Bronchogenic carcinoma and secondary aspergillosis--common yet unexplored: evaluation of the role of bronchoalveolar lavage-polymerase chain reaction and some nonvalidated serologic methods to establish early diagnosis

Abstract

Background: More cases of bronchogenic carcinoma have been reported in recent years, and these patients are more prone to secondary aspergillosis. However, the frequency of secondary aspergillosis in bronchogenic carcinoma still has not been defined clearly in the literature.

Methods: The current study population was comprised of 69 patients with bronchogenic carcinoma and 16 healthy controls. Histopathologic examination was done to identify carcinoma cell types and to categorize aspergillosis types. Bronchoalveolar lavage (BAL) fluids were collected for direct fungal examination, culture, Aspergillus polymerase chain reaction (PCR), and galactomannan (GM) detection using a 1-stage immunoenzymatic sandwich microplate assay; and blood samples were collected for fungal serology by double immunodiffusion (DID), enzyme-linked immunosorbent assay (ELISA), and dot blot assay (DBA). The sensitivity, specificity, positive predictive value, and negative predictive value were analyzed for various nonvalidated tests. Twenty-five patients had follow-up data available for an analysis of clinical and diagnostic outcomes.

Results: The cohort included patients with squamous cell carcinoma (n = 47), adenocarcinoma (n = 16), small cell carcinoma (n = 3), large cell carcinoma (n = 2), and undiagnosed type (n = 1), and patients were categorized with definite invasive pulmonary aspergillosis (IPA) (n = 6), probable IPA (n = 17), possible IPA (n = 13), and non-IPA (n = 33). Most patients were in the group ages 45 years to <60 years, and there was a preponderance of men (10.5:1). Cultures from 20 of 69 patients (29%) revealed the growth of Aspergillus species. Anti-Aspergillus antibodies were detected in 26 of 69 patients (37.7%) each by DID and DBA, whereas antibodies were detected in 28 of 69 patients (40.6%) by ELISA. GM was detected in BAL fluids from 25 of 69 patients (36.2%), whereas Aspergillus DNA was detected in 32 of 69 patients (46.4%) by PCR. The sensitivity of PCR and serologic tests (ELISA, DID, and DBA) was 100% for definite IPA, whereas the sensitivity of PCR was comparatively higher than that of serologic tests for probable IPA, possible IPA, and non-IPA.

Conclusions: The current study indicated that there frequently is an association between bronchogenic carcinoma and secondary aspergillosis, and definite IPA and probable IPA are common clinical problems in patients with nonsmall cell lung cancer.