Asian Journal of Surgery xxx (xxxx) xxx

Contents lists available at ScienceDirect

Asian Journal of Surgery

journal homepage: www.e-asianjournalsurgery.com

Review Article

Incentive spirometry is an effective strategy to improve the quality of

postoperative care in the patients undergoing pulmonary resection: A
systematic review and meta-analysis
Po-Chih Chang a, b, c, d, 1, Po-Huang Chen e, Ting-Hsuan Chang f, Kai-Hua Chen g,
Hong-Jie Jhou h, 1, Shah-Hwa Chou a, i, Ting-Wei Chang a, *
a
Division of Thoracic Surgery, Department of Surgery, Kaohsiung Medical University Hospital/Kaohsiung Medical University, Kaohsiung City, Taiwan
b
Weight Management Center, Kaohsiung Medical University Hospital/Kaohsiung Medical University, Kaohsiung City, Taiwan
c
Ph. D. Program in Biomedical Engineering, College of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan
d
Department of Sports Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan
e
Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei City, Taiwan
f
School of Medicine, China Medical University, Taichung City, Taiwan
g
Department of Surgery, Kaohsiung Medical University Hospital/Kaohsiung Medical University, Kaohsiung City, Taiwan
h
Department of Neurology, Changhua Christian Hospital, Changhua, Taiwan
i
Department of Surgery, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan

a r t i c l e i n f o a b s t r a c t

Article history: Postoperative pulmonary complications (PPCs) most commonly occur after thoracic surgery. Not only
Received 26 August 2022 prolonged hospital stay and increased financial expenses but also morbidity and even mortality may be
Received in revised form troublesome for those with PPCs. Herein, we aimed to conduct a comprehensive systematic review and
15 October 2022
meta-analysis of available data to examine the effectiveness of incentive spirometry (IS) to reduce PPCs
Accepted 11 November 2022
and shorten hospital stay. This systematic review and meta-analysis included 5 randomized controlled
Available online xxx
trials (RCT) and 3 retrospective cohort study (10,322 patients in total) in PubMed, Embase and Cochrane
Library until September 31, 2021. We assessed the clinical efficacy of IS using length of hospital stay, PPCs,
postoperative pneumonia, and postoperative atelectasis with meta-analysis, meta-regression and trial
sequential analysis (TSA). With this meta-analysis, the length of hospital stay in patients undergoing IS
was significantly shorter (1.8 days) than that in patients not receiving IS (MD ¼ 1.80, 95% CI ¼ 2.95
to 0.65). Patients undergoing IS also had reduced risk of PPCs (32%) and postoperative pneumonia
(17.9%) with statistical significance than patients not undergoing IS (PPC: OR ¼ 0.68, 95% CI ¼ 0.51e0.90)
(Pneumonia: OR ¼ 0.821, 95% CI ¼ 0.677e0.995).In meta-regression, the benefits of undergoing IS in
patients with preoperative predicted FEV1 of <80% in a linear fashion with decreasing PPCs. IS is an
effective modality to improve the quality of postoperative care for patients after pulmonary resection,
compared with the control group without using IS; and applying IS has favorable outcomes of shorter
length of hospital stay (1.8 days) and lower occurrence of PPCs (32% of risk reduction), which are
conclusive and robust based on our validation via TSA. Moreover, the IS device is more beneficial for
patients with preoperative predicted FEV1 of <80% than that in others.
© 2022 Asian Surgical Association and Taiwan Robotic Surgery Association. Publishing services by
Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/
licenses/by-nc-nd/4.0/).

