Perioperative physiotherapy in patients undergoing lung cancer resection

Abstract

Physiotherapy is considered an important component of the perioperative period of lung resection surgery. A systematic review was conducted to assess evidence for the effectiveness of different physiotherapy interventions in patients undergoing lung cancer resection surgery. Online literature databases [Medline, the Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, SCOPUS, PEDro and CINAHL] were searched up until June 2013. Studies were included if they were randomized controlled trials, compared 2 or more perioperative physiotherapy interventions or compared one intervention with no intervention, included only patients undergoing pulmonary resection for lung cancer and assessed at least 2 or more of the following variables: functional capacity parameters, postoperative pulmonary complications or length of hospital stay. Reviews and meta-analyses were excluded. Eight studies were selected for inclusion in this review. They included a total of 599 patients. Seven of the studies were identified as having a low risk of bias. Two studies assessed preoperative interventions, 4 postoperative interventions and the remaining 2 investigated the efficacy of interventions that were started preoperatively and then continued after surgery. The substantial heterogeneity in the interventions across the studies meant that it was not possible to conduct a meta-analysis. The most important finding of this systematic review is that presurgical interventions based on moderate-intense aerobic exercise in patients undergoing lung resection for lung cancer improve functional capacity and reduce postoperative morbidity, whereas interventions performed only during the postoperative period do not seem to reduce postoperative pulmonary complications or length of hospital stay. Nevertheless, no firm conclusions can be drawn because of the heterogeneity of the studies included. Further research into the efficacy and effectiveness of perioperative respiratory physiotherapy in this patient population is needed.

Pulmonary rehabilitation, Physiotherapy, Perioperative care, Lung cancer

INTRODUCTION

Lung cancer is responsible for the largest proportion of cancer-related deaths around the world [1]. Complete surgical resection with curative intent is the most effective treatment for localized non-small-cell lung cancers. The fact that the disease has usually spread by the time it is discovered means that it is sometimes appropriate to use radiation therapy and chemotherapy in combination with surgery. Unfortunately, only 15% of lung cancers are diagnosed at a localized stage and, thus, are candidates for lung resection, the 5-year survival rate in these cases being 52% [2].

For patients who are candidates for surgery, there is a high risk of postoperative pulmonary complications (PPCs) [3]. PPCs are common after abdominal, cardiac or thoracic surgery and are associated with high rates of mortality, high hospital costs and prolonged length of hospital stay (LOS) [4–7]. Currently, there is no standardized definition for PPCs and complications included in the different studies vary substantially. This explains why PPC rates in the literature range from 2 to 40% [8–11], problems usually considered PPC being: pneumonia, atelectasis, acute respiratory failure, need for reintubation, pulmonary oedema, bronchospasm, pneumothorax and prolonged air leaks.

Several strategies and interventions have been developed in an attempt to reduce the incidence of PPCs: screening for and modification of risk factors, optimization of preoperative status, patient education, intraoperative management and postoperative pulmonary care [12]. Physiotherapy has been regularly utilized in both pre- and postoperative care with the aim of preventing or reducing complications [13, 14] and has recently been recommended by the European Respiratory Society, the European Society of Thoracic Surgeons and the American College of Chest Physicians for providing functional benefits [15, 16].

Several high-quality studies and systematic reviews have assessed the efficacy of different physiotherapy interventions in cardiac and upper abdominal surgery [17–19]. To date, however, there have been few studies investigating the efficacy of physiotherapy interventions in lung cancer resection procedures and, thus, there is limited evidence on which to base treatment recommendations [20].

Therefore, the objective of our study was to review systematically the evidence for the efficacy of perioperative respiratory physiotherapy in patients undergoing pulmonary resection for lung cancer in terms of recovery of pulmonary function, recovery of exercise capacity, incidence of PPCs and LOS.

MATERIALS AND METHODS

Search and study selection

An electronic literature search was performed in MEDLINE, The Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, SCOPUS, PEDro and CINAHL to find potentially relevant randomized controlled trials (RCTs) published until 30 June 2013. The search strategy was designed to ensure maximum sensitivity, and no language restrictions were applied. The search strategy is shown in Table 1.

Table 1:

Search strategy used in this review

MEDLINE (Pubmed)

#1 ‘Lung neoplasms’ [Mesh]

#2 Lung resection surgery

#3 ‘Rehabilitation’ [Mesh]

#4 ‘Physical therapy modalities’ [Mesh]

#5 ‘Exercise’ [Mesh]

#6 Exercise training

#7 ‘Postoperative complications’ [Mesh]

#8 ‘Length of stay’ [Mesh]

#9 (#1 OR #2) AND #3 AND #7

#10 (#1 OR #2) AND #3 AND #8

#11 (#1 OR #2) AND #4 AND (#7 OR #8)

#12 (#1 OR #2) AND #5 AND (#7 OR #8)

#13 (#1 OR #2) AND #6 AND (#7 OR #8)

CENTRAL (The Cochrane Library)

#1 MeSH descriptor Lung Neoplasms explode all trees

#2 Lung Cancer

#3 (#1 OR #2)

