In this study, lung cancer patients with untreated COPD were actively treated for COPD. In the COPD intervention group, respiratory function was found to improve 2 weeks after inhalation therapy (especially with the use of UMEC/VI). The measured FEV1 value 3 months after surgery was similar to that before the operation (-0.05 mL vs. -0.25 mL, P = 0.0026) and was significantly higher than the predicted value (+ 0.33 vs. +0.04 mL, P < 0.001). Hence, we conclude that aggressive preoperative intervention for COPD can contribute to maintaining respiratory function. In addition, we found that the evaluated COPD interventions enabled radical and safe lobectomy without missing treatment opportunities in patients with poor respiratory function. In particular, UMEC/VI was found to be more effective than TIO (FEV1 improvement: 160 vs. 7 mL, P = 0.0005).
COPD is the third most prevalent disease worldwide [21]. In COPD, respiratory function worsens gradually and it takes time for symptoms to appear and for the diagnosis to be determined. In Japan, according to a report, 10.9% of people aged > 40 years are reported to have obstructive disorders, 9.4% are diagnosed with COPD, and 90.6% are undiagnosed and untreated COPD patients [9].
COPD is known to affect not only the course of respiratory diseases but also cardiovascular diseases, metabolic diseases, osteoporosis, nutritional disorders, and skeletal muscle dysfunction, resulting in decreased physical activity [1–8]. The degree of physical activity also correlates with prognosis, and lung resection in patients with COPD may further affect prognosis [22]. Moreover, the relationship between perioperative outcomes and COPD is considered poor not only for lung cancer but also for diseases of other organs [23–25]. This study was a relatively short-term (i.e., 3-month) study, and the long-term prognosis in regard to this preoperative intervention is unknown. In contrast, the effects of COPD inhalation therapy itself are well known, and it seems to be of great significance to introduce this intervention preoperatively, even in asymptomatic COPD patients. However, there are negative opinions in the medical community in regard to the costs of interventions for asymptomatic COPD patients. We note that, in this study, if a patient did not wish to continue treatment for COPD, the prescription was discontinued after 3-month study period.
COPD is also a known risk factor for various adverse outcomes in the perioperative period, and there have been various research reports evaluating this topic. Pulmonary resection in patients with COPD is not only associated with postoperative respiratory complications (atelectasis, persistent air leak, pneumonia) but is also associated with arrhythmia [3–8]. However, the frequency of complications is also influenced by the surgical approach. VATS is associated with a lower risk of complications than thoracotomy [10–13]. In this study, there was no significant difference in postoperative complications between the intervention and untreated groups, although the intervention group showed a trend toward fewer complications (32.8% vs. 41.9%, P = 0.49). The amount of bleeding, drainage period, and length of postoperative hospital stay were superior in the intervention group, but it cannot be concluded that this was due to the intervention because of complicating factors such as the comparatively long study period. However, previous reports have shown with certainty that preoperative interventions for untreated COPD help maintain good respiratory function [14–17]. In addition, volume reduction effects may be expected in regard to pulmonary emphysema-type COPD and upper lobectomy [26]; however, expectations are low for surgical procedures other than upper lobectomy. This study evaluated lung volume reduction effects in cases involving excision of the upper lobe, segment six lesions, and other excisions. Nevertheless, the intervention was considered effective.
Among diseases that require differentiation from COPD, it is difficult to distinguish COPD from asthma, and ACO is often diagnosed as a complicated disease [19]. COPD, asthma, and ACO are each treated mainly with airway dilators. Specifically, three drugs are implemented in treating these conditions: long-acting muscarinic antagonists (LAMAs), long-acting beta agonists (LABAs), and inhaled corticosteroids (ICSs). In this study, COPD medications were selected according to disease severity and combined with asthma medications. We assumed that asymptomatic patients may forget to use their drugs. Therefore, we selected drugs that only had to be inhaled once a day. UMEC/VI, as the combination drug, became the first choice among prescribing physicians after gaining approval for clinical use in Japan, because this drug shows a significantly better effect than TIO [27]. In this study, the patients were highly conscientious regarding their prescribed treatment, and there were no cases in which patients forgot to use their inhaler (likely because these patients were planning to undergo surgery). Since we enrolled many elderly male patients with lung cancer, there were concerns about commonly occurring side effects due to LAMAs, particularly dysuria, but none of the patients complained of worsening dysuria.
Moreover, the combination of ICSs and LABAs is recommended for asthma; however, ICS is associated with a risk of complications due to pneumonia [28]. It may therefore be safer not to add ICSs during the perioperative period. However, in patients with low pulmonary function, ICSs can be added in order to enhance respiratory function. In the future, we will investigate the long-term prognosis of lung cancer patients who have undergone COPD treatment intervention, evaluate symptoms, and examine the effects and complications of triple inhalation therapy using LAMAs, LAVAs, and ICSs.
Limitations
The limitations of this study include its retrospective design, involving two institutions, selection of inhaled drugs, diagnosis, and slight lung volume reduction effect. In addition, this work evaluated both TIO and UMEC/VI as interventions because of different hospital-level protocols specified at different time periods during the course of the study. Many other inhaled drugs and inhalation devices are used in clinical practice, and many studies have reported on each of these interventions. Other drugs or inhalation devices may be more effective. However, the purpose of this study was not to evaluate differences between inhaled drugs or devices, but instead to examine the specific effects of preoperative intervention. In cases where upper lobectomy or S6 resection was performed, it is undeniable that not only inhaled drug effects but also lung volume reducing effects were more likely to be observed. This observation was further evaluated in consideration of the resected areas and numbers of resections. The diagnosis was evaluated by spirometry after bronchodilator administration; however, some patients were nonsmokers, thereby making it difficult to rule out asthma [29].