H)

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F I G U R E 3 PresenceandseverityofCTabnormalitiesstratifiedbyPGD3status.A,Pleuraleffusion.B,Consolidation.C,Atelectasis.D,Centrilobularnodularity.E,Groundglassopacification.F,Interlobularseptalthickening.G,Airtrapping(expiratoryimage).H,Fibrosis

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(Table4).Thepresenceofanorganismon3-monthprotocolbron-choscopy did not differ by the presence or severity of any of the radiographic abnormalities (data not shown).

3.5  |  Atelectasis and future lung function

Recipient post- operative outcomes stratified by atelectasis are depicted in Supplementary Table S5. Peak post-transplant FEV1was lower in patientswith atelectasis on 3-monthCT in a lobe-dependentfashion(Figure5).AtelectasiswasstronglyassociatedwithpeakFEV1percentpredictedinanunadjustedlinearregres-sion model (p = .0007) and after adjustment for PGD3 status (p = .0066). Atelectasis was similarly associatedwith the risk ofbaseline lung allograft dysfunction both unadjusted (p = .0014) and adjusted for PGD3 status (p=.0069)(Figure6).Ofnoteinthelattermodel, PGD3 was no longer associated with baseline lung allograft dysfunction.Atelectasiswasnotassociatedwiththeriskoffuturedeath-censoredgrade1CLADonset,eitherunadjusted(p=.7789)or adjusted for PGD3 status (p=.7971).Atelectasison3-monthCTscanwas also not associatedwith highest CLAD grade achievedover the follow up period (p = .3717, Supplementary Figure S1).

4  |  DISCUSSION

Our findings indicate atelectasis at 3- months post- lung transplant is more frequent and more severe in PGD3 survivors. These CTchangesmayhelpidentifypatientsatriskforbaselinelungallograftdysfunction, which is associated with poorer survival after lung transplant.

Atelectasisistheregionalcollapseofalveolatedlungtissueandassociated volume loss. It can result from one or a combination of compression,airwayobstruction,respiratorymuscleweaknessandincreasedalveolarsurfacetensionasaconsequenceofdeficientsur-factant action.13 Surfactant deficiency has previously been demon-strated in a study of lung transplant biopsies, where up to 34% of the total cells in the samples underwent apoptosis following graft reperfusion in vitro.14 Themajority of these apoptotic cells weresurfactant-producingalveolar type IIpneumocytes.Anotherstudyfound significant biochemical alterations in the surfactant of lung transplant recipients both in the short- and long- term that correlated with decreased surfactant function.15 Impaired surfactant function isthoughttobeakeymechanismof lungdysfunction inacutere-spiratory distress syndrome, which has similar pathophysiology to PGD.16Bronchoscopicinstillationofexogenoussurfactanthasbeen

F I G U R E 4 Atelectasisseveritybyprimary graft dysfunction grade

Organism (bronchoalveolar lavage)

Overall (n = 237)

Grade 3 PGD (n = 50)

No Grade 3 PGD (n = 187) p- value

Bacterialinfection 55 (23) 16(32) 39(21) .130

Fungal infection 25 (11) 5 (10) 20 (11) 1.000

Bacterialorfungalinfection 74 (31) 19(38) 55(29) .303

Note: Countsarepresentedwithpercentages;meansarepresentedwithstandarddeviationsfornormallydistributeddata;mediansarepresentedwithinterquartilerangefornon-normallydistributed data.

TA B L E 4 Microbiologyon3-monthbronchoscopy

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effective for improving oxygenation in both acute respiratory dis-tress syndrome and severe PGD though it remains experimental.17,18 Itispossiblethattheapoptoticresponseandsubsequentsurfactantdysfunction may be especially pronounced with severe PGD, such that recovery is incomplete at 3- months post- transplant, resulting in the persistence of atelectasis.

Thereareotherpotentialexplanationsforatelectasisafterlungtransplant. An oversized donor may lead to atelectasis through

extrinsic compression. However, were this a strong driver of at-electasis in our study, we would have expected a relationship be-tween donor- recipient height ratio and atelectasis, which was not observed (Supplementary Table S2). We also addressed this viamodels adjusted for pTLC ratio and did not note a change in thePGD-atelectasis association.Adjustment for other baseline differ-encesassociatedwitheitheratelectasisorPGD–includingrecipientBMI,sex,pulmonarydiagnosis,bridgingtherapyanddonorethnicity

F I G U R E 5 PeakFEV1inlitersstratifiedby atelectasis severity

F I G U R E 6 Proportionofpatientswithbaseline lung allograft dysfunction by historyofatelectasisof3-monthCT

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–didnotalterthestrengthoftherelationshipbetweenPGD3andpost-transplantatelectasis.Anotherpossibilityispost-transplantdi-aphragmatic dysfunction, which can occur as the result of phrenic nerve trauma.19Thiscouldproducepassiveatelectasisthroughin-complete expansion of the chest, but we reviewed post- transplant clinically indicated diaphragm investigations – ultrasonography orfluoroscopy–anddidnotobserveadiscrepancybetweenpatientswith atelectasis or severe PGD and those without (Table 3 andSupplementaryTableS5).Despite this, thesewerenot routine in-vestigations, so this remains a potential contributor. Finally, the pres-ence of atelectasis was strongly associated with presence and extent of pleural effusions after transplant in our study. Our study cannot clarify whether the effusions are an atelectasis cause or effect, or rather simply an associated phenomenon that tends to occur with atelectasis. However, were pleural effusions the primary driver of the atelectasis findings, we would expect to have observed a PGD- pleural effusion association, which we did not. We suspect based on this that the effusions may be reactive to the atelectasis but dis-entangling thesewould requireadedicatedstudywithadifferentdesign.

