ORIGINAL ARTICLE
Prolonged Air Leak After Pulmonary Resection Increases Risk
of Noncardiac Complications, Readmission, and Delayed
Hospital Discharge
A Propensity Score-adjusted Analysis
Adam Attaar, MD,  James D. Luketich, MD,  Matthew J. Schuchert, MD,  Daniel G. Winger, MS,y
Downloaded from https://journals.lww.com/annalsofsurgery by 01UGrXh3ipqzR4DKqW7bOJtSxsRVOheLV9OzOeHq2POX2t1GrKUD6m1aBQdlm0lX7bZxxCFBpuxAM3exuxdXARVaPXROhrEIELxLuiE5dAoxEXL1EbBXOmtN5qOe2K0cl7bPi36/SOM4st4r1MMZ7w== on 03/16/2021
Inderpal S. Sarkaria, MD,  and Katie S. Nason, MD, MPH  z§
Objective: The aim of the study was to determine whether prolonged air leak
(PAL) is associated with postoperative morbidity and mortality following
pulmonary resection after adjusting for differences in baseline characteristics
using propensity score analysis.
Summary Background Data: Patients with PAL after lung resection have
worse outcomes than those without PAL. However, adverse postoperative
outcomes may also be secondary to baseline risk factors, such as poor lung
function.
Methods: Patients who underwent pulmonary resection for lung
cancer/nodules (1/2009 –6/2014) were stratified by the presence of PAL
[n ¼ 183 with/1950 without; defined as >5 d postoperative air leak;
n ¼ 189 (8.3%)]; probability estimates for propensity for PAL from
31 pretreatment/intraoperative variables were generated. Inverse proba-
bility-of-treatment weights were applied and outcomes assessed with
logistic regression.
Results: Standardized bias between groups was significantly reduced
after propensity weighting (mean ¼ 0.18 before vs 0.08 after, P < 0.01).
After propensity weighting, PAL was associated with increased odds of
empyema (OR ¼ 8.5; P < 0.001), requirement for additional chest tubes
for pneumothorax (OR ¼ 7.5; P < 0.001), blood transfusion (OR ¼ 2;
P ¼ 0.03), pulmonary complications (OR ¼ 4; P < 0.001), unexpected
return to operating room (OR ¼ 4; P < 0.001), and 30-day readmission
(OR ¼ 2; P ¼ 0.009). Among other complications, odds of cardiac
complications (P ¼ 0.493), unexpected ICU admission (P ¼ 0.156), and
30-day mortality (P ¼ 0.270) did not differ. Length of hospital stay was
prolonged (5.04 d relative effect, 95% confidence interval, 3.77 – 6.30;
P < 0.001).
Conclusions: Pulmonary complications, readmission, and delayed hospital
discharge are directly attributable to having a PAL, whereas cardiac
From the Department of Cardiothoracic Surgery, Division of Thoracic and
Foregut Surgery, Pittsburgh, PA; yClinical and Translational Science Institute,
University of Pittsburgh, Pittsburgh, PA; zInstitute for Healthcare Delivery and
Population Science, University of Massachusetts Medical School-Baystate,
Springfield, MA; and §Department of Surgery, University of Massachusetts
Medical School-Baystate, Springfield, MA.
Award Numbers K07CA151613 (to KSN) and UL1-TR-001857 from the National
Cancer Institute and National Institutes of Health supported the study. The
content is solely the responsibility of the authors, and does not represent the
official views of the funding source.
The authors report no conflicts of interest.
Supplemental digital content is available for this article. Direct URL citations
appear in the printed text and are provided in the HTML and PDF versions of
this article on the journal’s Web site (www.annalsofsurgery.com).
Reprints: Katie S. Nason, MD, MPH, 2 Medical Center Dr, Suite 205 Medical
Office Building, Springfield, MA 01060.
E-mail: Katie.NasonMD@baystatehealth.org.
Copyright ß 2019 Wolters Kluwer Health, Inc. All rights reserved.
ISSN: 0003-4932/19/27301-0163
DOI: 10.1097/SLA.0000000000003191
Annals of Surgery  Volume 273, Number 1, January 2021
Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.
complications, unexpected admission to the ICU, and 30-day mortality are
not after propensity score adjustment.
Keywords: air leak, boosted regression, clinical care pathways,
complications, fast tracking, inverse probability treatment weighting, lung
cancer, persistent air leak, prolonged air leak, pulmonary resection
(Ann Surg 2021;273:163–172)
P rolonged air leak (PAL) is defined by the Society of Thoracic
Surgeons General Thoracic Surgery Database (STSGTSD) as a
parenchymal air leak lasting >5 days. PAL complicates 6% to 18%
of lung resections.1– 7 Various surgical centers have reported that
PAL increases postoperative morbidity and mortality with a length-
ened hospital stay,4,5,7 –18 and increased incidence of empy-
ema9,10,14,19 commonly reported. Data conflict over higher
incidences of pneumonia,17,19 mortality,5,20 readmission to the
ICU,5,17 30-day readmission,4 and cardiac complications.16 Numer-
ous studies have investigated the risk factors of PAL; consistently
reported risk factors include older age,1,14 male sex,2,6,21 lower body
mass index,2,3,6,7,21 reduced pulmonary function,1 –7,21 upper lobec-
tomy,1,2,5,22 pleural adhesions,1– 3 and undergoing anatomic lung
resection,2,4,7 among others. Thus, we recognize the PAL population
is distinct in demographics, medical history, and surgical treatment.
These differences confound the relationship of PAL and other
postoperative complications.
Baseline differences that confound the association between
PAL and outcomes of interest (eg, mortality) can be balanced using
propensity score analysis, allowing ‘‘apples to apples’’ compari-
son.23,24 Two published studies14,16 have used propensity score
methods to assess the complications of air leak, but were limited
by differing conclusions on cardiopulmonary risk, small sample size,
and use of logistic regression, which can be prone to less stable, less
precise, and more biased estimates in moderate-sized datasets.25
We hypothesized that the previously reported worse postop-
erative course of PAL patients can primarily be attributed to differ-
ences in baseline characteristics rather than PAL occurrence, and
investigated the relationship of PAL and postoperative morbidity and
mortality after adjustment with propensity score weighting.
METHODS
Patient Population and Data Definitions
We collected data using variables defined by the STSGTSD
(http://www.sts.org/national-database) in versions 2.081 and 2.2.
Trained personnel abstracted patient data 4 to 6 weeks after operation
for real-time quality monitoring and national benchmarking via
biannual data submission to the STSGTSD National Data Center.
Our Institutional Review Board gave approval for use of this data.
www.annalsofsurgery.com | 163
Attaar et al
Pulmonary resection was performed (n ¼ 2485; from
January 1, 2009 to June 30, 2014) at 8 hospital sites for malignant
and benign lung tumors or nodules using International Classification
of Diseases, Ninth Revision26 diagnosis codes (197.0, 212.3, 162.2,
162.3, 162.4, 162.5, 162.9, and 518.89), excluding pneumonectomy,
bilobectomy, and extended chest wall/diaphragm resections. Data-
base variables included a wide range of perioperative data: patient
demographics, preoperative evaluation, surgical procedures, cancer
staging, and postoperative events. We excluded 59 patients who had
undergone sleeve lobectomy to minimize confounding parenchymal
and anastomotic air leaks; 31 patients from 2 hospital sites who did
not submit patients to the database over the entire study time frame;
and 5 patients who died by day 5 or before (PAL definition). Multiple
lung resections were noted in 111 patients; data for the most recent
surgery date were used and previous encounter(s) excluded.
Outcomes
PAL was defined as an air leak that persisted for >5 days
postoperatively. Outcomes of interest included pulmonary, cardiac,
infective, readmission, and mortality adverse events that occurred
within 30 days of surgery or during the same admission regardless of
length of stay.
Estimating Propensity Scores
Propensity scores for the probability of PAL conditional on
observed characteristics were generated using generalized boosted
regression. Compared with traditional logistic regression models,
generalized boosted regression accounts for nonlinearity, better
tolerates collinearity, remains insensitive to outliers, and models
interaction terms, which is important in a moderate-size dataset that
has many potential confounders.25,27 We used the R package twang
using model refined specifications of 15,000 trees, maximum inter-
action depth of 3, shrinkage of 0.0005, and 50% bag fraction28. We
selected the 31 baseline variables shown in Table 1. The only
significantly missing data were for %FEV1 (percent forced expira-
tory volume in 1 s); for our main model, we balanced on the observed
values of each covariable as well as the missing data pattern for
%FEV1.29,30
Propensity Weighting and Outcome Analysis
We explored different balancing techniques (Supplemental
Table 1, http://links.lww.com/SLA/B558)27 and chose IPTW
(inverse probability treatment weighting) given good reduction in
standardized bias, advantage of retaining all patients in the outcome
evaluation, and ability to estimate the average treatment effect
(ATE).32 We assessed balance using absolute standardized mean
difference; differences 20% to 40% were considered as moderate
imbalance, and between 10% and 20% residual imbalance, and
<10% minimal imbalance.31 We further adjusted for those covari-
ables that had postweighting standardized difference >10%, and are
known significant risk factors for PAL from previous studies used a
generalized logistic model (R packages survey and glm) to achieve
doubly-robust estimation.31
Sensitivity Analyses
We calculated the treatment effect estimates using 3 alternate
models by performing the analysis described above except for the
following difference: (1) included patients if in the overlap in propensity
scores of PAL and non-PAL cases (ie, region of common support) 33; (2)
excluded patients missing on %FEV1 (ie, complete case analysis); (3)
performed and compared results from 2:1 nearest neighbor propensity
matching (R nonrandom package)32 (further information on the spec-
ifications of 2:1 matching available in appendix).
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Annals of Surgery  Volume 273, Number 1, January 2021
Statistical Analysis
We compared baseline characteristics and outcomes using chi-
squared test or Fisher exact test for categorical variables expressed as
frequencies, and Student t test or Wilcoxon rank sum test for
continuous variables expressed as mean  1 SD or median/inter-
quartile range. We performed statistical analysis using Stata/SE 14.1
(StataCorp, 2015; College Station, TX: StataCorp LP) and R version
3.2.3 (R Foundation for Statistical Computing, Vienna, Austria).
Unless otherwise indicated, P values were 2-tailed; statistical signif-
icance was defined by P < 0.05.
RESULTS
Baseline Characteristics and Propensity Adjustment
A total of 2280 patients underwent pulmonary resection for
lung cancer/lung tumors between January 2009 and June 2014. The
distribution of the baseline characteristics and outcomes stratified by
PAL status are shown in Table 1 and Table 2, respectively. Incidence
of PAL was 8.3% (189/2280). The majority of operations in our study
were video-assisted thoracoscopic (VATS) lobectomy/segmentec-
tomy for primary lung cancer. A total of 2133 patients who had
complete data on baseline characteristics were included in the
propensity score analysis. Before propensity score weighting, 19
of the 31 variables were more than minimally imbalanced (stan-
dardized mean difference >0.1), and 7 variables more than moder-
ately imbalanced (standardized mean difference >0.2) with an
average mean difference of 0.18  0.18. Procedure type (45%),
surgical approach (40%), COPD (38%), %FEV1 (36%), BMI
(34%), smoking history (26%), and reoperation (25%) had more
than moderate imbalance (Figure 1). The percent relative influence
(a model diagnostic) of the variables (variables >1% shown) in the
creation of the propensity scores is shown in Figure 2. Figure 3 shows
an unweighted and weighted histogram of the distribution of pro-
pensity scores. It depicts that, after adjustment, the characteristics of
patients with and without PAL are more comparable with respect to
their probability of PAL (ie, their propensity score). After weighting,
the average mean standardized difference improved to 0.08  0.06
(Figure 1). To allow doubly-robust estimation of effect size, we
included age, BMI, surgical approach, and procedure type in addition
to PAL in a multivariable weighted logistic regression; these cova-
riables are known important risk factors for PAL that had residual
imbalance after weighting.
Risk of Cardiac, Pulmonary, and Infective
Postoperative Adverse Events
After adjustment, PAL patients had 8.5 times the odds of
empyema, 7.5 times the odds of pneumothorax, 2 times the odds of
blood transfusion with packed red blood cells, 3 times the odds of
other recorded pulmonary event, and 53 times the odds of being
discharged with a chest tube, compared with patients without PAL
(Table 3). There was a trend toward higher odds of atelectasis
requiring bronchoscopy. All other cardiac, pulmonary, and infective
postoperative events did not significantly differ between those with
and without PAL after adjustment. Initial ventilatory support >48 h,
reintubation, other pulmonary event, and atrial arrhythmia, which
had shown strong associations with PAL (P < 0.001) before propen-
sity score adjustment, were no longer significant (Table 3). There was
a trend toward higher odds of pneumonia that was not significant
after propensity adjustment. PAL patients had significantly higher
odds of 1 cardiac complication or 1 pulmonary complication
before adjustment. After adjustment, PAL patients had 3.5 times the
odds of overall pulmonary complications, but no significantly higher
risk of overall cardiac complications.
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Annals of Surgery  Volume 273, Number 1, January 2021 Prolonged Air Leak Worsens Outcomes