#4 MeSH descriptor Rehabilitation explode all trees

#5 Physical therapy

#6 MeSH descriptor Exercise explode all trees

#7 Exercise training

#8 MeSH descriptor Postoperative Complications explode all trees

#9 MeSH descriptor Length of Stay explode all trees

#10 (#3 AND #4)

#11 (#3 AND #5)

#12 (#3 AND #6)

#13 (#3 AND #7)

#12 (#10) AND (#8 OR #9)

#13 (#11) AND (#8 OR #9)

#14 (#12) AND (#8 OR #9)

#15 (#13) AND (#8 OR #9)

EMBASE (Ovid)

#1 lung cancer

#2 lung neoplasms

#3 rehabilitation

#4 physical therapy

#5 exercise training

#6 postoperative complications

#7 length of stay

#8 (#1 OR #2) AND (#3 OR #4 OR #5)

#9 (#8) AND (#6 OR #7)

PEDro

#1 lung cancer

#2 lung neoplasms

#3 rehabilitation

#4 physical therapy

#5 exercise training

#6 postoperative complications

#7 length of stay

#8 (#1 OR #2) AND (#3 OR #4 OR #5)

#9 (#8) AND (#6 OR #7)

Studies were included if they were RCTs, compared 2 or more perioperative physiotherapy interventions or compared 1 intervention with no intervention, included only operable patients undergoing lung cancer resection and assessed at least 2 or more of the following variables: functional capacity parameters, PPCs or LOS. Reviews and meta-analyses were excluded.

Thereafter, a backward search was performed, reviewing reference lists of included articles in search of further relevant citations.

The titles and abstracts of all references obtained in the search were screened. The full text of those that were eligible was assessed against the inclusion criteria independently by two authors (A.R-L., J.S.). Disagreements were resolved by consensus with a third author (I.L-A.).

Risk of bias assessment and data analysis

Following the recommendations of the Cochrane Handbook for Systematic Reviews [21], the risk of bias of the studies included was independently assessed by three reviewers (A.R.-L., J.S. and I.L-A.). Unpublished data were requested when necessary from the authors of the original studies. Disagreements were resolved by consensus. In our analysis, the maximum possible score was 10, given that it was not possible to blind the patient and the therapist administering the intervention and, therefore, results must be considered cautiously. These 2 items were marked as ‘not applicable’. Studies that met ≥5 of the 10 proposed criteria were considered to have a low risk of bias.

The variability in the outcome measures and the heterogeneity of the interventions across the studies meant that it was not possible to conduct a meta-analysis. Therefore, a qualitative analysis was carried out, assessing the methodological quality of the included trials and the consistency of their findings.

RESULTS

Study selection and characteristics

The electronic search yielded 470 references. Studies were classified into 3 different sub-groups according to the stage at which the interventions were carried out: studies in which patients received the intervention preoperatively, those in which the intervention was carried out postoperatively and those that included a combined intervention starting preoperatively and continuing after surgery. Assessment of the title and abstract resulted in 19 studies initially being selected for their potential relevance and significance for inclusion in this review [22–40]. Five assessed a preoperative intervention [22, 23, 30, 32, 34], 8 a postoperative intervention [24–27, 33, 37, 38, 40] and the remaining 6 included a preoperative intervention that continued after surgery [28, 29, 31, 35, 36, 39].

After their full text had been read, 11 studies were excluded: 7 because they were not randomized studies [30–36] and 4 for not providing data on at least 2 of the outcome measures of interest [37–40 ]. A flow diagram of the selection of studies is presented in Fig. 1.

Figure 1:

Flow diagram. RTC: randomized clinical trial.

The remaining 8 studies [22–29] were selected for inclusion in this systematic review. They included a total of 599 patients who underwent anatomical resection with curative intent for lung cancer. Details of the studies and of the interventions are summarized in Tables 2 and 3, respectively.

Table 2:

