Validation of Histoplasmosis Enzyme Immunoassay to Evaluate Suspicious Lung Nodules

Ann Thorac Surg. 2020 Jul 16;S0003-4975(20)31149-8. doi: 10.1016/j.athoracsur.2020.05.101. Online ahead of print.


Background: Granulomas caused by infectious lung diseases can present as indeterminate pulmonary nodules (IPN). This study aims to validate an enzyme immunoassay (EIA) for histoplasma immunoglobulins G and M (IgG, IgM) for diagnosing benign IPN in areas with endemic histoplasmosis.

Methods: Prospectively collected serum samples from patients at Vanderbilt University Medical Center (VUMC, n=204), University of Pittsburgh Medical Center (UPMC, n=71), and University of Cincinnati (UC, n=51) with IPN measuring 6-30mm were analyzed for histoplasma IgG and IgM with EIA. Diagnostic test characteristics were compared to results from VUMC pilot cohort (n=127). A multivariable logistic regression model was developed to predict granuloma in IPN.

Results: Cancer prevalence varied by cohort: VUMC pilot 60%, VUMC validation 65%, UPMC 35%, UC 75%. Across all cohorts, 19% of patients had positive IgG titers, 5% positive IgM, and 3% both positive IgG and IgM. Of patients with benign disease, 33% were positive for at least one antibody. All patients positive for both IgG and IgM antibodies at acute infection levels had benign disease (n=13), with a positive predictive value of 100%. The prediction model for granuloma in IPN demonstrated an area under receiver operating curve 0.84 and Brier score of 0.10.

Conclusions: This study confirmed that histoplasma EIA testing can be useful for diagnosing benign IPN in areas with endemic histoplasmosis in a population at high risk for lung cancer. Integrating histoplasma EIA testing into the current diagnostic algorithm where histoplasmosis is endemic could improve management of IPN and potentially decrease unnecessary invasive biopsies.