TABLE 1. Baseline Characteristics of Patients With or Without Prolonged Air Leak Used to Generate Propensity Scores
Prolonged Air Leak
Variables Total n ¼ 2280 No n ¼ 2091 Yes n ¼ 189 P
Demographics
Age (mean  SD) 65  12 65  12 67  11 0.015
2
BMI, kg/m (mean  SD) 28  7 29  7 26  5 <0.001
Sex
Female 1277 (56) 1178 (56) 99 (52) 0.294
Male 1003 (44) 913 (44) 90 (48)
Race/ethnicity
White 2133 (94) 1950 (93) 183 (97) 0.056
Other race/ethnicity 147 (6) 141 (7) 6 (3)
Treatment variables
Surgery year
2009 431 (19) 396 (19) 35 (19) 0.984
2010 405 (18) 368 (18) 37 (20)
2011 445 (20) 411 (20) 34 (18)
2012 431 (19) 396 (19) 35 (19)
2013 392 (17) 359 (17) 33 (18)
2014 (end 6/14) 176 (8) 161 (8) 15 (8)
Surgeon <0.001
A 414 (18) 367 (18) 47 (25)
B 351 (15) 317 (15) 34 (18)
C 342 (15) 303 (15) 39 (21)
D 202 (9) 188 (9) 14 (7)
E 189 (8) 175 (8) 14 (7)
F 173 (8) 167 (8) 6 (3)
G 148 (7) 131 (6) 17 (9)
H 132 (6) 127 (6) 5 (3)
I 100 (4) 96 (5) 4 (2)
Surgeons <100 casesy 229 (10) 220 (11) 9 (5)
Disease category
Stage I 1012 (46) 916 (45) 96 (52) 0.002
Stage II 223 (10) 192 (9) 31 (17)
Stage III/IV 113 (5) 103 (5) 10 (5)
Benign tumor 80 (4) 74 (4) 6 (3)
Metastatic tumor 506 (23) 478 (24) 28 (15)
Benign nodule 284 (13) 269 (13) 15 (8)
Procedure type
Lobe/Segment 1500 (66) 1339 (64) 161 (85) <0.001
Wedge resection 780 (34) 752 (36) 28 (15)
Comorbidities
Smoking history
Never smoker 678 (30) 649 (31) 29 (15) <0.001
Past smoker 1155 (51) 1042 (50) 113 (60)
Current smoker 447 (20) 400 (19) 47 (25)
Zubrod score
0 162 (7) 152 (7) 10 (5) 0.032
1 1728 (76) 1594 (77) 134 (71)
2–5 382 (17) 338 (16) 44 (23)
ASA classification
I/II 276 (12) 262 (13) 14 (7) 0.077
III 1749 (77) 1596 (76) 153 (81)
IV 255 (11) 233 (11) 22 (12)
Hypertension 1269 (56) 1171 (56) 98 (52) 0.271
Coronary artery disease 479 (21) 434 (21) 45 (24) 0.329
Peripheral vascular disease 221 (10) 196 (9) 25 (13) 0.087
Interstitial fibrosis 27 (1) 23 (1) 4 (2) 0.217§
Diabetes 419 (18) 392 (19) 27 (14) 0.077
COPD 754 (33) 660 (32) 94 (50) <0.001
Cerebrovascular disease 138 (6) 125 (6) 13 (7) 0.622
Preoperative chemotherapy 464 (20) 430 (21) 34 (18) 0.395
Preoperative radiation Therapy 308 (14) 279 (13) 29 (15) 0.446
Steroids 124 (5) 112 (5) 12 (6) 0.565
Prior cardiothoracic surgery 503 (22) 450 (22) 53 (28) 0.040
z
Reoperation 283 (13) 245 (12) 38 (20) 0.001
Laboratory
FEV1, % predicted (13.0% missing; mean  SD) 83  22 84  21 76  24 <0.001
Last hemoglobin (mean  SD) 12.1  1.7 12.2  1.7 12.0  1.8 0.238
Last creatinine, median [IQR] 0.88 [0.7–1] 0.90 [0.7–1] 0.80 [0.7–1] 0.582ô
Operative details
Status Elective 2178 (96) 1993 (96) 185 (98) 0.181
Urgent/Emergent 89 (4) 85 (4) 4 (2)

