Preoperative Pneumococcal and Influenza Vaccination to Prevent Postoperative Pulmonary Infection in Patients Undergoing Lung Resection for Pulmonary Nodules or Lung Cancer

Background: Postoperative pneumonia (POP) is a common complication of lung cancer surgery, with reported incidences of 4% to 24%. It increases mortality, prolongs hospital stay, raises medical costs and worsens long-term prognosis; older patients are at particular risk of severe pneumonia and acute respiratory failure. Surgical stress causes transient perioperative immunosuppression, and influenza virus and Streptococcus pneumoniae act synergistically in causing disease. Observational data suggest that perioperative vaccination reduces postoperative pneumonia after major surgery, but thoracic surgery has rarely been studied. Beyond pathogen-specific antibodies, vaccination may also induce "trained immunity", reprogramming innate immune cells to respond more effectively to non-specific pathogens.

Design: Multicenter, prospective, randomized, open-label, blinded-endpoint (PROBE) trial. Approximately 1278 patients aged 50 years or older scheduled for anatomical lung resection (segmentectomy, lobectomy, sleeve resection, etc.) for pulmonary nodules or lung cancer will be randomized 1:1 to the vaccination group or the no-vaccination group and followed until 180 days after surgery.

Randomization: Computer-generated block randomization sequence produced by an independent statistical team (SAS or R), stratified by site with equal allocation at each site. Allocation is concealed through a central interactive web response system (IWRS) or sealed numbered envelopes. An unblinded team, trained and bound by a confidentiality agreement, performs screening, randomization and collection of vaccination information only. The surgical team and the outcome assessors are blinded to group assignment. No single site may enroll more than 50% of the total sample.

Interventions: Vaccination group: 23-valent pneumococcal polysaccharide vaccine (0.5 mL) plus quadrivalent split-virion influenza vaccine (0.5 mL), administered intramuscularly in separate upper arms at a community health service center or designated vaccination site, completed 14 to 28 days before surgery. Control group: no vaccination and no placebo; surgery is likewise scheduled 14 to 28 days after randomization to balance timing, during which routine preoperative respiratory exercises are permitted. Clinically indicated concomitant treatment (e.g., prophylactic antibiotics, analgesics, nutritional support) is permitted; anti-infective drugs, immunomodulators and potent antitussives/sedatives are recorded.

Primary endpoint definition: Postoperative pulmonary infection is defined using modified US CDC/NHSN criteria and requires all three of: (1) imaging (required): new or progressive infiltrate, consolidation or ground-glass opacity on chest X-ray/CT, after excluding normal postoperative atelectasis, pulmonary edema, pulmonary embolism and tumor progression; (2) at least 1 clinical sign: fever greater than 38 degrees C without other identified cause, WBC 4000/mm3 or less or 12,000/mm3 or more, or altered mental status without other cause in patients aged 70 or older; (3) at least 2 respiratory signs: new purulent sputum/change in sputum character/increased secretions or suctioning; dyspnea, tachypnea (greater than 24/min) or new/worsening cough; rales or bronchial breath sounds; worsening gas exchange (PaO2/FiO2 240 mmHg or less, SpO2 decrease of 5% or more, increased oxygen or ventilator requirement). Findings within postoperative days 3 to 5 are not counted as infection unless persistent or worsening; CRP and procalcitonin trends support the diagnosis. Microbiological evidence confirms but is not required.