The Role of Pulmonary Function Tests in Differentiating Non-Infectious Pulmonary Complications in Patients with Hematological Malignancies

Background: Differentiating between non-infectious pulmonary complications (NIPCs) and infectious pneumonia (IP) in patients with hematological malignancies is a critical yet challenging clinical dilemma due to overlapping clinical and radiological presentations. The diffusing capacity for carbon monoxide (DLCO) in pulmonary function tests can indicate pathophysiological differences and act as a discriminative measure. This study aimed to evaluate the diagnostic utility of pulmonary function tests (PFTs) in this differential diagnosis.

Methods: This retrospective cohort study included 245 hospitalized patients with hematological malignancies and newly developed pulmonary infiltrates at the Fourth Affiliated Hospital of Soochow University (Suzhou Dushu Lake Hospital) between January 1, 2021 and December 31, 2025. Patients were classified into NIPC (n=78) and IP (n=167) groups based on comprehensive, multidisciplinary diagnostic criteria. PFT parameters were measured within 48 hours of admission. Multivariate logistic regression and receiver operating characteristic (ROC) curve analyses identified independent predictors and assessed diagnostic performance.

Results: The NIPC group demonstrated a significantly lower percent predicted DLCO compared to the IP group (52.4% ± 14.8% vs. 68.9% ± 16.3%, P < 0.001). Other PFT parameters, including forced vital capacity (FVC), FEV1/FVC ratio, and total lung capacity (TLC) , showed no significant differences. In multivariate analysis, DLCO was an independent predictor for NIPCs (Odds Ratio [OR] = 0.92, 95% Confidence Interval [CI]: 0.90-0.95, P < 0.001). The area under the ROC curve (AUC) for DLCO was 0.84 (95% CI: 0.79-0.89). At an optimal cutoff value of 58% predicted, DLCO yielded a sensitivity of 80.8% and specificity of 76.0%. The combination of DLCO with the absence of fever further improved diagnostic accuracy (AUC = 0.88).

Conclusions: PFTs, specifically DLCO, play a crucial and independent role in differentiating NIPCs from IP in patients with hematological malignancies. A severely impaired DLCO is a strong indicator of a non-infectious etiology. Integrating PFTs into the initial diagnostic workup may facilitate earlier and more accurate differentiation, guiding appropriate therapeutic decisions.