Preoperative hospitalization <1 d 2122 (93) 1939 (93) 183 (97) 0.037
1 d 156 (7) 150 (7) 6 (3)
Laterality Left 912 (40) 851 (41) 61 (32) 0.017

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Attaar et al Annals of Surgery  Volume 273, Number 1, January 2021

TABLE 1. (Continued)
Prolonged Air Leak
Variables Total n ¼ 2280 No n ¼ 2091 Yes n ¼ 189 P
Right 1343 (60) 1215 (59) 128 (68)
Missing 25 (1.1) 25 (1.2) 0 (0)
Robot-assisted surgery 82 (4) 79 (4) 3 (2) 0.121
Surgical approach Thoracotomy 566 (25) 489 (23) 77 (41) <0.001
VATS 1714 (75) 1602 (77) 112 (59)
Values n (%), and <1% missing unless indicated otherwise.

Entered in model as continuous variable.
ySurgeons anonymously lettered. Nine surgeons with <100 operated cases in study period were categorized together.
zCardiac or thoracic reoperation that affects operative field.
§Fisher exact test.
ôWilcoxon rank-sum test.
BMI indicates body mass index, %FEV1, percentage of predicted value of forced expiratory volume in 1 s; DLCO, diffusing capacity of carbon monoxide; ASA, American
Association of Anesthesiology; COPD, chronic obstructive pulmonary disease; VATS, video-assisted thoracic surgery SD, standard deviation; OR, operating room; IQR, interquartile
range.