Characteristics of the studies included

Study	Methods	Participants	Interventions	Outcomes
Preoperative intervention
Morano et al. (Brazil) [22]	RCT The randomization was done in ‘blocks’ of 4, and individual allocations were placed in sealed envelopes Single-blinded study (outcome assessor)	24 patients with: (i) non-small-cell lung cancer resection by open thoracotomy or by VATS; and (ii) previous pulmonary disease, interstitial lung disease or obstructive airway disease, with impaired respiratory function by spirometry 12 patients received pulmonary rehabilitation and 12 received chest physical therapy Final analysis of the postoperative outcome was based on data from 21 patients: 12 from pulmonary rehabilitation arm, 9 from the chest physical therapy arm (3 patients being excluded because of inoperable cancer) 20 patients underwent resection by open thoracotomy and 1 by VATS No significant baseline differences between groups	Treatments administered over a period of 4 weeks, 5 sessions per week Pulmonary rehabilitation group: focused on incremental strength and endurance training through aerobic exercise Chest physical therapy group: included instructions about and practice of techniques for lung expansion	Follow-up: 4 weeks Functional parameters: PPCs LOS
Benzo et al. (USA) [23]	RCT Used central randomization for allocation concealment Single-blinded study (outcome assessor)	Randomized patients with lung cancer resection by open thoracotomy or by VATS (at least lobe) and moderate-to-severe COPD 10 patients received preoperative pulmonary rehabilitation using a customized protocol versus 9 patients in the control group No differences in frequency of open thoracotomies, pneumonectomies or VATS between groups No significant baseline differences between groups Final analysis of postoperative outcome was based on data from 17 patients: 9 from the pulmonary rehabilitation group and 8 from the control group (2 patients being excluded because of inoperable cancer)	Treatments administered over a period of 1 week, 2 sessions a day Control group received no presurgical treatment Intervention group completed a customized protocol based on self-efficacy-based exercise prescription	Follow-up: 1 week PPCs LOS
Postoperative intervention
Agostini et al. (UK) [24]	RCT A randomization in blocks of 4 on postoperative day 1 was performed Single-blinded study (outcome assessor)	184 randomized patients over 18 years old. Patients were excluded if they underwent emergency thoracotomy, procedures involving the mediastinum and chest wall, had planned lung resection via VATS were immobile preoperatively or were unable to perform preoperative spirometry or allocated breathing exercise 88 patients were allocated to the control group and 92 to the intervention group (3 patients being excluded) Significant differences were found in age and American Society of Anaesthesiologists scores between groups (higher in the control group). No differences were observed in other baseline characteristics	Treatments administered from day 1 post-surgery until hospital discharge Control group: thoracic expansion exercises Intervention group: same as controls but with the use of the Coach 2 incentive spirometer	Follow-up: from day 1 post-surgery until hospital discharge Functional parameters: PPCs LOS
Arbane et al. (UK) [25]	RCT The randomization was performed using computer-generated tables Single-blinded study (outcome assessor)	53 patients undergoing lung resection for non-small-cell lung carcinoma were randomized. Patients were excluded if there was no lung resection, if they underwent pneumonectomy and if stay in intensive care unit post-surgery was longer than 48 h Final analysis of the postoperative outcome was based on data from 51 patients: 25 from control group and 26 from the intervention group 49 patients underwent resection by open thoracotomy and 2 by VATS No significant baseline differences between groups	Treatments administered from day 1 post-surgery to day 5 post-surgery, and there was a further 12-week programme of home support Control group: standard medical and/or nursing care Intervention group: same as controls plus a programme that incorporated daily strength and mobility training	Follow-up: from day 1 post-surgery to week 12 after discharge Functional parameters: Quadriceps muscle strength by magnetic stimulation Quality of life PPCs LOS
Ludwig et al. (Germany) [26]	RCT The randomization was performed preoperatively according to year of birth	135 patients: 80 from control group 55 from intervention group The surgical approach was a muscle-sparing thoracotomy in all cases No significant baseline differences between groups	Control group: standard postoperative treatment Intervention: same as controls plus IPPB	Follow-up: from day 1 post-surgery until hospital discharge Functional parameters: PPCs LOS
Reeve et al. (New Zealand) [27]	RCT A randomization table was generated by a computer Single-blinded study (outcome assessor)	76 randomized patients over 18-years old undergoing elective lung cancer resection via open thoracotomy. Exclusion criteria were: not wanting to participate, not understanding written or spoken English, having tumour invasion into chest wall or brachial plexus, having received physiotherapy for respiratory or shoulder problems within the 2 weeks before admission for surgery, having developed PPCs before randomization or remained mechanically ventilated for more than 24 h after surgery 42 participants in the treatment group and 34 in the control group No significant baseline differences between groups, with the exception of a higher proportion of obese patients in the treatment group	Control group: standard medical and/or nursing Intervention group: same as controls plus daily chest physiotherapy	Follow-up: until discharge PPCs LOS
Preoperative intervention that continued postoperatively
Pehlivan et al. (Turkey) [28]	RCT Randomization was performed according to a random-number generator Single-blinded study (outcome assessor)	60 lung cancer operable patients (stage IA to IIIB) without major cardiac morbidity (American Society of Anaesthesiologists II or better) were randomized 30 patients allocated to each group No dropouts reported No significant baseline differences between groups except in mean peak expiratory flow and diffusion lung capacity for carbon monoxide, which were significantly lower in the intervention group	Control group: routine postoperative physical therapy Intervention group: same as controls plus perioperative intensive physical therapy	Follow-up: from 1 week before the planned surgery until discharge Functional parameters: PPCs LOS
Perrin et al. (France) [29]	RCT The randomization was performed using computer-generated numbers and individual allocations were placed in sealed envelopes Single-blinded study (outcome assessor)	39 patients with a preoperative forced expiratory volume in 1 s of <70% of the predicted value scheduled for elective lobectomy for lung cancer Patients were excluded for 1 or more of the following: incisions other than posterolateral thoracotomy, pneumonectomy, previous treatment with NIPSV or continuous positive airway positive pressure, postoperative haemodynamic instability or acute respiratory failure that required endotracheal mechanical ventilation, pregnancy, mental retardation or other severe cognitive disorders, or inability to provide informed consent 18 patients in the control group (without NIPSV) and 14 patients with NIPSV in the study group Final analysis of the postoperative outcome was based on data from 32 patients, 1 patient being excluded from the control group for immediate postoperative acute respiratory failure related to bilateral pneumothorax and 6 patients excluded from the NIPSV group (3 for pneumonectomy and 3 for minor pulmonary resection) No significant baseline differences between groups, except that patients in the study group smoked significantly more than those in the control group	Control group: standard chest physiotherapy treatment Intervention group: same as controls plus NIPSV	Follow-up: from 7 days before surgery to 3 days after surgery Functional parameters: PPCs LOS

