Although pulmonary aspergillosis in non-agranulocytic patients has increased with the development of society, the frequency remains low relative to that in agranulocytic patients. So far, few data are available in non-agranulocytic cases, and most of them are case reports [11–14]. Consequently, more cases and more studies are urgently needed to understand non-agranulocytic pulmonary aspergillosis, so as to provide more references or clues for the diagnosis and treatment of the disease. In this article, 58 cases were reported, and the sample size was rare and higher. IPA is a life-threatening infection in patients mainly with prolonged neutropenia. One clinical challenge of non-agranulocytic IPA cases is the frequently lack of specific clinical features, especially in those without underlying disease . In our study, we roundly compared clinical features between IPA and CPA cases with relevant diagnostic methods commonly used in clinic (Table 2), including microbial cultivation, thoracic CT and serum detection. Some special characteristics for IPA were spotted, such as shorter disease course, frequent infiltrates, special lobe of lung, lower serum albumin level, which might be used for differential diagnosis or auxiliary diagnosis.
The diagnosis gold standard of pulmonary aspergillosis mainly relies on chest imaging, microbial culture and histopathological examination. However, the imaging manifestations are poor in specificity for non-agranulocytic patients, and the phenomenons of “the same disease with different image, and the different disease with same image” exist [16, 17]. As for microbiological and histopathological examination, it is difficult to obtain pathological specimens, positive rate of culture is low, and possibly contaminated and colonized. Therefore, the clinical diagnosis of non-agranulocytic pulmonary aspergillosis is difficult, and it is not always feasible to obtain histo- or cytopathological demonstration of the fungus in order to meet the gold standard . As a non-invasive diagnostic method of pulmonary mycosis, the detection of serum antigens and antibodies has attracted more and more attention. G test and GM test are mainly used for the clinical diagnosis of IPA in agranulocytic patients, but the positive rate of IPA in non-agranulocytic is too low to meet clinical needs [19, 20]. For patients with agranulocytosis or severe immunosuppression, it is difficult for the body to produce an immune response. Accordingly, the detection of specific antibodies against Aspergillus is of little significance. With the increase of non-agranulocytosis and non-immunocompromised host, the diagnostic significance of antibody detection for pulmonary aspergillosis needs to be reevaluated. Serum Aspergillus antibody detection is mainly used in the diagnosis of CPA [21, 22]. Meanwhile, the diagnostic value of Aspergillus antibody is not clear for IPA in non-agranulocytic patients because of varying results . Additionally, diagnosing chronic pulmonary aspergillosis (CPA) is complicated, and there are limited data available . Here, we compared the performances of G test, GM test, Aspergillus IgG antibody by using serum samples from non-agranulocytic patients with underlying pulmonary aspergillosis diseases, and further subdivided IPA and CPA (Table 3A-C). There are few studies on serum Aspergillus IgM antibody, and its significance in the diagnosis of pulmonary aspergillosis is not clear. This study showed that there was no significant difference in serum Aspergillus IgM antibodies between pulmonary aspergillosis, bacterial pneumonia and healthy people. The reasons may include: 1. IgM is the earliest immunoglobulin produced after infection or immunization. It has strong bactericidal and regulatory effects, but its content in blood is low, half-life is short, and it is susceptible to interference factors. 2. Non-granulocyte-deficient hosts may undergo a period of Aspergillus colonization and slow invasion before infection due to their relatively sound immune function. IgM often occurs in the early stage of infection. Therefore, Aspergillus IgG antibody detection is more significant than Aspergillus IgM antibody detection. Our results revealed that Aspergillus IgG antibody reflected the greatest differences among pulmonary aspergillosis (even IPA and CPA subdivision), bacterial pneumonia and healthy group (P < 0.0001) (Table 3 A, B). It was indicated that Aspergillus IgG antibody might a potential diagnostic index for pulmonary aspergillosis in non-agranulocytic patients, and it was further evaluated the performance through ROC curves.
As exhibited in Fig. 1, Aspergillus IgG had notable different in pulmonary aspergillosis (even IPA and CPA subdivision), bacterial pneumonia and healthy group (P < 0.05), and both the specificity and sensitivity were 40.5–95.2% and 58.8–95.2%, and the highest AUC 0.873. Previous studies have shown that the sensitivity and specificity of Aspergillus IgG antibody detection for CPA diagnosis are 75–96% and 97–99% . The specificity and sensitivity were lower than the previous report, it might because that the underlying condition of the research population and the experimental methods are different. Our study further certified that serum Aspergillus IgG antibody had a better performance for distinguish CPA than IPA. From acute invasive infection to chronic consumptive diseases, different types of pulmonary aspergillosis can overlap with each other. Generally, IPA occurs in patients with impaired immune function in varying degrees, while CPA occurs in patients without or with impaired immune function in a lower degree. Therefore, serum Aspergillus antibody levels differ in different types of pulmonary aspergillosis, which is of greater significance to patients with CPA. Above all, we suspected that serum Aspergillus IgG has certain clinical value in the diagnosis of pulmonary aspergillosis in non-agranulocytic patients, especially for non-agranulocytic CPA. Howbeit, it was believed that serum Aspergillus IgG could not replace the traditional isolation and culture of fungi, and should be combined with other diagnostic methods and clinical practice. In addition, further studies were needed to determine the role of Aspergillus specific antibodies in the pathogenesis, diagnosis and treatment of aspergillosis.