A clinically actionable nomogram for predicting invasive pulmonary aspergillosis: A nested case-control study

Invasive pulmonary aspergillosis (IPA) is a life-threatening infection with high mortality, often misdiagnosed due to non-specific symptoms. The lack of effective early prediction models delays treatment and worsens outcomes. To identify independent IPA risk factors and develop a clinically actionable nomogram for early prediction, we conducted a nested case-control study within a 10-year cohort of 27 100 pulmonary infection patients. The cohort was split into training (70%) and testing (30%) sets. In the training set, 1002 IPA cases (proven or probable, as defined by European Organization for Research and Treatment of Cancer and Mycosis Research Group Education and Research Consortium 2020 criteria) were included, alongside 2004 randomly selected pneumonia controls (1:2 ratio). A nomogram was developed using multivariable logistic regression in the training set and was evaluated by held-out internal validation in the testing set. Model performance was primarily assessed via area under the curve (AUC), calibration, and decision curve analysis (DCA). Nine independent IPA predictors were identified: bronchiectasis (odds ratio [OR]= 7.07), pulmonary tuberculosis (OR = 2.20), diabetes (OR = 2.09), positive serum galactomannan (GM) test (OR = 1.76), mechanical ventilation (OR = 1.74), connective tissue disease (OR = 1.73), positive serum (1,3)-β-d-glucan (G) test (OR = 1.48), sputum (OR = 1.33), and neutrophil-to-lymphocyte ratio (OR = 1.01). The nomogram demonstrated moderate stable discrimination (training AUC: 0.73; testing AUC: 0.75), with excellent calibration (Brier scores: 0.183 and 0.110). DCA confirmed clinical utility across wide risk thresholds. In conclusion, this novel nine-variable nomogram using routine clinical data provides a practical tool for early IPA risk estimation, potentially guiding timely decisions and improving outcomes. External validation is warranted.