RCT: randomized control trial; PPCs: postoperative pulmonary complications; LOS: length of hospital stay; COPD: chronic obstructive pulmonary disease; VATS: video-assisted thoracoscopic surgery; IPPB: intermittent positive pressure breathing; NIPSV: non-invasive pressure support ventilation.

Table 3:

Details of interventions

Study	Intervention group	Control group
Preoperative intervention
Morano et al. (Brazil) [22]   Treatments administered over a period of 4 weeks, 5 sessions per week  Co-interventions: all patients participated in classes about the importance of preoperative and postoperative care, knowledge of surgical process, energy conservation techniques, relaxation and stress management techniques, importance of nutrition and when it was necessary to seek medical attention	Pulmonary rehabilitation group: UE incremental training: 15 repetitions per minute of diagonal movement patterns with an incremental load. LE incremental endurance training on a treadmill of up to 30 min on a treadmill. Exercise intensity was based on 80% of maximum load achieved during treadmill incremental test Inspiratory muscle training: performed daily in sessions of 10–30 min with Threshold Inspiratory Muscle Trainer. Training was incremental until of 60% of their maximal inspiratory pressure was reached. Flexibility, stretching and balance exercises were included as warm-up and cool-down section of each session	Chest physical therapy group: instructions about techniques for lung expansion: sustained maximal inspiration, fractional inspiration with or without a hold, breathing diaphragmatic patterns, pursed lips and flow-based incentive spirometry (no inspiratory muscle training)
Benzo et al. (USA) [23]   Treatments administered over a period of 1 week, 2 sessions a day	Control group + intervention: LE 20 min of endurance training on treadmill or Nu-Step; UE endurance training by arm-R-size exercises or an arm-ergometer or Nu-step Thera-band-resisted strengthening exercises, alternating between UE/LE every day Inspiratory muscle training performed using Threshold Inspiratory Muscle Trainer or P-Flex valve with a goal of 15–20 min of slow breathing per day	Patients received no presurgical assistance The importance of patient’s role in their recovery during the postoperative period (resilience when facing pain, pulmonary toilet exercises, early deambulation, etc.) was emphasized
Postoperative intervention
Agostini et al. (UK) [24]   Treatments administered from day 1 post-surgery until hospital discharge	Control group + incentive spirometry with the Coach 2 device	Thoracic expansion exercises. Participants commenced their exercises on the morning of postoperative day 1 and were encouraged to repeat their allocated breathing exercise independently 10 times hourly during waking hours. Treatment also included supported coughing, early mobilization and active shoulder exercises
Arbane et al. (UK) [25]   Treatments administered from day 1 post-surgery to day 5 post-surgery and a further 12-week programme of home support	Usual care plus twice-daily additional strength and mobility training that comprised walking as able, marching on the spot and recumbent bike exercises working between 60 and 80% of their maximal heart rate for at least 5 min up to a maximum of 10 min per exercise; seated leg raises with incremental load. Within 2 weeks of discharge and once a month for 3 visits in total, patients were followed up at home and encouraged to continue the individualized exercise programme	Usual care included daily routine physiotherapy treatments, airway clearance techniques, mobilization as able and UE activities. They received monthly telephone calls providing only education from the research team
Ludwig et al. (Germany) [26]   Treatments administered from day 1 post-surgery until hospital discharge	Control group + IPPB IPPB of 15–20 mmHg was carried out at least 3 times a day	The rehabilitation programme included pressure expiration, diaphragmatic breathing, postural correction, stretching and shoulder girdle movements. Early mobilization was favoured at the bedside on the first day. Strict pain management was carried out in all patients to not exceed 4 of 10 on a visual pain scale at all times
Reeve et al. (New Zealand) [27]   Treatments administered daily until discharge. Nurse-to-patient ratio: 1/3–4 patients	Control + intervention that comprised deep breathing and coughing exercises, assistance with ambulation, and a progressive shoulder and thoracic cage mobility exercise programme. On discharge from hospital, participants were given an exercise and advice sheet with exercises to continue at home	Medical and nursing usual care included early and frequent position changes in bed, sitting out of bed from the first postoperative day, early ambulation and frequent pain assessment All patients received preoperatively a booklet with advice about exercise following lung surgery that explained the need for postoperative breathing and coughing exercises, early ambulation and shoulder mobility exercises
Preoperative intervention that continued postoperatively
Pehlivan et al. (Turkey) [28]   Treatments administered 1 week before the planned surgery until postoperative discharge Patients who smoked were advised to give up	Control group + intensive physical therapy programme that included chest physiotherapy and walking exercise 1 week before planned surgery that continued with the same frequency during the postoperative period until discharge. Chest physiotherapy was applied twice a day and comprised diaphragmatic, pursed lip and segmental breathing exercises, usage of incentive spirometry and coughing exercises Patients walked on a treadmill up to 3 times a day depending on the patient´s tolerance	Patients were discharged 1 day after mediastinoscopy and recalled the night before the planned resectional surgery. Routine physical therapy was performed postoperatively until discharge. Patients were encouraged to wander in and around the surgical centre throughout the day
Perrin et al. (France) [29]   Treatments administered for 7 days at home before surgery and for 3 days postoperatively After surgery, all patients were placed in the ICU for at least 4 days	Control + NIPSV: NIPSV was provided with a pressure-preset ventilator in a spontaneous mode. Patients were required to perform NIPSV at least 5 times a day 1 h each time. Postoperatively, the same NIPSV regimen was required with the exception of the first 2 h following surgery. Oxygen concentration with NIPSV during the study was 0.21	Chest physiotherapy was performed with the same regime during the preoperative period at home and during the postoperative phase. Patients were instructed to take 4–5 maximal inspirations and then to cough every 3 min for 15 min, and to carry out deep-breathing exercises with the aid of a deep breathing exerciser (Triflo, Chesebrough-Pond’s, Inc.)

