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Inhaled COPD Medications Associated With Negative Postoperative Outcomes in Patients With Early-Stage NSCLC


Inhaled chronic obstructive pulmonary disease (COPD) medications prescribed before surgery in patients with early-stage non–small cell lung cancer (NSCLC) were associated with both short- and long-term outcomes.

Inhaled chronic obstructive pulmonary disease (COPD) medications prescribed preoperatively in patients undergoing surgery for early-stage non–small cell lung cancer (NSCLC) were associated with several postoperative outcomes, including decreased overall survival (OS), according to a study published in the Journal of Thoracic Disease.

The researchers explained that surgical resection is the preferred treatment for functionally fit patients with early-stage NSCLC and adequate pulmonary function. Conversely, those with comorbid COPD face surgery-related challenges; patients with NSCLC frequently have comorbid COPD since tobacco use is a known risk factor for both diseases. They explained that severe COPD in patients with early-stage NSCLC increases the risk of postoperative complications and reduces the extent of lung that can be safely resected. Because of this, patients with both COPD and NSCLC require comprehensive preoperative optimization to undergo surgical resection, focusing on smoking cessation, pulmonary rehabilitation, and optimal medical therapy.

Currently, it remains unknown if the number and type of preoperatively prescribed inhaled COPD medications are associated with COPD disease severity, postoperative outcomes, and survival in patients with early-stage NSCLC requiring resection. Consequently, further assessment of COPD using inhaled COPD medications may predict post-operative outcomes and OS in patients with NSCLC undergoing surgery.

To determine this relationship, the researchers used a Veterans Health Administration (VHA) dataset of patients with early-stage NSCLC who underwent surgical treatment from 2006 to 2016. They identified patients with NSCLC by using the International Classification of Diseases (ICD) for Oncology, Third Edition; also, they confirmed surgical treatments using either ICD-9, ICD-10, or Current Procedural Terminology codes.

Inhaled COPD medications | Image Credit: Orawan - stock.adobe.com

Inhaled COPD medications | Image Credit: Orawan - stock.adobe.com

Additionally, the researchers obtained patients' prescriptions using the Corporate Data Warehouse (CDW) Pharmacy Outpatient database, which provides access to specific drug information. In particular, they obtained details of all prescriptions filled by veterans from 1 year before surgery up to 14 days before surgery. Based on the Global Initiative for COPD (GOLD) guidelines, the researchers classified the inhaled COPD medications into categories, namely short-acting beta-2 agonists (SABAs), long-acting beta 2 agonists (LABAs), muscarinic antagonists, and corticosteroids.

The study's primary outcome was OS, which the researchers defined as the time between the date of surgery and all-cause death. They also assessed several secondary outcomes, namely the presence of a major complication, disease-free survival, 30-day mortality, 90-day mortality, 30-day readmission, and a prolonged hospital LOS (length of stay) of 14 days or greater.

The researchers identified 9741 total veterans receiving surgery for early-stage NSCLC; the median age was 67.0 (interquartile range [IQR], 62.3-73.0) years. Most patients were white (n = 8060; 82.7%), male (n = 9383; 96.3%), and smokers at the time of diagnosis (n = 5697; 58.5%).

Of the population, 63.2% (n = 6154) were diagnosed with COPD. The researchers found that increased COPD severity was associated with an increased number of prescribed inhaled COPD medications (P < .00001). Consequently, 9.9% (n = 961) of the study population were prescribed 1 COPD inhaled medication, 15.5% (n = 1510) were prescribed 2 medications, 8.7% (n = 846) were prescribed 3 medications, 9.8% (n = 956) were prescribed 4 medications, and 2.3% (n = 225) were prescribed 5 medications. Conversely, 53.8% (n = 5243) did not receive a prescription for any medications.

Also, in terms of surgery, the researchers determined that 6907 (70.9%) patients underwent lobectomy, 2139 (22%) underwent wedge resection, 540 (5.5%) underwent segmentectomy, and 155 (1.6%) underwent pneumonectomy. Of these patients, 1281 (14.2%) experienced major postoperative complications. More specifically, the rates of 30-day postoperative mortality and readmission were 2.2% (n = 196) and 7.6% (n = 685), respectively. Also, the median hospital LOS was 7 (IQR, 2.5-11.4) days, and the rate of prolonged hospital stay was 15.6% (n = 1332). Lastly, deaths occurred in 5760 patients over a median follow-up of 6.1 (IQR, 2.5-11.4) years; the researchers found 3853 (66.9%) mortality cases to have an ICD diagnosis of COPD.

Overall, patients with a greater number of prescribed inhaled COPD medications had prolonged hospital LOS (adjusted odds ratio [aOR], 1.119; 95% CI, 1.076–1.165), more major complications (aOR, 1.117; 95% CI, 1.074–1.163), increased 90-day mortality rates (aOR, 1.088; 95% CI, 1.013–1.170), and decreased OS (adjusted hazard ratio [aHR], 1.061; 95% CI, 1.042–1.080). Additionally, in patients with preserved lung function (forced expiratory volume in the first second [FEV1] ≥ 80% predicted), a greater number of prescribed inhaled COPD medications was associated with increased 30-day mortality rates (aOR, 1.265; 95% CI, 1.062–1.505), prolonged hospital LOS (aOR, 1.130, 95% CI; 1.051–1.216), more major complications (aOR, 1.147; 95% CI, 1.064–1.235), and decreased OS (aHR, 1.058; 95% CI, 1.022–1.095).

The researchers acknowledged their study’s limitations, one being that their study population consisted primarily of male US veterans. Consequently, more research is warranted to validate if their findings are true for those outside of the VHA, including women. Despite any limitations, the researchers made future suggestions based on their findings.

“This current study provides insight into the potential benefits of medication optimization for COPD prior to elective lung cancer resection," the authors wrote. "Based on our findings, routine assessment of each patient's medications prior to elective NSCLC resection may help identify those patients at risk for adverse outcomes."


Tohmasi S, Eaton DB Jr, Heiden BT, et al. Inhaled medications for chronic obstructive pulmonary disease predict surgical complications and survival in stage I non-small cell lung cancer. J Thorac Dis. 2023;15(12):6544-6554. doi:10.21037/jtd-23-1273

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