TABLE 2. Postoperative Major Adverse Events, Mortality, and Length of Stay in Patients With or Without Prolonged Air Leak
Prolonged Air Leak
Complications Total n ¼ 2280 No n ¼ 2091 Yes n ¼ 189 P
Pulmonary
Atelectasis req. bronchoscopy 162 (7.1) 135 (6.5) 27 (14.3) <0.001
Pneumonia 145 (6.4) 124 (6.0) 21 (11.1) 0.005
ARDS 27 (1.2) 23 (1.1) 4 (2.1) 0.276
Bronchopleural fistula 6 (0.3) 4 (0.2) 2 (1.1) 0.082
Pulmonary embolus 23 (1.0) 20 (1.0) 3 (1.6) 0.432
Pneumothorax req. chest tube reinsertion 104 (5) 65 (3.1) 39 (20.6) <0.001
Initial ventilatory support >48 h 47 (2.1) 37 (1.8) 10 (5.3) 0.004
Reintubation 93 (4.1) 76 (3.6) 17 (9.0) <0.001
Tracheostomy 53 (2.3) 46 (2.2) 7 (3.7) 0.201
Discharged with chest tube 110 (4.8) 28 (1.3) 82 (43.6) <0.001
Other pulmonary event 80 (3.5) 63 (3.0) 17 (9.0) <0.000
>1 pulmonary eventy 392 (17.2) 313 (15.0) 79 (41.8) <0.000
Cardiovascular
Atrial arrhythmia req. treatment 183 (8.0) 157 (7.5) 26 (13.8) 0.002
Ventricular arrhythmia req. treatment 7 (0.3) 5 (0.2) 2 (1.1) 0.109
Myocardial infarct 7 (0.3) 7 (0.3) 0 (0.0) 1.000
DVT req. treatment 20 (0.9) 19 (0.9) 1 (0.5) 1.000
Other cardiovascular eventz 23 (1.0) 18 (0.9) 5 (2.6) 0.036
>1 cardiovascular event§ 219 (9.6) 189 (9.0) 30 (15.9) 0.002
Infective/Other
Empyema 15 (0.7) 6.0 (0.3) 9 (4.8) <0.001
Another infection req. antibiotics 38 (1.7) 33 (1.6) 5 (2.6) 0.239
Sepsis 26 (1.1) 20 (1.0) 6 (3.2) 0.017
Other events req. OR return with anesthesia 56 (2.5) 43 (2.1) 13 (6.9) <0.001
Chylothorax 11 (0.5) 8 (0.4) 3 (1.6) 0.056
Renal failure 26 (1.1) 23 (1.1) 3 (1.6) 0.471
Packed red blood cells 160 (7.0) 130 (6.2) 30 (15.9) <0.001
Readmission/Mortality
Unexpected return to ORô 77 (3.4) 53 (2.6) 24 (13) <0.001
Unexpected admission ICU 101 (4.5) 83 (4.0) 18 (9.5) <0.001
Mortality at discharge 28 (1.2) 23 (1.1) 5 (2.6) 0.076
30-d readmissionjj 171 (7.6) 143 (6.9) 28 (15.2) <0.001
30-d mortality 33 (1.4) 26 (1.2) 7 (3.7) 0.007
Length of stay, days; median [IQR] 4 [3–7] 4 [3–6] 10 [8–14] <0.001
Values n (%), and <1% missing unless indicated otherwise.

Other pulmonary event—another pulmonary event in the postoperative period.
Fisher exact test.
y1 pulmonary complication—any of the following: atelectasis requiring bronchoscopy, pneumonia, ARDS, bronchopleural fistula, pulmonary embolus, pneumothorax requiring
chest tube reinsertion, initial ventilator support >48 h, reintubation, tracheostomy, other pulmonary event.
z1 cardiac complication—any of the following: atrial arrhythmia req. treatment, ventricular arrhythmia requiring treatment, myocardial infarct, DVT requiring treatment, other
cardiovascular event.
§Other cardiovascular event—any other CV event including distal arterial embolism in the postoperative period.
ô1.7% missing (39/2280).
jj1.3% missing (30/2280).
Req. indicates requiring; ARDS, acute respiratory distress syndrome; DVT, deep vein thrombosis; OR, operating room; ICU, intensive care unit; IQR, interquartile range.

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Annals of Surgery  Volume 273, Number 1, January 2021 Prolonged Air Leak Worsens Outcomes

%FEV1 Unmeasured
Procedure Type
Surgical Approach
COPD
%FEV1
BMI
Smoking History
Reoperaon
Age
Laterality
Surgeon
Prior CT Surgery
Race
Diabetes
Disease Category
Status
PVD
Zubrod Score
Robot -Assisted Surgery
Preop Hospitalizaon
Hemoglobin
ASA Class
Hypertension
Preop Radiaon
Therapy
Sex
Creanine Unweighted
Preop Chemotherapy
Intersal Fibrosis
Propensity Weighted
CAD
Cerebrovascular Disease
Surgery Year
Steroids
0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%
Standardized % Bias
FIGURE 1. Absolute standard difference between patients with and without prolonged air leak for each of the 31 potential
confounders: unweighted and weighted samples.

Risk of Unexpected Return to Operating Room,
Intensive Care Unit, and 30-day Readmission
After adjustment, PAL patients had 4 times the odds of
unexpected return to the operating room and 2 times the odds of
30-day readmission compared with patients without PAL. There were
significantly higher odds of unexpected admission to ICU before
adjustment, but after adjustment, PAL patients demonstrate no
significantly higher risk.
Mortality and Length of Stay
The overall rate of 30-day mortality was significantly higher
in patients with PAL (Table 2). Before adjustment, PAL patients had
2.5 times the odds of 30-day mortality, and a trend toward higher
odds of mortality at discharge compared with patients without PAL
(Table 3). After adjustment, there were no significantly higher odds
of either 30-day or discharge mortality. PAL patients had a median
length of stay of 10 days compared with 4 days in patients without
PAL. After propensity adjustment in terms of relative effect attribut-
able to PAL, PAL patients had a statistically significant 5-day longer
length of stay compared with 6 days estimated before adjustment
(Table 3).
Sensitivity Analyses
We calculated treatment effect estimates using 3 alternate
propensity score models: IPTW using only region of common
support; IPTW excluding the patients with missing %FEV1 data;
and nearest neighbor 2:1 matching. All outcomes remained
unchanged with regard to their significance except for blood trans-
fusion, which was no longer significant in complete case analysis and
nearest neighbor matching, and pulmonary embolus, which became
significant in complete case analysis (Table 4).
DISCUSSION
Previous works1– 6, including a clinical prediction model for
PAL published at our institution,7 have shown that patients who had
an occurrence of PAL generally have poorer lung function, more
comorbid illnesses, and had required more invasive surgical treat-
ment. To investigate the postoperative morbidity and mortality
directly attributable to PAL requires controlling for differences in
baseline characteristics. After forming 2 well-balanced groups using
propensity weighting under a generalized boosted regression frame-
work (overall mean bias was reduced from 18% to 8%), we found
that, compared with patients without PAL, PAL patients have
increased rates of empyema, blood transfusion, overall pulmonary
complications, unexpected return to operating room, 30-day read-
mission, and requiring chest tube for pneumothorax. There was a
trend toward increased rate of atelectasis requiring bronchoscopy.
Equally significant, we found PAL does not lead to increased cardiac
complications (eg, atrial arrhythmia), unexpected admission to the
ICU, or 30-day mortality. There was a 5-day increase in length of
hospital stay that was attributable to PAL. We conclude that PAL
increases the likelihood of postoperative morbidity and delays

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Attaar et al Annals of Surgery  Volume 273, Number 1, January 2021