UE: upper extremity; LE: lower extremity; IPPB: intermittent positive pressure breathing; ICU: intensive care unit; NIPSV: non-invasive pressure support ventilation.

Assessment of risk of bias

The assessment of the risk of bias is shown in Table 4. Six articles described the randomization and allocation concealment procedure [22, 24–27, 29], whereas Benzo et al. [23] and Turna and co-workers [28] provided these data on request. Seven studies [22–25, 27–29] were single blinded. It was not possible to establish whether the remaining study was blinded, because it was not stated in the article and we failed to contact the authors [26].

Table 4:

Risk of bias of the studies included

Sources of risk of bias		Preoperative intervention			Postoperative intervention			Preoperative intervention that continued postoperatively
		Morano et al. (Brazil) [22]	Benzo et al. (USA) [23]	Agostini et al. (UK) [24]	Arbane et al. (UK) [25]	Ludwig et al. (Germany) [26]	Reeve et al. (New Zealand) [27]	Pehlivan et al. (Turkey) [28]	Perrin et al. (France) [29]
A	1. Was the method of randomization adequate?	Yes	Yes	Yes	Yes	No: according to year of birth	Yes	Yes	Yes
B	2. Was treatment allocation concealed?	Yes	Yes	Yes	Yes	Not described	Yes	Yes	Yes
C	Was knowledge of allocated interventions adequately prevented during the study?
	3. Was the patient blinded to the intervention?	Not applicable	Not applicable	Not applicable	Not applicable	Not applicable	Not applicable	Not applicable	Not applicable
	4. Was the care provider blinded to the intervention?	Not applicable	Not applicable	Not applicable	Not applicable	Not applicable	Not applicable	Not applicable	Not applicable
	5. Was the outcome assessor blinded to the intervention?	Yes	Yes	Yes	Yes	Not described	Yes	Yes	Yes
D	Were incomplete outcome data adequately addressed?
	6. Was the dropout rate described and acceptable?	Yes	Yes	Yes	Yes	Not described	Yes	No	Yes
	7. Were all randomized participants analysed in the group to which they were allocated?	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes
E	8. Are reports of the study free of suggestion of selective outcome reporting?	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes
F	Other sources of potential bias:
	9. Were the groups similar at baseline regarding the most important prognostic indicators?	Yes	Yes	No: >age and ASA score in the control group	Yes	Yes	No: >proportion of individuals were obese in the treatment group	No: <mean PEF and DLCO in intervention group	No: study group smoked significantly more than the control group (P = 0.04)
	10. Were co-interventions avoided or comparable?	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes
	11. Was the compliance acceptable in all groups?	Yes	Yes	Yes	Not described	Yes	Yes	Yes	Yes
	12. Was the timing of the outcome assessment in all groups similar?	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes
Total		10/10	10/10	9/10	9/12	6/10	9/10	8/10	9/10

ASA: American Society of Anaesthesiologists; PEF: peak expiratory flow; DLCO: diffusion lung capacity for carbon monoxide.

The losses to follow-up reported in the original articles were 12.5% [22], 10.5% [23], 2.17% [24], 3.77% [25], 3.94% [27] and 17.95% [29], and Turna and co-workers [28] provided these data on request (20%). The dropout rate in the remaining study was not stated in the article and, as noted above, we were unsuccessful in contacting the authors [26].

Seven studies achieved a score of 8, 9 or 10 out of 10 [22–25, 27–29], whereas one study scored 6 [26] and was considered to have several methodological flaws. There was no disagreement between the reviewers regarding the data extraction or assessment of the risk of bias.