1. Introduction occur after thoracic surgery, with a reported incidence of 25%e

Postoperative pulmonary complications (PPCs) most commonly
* Corresponding author. No. 100, Tzyou 1st Road, Kaohsiung City, 80756, Taiwan.
E-mail address: drchangtingwei@gmail.com (T.-W. Chang).
1
Contributed equally.
49%,1,2 and are frequently defined as pneumonia, respiratory failure
necessitating noninvasive/invasive mechanical ventilation, or
atelectasis requiring bronchoscopy.2 Not only prolonged hospital
stay and increased financial expenses but also morbidity and even
mortality may be troublesome for those with PPCs. Compared with
other procedures, pulmonary resections presented with a higher

https://doi.org/10.1016/j.asjsur.2022.11.030
1015-9584/© 2022 Asian Surgical Association and Taiwan Robotic Surgery Association. Publishing services by Elsevier B.V. This is an open access article under the CC BY-NC-
ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Please cite this article as: P.-C. Chang, P.-H. Chen, T.-H. Chang et al., Incentive spirometry is an effective strategy to improve the quality of
postoperative care in the patients undergoing pulmonary resection: A systematic review and meta-analysis, Asian Journal of Surgery,
https://doi.org/10.1016/j.asjsur.2022.11.030
P.-C. Chang, P.-H. Chen, T.-H. Chang et al.
incidence of PPCs (15%e37.5%).3 PPCs are also independent and
crucial risk factors of 30-day mortality and have negative long-term
impacts on the clinical outcome.1,3 An effective strategy should be
developed to reduce the risk of PPCs in patients undergoing pul-
monary resection.
Based on the concept of maintaining sustained maximal inspi-
ration to prevent atelectasis, incentive spirometry (IS) is currently a
common pulmonary rehabilitation tool for patients undergoing
major surgeries to prevent the occurrence of PPCs due to its con-
venience and inexpensiveness.4e6
However, some conflicts still exist among different studies. Liu
et al.‘s study using the Taiwan Health Insurance Database disclosed
that IS itself could reduce the risk of pneumonia and related hos-
pitalization cost for patients undergoing pulmonary lobectomy.5
Pantel et al7 conducted a randomized control trial (RCT) for
severely obese patients undergoing bariatric surgery and found
that IS did not have a positive impact on PPCs or postoperative
hypoxemia. In 2014, a meta-analysis demonstrated that no evi-
dence supported the effectiveness of IS to prevent PPCs in upper
abdominal surgery.8 In 2011, clinical practice guidelines for IS
proposed by the American Association for Respiratory Care did not
suggest the role of routinely using IS in patients after coronary ar-
tery bypass grafting or upper abdominal surgery.9 Nevertheless, no
systematic review and meta-analysis validated the effectiveness of
IS for patients after pulmonary resection.
With the advancement of low-dose computed tomography, the
frequency of identifying small, resectable pulmonary lesions
increased, so did the volume of pulmonary surgeries.10 Therefore,
enhanced recovery has become an important issue after lung sur-
gery to decrease the risk of complications and shorten the hospital
stay.11 Besides a thorough preoperative evaluation and minimally
invasive surgical manipulation, IS is a standard adjunct post-
operative chest physiotherapy. However, the solid evidence of
routinely applying IS in pulmonary resection is limited. To the best
of our knowledge, no meta-analysis has investigated the definite
benefits of IS in pulmonary resection. Herein, we aimed to conduct
a comprehensive systematic review and meta-analysis of available
data to examine the effectiveness of IS to reduce PPCs and shorten
hospital stay.
2. Materials and methods
The study followed the Preferred Reporting Items for Systematic
Reviews and Meta-Analyses reporting guidelines: the PRISMA 2020
statement (Table S1 PRISMA list).12 This protocol for systemic re-
view has been registered with the Open Science Framework plat-
form (available at https://osf.io/dntwk, accessed on 12 October
2021).
2.1. Search strategy
PubMed, Embase, and the Cochrane Library were comprehen-
sively searched for related literature published from inception to
