*3.2. Correlation among Fungi, Clinical Outcome of Asthmatic Patients, and Cytokines*

The association between fungal sensitization and worse asthmatic outcomes has previously been reported. We first examined the relationship between fungi species and clinical outcomes. The correlation analysis results found that no significant relationship between fungi species and asthmatic outcomes, including pulmonary function testing result, ACT score, steroid use, ED visit times, and admission times (Figure 1A). Next, we evaluated the association between fungi species and immune markers. The results demonstrated that IL-6 and IL-17A have a positive relation with most fungi species. IL-6 was especially positively associated with *Aspergillus flavus, Aspergillus niger, Botrytis cinerea, Trichophyton rubrum, Cladosporium herbarum, Aspergillus fumigatus*, and *Candida albicans*. IL-17 had a particularly positive association with *Botrytis cinerea, Saccharomyces*, and *Candida albicans* (Figure 1B). However, only IL-17 was positively associated with ED visit times and FEV1 (Figure 1C).

(**A**)

**Figure 1.** *Cont*.


**Figure 1.** *Cont*.

**Figure 1.** Correlation matrix plot between (**A**) fungus and asthma-related outcomes, (**B**) inflammatory cytokine and asthma-related outcomes, and (**C**) fungus and inflammatory cytokine. \* *p* < 0.05, \*\* *p* < 0.01, \*\*\* *p* < 0.001.

*3.3. Correlation among Botrytis cinerea, Saccharomyces, and Candida albicans and ED Times and IL-17A*

A strong positive correlation was observed between IL-17A and *Botrytis cinerea*, *Candida albicans*, and *Saccharomyces* (*Botrytis cinerea*: r = 0.34, *p* < 0.0001; *Candida albicans*: r = 0.36, *p* < 0.0001; *Saccharomyces*: r = 0.39, *p* < 0.0001). The correlation between IL-17A and ED visit times was positively significant. ED visit times had no significant correlation with *Botrytis cinerea, Candida albicans, and Saccharomyces* (Figure 2).

**Figure 2.** *Cont*.

**Figure 2.** The scatter matrix, histogram, and Spearman rank correlation matrix among (**A**) *Botrytis cinerea*, (**B**) *Saccharomyces*, and (**C**) *Candida albicans* and ED times and IL-17A. \* *p* < 0.05, \*\*\* *p* < 0.001.

*3.4. IL-17A Levels in Asthmatic Patients with and without Fungal Sensitization Grouped by ED Visit Times*

Previous studies indicated that fungal sensitization is associated with increased asthma severity and poorer clinical outcomes. However, we only observed a correlation between IL-17A and sensitized to various fungi (*Botrytis cinerea, Saccharomyces*, and *Candida albicans*), as well as between ED visit times and IL-17A, but not between fungal sensitization and ED visit times. Thus, we further investigated the IL-17A Levels in asthmatic patients with or without fungal sensitization stratified by ED visit times. The results show that patients who were sensitized to *Botrytis cinerea* had higher levels of IL-17 than patients without sensitization to *Botrytis cinerea* (Figure 3A). Patients with *Saccharomyces* had no ED visit event (Figure 3B). Conversely, patients with an ED visit (1 time) sensitized to *Candida albicans* had higher IL-17A compared to patients who were not sensitized, but without significant difference (Figure 3C).

## *3.5. Role of IL-17A in the Associations between Candida albicans and ED Visit Times*

To clarify the role of IL-17A in the relationship between *Candida albicans* sensitization and ED visit times. We investigated the role played by IL-17A in transmitting *Candida albicans* sensitization changes to ED visit times in asthmatic patients using mediation analysis. The total effect of *Candida albicans* on ED visit times was −0.106 (95% CI: −0.454, 0.133). IL-17A had a significant positively mediating effect (ME) on the association between *Candida albicans* and ED visit times (ME = 0.0175, 95% CI: 0.012, 0.528) (Figure 4).

**Figure 3.** *Cont*.

**Figure 3.** Comparing IL-17A levels in asthmatic patients with fungal sensitization and nonsensitization grouped by ED visit times. *Botrytis cinerea* (**A**); *Saccharomyces* (**B**); *Candida albicans* (**C**). \* *p* < 0.05.

**Figure 4.** The contribution of IL-17A for the association between *Candida albicans* and ED visits. Single mediation models and regression coefficients (β), with 95% confidence intervals (95% CI) examining potential mediators of IL-17A.