Outcome measures

The findings of the studies included are summarized in Table 5. All studies measured PPCs and LOS, although the criteria used to measure PPCs varied across them. Other outcome measures used were functional parameters, such as the forced expiratory volume in 1 s (FEV₁), percentage of predicted FEV₁, forced vital capacity (FVC), percentage of predicted FVC, maximal inspiratory pressure, maximal expiratory pressure, 6-min walk test (6MWT), shuttle walk test, blood gas measurements [pH, PaCO₂, PaO₂, ventilation/perfusion ratio (V/Q)] and quadriceps strength.

Table 5:

Summary of results

Study	Functional parameters	PPCs	LOS
Preoperative intervention
Morano et al. (Brazil) [22]	Improvement in pulmonary rehabilitation group from baseline to 4 weeks of follow-up: FVC: 1.47L(1.27–2.33L) vs 1.71L (1.65–2.80L); P = 0.02 %ppFVC: 62.5% (49–71%) vs 76% (65–79.7%); P = 0.01 6MWT: 425.5 ± 85.3 vs 475 ± 86.5 m; P = 0.00 MIP: 90 ± 45.9 vs 117.5 ± 36.5 cm H2O; P = 0.00 MEP: 79.7 ± 17.1 vs 92.9 ± 21.4 cm H2O; P = 0.00 No improvements observed in chest physical therapy group	Pulmonary rehabilitation vs chest physical therapy group: Prolonged need for chest tubes: 4.5 ± 2.9 vs 7.4 ± 2.6 days; P = 0.03 PPCs (pneumonia, bronchopleural fistula, bronchospasm, severe atelectasis): 16.7–77.8%; P = 0.01	Pulmonary rehabilitation vs chest physical therapy group: 7.8 ± 4.8 vs 12.2 ± 3.6 days; P = 0.04
Benzo et al. (USA) [23]	No differences observed between groups in shuttle walk test	Intervention vs control group: Prolonged need for chest tubes: 4.7 vs 9.0 days; P = 0.03 Incidence rate of prolonged need for chest tubes (>7 days): 11 vs 63%; P = 0.003	Intervention vs control group: 6.4 vs 11.1 days; P = 0.058
Postoperative intervention
Agostini et al. (UK) [24]	Intervention group vs control group: FEV1 on postoperative day 4: 40 ± 16 vs 41 ± 14%; P = 0.817 %ppFEV1 achieved on postoperative day 4: 72 ± 19 vs 71 ± 21%; P = 0.744	Intervention group vs control group: PPCs: 12.5 vs 15%; P = 0.803 Rescue mini-tracheostomy: 9% (7/80) vs 3% (2/78); P = 0.167	Intervention group vs control group: 6 days (3) vs 5 days (3); P = 0.047 Once higher ASA scores and age of the control group had been taken into account and adjusted for, the difference in LOS was no longer significant (P = 0.186)
Arbane et al. (UK) [25]	Intervention group vs control group: 6MWD: both groups experienced significant deterioration 5 days postoperatively compared with preoperatively, performance then returning to preoperative levels by postoperative week 12, with no differences between groups: 131.6 (101.8) m vs 128.0 (90.7) m; P = 0.89) Quadriceps strength over 5-day in-patient period: 4.0 (21.2) kg vs −8.3 (11.3) kg; P = 0.04 between groups	Intervention group vs control group: PPCs (pneumonia, respiratory complications requiring additional ventilatory support and/or return to high-dependency care) 2 vs 3; P >0.05	Intervention group vs control group: 8.9 days (SD 3.3) vs 11.0 days (SD 8.9); P >0.05
Ludwig et al. (Germany) [26]	Intervention group vs control group: Differences in pre- and postoperative lung function test results between groups were not statistically significant	Intervention group vs control group: PPCs: 27 vs 19%; no significant differences between the 2 groups	Intervention group vs control group: 11 (6–37) vs 11 (5–41) days; differences not statistically significant
Reeve et al. (New Zealand) [27]	Not assessed	Intervention group vs control group: PPCs (not detailed): 4.8 vs 2.9%; P = 1.00	Intervention group vs control group: 6.0 vs 6.0 days; P = 0.87
Preoperative intervention that continued postoperatively
Pehlivan et al. (Turkey) [28]	Pulmonary function test parameters did not differ between two groups after IPT period before operation IPT significantly increased preoperative PaO2 (before IPT: 76.75 ± 9.97 mmHg vs after IPT: 79.01 ± 9.44 mmHg; P <0.001) and decreased PaCO2 (before IPT: 38.09 ± 5.95 vs 36.63 ± 3.85 mmHg; P <0.004)	IPT group vs control group: PPCs: 3.3 vs 16.7% (P = 0.04)	IPT group vs control group: 5.40 ± 2.67 vs 9.66 ± 3.09 days (P <0.001)
Perrin et al. (France) [29]	Intervention group vs control group: Regarding pre- and postoperative periods, the intervention significantly improved pulmonary function parameters (FVC: P = 0.03; FEV1: P = 0.02) and overall changes in arterial blood gases with the patient breathing in room air (pH: P = 0.0003; PaCO2: P = 0.04; PaO2: P = 0.0006)	Intervention group vs control group: (i) PPCs: 14.2 vs 38.9% (P = 0.15)	Intervention group vs control group: (i) 12 ± 1 vs 19 ± 3 days (P = 0.04)

PPCs: postoperative pulmonary complications; LOS: length of hospital stay; FVC: forced vital capacity; %ppFVC: percentage of predicted FVC; 6MWT: 6-min walk test; MIP: maximal inspiratory pressure; MEP: maximal expiratory pressure; FEV₁: forced expiratory volume in 1 s; %ppFEV₁: percentage of predicted FEV₁; ASA: American Society of Anaesthesiologists; HDU: high-dependency unit; ICU: intensive care unit; IPPB: intermittent positive pressure breathing; NIPSV: non-invasive pressure support ventilation; PaCO₂: arterial carbon dioxide tension; PaO₂: arterial oxygen tension; IPT: intensive physical therapy; SD: standard deviation.