September 31, 2021, without language restrictions. We used the
following keywords to establish the search protocol: “incentive
spirometry,” “pulmonary resection,” and “lung resection” by two
independent authors (TWC and KHC). We manually screened
original studies, previous systematic reviews, and conference ma-
terials to identify qualified publications. If the results from the same
clinical trial have been reported in two or more publications, the
most complete and recent one was used in the meta-analysis.
2.2. Study selection
Studies meeting the following criteria were included: patients
2
Asian Journal of Surgery xxx (xxxx) xxx
with 18 years of age and older; observation and phase II or III
prospective clinical trial of IS in patients who underwent pulmo-
nary resection; and sufficient data provided on length of hospital
stay, PPCs, postoperative pneumonia, and atelectasis. We excluded
studies with (1) overlapping or duplicate publication, (2) necessary
data but could not be extracted, and (3) conference abstracts, re-
views, letters, and case reports.
2.3. Data extraction and outcome measures
Two independent researchers (TWC and THC) collected the
following outcomes: the length of hospital stay, PPCs, postoperative
pneumonia, and atelectasis. If disagreements existed, another
author (H.J.J.) was consulted for a third-party decision. The primary
outcome was the length of hospital stay, and the secondary
outcome included PPCs, postoperative atelectasis, and post-
operative pneumonia. The length of hospital stay represents the
duration of hospitalization. PPCs are defined as one or more of the
following: atelectasis requiring bronchoscopy, respiratory failure
requiring noninvasive or invasive mechanical ventilation, pneu-
monia treated with antibiotics, postoperative air leak of >30% chest
cavity confirmed by chest X-ray, or pulmonary embolism.2,13 Post-
operative atelectasis represents lobar or pulmonary collapse
confirmed by chest X-ray.14 Postoperative pneumonia represents
pneumonia that occurs 48 h after admission.14,15
2.4. Data synthesis and analysis
Statistical analysis was performed following the Cochrane
Handbook for Statistical Review of Interventions (version 5.4).16
Dichotomous variables were estimated by odds ratios (ORs) with
95% confidence intervals (CIs). Continuous variables were calcu-
lated with the mean difference (MD) with 95% CIs. The inverse
variance method was used to estimate both dichotomous and
continuous outcomes. Both random-effects models (DerSimo-
nianeLaird estimator)17 and fixed-effect model were reported.
Random-effects model is that each study has an underlying true
effect, and fixed-effects model is that there is a single true value
underlying all studies results. The authors interpreted the admin-
istration of fixed-effects or random-effects with statistical hetero-
geneity. If an estimate of the between-study variance, known as
tau-squared, was low (or zero), then the fixed-effect model was
chosen; otherwise, we would choose random-effects. Statistical
heterogeneity was assessed by Cochran's Q statistic and measured
using the I2 statistic (values of <25% indicate low; 25%e75%,
moderate; and >75%, considerable heterogeneity).18 Furthermore,
an a priori meta-regression was planned to explore the influence of
study characteristics on the pooled effect estimates.19 Sensitivity
analysis was conducted to investigate the possible impact of
different study designs, enrolling RCTs and excluding cohort studies
across all the outcomes. Besides, in order to take into account all
sources of variations and provide more accurate estimates for small
samples, we conducted another meta-analysis using Bayesian
approach. On the other hands, we performed influential analysis of
outlier detection using leave-one-out method, which assessed the
influence of individual studies by performing a series of meta-
analyses that excluded one of the studies at each meta-analysis.
We could determine whether the results shift with the exclusion
of a specific study, and provided evidence of one potential outlier. A
p-value of <0.05 was considered statistically significant. All statis-
tical analyses were performed using the “metafor” and “meta”20,21