Surgeon

BMI

%FEV1

Hemoglobin

Age

Disease Category

Surgical Approach

Smoking History

Reoperaon

Creanine

Laterality

Surgery Year

Procedure Type

Zubrod Score

Preop Hospitalizaon

0% 5% 10% 15% 20% 25%

Relave Influence
FIGURE 2. Percent relative influence of each variable (variables >1% shown) contributing to creation of the propensity score.

hospital discharge; accordingly, the development and implementa-
tion of clinical care pathways for PAL patients require consideration,
anticipation, and proactive management of these complications.
Previous observational studies have reported PAL being asso-
ciated with lengthened hospital stay,4,5,7–18 increased incidence of
empyema,9,10,14,19 pneumonia,17,19 mortality,5,20 readmission to the
ICU,5,17 and 30-day readmission.4 Before propensity score adjust-
ment, we found that higher rates of pneumonia, atelectasis, atrial
arrhythmia, initial ventilator support >48 hours, sepsis, unexpected
admission to the ICU, and 30-day mortality were all strongly

Histogram Propensity Scores Histogram Weighted Propensity Scores

FIGURE 3. Histogram of the distribution of unweighted and weighted propensity score for patient with and without PAL illustrative
of the efficacy of inverse probability of treatment weighting in creating a ‘‘pseudo-population’’ that is more similar in their
probability of having PAL. PAL patients who were less expected to get PAL conditional on observed baseline characteristics (ie, lower
propensity scores) are weighted up to account for the many patients like them who did not get PAL. PAL Patients who were expected
to get PAL (ie, higher propensity scores) are weighted down since they are overrepresented in the data.

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Annals of Surgery  Volume 273, Number 1, January 2021 Prolonged Air Leak Worsens Outcomes

TABLE 3. Unadjusted and Adjusted Odds Ratio Estimates of Major Adverse Events, Mortality, and Length of Stay in Patients
With Prolonged Air Leak Compared With Those Without
Before Propensity Weighting After Propensity Weighting
Outcome OR 95% CI P OR 95% CI P
Pulmonary
Atelectasis req. bronchoscopy 2.48 1.59–3.88 <0.001 1.67 0.97–2.89 0.066
Pneumonia 2.03 1.23–3.36 0.055 1.15 0.57–2.33 0.695
ARDS 2.15 0.73–6.38 0.352 1.18 0.38–3.67 0.775
Pulmonary embolus 1.79 0.52–6.13 0.432 2.69 0.79–9.22 0.115
Pneumothorax req. chest tube reinsertion 7.59 4.89–11.78 <0.001 9.22 4.32–19.66 <0.001
Initial ventilatory support >48 h 3.10 1.46–6.60 0.003 1.72 0.75–3.97 0.203
Reintubation 2.83 1.63–4.94 <0.001 1.78 0.87–3.65 0.115
Tracheostomy 1.76 0.78–3.98 0.172 0.89 0.38–2.10 0.795
Discharged with chest tube 55.15 34.15–89.04 <0.001 52.81 29.72–93.86 <0.001
Other pulmonary eventy 3.28 1.87–5.76 <0.001 3.17 1.47–6.87 0.003
>1 pulmonary eventz 3.96 2.88–5.45 <0.001 3.67 2.22–6.06 <0.001
Cardiovascular
Atrial arrhythmia req. treatment 2.03 1.30–3.18 0.002 1.19 0.72–1.99 0.494
DVT req. treatment 0.59 0.08–4.44 0.608 0.24 0.03–1.84 0.169
Other cardiovascular event§ 3.40 1.23–9.38 0.018 2.62 0.77–8.87 0.122
>1 cardiovascular eventô 1.96 1.29–2.99 0.002 1.19 0.73–1.93 0.493
Infective/Other
Empyema 20.12 6.67–60.70 <0.001 8.39 2.56–27.45 <0.001
Another infection req. antibiotics 1.38 0.48–3.96 0.546 1.37 0.34–5.62 0.658
Sepsis 3.85 1.50–9.90 <0.005 1.71 0.62–4.65 0.297
Renal failure 1.53 0.45–5.18 0.495 1.40 0.31–6.23 0.660
Packed red blood cells 2.39 1.55–3.71 <0.001 2.16 1.05–4.41 0.036
Other events req. OR return with anesthesia 3.47 1.83–6.60 <0.001 1.85 0.93–3.70 0.073
Readmission/Mortality
Unexpected return to OR 4.92 2.92–8.27 <0.001 3.96 2.15–7.26 <0.001
Unexpected admission ICU 2.33 1.35–4.01 0.002 1.65 0.83–3.30 0.156
Mortality at discharge 2.58 0.96–6.93 0.060 1.20 0.43–3.39 0.693
30-d readmission 2.45 <0.001 1.57–3.83 2.12 1.20–3.73 0.009
30-d mortality 2.72 1.10–6.74 0.031 1.94 0.60–6.26 0.270
Length of stay, days [relative effect] 6.26 5.08–7.44 <0.001 5.04 3.77–6.30 <0.001
Unable to calculate adjusted logistic odds ratio estimates for bronchopleural fistula, ventricular arrhythmia, myocardial infarct, and chylothorax given small number of events.

Indicate type of propensity weighting.
yOther pulmonary event—another pulmonary event in the postoperative period.
z>1 pulmonary complication—any of the following: atelectasis requiring bronchoscopy, pneumonia, ARDS, bronchopleural fistula, pulmonary embolus, pneumothorax requiring
chest tube reinsertion, initial ventilator support >48 h, reintubation, tracheostomy, other pulmonary event.
§Other cardiovascular event—any other CV event including distal arterial embolism in the postoperative period.
ô>1 cardiac complication—any of the following: atrial arrhythmia req. treatment, ventricular arrhythmia requiring treatment, myocardial infarct, DVT requiring treatment, other
cardiovascular event.
Req. indicates requiring; ARDS, acute respiratory distress syndrome; DVT, deep vein thrombosis; OR, operating room; ICU, intensive care unit; CI, confidence interval.

