DISCUSSION
In this cohort, the female-to-male ratio was highest in the 51-60 years’ group, corresponding to the age of menopause. This may implicate the association of post-menopausal hormonal changes and the formation of SFB, and explain the female predominance, especially in the elderly. Additionally, patients with MSFB without IH on CT images were more likely to have DM, adjacent maxillary odontogenic pathologies, and partial opacification of the sinus compared to those with IH; female predominance was not seen in this patient group.
Studies have shown that SFB mostly occurs in older individuals and has a female predominance.5-8. However, there is no consensus on the explanation for this phenomenon. Our study focused on unilateral MSFB; the impact of age and sex were analyzed. We observed that the female-to-male ratio was highest at 51-60 years of age (2.02). The mean age (SD) at menopause in Taiwan is 50.2 (±4.0) years.18 This suggests that post-menopausal hormonal changes may be associated with the formation of SFB. Although the precise mechanism is not clear, the nasal mucosa is affected by changes in female sex hormones.19 Özler et al. and Gumussoy et al. both reported on the prolongation of nasal mucociliary clearance times in menopausal women.20,21 Impaired mucociliary activity may weaken the defense mechanism of the nasal respiratory epithelium, resulting in failed clearance of airborne fungal spores and formation of SPB.
However, female predominance was not seen in the MSFB without IH group on CT scan images. In this group, patients were more likely to have DM and adjacent maxillary odontogenic pathologies. We hypothesized that both these factors contributed more directly to impair sinonasal ciliary function and increase risk of local infection and/or inflammation in the maxillary sinus than sex hormones; the gender-related difference was therefore diminished in this group.
The SFB is the most common FRS, but its incidence in the general population is unknown. Recent studies have shown that the incidence of SFB is increasing since the mid-2000s.2-5 In this study, we analyzed the data of 713 patients with SFB treated at a single medical center between 2005 to 2018. In 2005, the proportion of SFB cases in the total number of cases of ESS was only 5.5%, but exceeded 10% since 2008. Although these results may not represent the exact annual incidence of SFB in Taiwan, they have reflected an increasing tendency. Improved awareness of the disease, improved diagnostic tools and techniques, broad-spectrum antibiotic use, and aging of the population may have contributed to this phenomenon.5Among these causes, we speculated that the extensive use of CT scans may have been the most important factor. National health insurance pays in full for indicated CT scans in Taiwan since 1995. The database shows that the utilization of CT scans in Taiwan has increased between 1997 and 2008.22 In addition, the popularity of dental implants increased the possibility of discovering asymptomatic MFSB during the pre-procedure evaluation.
In the current study, patients with MSFB without IH on CT scan images were more likely to have DM and adjacent maxillary odontogenic pathologies. Both these clinical features contributed to increased susceptibility to secondary bacterial infections. The clinical symptoms may be more severe, resulting in timely visits to healthcare facilities. The early diagnosis of SFB in this study group may have corresponded to the relatively high proportion of partial opacification of sinuses on CT scan images. We may consider patients with MSFB without IH on CT scan images to have early-stage MSFB. Short disease duration and inadequate fungal metabolic metal deposition resulted in partial opacification of sinuses without IH on CT scan images.
Unlike invasive FRS, SFB usually occurred in immune competent patients. The relationship between SFB and chronic disease has not been confirmed.16 In our study population, the prevalence of DM in MSFB patients was 14.8%, which is higher than the prevalence of 8.35% (2005-2008) and 9.1% (2015-2018), respectively, in the general population in Taiwan.23 This observation suggests that there may be a correlation between DM and the occurrence of SFB. Hyperglycemic acidosis may impair oxidative and non-oxidative mechanisms of phagocyte fungal clearance, a major component of innate human immunity.24 Altered microvascularization of the nasal mucosa in patients with DM also results in decreased mucociliary clearance.25 Post-operative strict glycemic control must be instituted to prevent recurrence.
Aspergillus species are the most frequently encountered organisms in MSFB, only based on histological evidence.11 However, only few studies have evaluated fungal cultures of MSFB because of the low culture-positive rates resulting from poor viability of the fungal hyphae. Liu et al. collected 669 samples from SFB for microbial cultivation, and fungi were discovered in 151 (22.6%) samples. Among them, Aspergillus spp. (72.8%) was the most prevalent fungal species.5 In our study, fungal culture was performed in 211 MSFB cases (171 with IH and 40 without IH); it yielded a 13.74% positivity rate. Aspergillus spp. was the most dominant species (13 in IH group and 1 in non-IH group); however, there was no significant difference in the Aspergillus culture-positivity rate between these two groups. The correlation between the fungal species of MSFB and IH on CT scan images remains unclear. Future studies utilizing next-generation sequencing for identifying fungal species may help clarify the exact mechanism.
This study has several limitations that warrant consideration. First, we only enrolled patients who underwent ESS for SFB; this may have introduced some degree of selection bias. Second, this study had a retrospective case-control design. We defined patients with adjacent odontogenic infection based on CT findings and related medical records; we could not determine cases with endodontic treatment and the disease course of the dental problem. Third, information regarding microbiology was not available for most patients in this study; different species of fungi may demonstrate different CT imaging features. A large-scale prospective study is thus needed for further information.