packages of the R software version 4.1.0 (R Foundation for Statistical
Computing, Vienna, Austria).22
P.-C. Chang, P.-H. Chen, T.-H. Chang et al.
2.5. Bias assessment and quality assessment
We identified the asymmetry of funnel plots and used Egger's
tests to evaluate publication bias.23,24 The quality of RCTs (Sup-
porting Information 4 Tables S4e1) was appraised by THC and TWC
using the Cochrane Handbook for Systematic Reviews of In-
terventions.25 The NewcastleeOttawa Scale (Supporting Informa-
tion 4 Tables S4e2) was also used to assess the quality of
prospective non-randomized studies.26 The Grading of Recom-
mendations Assessment, Development, and Evaluation (GRADE)
methodology27 was used to assess the certainty of evidence from
the included studies (GRADEpro GDT: GRADEpro Guideline
Development Tool. McMaster University, 2020)28(Supporting In-
formation 5 Table S5).
2.6. Trial sequential analysis (TSA)
Limited data and lack of power in meta-analyses may lead to
type I or II error in the results of the conventional meta-analysis.29
To achieve conclusive results, TSA was applied to calculate the
diversity-adjusted required information size (RIS) and trial
sequential monitoring boundaries.30 This method was more rele-
vant when analyzing cumulative heterogeneous results and de-
creases false-positive results of a meta-analysis. The models were
set at an alpha of 5% and a power of 80% for all outcomes. TSA was
performed using the TSA software version 0.9.5.10 Beta (Copen-
hagen Trial Unit, Copenhagen, Denmark).31
3. Results
A total of 51,643 articles were identified, and 49,940 articles
were left after removing the duplicates. No language restriction was
applied. After screening the titles and abstracts, a total of 25
potentially associated articles remained. Ultimately, eight articles
fulfilled the inclusion criteria for meta-analysis after the full-text
review (Fig. 1).2,5,13,14,32e35 Table 1 summarizes the basic charac-
teristics of eight studies, including five RCTs,2,13,33e35 published
Fig. 1. PRISMA flow diagram of the study selection. . Flow diagram for the identification process for eligible studies.
3
Asian Journal of Surgery xxx (xxxx) xxx
between 1996 and 2018, and three retrospective cohort
studies,5,14,32 published between 2006 and 2021. A total of 10,322
participants, including 6202 receiving IS and 4115 not receiving IS,
were identified. The mean age of enrolled patients was 65.54 years,
and only three studies (Agostini et al33; Pehlivan et al34; and Varela
et al14) mentioned the body mass index (BMI) of patients, and with
the mean BMI of 25.86 kg/m2. The background characteristics of
patients and enrolled studies are shown in Table 1.
3.1. Primary outcome: Length of hospital stay
In the meta-analysis of all enrolled studies regarding the length
of hospital stay, 5990 and 3908 patients were enrolled in the group
with and without IS, respectively.5,13,14,32e34 The length of hospital
stay in patients undergoing IS was significantly shorter (1.8 days)
than that in patients not receiving IS in the random-effects model
meta-analysis with high heterogeneity among the studies
(random-effects MD ¼ 1.80, 95% CI ¼ 2.95 to 0.65; I2 ¼ 88%,
Cochran Q p-value <0.01; Fig. 2). In TSA, the cumulative number of
patients did not reach the RIS, but the Z-curves surpassed the
traditional significance boundary and crossed the sequential
monitoring boundaries for the adjusted significance threshold in
favor of IS, suggesting that the current outcome had a conclusive
and robust result. The TSA-adjusted estimate with 95% CI was
MD 1.8 (95% CI 3.34, 0.26; Fig. 3).
3.2. Secondary outcome
3.2.1. PPCs
In the outcome of PPCs, meta-analysis enrolled 6 studies (6202
and 4115 patients in the IS group and without IS group,
respectively).2,5,13,14,32e35 Patients undergoing IS had reduced risk
of PPCs (32%) with statistical significance than patients not un-
dergoing IS in the random-effects meta-analysis with moderate
heterogeneity among studies (random-effects OR ¼ 0.68, 95%
CI ¼ 0.51e0.90; I2 ¼ 31%, Cochran Q p-value for
heterogeneity ¼ 0.18; Fig. 2). In TSA, the cumulative number of
P.-C. Chang, P.-H. Chen, T.-H. Chang et al. Asian Journal of Surgery xxx (xxxx) xxx