associated with PAL. After adjustment, these complications were no
longer significantly associated with PAL.
Only 2 prior studies have studied the consequences of air leak
using propensity score methods.13,16 Okereke et al’s case matched
lobectomy patients (n ¼ 82) with any air leak beginning in the
immediate postoperative period to those without air leak, and showed
an increase in overall respiratory and overall cardiac complica-
tions.16 Brunelli et al (n ¼ 85) in a case-matched analysis of PAL
(defined air leak at >7d) after lobectomy reported increased risk of
empyema but not of overall cardiac and pulmonary morbidity.14 Both
studies found increase length of hospital stay and no increase in
hospital mortality. The specific events represented by our overall
cardiac and pulmonary composite variables were similar to the 2
prior studies but with some differences in included outcomes and
definitions. We had a broader inclusion criteria for the study popu-
lation (inclusion of wedge resections, segmentectomy, and thoraco-
scopic approach), larger sample size, and controlled on a larger set of
potential confounders using a more rigorous statistical analysis.
Our finding that PAL directly contributes to pulmonary com-
plications like pneumothorax, pulmonary space infection such as
empyema, and the trend to toward increased rate of atelectasis has
biological plausibility due to residual space defect. The increased
rates of unexpected admission to the OR and 30-day readmission
could, in part, be explained by postoperative intervention for unre-
solved air leaks. The increased rate of blood transfusion is an
outcome that has not been previously studied, and likely multifacto-
rial from prolonged chest tube drainage or length of stay. The finding
of no increased rate of 30-day mortality, unexpected admission to the
ICU, and overall cardiac complications corresponds with PAL rarely
being a life-threatening complication; rather the major consequence
is prevention of patient discharge and return to mobility. Seely et al
classify PAL in their severity of thoracic morbidity and mortality
(TM&M) classification system as primarily a grade 2 minor com-
plication, which is one that requires pharmacologic treatment or
minor intervention; in 13% of cases in their population of lung
resection patients, however, PAL was a grade 3 or 4 major compli-
cation, requiring more aggressive therapies or surgical interven-
tion.34 The study reaffirms the surgeon’s awareness that air leaks
are frequent and manageable, but can quickly escalate the risk of
morbidity and mortality if not properly and promptly addressed.
Three principal factors contribute to delayed hospital dis-
charge after lung resection: air leaks, pain control, and other

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 Attaar et al

TABLE 4. Sensitivity Analyses of Adjusted Odds Ratio Estimates of Reported Outcomes Shown in Table 3 to Varying Propensity Model Specifications
Model Specification IPTW of Table 3 IPTW Using Common Support IPTW Complete Case Analysis on %FEV1 Nearest Neighbor Matching 2:1
Sample Size (No PAL/PAL) 86/180
Outcome 1950/183 1742/169 Odds Ratio (95% CI) 356/179
Pulmonary
Atelectasis req. bronchoscopy 1.67 (0.97–2.89) 1.67 (0.95–2.91) 1.67 (0.96–2.91) 1.59 (0.91–2.76)

170 | www.annalsofsurgery.com
Pneumonia 1.15 (0.57–2.33) 1.08 (0.53–2.23) 1.21 (0.59–2.46) 0.94 (0.53–1.67)
ARDS 1.18 (0.38–3.67) 1.21 (0.39–3.72) 1.20 (0.38–3.82) 1.01 (0.30–3.42)
Pulmonary embolus 2.69 (0.79–9.22) 2.94 (0.83–10.42) 3.50 (1.01–12.12) 1.19 (0.27–5.28)
Pneumothorax req. chest tube reinsertion 9.22 (4.32–19.66) 8.60 (4.14–17.84) 6.28 (3.47–11.39) 6.16 (3.26–11.64)
Initial ventilatory support >48 h 1.72 (0.75–3.97) 1.87 (0.81–4.28) 2.18 (0.86–5.52) 1.76 (0.68–4.57)
Reintubation 1.78 (0.87–3.65) 1.74 (0.84–3.60) 1.88 (0.91–3.90) 1.49 (0.73–3.07)
Tracheostomy 0.89 (0.38–2.10) 0.92 (0.39–2.16) 0.83 (0.38–2.16) 0.98 (0.37–2.62)
Other pulmonary event 3.17 (1.47–6.87) 3.38 (1.57–7.25) 3.18 (1.63–7.95) 2.16 (1.12–4.18)
>1 pulmonary eventy 3.67 (2.22–6.06) 3.62 (2.22–5.91) 3.07 (2.02–4.66) 2.35 (1.55–3.55)
Cardiovascular
Atrial arrhythmia req. treatment 1.19 (0.72–1.99) 1.18 (0.69–2.00) 1.27 (0.76–2.13) 1.44 (0.82–2.55)
DVT req. treatment 0.24 (0.03–1.84) 0.24 (0.03–1.84) 0.24 (0.03–1.88) 0.39 (0.04–3.50)
Other cardiovascular eventz 2.62 (0.77–8.87) 2.48 (0.78–7.90) 3.08 (0.83–11.41) 2.37 (0.62–9.04)
>1 cardiovascular event§ 1.19 (0.73–1.93) 1.16 (0.70–1.91) 1.29 (0.79–2.12) 1.32 (0.77–2.26)
Infective/Other
Empyema 8.39 (2.56–27.45) 7.83 (2.10–29.28) 7.74 (2.40–25.02) 11.34 (2.25–57.15)
Another infection req. antibiotics 1.37 (0.34–5.62) 1.46 (0.36–5.88) 1.46 (0.35–6.08) 0.81 (0.24–2.70)
Sepsis 1.71 (0.62–4.65) 1.69 (0.61–4.67) 1.84 (0.66–5.08) 1.53 (0.50–4.62)
Renal failure 1.40 (0.31–6.23) 1.29 (0.31–5.28) 1.67 (0.33–8.35) 0.87 (0.22–3.41)
Packed red blood cells 2.16 (1.05–4.41) 2.19 (1.11–4.31) 1.52 (0.93–2.49) 1.25 (0.74–2.11)

ß
Other events req. OR return with anesthesia 1.85 (0.93–3.70) 1.87 (0.92–3.80) 1.91 (0.95–3.86) 2.10 (0.95–4.67)
Readmission/Mortality
Unexpected return to OR 3.96 (2.15–7.26) 3.84 (2.11–6.99) 4.36 (2.30–8.27) 3.51 (1.84–6.69)
Unexpected admission ICU 1.65 (0.83–3.30) 1.66 (0.80–3.42) 1.92 (0.94–3.90) 1.58 (0.82–3.08)
Discharged with chest tube 52.81 (29.72–93.86) 48.53 (27.39–86.01) 57.60 (32.85–100.98) 32.61 (15.07–70.54)
Mortality at discharge 1.20 (0.43–3.39) 1.42 (0.49–4.05) 1.34 (0.45–3.96) 1.72 (0.50–5.92)
30-d readmission 2.12 (1.20–3.73) 2.10 (1.20–3.70) 2.52 (1.44–4.42) 1.90 (1.07–3.36)
30-d mortality 1.94 (0.60–6.26) 2.17 (0.70–6.70) 2.58 (0.68–9.82) 2.01 (0.62–6.50)
Length of stay, days [relative effect] 5.04 (3.77–6.30) 4.99 (3.68–6.29) 4.68 (3.28–6.09) 4.46 (2.71–6.21)
Unable to calculate adjusted logistic odds ratio estimates for bronchopleural fistula, ventricular arrhythmia, myocardial infarct, and chylothorax given small number of events.