None of the studies reported data on adverse effects or events.

RESULTS OF INDIVIDUAL STUDIES

Preoperative interventions

Two studies [22, 23] investigated a preoperative intervention that included a total of 43 patients with a mean age (standard deviation [SD]) of 68.95 years (7.68), of whom 18 (41.86%) were men.

Morano et al. [22] designed a study with 24 preoperative patients comparing 2 different interventions: 1 intervention focused on progressive strength and endurance training through aerobic exercise, while the other was based on breathing exercises for lung expansion. The assessment made at the completion of the 4-week interventions showed that most functional parameters in the group that focused on strength and endurance training improved from baseline to the end of the intervention, whereas no such improvements were seen in the group that was treated with lung expansion techniques. The results also showed that the patients who underwent strength and endurance training had a lower incidence rate of postoperative respiratory morbidity, had a shorter period of need for chest tubes and a shorter LOS than those in the other group.

Benzo et al. [23] reported 2 studies, but the first study had poor recruitment and was finally stopped. Thus, data from the first study have not been included in this review. The second study tested the effectiveness of a preoperative intervention lasting 1 week versus usual care, which acted as a control group, in 19 patients. The intervention group completed a customised protocol involving self-efficacy-based exercise prescription. Compared with the control group, the intervention group needed a chest tube for fewer days and had a lower incidence rate of prolonged chest tubes. However, there were no statistically significant differences between the groups with regard to the incidence of PPCs or LOS.

Postoperative interventions

Four studies [24–27] investigated a postoperative intervention and included a total of 448 patients with a mean age (SD) of 64.67 (10.44) years, of whom 52% were men.

Agostini et al. [24] assessed whether the use of incentive spirometry (IS) enhanced early recovery of lung function or improved patients' outcome following thoracotomy and lung resection. A total of 184 patients were recruited, all of whom were treated with standard postoperative physiotherapy. In addition, a group of patients performed thoracic expansion exercises with a Coach 2 incentive spirometer. The use of this device was not associated with any additional benefits with regard to functional parameters, PPCs or LOS when compared with patients who received only standard postoperative physiotherapy.

In a study with 53 patients, Arbane et al. [25] compared the standard medical and/or nursing care with a programme that also incorporated daily strength and mobility training. The assessment on postoperative day 5 showed that both groups had experienced a significant deterioration in 6MWT performance compared with the preoperative measurement, with no significant differences being observed between groups. Both groups returned to preoperative functional levels by 12 weeks postoperation and no differences were observed between groups in PCCs or LOS.

Ludwig [26] conducted a study involving 135 patients to determine whether intermittent positive pressure breathing (IPPB) can prevent the occurrence of atelectasis and improve postoperative lung function. All patients underwent standard postoperative treatment; in addition, the intervention group was treated with IPPB. Results showed no statistical differences between groups in terms of modification of lung function, development of PPCs or LOS.

Reeve et al. [27] conducted a study of 76 patients comparing the standard medical and/or nursing care with the addition of a daily chest physiotherapy intervention until discharge. The evaluation made at the time of discharge showed no statistically significant differences between groups in LOS or the development of PPCs.

Preoperative interventions that continued postoperatively

A total of 99 patients were included in 2 studies [28, 29]. The mean (SD) age of all 99 participants was 58.96 (6.26) years. Although the distribution of the sample by sex was not described in either of the articles, Pehlivan et al. [28] provided this information on request: in their study, 90% were men.

This study [28] was conducted with 60 operable lung cancer patients where the aim was to investigate the effect of perioperative intensive physical therapy on lung function parameters, PPCs and LOS. The control group received no preoperative intervention. The results showed no statistically significant differences in pulmonary function parameters before surgery between groups. By contrast, the intervention group had a lower incidence rate of PPCs and a shorter LOS than the control group. It is important to note, however, that the groups were not comparable at baseline, the intervention group having lower values of mean peak expiratory flow and lung capacity for carbon monoxide.

In a study with 39 patients, Perrin et al. [29] investigated whether the prophylactic use of non invasive pressure support ventilation (NIPSV) administered perioperatively could reduce the postoperative pulmonary function impairment. Patients received standard treatment either with or without NIPSV. Both during the pre- and postoperative period, the results showed that subjects who underwent NIPSV significantly improved their pulmonary function parameters. Furthermore, those who underwent NIPSV had better overall changes in the arterial blood gases when breathing room air and significantly shorter LOS.