Table 1
Basic characteristics of the included studies.

Author Design (Country) Patient Age (mean, Male BMI (mean, Predicted FEV1 Predicted DLCO Surgical approach Extent of resection (type,
year number(n) years) (%) kg/m2) (mean,%) (mean,%) (type, numbers) numbers)

Kong, Retrospective cohort 1427 58.50 43.94 NR NR NR VATS: 1363 Lobectomy: 723
2021 study (China) Thoracotomy: 64 Lobectomy þ segmentectomy:
55
Segmentectomy: 585
Liu, 2019 Retrospective cohort 7549 63.20 59.30 NR NR NR VATS: 1404 Pneumonectomy: 11
study (Taiwan) Thoracotomy: 6145 Lobectomy: 6951
Wedge resection: 587
Malik, RCT (Canada) 387 67.05 49.90 NR 82.50 77.54 VATS: 161 Pneumonectomy: 14
2018 Robotic: 85 Bilobectomy: 12
Thoracotomy: 141 Lobectomy: 233
Segmentectomy: 48
Wedge resection: 80
Lai, 2016 RCT (China) 48 63.56 58.33 NR NR NR VATS: 32 Pneumonectomy: 2
Thoracotomy: 16 Lobectomy: 26
Segmentectomy or wedge
resection: 20
Agostini, RCT (The UK) 180 67.44 47.78 27 76.02 NR VATS: 0 Pneumonectomy: 19
2013 Thoracotomy: 180 Lobectomy: 103
Segmentectomy or wedge
resection: 50
Sleeve resection: 8
Pehlivan, RCT (Turkey) 60 54.43 NR 23.55 71.22 73.81 NR Pneumonectomy: 17
2011 Lobectomy: 43
Varela, Cross-sectional study 639 63.48 NR 25.76 68.94 NR NR Lobectomy: 639
2006 (Spain)
Weiner, RCT (Israel) 32 61.50 71.86 NR 60.81 NR NR Pneumonectomy: 11
1996 Lobectomy: 21

BMI ¼ body mass index; FEV1 ¼ forced expiratory volume in 1 s; DLCO ¼ diffusion capacity of carbon monoxide; VATS ¼ video-assisted thoracic surgery; RCT ¼ randomized
control trial; UK ¼ United Kingdom; NR ¼ no report.

patients exceed the RIS of 5828, and the Z-curves surpassed the
traditional significance boundary in favor of the IS group, sug-
gesting that the outcome of patients undergoing IS that could
reduce PPCs was conclusive and robust (Fig. 3).
3.3. Postoperative pneumonia
In the outcome of postoperative pneumonia, the meta-analysis
enrolled five studies (5305 and 3350 patients with and without
IS, respectively).2,5,13,14,35 Patients undergoing IS had lower risks of
postoperative pulmonary pneumonia (17.9%) with statistical sig-
nificance than patients not undergoing IS in the fixed-effect meta-
analysis with low heterogeneity among studies (fixed-effect
OR ¼ 0.821, 95% CI ¼ 0.677e0.995; I2 ¼ 0%, Cochran Q p-value for
heterogeneity ¼ 0.75; Fig. 2). In TSA, the cumulative number of
patients exceed the RIS of 7,809, and the Z-curves surpassed the
traditional significance boundary in favor of the IS group, sug-
gesting that the outcome of patients undergoing IS had reduced
occurrence of postoperative pneumonia was conclusive and robust
(Fig. 3).
3.4. Postoperative atelectasis
3.5. Meta-regression
Meta-regression analysis examined the association of the
following six variables (publication year, mean age, sex ratio, mean
BMI, preoperative predicted forced expiratory volume in 1 s (FEV1),
and percentage of patients with chronic obstructive pulmonary
disease [COPD]) and all outcomes (Table 2). The meta-regression
analysis showed no difference in the risk ratio of interactions be-
tween all outcomes and overall variables, except between the
outcomes of PPCs and the variable of preoperative predicted FEV1. A
borderline significant benefit was found that the incidence of PPCs
was lower in patients with lower FEV1 undergoing IS compared to
those not undergoing IS (ORs for interaction ¼ 1.057, 95%
CI ¼ 1.000e1.117; p-value ¼ 0.0493; Table 2).
In linear meta-regression interaction analysis, FEV1 significantly
modified the incidence of PPCs in a linear trend. Furthermore, the
ORs of PPCs decreased with decreasing baseline FEV1. As the cut-off
predicted FEV1 was lower than approximately 80%, the upper 95%
CI of PPC incidence ORs equaled to 1 and then the incidence of PPCs
decreased (Fig. 4). Overall, these results indicated that the benefits
of undergoing IS in patients with preoperative predicted FEV1 of
<80% in a linear fashion with decreasing PPCs.

