Construction of a checkpoint inhibitor-related pneumonia diagnostic model based on exhaled nitric oxide: a prospective observational study.

Background: Checkpoint inhibitor-related pneumonia (CIP) is a complication of immune checkpoint inhibitors (ICIs) with high mortality. There is still a lack of effective biomarkers to identify CIP. Exhaled nitric oxide (eNO), an airway inflammatory marker, can be obtained by non-invasive methods, but its value in CIP is unknown. The purpose of this study was to investigate the value of eNO in CIP.

Methods: Lung cancer patients who received ICIs were included at Nanfang Hospital, Southern Medical University. Fractional eNO at expiratory flow rates of 50 and 200 mL/s (FeNO50 and FeNO200) were measured. The alveolar concentration of nitric oxide (CaNO) was calculated based on the two-compartment model of airway and alveoli. The optimal CaNO cut-off value was determined by the receiver operating characteristic (ROC) curve. eNO, clinical characteristics, and laboratory tests were analyzed to find out the risk factors for CIP by logistic regression analysis. A multi-indicator model based on best risk factors for CIP was developed and internally validated.

Results: CaNO was significantly elevated in the CIP group [8.1±5.0 vs. 4.9±3.1 parts per billion (ppb), P<0.001]. The area under the curve (AUC) of CaNO to differentiate CIP was 0.728 [95% confidence interval (CI): 0.670-0.786; P=0.001]. The best cut-off value of CaNO was 6.350 ppb. Increased CaNO [odds ratio (OR), 1.30; 95% CI: 1.19-1.43; P<0.001], emphysema reported on chest computed tomography (CT) (OR, 2.54; 95% CI: 1.41-4.60), a small amount of pleural effusion reported on chest CT (OR, 2.48; 95% CI: 1.37-4.50), pre-existing radiotherapy (OR, 3.89; 95% CI: 1.96-7.73) and the lower counts of lymphocyte cell in peripheral blood (OR, 0.69; 95% CI: 0.44-1.10) were independently associated with CIP. The five factors were incorporated into a multi-indicator model with a good predictive accuracy of 0.821.

Conclusions: CaNO may be a new marker for identifying CIP. Increased CaNO, pre-existing radiotherapy and emphysema reported on chest CT, a small amount of pleural effusion reported on chest CT, and lower count of lymphocyte cell in peripheral blood are independently associated with CIP.