For this retrospective study, we searched the electronic medical record database of our institution to identify 848 patients who had undergone anatomical lung resections regardless of their underlying disease, including lung cancer or metastatic lung tumors, between April 2010 and March 2019 at our hospital. While neither patient age nor preexisting conditions were considered as exclusion criteria, patients who underwent partial resections were not included in this study because their postoperative decreases in lung function were thought to be less substantial than those of patients undergoing anatomical lung resections and because patients who originally had poor lung function and chose to undergo reduction surgery were included. We excluded 414 patients (1) who appear to have low pulmonary function due to narrowing or obstruction of the central airway by the tumor (2) who had undergone previous inhalation therapy for treatment of COPD, asthma, or other respiratory conditions at the time of their initial preoperative examination; (3) whose postoperative follow-up was conducted at another hospital; or (4) whose postoperative respiratory function could not be assessed. Thus, 434 patients were included in this study. The patients placed in the COPD group were potentially unaware of their condition.

All patients in this study underwent respiratory function testing at their initial medical examination. Using these results, patients were classified into either the COPD group (FEV1.0% ≤ 70%) (241 patients) or the non-COPD group (FEV1.0% > 70%) (193 patients). At this time, the severity of COPD was also evaluated based on the GOLD criteria [15].

Regardless of study group, all patients who smoked were counseled regarding smoking cessation beginning at their initial medical examination. In addition, all study patients received preoperative respiratory rehabilitation with an incentive spirometer (COACH 2™; Smiths Medical, Minneapolis, MN, USA). Patients in the COPD group also initiated inhalation therapy with either a LAMA (COPD-LAMA group; 51 patients; April 2010 to July 2012), an ICS/LABA (COPD-ICS/LABA group; 112 patients; August 2012 to January 2016), or a LAMA/LABA (COPD-LAMA/LABA group; 78 patients; February 2016 to March 2020), with modifications in pharmacotherapy regimens as drugs became available. The choice of drug was determined only by the launch date of the drug, and only one drug was used during a specific period. The drug was prescribed according to the results of respiratory function testing at the initial examination and was used until admission for surgery. The dosage and administration volume of the inhalant used in this study were as per manufacturer’s instructions. Therapeutic interventions were stopped just before surgery, and no study-related postoperative therapeutic interventions were performed owing to poor medication compliance because the majority of patients had mild COPD and lacked subjective symptoms.

Additional respiratory function testing was performed immediately before surgery, at 1 month after surgery, and at 6 months after surgery. A flowchart of the protocol used for respiratory function testing and treatment in study patients is presented in Fig. 1.

Study flowchart showing the clinical protocol for performing respiratory function testing of study patients. COPD, chronic obstructive pulmonary disease; FEV1.0, forced expiratory volume in 1.0 s; ICS, inhaled corticosteroid; LABA, long-acting β2-agonist; LAMA, long-acting muscarinic antagonist

Patient age; sex; history of hypertension, diabetes, and/or smoking; duration of the preoperative intervention; vital capacity (VC) and %VC; FEV1.0, %FEV1.0, and FEV1.0%; %DLco at the initial visit, pathological diagnosis (adenocarcinoma, squamous cell carcinoma, and other pathologic type) were compared between the four study groups (non-COPD, COPD-LAMA, COPD-ICS/LABA, and COPD-LAMA/LABA). Initial GOLD stages were also compared between the three COPD subgroups (COPD-LAMA, COPD-ICS/LABA, and COPD-LAMA/LABA).

The amount of change in FEV1.0 (i.e., FEV1.0 after intervention—FEV1.0 before intervention), amount of change in %FEV1.0 (i.e., %FEV1.0 after intervention—%FEV1.0 before intervention), and rate of change in FEV1.0 (i.e., FEV1.0 after intervention/FEV1.0 before intervention) in each group were also compared based on data from the initial visit, preoperative visit, and 1- and 6-month postoperative visits.

For patients undergoing lobectomies (with the exception of those undergoing segmentectomies, combined resections with surrounding organs, bi-lobectomies, bronchoplasties, or pneumonectomies), the amount of change in FEV1.0 and rate of change in FEV1.0 of each group immediately before surgery and at 1 and 6 months after surgery were compared with the FEV1.0 at the initial visit. Additionally, the rate of change in the FEV1.0 at 1 and 6 months after surgery was compared with the FEV1.0 values obtained immediately before surgery in all study groups.

Data are presented as the mean ± standard deviation or the median with interquartile range. Comparisons between two groups were assessed using Student’s t-tests for normally distributed variables. Comparisons between three or four groups were assessed using analysis of variance, with comparisons between each group assessed by the Tukey–Kramer method. A p-value of < 0.05 was considered reflective of statistical significance. The JMP software program, version 11 (SAS Institute Inc., Cary, NC, USA), was used for all statistical analyses.