In the outcome of postoperative atelectasis, the meta-analysis 3.6. Sensitivity analysis

enrolled four studies (368 and 766 patients with and without IS,
respectively).2,13,14,34 Patient undergoing IS had no difference in the
risk of postoperative atelectasis than in patients not undergoing IS
in the random-effects meta-analysis with low heterogeneity among
studies (random-effects OR ¼ 0.58, 95% CI ¼ 0.22e1.54; I2 ¼ 24%,
Cochran Q p-value ¼ 0.27; Fig. 2). In TSA, the cumulative number of
patients did not exceed the RIS of 2644, and the Z-curves crossed
neither the traditional significance boundary nor the sequential
monitoring boundary, suggesting the current outcome was incon-
clusive (Fig. 3).
4
We performed the sensitivity analysis with excluding cohort
studies across all the outcomes. Among the analyses excluding
cohort studies, patients undergoing IS had significantly shorter
length of hospital stay (MD ¼ 2.32, 95% CI ¼ 4.24 to 0.39), no
difference in PPCs (OR ¼ 0.80, 95% CI ¼ 0.51e1.24), no difference in
postoperative pneumonia (OR ¼ 0.65, 95% CI ¼ 0.31e1.35), and no
difference in postoperative atelectasis (OR ¼ 1.00, 95%
CI ¼ 0.41e2.43). The result of primary outcomes, length of hospital
stay, remained consistent in the sensitivity analysis (Supporting
P.-C. Chang, P.-H. Chen, T.-H. Chang et al. Asian Journal of Surgery xxx (xxxx) xxx

Fig. 2. Meta-analysis of outcomes regarding the effectiveness of incentive spirometry in patients undergoing pulmonary resection
(A) length of hospital stay (B) postoperative pulmonary complications (C) postoperative pneumonia (D) postoperative atelectasis.
MD ¼ mean difference; CI ¼ confidence interval; I2 ¼ I square statistic; X2 ¼ Cochran's Q test.

Information 7 Fig. S1). In the sensitivity analysis using Bayesian
approach meta-analysis, the results of the Bayesian approach meta-
analysis were consistent with the results of Frequentist approach
(Supporting Information 8 Fig. S2). In the influential analysis using
leave-one-out method, the results revealed that the shift was mini-
mal and the trends of results were consistence to the conclusion,
indicating no potential outlier (Supporting Information 9 Fig. S3).
4. Discussion
To our best knowledge, this is the first meta-analysis to analyze
the effectiveness of using IS for patients undergoing pulmonary
resection to shorten the length of hospital stay and reduce the risk
of PPCs, including significant atelectasis, pneumonia, or respiratory
failure. Our results suggest that IS is an effective modality to
improve the quality of postoperative care for patients after pul-
monary resection, compared with the control group without using
IS; and applying IS has favorable outcomes of shorter length of
hospital stay and lower occurrence of PPCs, which are conclusive
and robust based on our validation via TSA. Moreover, the IS device
is more beneficial for patients with preoperative predicted FEV1 of
<80% than that in others.
Performing pulmonary surgery via general anesthesia with
endotracheal intubation remains one of the solutions to excise the
lesions or obtain an adequate specimen for tissue proof. In which,
muscle relaxant with a relatively higher concentration of oxygen
supplement is routinely used, which might lead to decreased
muscle tone and atelectasis.4 Deep breathing exercise is optimal
chest physiotherapy to re-expand the collapsed alveoli and recruit
lung parenchyma.4 Not only a convenient and inexpensive device,
but IS can also help patients maintain sustained maximal inspira-
tion with a slow and long holding for several seconds via the visual
guidance reciprocally. Since the IS device was originally designed
by Bartlett et al in the 1980s, two different types of IS (volume-
oriented and flow-oriented) are available at present and patients’
compliance is the key element for successful IS training.36,37