We further addressed the possibility that allograft microbiology couldproduceconfoundingimagingchangesonCTscansandeventhatPGD3itselfcouldincreasetheriskofsubsequentbacterialorfungal colonization or infection. If PGD were to produce permanent structural abnormalities in the lung, microbial defense could be im-paired.20,21 We were surprised to observe no such association, even with a refined list of clinically relevant organisms (Supplementary TableS4).ThismaysuggestPGD’seffectsonmicrobialdefenseofthetransplantedlungsnotedinpriorstudies–forexample,impair-mentsinmucociliaryfunction–maynotpersist.22 It also suggests that imaging changes on routine post- transplant imaging are not consistently accounted for by infection.

The associations between severe PGD, atelectasis and base-line lungallograftdysfunctionarenotable.Baseline lungallograftdysfunction is a physiologic entity after lung transplantation where lung function fails to reach population- referent normal thresholds. Inourstudy,CTevidenceofatelectasisatthreemonthswasasso-ciatedwithareducedpeakFEV1andincreasedriskofBLAD,evenwhen adjusting for a prior severe PGD, and more widespread atel-ectasiswasassociatedwithgreaterriskofBLADinastepwisefash-ion (Figure6).This suggests thatpost-PGDatelectasismayserveasanidentifiableearlymarkerofriskbyhighlightingpatientswhoareless likelytonormalizetheir lungfunction.Thelackofassoci-ationwithCLADonsetorincreasedCLADgrademaysuggestthatthesesamepatientsarenotat increasedriskforprogressive lungfunction loss. The findings also raise the question as towhetherinterventionsatthisearlystage–intensiveongoingphysiotherapy,incentive spirometry and even potentially exogenous surfactant at thetimeofPGDorotherwise–couldmodifythisfindingorlong-term lung function ingeneral.Thesequestionsawait adedicatedstudy of this group.

Our study has limitations. The single-center designmay intro-duce center- specific effects and, as with all single center studies,

would benefit from validation in a second cohort. Second, the retro-spective design resulted in some cases with missing data which could notbeanalyzed.Third,CTabnormalitieswouldideallybescoredinterms of percentage of involved lung tissue, however many of these abnormalities(includingatelectasis)lackaformalmethodfordoingthis, so ordinal lobe involvement was used as a surrogate. Finally, clinical interpretationofchestCThasdemonstrated interobservervariability, resulting in an intrinsic error rate.23Atourinstitution,ra-diologistsreportingpost-lungtransplantCTscansareexperiencedsubspecialists in thoracic radiology, which mitigates this to some de-gree.Also,thistypeoferrorwouldlikelyweakenassociationsratherthanproducefalsepositives,soit isunlikelytherobustatelectasisassociation is the result of this.

We have demonstrated a relationship between severe primary graftdysfunction,atelectasison3-monthpost-transplantCTimag-ing,andpoorpost-transplantlungfunction.Thissuggestsatelecta-sismaybean identifiable intermediarymarkerofpoorfuture lungfunction inPGDsurvivors.Thepathophysiologyof thesechangeswarrants further investigation.

ACKNOWLEDG EMENTSWeacknowledgeAlbertaHealthServices, the clinicianswho carefor the patients, and the patients themselves who made this study possible.

CONFLIC TS OF INTERE S TTheauthorsofthismanuscripthavenoconflictsofinteresttodis-close.ThisstudywaspresentedinposterformattheannualmeetingoftheInternationalSocietyforHeartandLungTransplantation,heldvirtuallyinApril2020.

AUTHORS CONTRIBUTIONDJLparticipated in researchdesign,collecteddata,participated intheanalysis,helpedprepareandfinalizethemanuscript.JA,JW,AK,AH,RV,JN,DL,KDhelpedformulatethestudyandpreparethefinalversion of the manuscript. KH designed the study, conducted the main analyses, and prepared then finalized the manuscript.

DATA AVAIL ABILIT Y S TATEMENTThedatathatsupportthefindingsofthisstudyareavailablefromthecorrespondingauthoruponreasonablerequest.

ORCIDDavid Li https://orcid.org/0000-0002-7512-9672 Alim Hirji https://orcid.org/0000-0002-6879-2345 Kieran Halloran https://orcid.org/0000-0002-5615-6974

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SUPPORTING INFORMATIONAdditional supporting information may be found online in theSupporting Information section.

How to cite this article:LiD,AbeleJ,WeinkaufJ,etal.Atelectasisinprimarygraftdysfunctionsurvivorsafterlungtransplantation. Clin Transplant. 2021;00:e14315. https://doi.org/10.1111/ctr.14315