Other pulmonary event—another pulmonary event in the postoperative period.
y>1 pulmonary complication—any of the following: atelectasis requiring bronchoscopy, pneumonia, ARDS, bronchopleural fistula, pulmonary embolus, pneumothorax requiring chest tube reinsertion, initial ventilator support
>48 h, reintubation, tracheostomy, other pulmonary event.
p
zOther cardiovascular event—any other CV event including distal arterial embolism in the postoperative eriod.
§>1 cardiac complication—any of the following: atrial arrhythmia req. treatment, ventricular arrhythmia requiring treatment, myocardial infarct, DVT requiring treatment, other cardiovascular event.

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Req. indicates requiring; ARDS, acute respiratory distress syndrome; DVT, deep vein thrombosis; OR, operating room; ICU, intensive care unit; CI, confidence interval.
Annals of Surgery  Volume 273, Number 1, January 2021

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Annals of Surgery  Volume 273, Number 1, January 2021
postoperative complications.35 Fast tracking or enhanced recovery
pathways (ERPs) are multimodal clinical care pathways to reduce
hospital costs and increase patient satisfaction through early dis-
charge.36 A 2012 cost analysis looking at any air leak after pulmo-
nary resection using Medicare data found that an air leak diagnosis
increases hospital costs by 15%.37 For PAL, the cost is greater;
another US study using a database of 27,336 lung resections found a
$15,636 increase (35% increase) in health care expenditures due to
PAL.38 Fast tracking studies in thoracic surgery have proposed
modifying care elements such as chest tube protocols (eg, early
water seal, discharge with Heimlich valve system, digital chest
drainage systems),39 optimal pain control with adjunctive use of
epidural and regional anesthesia,40 and implementation of aggressive
postoperative rehabilitation.41 A few small prospective studies have
investigated the feasibility of early discharge of PAL patients with
chest tube or Heimlich valves, and have demonstrated reductions in
hospital stay without increased patient morbidity.42–44 Our findings
support the possibility of early discharge for the majority of PAL
patients. Future risk modeling is needed to address the prevention and
monitoring of the pulmonary complications due to PAL, to identify
the subset of PAL patients that will require hospital readmission and
surgical intervention, and to recognize the perioperative character-
istics that do directly lead to the increased mortality and cardiac
complications. Randomized controlled trials and multicenter inves-
tigation in this area would support the creation and adoption of early
discharge pathways that yield immense cost savings and stream-
lined, personalized care without negatively impacting patient safety.
Strengths and Limitations
We developed our model from a large database using rigorous
statistical analysis based on published guidelines.25,27,28,32 The
appropriate implementation of propensity score analysis has been
advocated in thoracic surgery45; generalized boosted regression with
IPTW represents a novel and underutilized technique that can more
accurately model the complexities of datasets, allowing for less
biased and more precise estimates of exposure effect.
Propensity score methods assume that all confounding factors
that could influence PAL and/or the outcome be accounted for;
however, the existence of unmeasured confounders that were not
captured by STSGTSD was unavoidable. On the measured con-
founders, we produced a well-balanced propensity score model with
minimal residual bias. Our additional sensitivity analyses confirmed
robustness of results to varying model specifications. The purpose of
our study was to determine those complications directly attributable
to PAL, so we do not address a significant and separate research
question of which baseline characteristics that differ between
patients with and without PAL most contribute to important and
frequent complications like pneumonia, atrial arrhythmia, and unex-
pected admission to the ICU.
CONCLUSION
PAL is associated with increased rates of empyema, blood
transfusion, overall pulmonary complications, and 30-day readmis-
sion, but not with cardiac complications, unexpected admission to the
ICU, or 30-day mortality after propensity score adjustment. Early
hospital discharge may be feasible and safe in appropriately selected
PAL patients.
ACKNOWLEDGMENTS
The authors thank Connie Timko and Karan Moore for
assistance with data acquisition, Li Wang and Nalyn Siripong for
their statistical expertise, and Aubri Drake for assistance with
manuscript submission.
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Prolonged Air Leak Worsens Outcomes
REFERENCES
1. Lee L, Hanley SC, Robineau C, et al. Estimating the risk of prolonged air leak
after pulmonary resection using a simple scoring system. J Am Coll Surg.
2011;212:1027–1032.
2. Rivera C, Bernard A, Falcoz PE, et al. Characterization and prediction of
prolonged air leak after pulmonary resection: a nationwide study setting up the
index of prolonged air leak. Ann Thorac Surg. 2011;92:1062–1068.
3. Brunelli A, Varela G, Refai M, et al. A scoring system to predict the risk of
prolonged air leak after lobectomy. Ann Thorac Surg. 2010;90:204–209.
4. Liang S, Ivanovic J, Gilbert S, et al. Quantifying the incidence and impact of
postoperative prolonged alveolar air leak after pulmonary resection. J Thorac
Cardiovasc Surg. 2013;145:948–954.
5. Elsayed H, McShane J, Shackcloth M. Air leaks following pulmonary resec-
tion for lung cancer: is it a patient or surgeon related problem? Ann R Coll Surg
Engl. 2012;94:422–427.
6. Gilbert S, Maghera S, Seely AJ, et al. Identifying patients at higher risk of
prolonged air leak after lung resection. Ann Thorac Surg. 2016;102:1674–1679.
7. Attaar A, Winger DG, Luketich JD, et al. A clinical prediction model for
prolonged air leak after pulmonary resection. J Thorac Cardiovasc Surg.
2017;153. 690-699.e2.
8. Irshad K, Feldman LS, Chu VF, et al. Causes of increased length of
hospitalization on a general thoracic surgery service: a prospective observa-
tional study. Can J Surg. 2002;45:264–268.
9. Bhatnagar NK, Berndt S. A solution to prolonged air leak after video-assisted
thoracoscopic lobectomy. Ann Thorac Surg. 1995;59:260–261.
10. Varela G, Jimenez MF, Novoa N, et al. Estimating hospital costs attributable to
prolonged air leak in pulmonary lobectomy. Eur J Cardiothorac Surg.