5
P.-C. Chang, P.-H. Chen, T.-H. Chang et al.
Fig. 3. Trial sequential analysis (A) length of hospital stay (B) postoperative pulmo-
nary complications (C) postoperative pneumonia (D) postoperative atelectasis.
Poor adherence to using IS might contribute to unsatisfactory
pulmonary rehabilitation; moreover, caution should also be taken
for emphysematous patients with aggressive IS training to prevent
the possible, but rare complication of secondary pneumothorax.38
The patient adherence of IS is fundamentally important in IS
implementation.39e41 Nevertheless, several ongoing RCTs are
currently evaluating the efficacy of IS to reduce PPCs or improve
6
Asian Journal of Surgery xxx (xxxx) xxx
adherence to IS following pulmonary resection.42e44 The findings
of these studies might provide more concrete evidence regarding
the effectiveness of IS and the proper strategy to increase its
adherence.42e44
In contrary to the controversial results for those with upper
abdominal or cardiac surgery, IS itself could reduce PPCs and
related hospital stay after pulmonary resection based on our sys-
tematic review and meta-analysis. Not only the atelectasis due to
reduced muscle tone and higher oxygen concentration during
general anesthesia but also the additional inflammation from
intraoperative pulmonary manipulation and one-lung ventilation
with high pressure over the ventilated lung would lead to increased
concentration of plasma and bronchoalveolar lavage cytokines,
indicating the systemic and pulmonary inflammatory response
during and after pulmonary resection, and could allow patients to
have more PPCs after pulmonary surgery accordingly. Given the
higher vulnerability of PPCs than upper abdominal or cardiac sur-
gery, an active pulmonary rehabilitation program would play a vital
role for patients undergoing pulmonary resection, and IS itself
could be a convenient and inexpensive respiratory rehabilitation
adjunct based on the clinical efficacy of reducing PPCs and short-
ening hospital stay.
Several attempts have been made to identify the significant
preoperative risk factors of PPCs, and numerous risk factors were
identified, such as higher BMI (30 kg/m2), smoking history, COPD,
or American Society of Anesthesiologists score of  3.45 Moreover,
some postulated that the preoperative spirometry test with lower
FEV1 could be a dominant determinant. We also demonstrated that
using IS for patients with low preoperative predicted FEV1 (<80%),
such as COPD, could reduce PPCs after their pulmonary resection
via the meta-regression plot (Fig. 4). In 2018, a retrospective
observational study analyzed 898 patients who underwent lapa-
roscopic surgery and found that lower preoperative forced vital
capacity might predict PPCs, but no FEV1 or FEV1/FVC.46 Another
analysis (2018) from a single high-volume institution suggested
using pulmonary function alone to predict short-term PPCs
following pulmonary resection should be cautiously performed,
and associated parameters, such as FEV1 or diffusion capacity for
carbon monoxide, might not be reliable to identify high-risk pop-
ulations.47 In 2019, a retrospective study with 117 patients under-
going pulmonary resection disclosed that lower preoperative FEV1
was related to postoperative pneumonia, and preoperative cardiac
and pulmonary functions were unable to predict the duration of
hospitalization.48 Although further studies are required to promote
our understanding of preoperative risk factors of PPCs after pul-
monary resection, our meta-regression herein demonstrates the
clinical effectiveness of IS in reducing the incidence of PPCs in the
subgroup of patients with preoperative predicted FEV1 of <80%.
We herein conducted some modifications to increase the
strength of evidence. First, we strictly adhered to standardized
guidelines based on the PRISMA statement to improve the report of
systematic reviews.49 Second, due to the existing heterogeneity of
length of hospital stay and PPCs within our meta-analysis, meta-
regression was performed for parameters from the enrolled studies,
including the publication year, mean age, sex ratio, mean BMI,
preoperative predicted FEV1, and percentage of patients with
COPD) to categorize possible meaningful subgroups. Thus, we
found that the benefit of receiving IS for the group of preoperative
predicted FEV1 of <80% in a linear fashion with decreasing PPCs
(Fig. 4). Third, critical appraisal with the GRADE methodology for
enrolled studies was performed to evaluate the evidence of results.
Nevertheless, several limitations were found within our meta-
analysis. First, though focusing on applying IS for patients
receiving pulmonary resection, the definite timing of using IS (pre-
and postoperatively), the employed protocols, and analgesic
P.-C. Chang, P.-H. Chen, T.-H. Chang et al. Asian Journal of Surgery xxx (xxxx) xxx

Table 2
Meta-regression analysis of heterogeneity for length of hospital stay, postoperative pulmonary complication, postoperative pneumonia and postoperative atelectasis.

