Lung cancer continues to be the leading cause of cancer death worldwide and poses to be a threat to human health and economic burden (1). Surgical resection with lymph node dissection remains the optimal curative treatment for resectable lung cancer patients (2). However, surgery directly impairs postoperative respiratory function, and the incidence of postoperative pulmonary complications (PPCs) is as high as 19%-59% due to reasons such as reduced lung volume, weakened respiratory muscle strength and reduced cough efficiency (3). As a result, PPCs not only seriously affect the recovery of cardiopulmonary function, but also prolong the length of hospital stay and increase the cost of hospitalization. Consequently, PPC is one of the leading causes of postoperative death and treatment failure (4).

Several clinical studies have defined risk factors for PPC and consensus risk factors including advanced age, poor lung function status, smoking history, chronic obstructive pulmonary disease (COPD), American Society of Anesthesiologists (ASA) score ≥ 3, and long duration of surgery (5–7). Complications such as postoperative pneumonia, atelectasis and pleural effusion resulting in PPC are mostly caused by the reduced efficiency of cough. As a consequence, this may result in excessive accumulation of pulmonary secretions, increasing the risk of airway obstruction and postoperative respiratory infection (8). Peak expiratory flow (PEF) is usually defined as the maximum airflow rate that a person can exhale over a period of 10 milliseconds, which is a sensitive indicator of coughing ability, reflecting airway resistance and respiratory muscle strength (9). Thus, we hypothesized that preoperative PEF would be an effective indicator to predict PPCs that may arise in surgical lung cancer patients.

In the present study, we conducted a prospective cohort study to investigate the correlation between preoperative PEF and clinical outcomes in patients with lung cancer undergoing anatomic lobectomy or segmentectomy.

Pulmonary complications are the principal factors affecting postoperative rehabilitation of lung cancer patients. In addition to optimizing the perioperative process, key objectives of postoperative rapid lung rehabilitation are the prevention and reduction of postoperative pulmonary complications. Therefore, the first step to promote rapid postoperative recovery of lung cancer patients is to identify and evaluate the risk factors of PPCs that enable reasonable intervention. These risk factors vary due to inconsistent definitions and standards of PPCs in various studies, differences in inclusion and exclusion criteria, ethnic and cultural differences, and treatment of complications. Advanced age, smoking history, COPD and reduced lung function have been consistently identified as risk factors in several studies (14–16). Prior to surgery, examination of pulmonary function aids in assessing the risk of pulmonary surgery (17, 18). The perioperative utility of PEF remains debatable since it is mostly used for the diagnosis and follow-up of asthma (19), with relatively few applications in pulmonary surgery. A significant finding of our study was that low PEF values independently predicted the occurrence of PPCs for lung cancer patients undergoing resection. Both female and male patients with PEF under cutoff value reported adverse clinical outcomes, including higher PPCs rate, prolonged length of stay, and increased hospital costs.

The respiratory muscles force and the severity of airway obstruction are closely related to PEF, which can be measured easily, using a portable mechanical or electronic flow meter that is easy to operate and cost-effective. It can be used at home or by the patient’s bedside and only requires the examinee to exhale quickly and forcefully. The process of detecting PEF is similar to coughing, wherein rapid and powerful contraction of the diaphragm and abdominal muscle increase intra-abdominal pressure. Since abdominal contents are virtually incompressible, the volume of the abdominal cavity changes little. The diaphragm then lifts and compresses the chest cavity, and the intercostal muscle retracts, rapidly reducing the volume of the chest cavity, extruding lungs to form high-pressure gas resulting in rapid exhalation (20). Cough is an effective self-protection method for clearing respiratory secretions, and it is also an essential auxiliary means to eliminate pleural effusion and pneumatosis after lung surgery (8, 21). In recent years, advances in and popularity of thoracoscopic surgery has reduced surgical chest wall trauma, but patients with weak respiratory muscles strength who have had lung resection exhibit clinical issues such as poor coughing ability and efficiency, resulting in sputum retention that leads to pulmonary complications. Additionally, lung cancer patients with COPD reach up to 40%-70%. These patients have hypersecretion of mucous glands in the respiratory tract. Meanwhile, the anesthetic drugs and tracheal intubation stimulation could increase airway secretions. The combined effect of coughing impairment and hypersecretion of airway increases the risk of pulmonary infection (22).

Prior to our study, the correlation between PEF and PPCs was controversial. The British Thoracic Society guideline for the physiotherapy management of the spontaneously breathing patient suggests that when the PEF of patients with neuromuscular disease equal to or less than 270 ml/L, the strategies for assisted airway clearance should be used (23). Kulnik et al. found that the strong cough (with high peak cough flow) could protect from aspiration-related pneumonia in patients with stroke and swallowing problems (24). However, Colucci and colleagues drew a negative conclusion that there was no association between the PEF and PPCs in patients who underwent open upper abdominal surgery (8). Our results showed that the PEF of surgical lung cancer patients with PPCs was significantly lower compared to those without PPCs, and low PEF was an independent risk factor for PPCs in the multivariable analysis. We recommend separate gender-based analysis of PEF since it is significantly affected by skeletal muscle strength. The ROC curve calculated that the optimal cutoff value for predicting PPC by PEF was 320 L/min for male patients and 250 L/min for female patients. If the PEF was lower than the cutoff values, PPCs were significantly likely to occur after surgery, both in male and female patients, compared to patients with PEF higher than the cutoff value. Meanwhile, postoperative hospitalization days and hospitalization costs were significantly higher in the low PEF group, compared to high PEF group. Our study provides a new perspective for screening high-risk patients before lung cancer surgery based on these results. Ishida et al. reported that the thickness of the external oblique muscle might be associated with PEF (20), which may help in improving PEF, through such exercise training modalities as oblique crunch and side bridge. These related exercises could be considered as a part of pulmonary rehabilitation program to enhance the respiratory strength and cough efficiency.

Our prospective cohort study demonstrated that low PEF serves as an independent risk predictor of PPCs for lung cancer patients undergoing lobectomy and segmentectomy. Therefore, considering PEF cutoff value in the perioperative risk assessment for lung cancer patients may be of benefit.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The studies involving human participants were reviewed and approved by Regional Ethics Committee of Sichuan University West China Hospital (No. 2016-121). The registration number was ChiCTR-COC-17010720, which was obtained from the Chinese Clinical Trial Registry. The study adhered to the tenets of the Declaration of Helsinki. The patients/participants provided their written informed consent to participate in this study.

GC, YW, and YL contributed to the conception, design of the study. SC and KZ contributed equally as first authors. All authors contributed to the intellectual conception revision of important intellectual content, and approval of the final version of this manuscript.

This study was supported by Chengdu Science and Technology Support Program (2019-YF05-00373-SN).

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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