2005;27:329–333.
11. Abolhoda A, Liu D, Brooks A, et al. Prolonged air leak following radical upper
lobectomy: an analysis of incidence and possible risk factors. Chest.
1998;113:1507–1510.
12. Rice TW, Kirby TJ. Prolonged air leak. Chest Surg Clin North Am.
1992;2:803–811.
13. Bardell T, Petsikas D. What keeps postpulmonary resection patients in
hospital? Can Respir J. 2003;10:86–89.
14. Brunelli A, Xiume F, Al Refai M, et al. Air leaks after lobectomy increase the
risk of empyema but not of cardiopulmonary complications: a case-matched
analysis. Chest. 2006;130:1150–1156.
15. Stolz AJ, Schutzner J, Lischke R, et al. Predictors of prolonged air leak
following pulmonary lobectomy. Eur J Cardiothorac Surg. 2005;27:334–336.
16. Okereke I, Murthy SC, Alster JM, et al. Characterization and importance of air
leak after lobectomy. Ann Thorac Surg. 2005;79:1167–1173.
17. DeCamp MM, Blackstone EH, Naunheim KS, et al. Patient and surgical
factors influencing air leak after lung volume reduction surgery: lessons
learned from the National Emphysema Treatment Trial. Ann Thorac Surg.
2006;82:197–206.
18. Stephan F, Boucheseiche S, Hollande J, et al. Pulmonary complications
following lung resection: a comprehensive analysis of incidence and possible
risk factors. Chest. 2000;118:1263–1270.
19. Liberman M, Muzikansky A, Wright CD, et al. Incidence and risk factors of
persistent air leak after major pulmonary resection and use of chemical
pleurodesis. Ann Thorac Surg. 2010;89:891–898.
20. Sanchez PG, Vendrame GS, Madke GR, et al. Lobectomy for treating
bronchial carcinoma: analysis of comorbidities and their impact on postoper-
ative morbidity and mortality. J Bras Pneumol. 2006;32:495–504.
21. Pompili C, Falcoz PE, Salati M, et al. A risk score to predict the incidence of
prolonged air leak after video-assisted thoracoscopic lobectomy: an analysis
from the European Society of Thoracic Surgeons database. J Thorac Car-
diovasc Surg. 2017;153:957–965.
22. Brunelli A, Monteverde M, Borri A, et al. Predictors of prolonged air leak after
pulmonary lobectomy. Ann Thorac Surg. 2004;77:1205–1210.
23. Rubin DB. The use of matched sampling and regression adjustment to remove
bias in observational studies. Biometrics. 1973;29:185–203.
24. Rosenbaum PR, Rubin DB. Constructing a control group using multivariate
matched sampling methods that incorporate the propensity score. Am Stat.
1985;39:33–38.
25. Lee BK, Lessler J, Stuart EA. Improving propensity score weighting using
machine learning. Stat Med. 2010;29:337–346.
26. Health UDo, Services H. ICD 9 CM. The International Classification of
Diseases. 9. Rev: Clinical Modification; Vol. 1: Diseases: Tabular List; Vol. 2:
Diseases: Alphabetic Index; Vol. 3: Procedures: Tabular List and Alphabetic
Index: US Government Printing Office; 1980.
www.annalsofsurgery.com | 171
Attaar et al
27. Harder VS, Stuart EA, Anthony JC. Propensity score techniques and the
assessment of measured covariate balance to test causal associations in
psychological research. Psychol Methods. 2010;15:234.
28. Ridgeway G, McCaffrey D, Morral A, et al. Toolkit for Weighting and
Analysis of Nonequivalent Groups: A Tutorial for the R TWANG Package.
RAND Corporation. 2014. https://www.rand.org/pubs/tools/TL136z1.html.
29. Cham H, West SG. Propensity score analysis with missing data. Psychol
Methods. 2016;21:427–445.
30. D’Agostino R Jr, Lang W, Walkup M, et al. Examining the impact of missing
data on propensity score estimation in determining the effectiveness of self-
monitoring of blood glucose (SMBG). Health Serv Outcomes Res Methodol.
2001;2:291–315.
31. Austin PC. An introduction to propensity score methods for reducing the
effects of confounding in observational studies. Multivariate Behav Res.
2011;46:399–424.
32. Austin PC, Stuart EA. Moving towards best practice when using inverse
probability of treatment weighting (IPTW) using the propensity score to estimate
causal treatment effects in observational studies. Stat Med. 2015;34:3661–3679.
33. Stürmer T, Rothman KJ, Avorn J, et al. Treatment effects in the presence of
unmeasured confounding: dealing with observations in the tails of the propensity
score distribution—a simulation study. Am J Epidemiol. 2010;172:843–854.
34. Seely AJ, Ivanovic J, Threader J, et al. Systematic classification of morbidity
and mortality after thoracic surgery. Ann Thorac Surg. 2010;90:936–942.
35. Campos JH. Fast track in thoracic anesthesia and surgery. Curr Opin Anaes-
thesiol. 2009;22:1–3.
36. Fiore JF Jr, Bejjani J, Conrad K, et al. Systematic review of the influence of
enhanced recovery pathways in elective lung resection. J Thorac Cardiovasc
Surg. 2016;151. 708-15 e1-6.
172 | www.annalsofsurgery.com
Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.
Annals of Surgery  Volume 273, Number 1, January 2021
37. Wood DE, Lauer LM, Layton A, et al. Prolonged length of stay associated with
air leak following pulmonary resection has a negative impact on hospital
margin. Clinicoecon Outcomes Res. 2016;8:187–195.
38. Swanson S, Miller D, McKenna R, et al. Economic burden of prolonged air
leak after lung resection: open versus video-assisted thoracoscopic surgery
(VATS). Value Health. 2014;17:A80.
39. Bryant AS, Cerfolio RJ. The influence of preoperative risk stratification on
fast-tracking patients after pulmonary resection. Thorac Surg Clin.
2008;18:113–118.
40. Sokouti M, Aghdam BA, Golzari SE, et al. A comparative study of
postoperative pulmonary complications using fast track regimen and con-
servative analgesic treatment: a randomized clinical trial. Tanaffos.
2011;10:12– 19.
41. Ueda K, Sudoh M, Jinbo M, et al. Physiological rehabilitation after video-
assisted lung lobectomy for cancer: a prospective study of measuring daily
exercise and oxygenation capacity. Eur J Cardiothorac Surg. 2006;30:
533–537.
42. McKenna RJ Jr, Mahtabifard A, Pickens A, et al. Fast-tracking after video-
assisted thoracoscopic surgery lobectomy, segmentectomy, and pneumonec-
tomy. Ann Thorac Surg. 2007;84:1663–1667.
43. Drahush N, Miller AD, Smith JS, et al. Standardized approach to prolonged
air leak reduction after pulmonary resection. Ann Thorac Surg. 2016;101:
2097–2101.
44. Cerfolio RJ, Bass CS, Pask AH, et al. Predictors and treatment of persistent air
leaks. Ann Thorac Surg. 2002;73:1727–1730.
45. Winger DG, Nason KS. Propensity-score analysis in thoracic surgery: when,
why, and an introduction to how. J Thorac Cardiovasc Surg. 2016;151:
1484–1487.
ß 2019 Wolters Kluwer Health, Inc. All rights reserved.