Moderators Variables Study ORinteraction (95% CI) P-value

Number (N)

Length of hospital stay Publication year 6 1217 (0.935e1.583) 0.1436

Gender 4 4324.856 (0.071e264620707.639) 0.1365
Age 6 1.156 (0.786e1.700) 0.4604
FEV1 3 1.494 (0.795e2.805) 0.2122
COPD 3 0.987 (0.966e1.009) 0.2402

Postoperative pulmonary complication Publication year 8 1.020 (0.985e1.057) 0.2722

Gender 6 3.009 (0.227e39.822) 0.4032
Age 8 1.055 (0.976e1.140) 0.1787
FEV1 5 1.057 (1.000e1.117) 0.0493
COPD 5 0.996 (0.982e1.010) 0.5653
Smoking status 3 0.324 (1.467 to 2.115) 0.7226

Postoperative pneumonia Publication year 5 1.024 (0.969e1.083) 0.3955

Gender 4 26.784 (0.008e85065.211) 0.4242
Age 5 0.901 (0.721e1.126) 0.3595
FEV1 3 0.996 (0.923e1.075) 0.9232
COPD 4 1.009 (0.987e1.032) 0.4396

Postoperative atelectasis Publication year 4 1.148 (0.999e1.318) 0.0515

Age 4 1.154 (0.897e1.486) 0.2656
FEV1 3 1.126 (0.998e1.269) 0.0534

adherence is crucial for the success of IS. The bedside request from
the physician in charged and the patient's health literacy may have
contribution to the compliance of IS, which were not reported in
the enrolled studies. Lastly, despite the comprehensive searches of
major databases, only a few studies and small patient numbers
were enrolled with different evidence level, patient numbers and
study design (In this study, both RCTs and retrospective study were
included). A paucity of clinical trials that evaluate the benefits of IS
was observed in patients who underwent pulmonary resection. As
a result, a cautious interpretation of results from this meta-analysis
is warranted.

5. Conclusion

As a strategy of pulmonary rehabilitation, IS could be an effec-

Fig. 4. Meta-regression plot of the predicted preoperative FEV1. In the linear meta-
regression interaction analysis, FEV1 significantly modified the incidence of post-
operative pulmonary complications (PPCs) in a linear trend. Furthermore, the odds
ratio of PPCs decreased accompanied by decreasing baseline FEV1. As the cut-off pre-
dicted FEV1 was lower than approximately 80%, the upper 95% CI of PPCs incidence
odds ratio equaled to 1 and then the incidence of PPCs decreased.
CI ¼ confidence interval; FEV 1 ¼ forced expiratory volume in 1 s.
tive approach to shorten the length of hospital stay and reduce the
occurrence of PPCs for patients undergoing pulmonary resection.
Additionally, patients with preoperative predicted FEV1 of <80%
would have a linear fashion with decreasing PPCs using IS. Despite
these striking findings, more researches to explore the application
of this adjunct among patients receiving pulmonary resection are
warranted.
Funding information
None to declare.

management postoperatively remain diverse among these enrolled

studies, which would contribute to the substantial heterogeneity Data availability statements
observed in our analysis (Supporting Information Table S6). Second,
the protocols of care implemented were also different between The data underlying this article are available in the article and in
intervention and control groups and among the enrolled studies. its online supplementary material.
Some studies applied the same protocol between intervention and
control groups, except for IS, but some studies din not include chest Declaration of competing interest
physiotherapy in the control group, which may be confounding
factors. Third, the clinical heterogeneity of included individuals, None to declare.
such as different comorbidities, smoking status, surgical approach,
and extent of resection, was a critical confounding factor that Acknowledgement
should be considered (For example, the postoperative courses were
different between the patients undergoing pneumonectomy, The authors acknowledge the support of Enago (www.enago.tw)
wedge resection or lobectomy/segmentectomy.) Fourth, patient for the English language review.
7
P.-C. Chang, P.-H. Chen, T.-H. Chang et al.
Appendix A. Supplementary data
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.asjsur.2022.11.030.
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