Neutrophil-associated Inflammation in Response to Klebsiella pneumoniae Infection Alters Chemotherapy Response in Patients with Non-small Cell Lung Cancer and Chronic Obstructive Pulmonary Disease
Ahmed T. Enad, Anwer Jaber Faisal, Baraa Ahmed SaeedIntroduction:
Non-Small Cell Lung Cancer (NSCLC) often occurs with Chronic Obstructive Pulmonary Disease (COPD), a disorder of chronic inflammation of the airways and associated predisposition to bacterial infections. This prospective multicenter cohort study investigates the association between Klebsiella pneumoniae–related neutrophil-driven inflammation and chemotherapy response in patients with stage III NSCLC and COPD.
Methods:
In this prospective multicenter cohort study, patients with stage III Non-Small-Cell Lung Cancer (NSCLC) and Chronic Obstructive Pulmonary Disease (COPD) were stratified depending on the presence or absence of confirmed infection with K. pneumoniae in the lungs. The chemotherapeutics used in all patients were carboplatin-paclitaxel. Serum interleukin-8 (IL-8) and calprotectin (S100A8/A9) were assessed as indicators of neutrophil recruitment and activation, whereas Carcinoembryonic Antigen (CEA) was assessed as an indicator of chemotherapy response. Biomarkers were assessed over time at baseline and during treatment. K. pneumoniae isolates were tested for biofilm formation ability and MDR phenotype.
Results:
Infected patients had significantly higher baseline levels of IL-8, calprotectin, and CEA than non-infected patients (p < 0.0001). Although chemotherapy was associated with significant decreases in inflammatory biomarkers in both groups, infected patients had persistent elevations throughout treatment (p < 0.0001).
Discussion:
CEA levels in infected patients decreased after the first chemotherapy cycles; no significant reduction was seen during subsequent chemotherapy cycles (p = 0.131).
Conclusion:
K. pneumoniae infection is strongly associated with persistent neutrophil-mediated inflammation and correlates with altered behavior of chemotherapy-related biomarkers in patients with Non-Small Cell Lung Cancer (NSCLC) who also have Chronic Obstructive Pulmonary Disease (COPD).