DISCUSSION

The studies included show substantial heterogeneity in terms of the type of interventions evaluated (aerobic training, thoracic expansion techniques, IPPS, IS NIPVS), the setting where interventions were delivered (inpatient, outpatient and home based), the duration of the interventions (ranging from 4 days to 1 week in the preoperative period and from day 1 to 12 weeks post-surgery), the outcomes measured and the definitions of the PPCs included. On this basis alone, even without considering the results, the conclusions should be considered with caution.

The use of a preoperative intervention comprising aerobic exercise in operable patients undergoing lung cancer resection [22, 23, 28] might provide favourable results in terms of improvement in the functional capacity and reduction in postoperative morbidity, but so far data are insufficient to draw any definitive conclusion. All studies reported a notable reduction in postoperative morbidity and LOS favouring the aerobic exercise group, even though in 1 of the studies differences did not reach statistical significance by a small margin (P = 0.058) [23]. These results are in agreement with the findings of previous non-randomized studies that concluded that a preoperative training programme could improve cardiorespiratory fitness in this patient population [32, 34, 40–42]. An improvement in cardiopulmonary function is thought to prepare resectable lung cancer patients for surgery and facilitate better postoperative recovery [43–49]. In fact, exercise tests are increasingly used during preoperative evaluation of lung resection candidates, given that there has been shown to be an association between performance during these tests and postoperative cardiopulmonary morbidity, mortality and costs after lung resection surgery [50–55].

On the other hand, the results suggest that the addition of different interventions to the usual care or to the standard physiotherapy in the postoperative period (IS, IPPS, breathing and coughing exercises) does not improve the results in terms of reduction of PPCs or LOS in patients undergoing lung cancer resection. Consistent with this, studies of lower methodological quality and smaller sample sizes not included in this review also show no improvements in PPCs or LOS, even though improvements in pulmonary function recovery have been reported [33, 37, 38, 56–61]. Therefore, the literature available to date does not support the use of interventions performed only during the postoperative period with the aim of reducing both postoperative complications and LOS. However, because of the highly variable interventions used and the methods utilized to assess them, it is not possible to establish the effectiveness of each individual intervention.

The surgical procedures were in all cases open thoracotomies and, therefore comparable, across the studies, except in 2 studies [one not reporting details [28] and the other describing no differences in the frequency of open or video-assisted thoracoscopic surgery (VATS) between the intervention and the control group [23]]. No studies reported data on adverse effects or events.

It was also observed that in 3 of the 8 studies included, the sex distribution of the sample showed a greater proportion of women than men [22–24] and, in the remaining studies, the proportion still did not reflect the rates of incidence and mortality patterns present in more developed countries, where the incidence rate among males is around twice that in women [62]. Clear differences in the biology, natural history and response to therapy have been found between men and women [63] and some studies have provided evidence to suggest that postoperative morbidity and mortality are lower in women than in men [63–65]. Further investigations that take into account sex-associated differences in the design of trials are required to confirm the preliminary findings of this review.

Only 4 studies took into account the importance of preoperative and postoperative self-care education and knowledge of the surgical process [22, 23, 25, 27]. The patient’s role in their recovery has long been considered a routine and important aspect of care [66, 67] because it is thought that it can improve patient outcomes and satisfaction with the surgical experience [68, 69].

To the best of our knowledge, this is the first systematic review investigating the efficacy of different physiotherapy interventions in lung cancer resection procedures. Previous reviews have limited their analysis mainly to a defined physiotherapy intervention (exercise [41], non-invasive ventilation [70]) or have included together studies that covered samples with different types of cancer [42] or different surgery procedures [57, 71]. A further systematic review studied the role of preoperative physiotherapy interventions in lung resection patients [40], but both RCTs and non-RCTs were included. Despite the differences, our findings are not in disagreement with what has been previously reported by these other reviews [40–42, 57, 70, 71].

Finally, more research is needed to clarify the role physiotherapy can have in the reduction of PPCs after lung surgical resection. PPCs have a significant clinical and economic impact associated with increased morbidity, LOS and associated costs [4–7]. Future research should explore the optimum programmes for different sub-groups of patients undergoing lung cancer resection surgery, the optimum type of exercise training and the optimum setting for its delivery. This knowledge would help to establish guidelines for clinicians and policymakers that would also succeed in increasing health-related quality of life in this patient population.

In conclusion, the most relevant finding of this systematic review is that presurgical interventions based on moderate-to-intense aerobic exercise in patients undergoing lung resection for lung cancer improve functional capacity and reduce postoperative morbidity, whereas interventions performed only during the postoperative period do not seem to reduce PPCs or LOS. Nevertheless, no firm conclusions can be drawn because of the heterogeneity of the studies analysed. This systematic review should encourage researchers to conduct studies to gather stronger evidence for this potentially important intervention.

ACKNOWLEDGMENTS

The authors are grateful to A. Turna [28] for providing the correct data on variables that had been reported incorrectly in his article abstract and to R. Benzo [23] and J.C. Reeve [27] for having provided additional data about their studies.

Conflict of interest: none declared.