Abstract
Objective
Fungal sensitization is known to be prevalent in chronic obstructive pulmonary disease (COPD) and it is recognized as a risk factor for severe asthma. However, its relationship to the development of asthmatic features in COPD remains unclear. Because the diagnostic criteria for asthma-COPD overlap (ACO) are not standardized, we focused on the specific asthmatic features that form the diagnostic basis of ACO, namely, blood eosinophilia and recurrent wheezing, to clarify how fungal sensitization contributes to their manifestation in COPD.
Methods
We retrospectively analyzed data from 72 patients with COPD who had specific immunoglobulin E (IgE) levels measured at the Tokyo Medical University Hospital between October 2019 and January 2024. The associations between fungal sensitization and clinical features, including the blood eosinophil count and recurrent wheezing, were analyzed.
Results
Fungal sensitization was observed in 38% of patients. Patients with fungal sensitization had significantly higher blood eosinophil counts than those without fungal sensitization, whereas no significant differences were found for other aeroallergens. Moreover, fungal sensitization was independently associated with both an elevated blood eosinophil count [≥300 cells/mm3; odds ratio (OR) 3.51, 95% confidence interval (CI) 1.21-10.20] and recurrent wheezing (OR 6.93, 95% CI 1.86-25.80).
Conclusion
Fungal sensitization was independently associated with an elevated blood eosinophil count and recurrent wheezing in patients with COPD. These findings suggest that fungal sensitization may play a biological role in the emergence of the asthmatic features that characterize the ACO phenotype in COPD.
Keywords: COPD, fungal sensitization, asthma, eosinophil, wheezing
Introduction
Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease characterized by chronic airway inflammation and airflow limitation resulting from both airway and parenchymal abnormalities, with the emphysema-dominant phenotype being relatively common in Japan. The clinical manifestations of COPD are highly diverse, including variability in the frequency of exacerbations, the extent of emphysema, and susceptibility to chronic airway infections (1). Asthma is also defined as a chronic inflammatory airway disease, and the coexistence of asthma and COPD, referred to as asthma-COPD overlap (ACO), is relatively common (2). ACO is clinically important because patients with this phenotype typically experience more frequent exacerbations and a higher symptom burden than those with COPD alone. Therefore, understanding the biological mechanisms that contribute to the development of ACO is clinically relevant.
Several factors have been proposed to explain the high prevalence of ACO. The underlying reasons are diverse, including overlapping risk factors and shared pathophysiological features between asthma and COPD (3). For example, long-term smokers with underlying asthma may develop a persistent airflow obstruction and emphysematous changes that are characteristic of COPD (4). Conversely, a subset of patients with COPD exhibits type 2 airway inflammation accompanied by clinical features characteristic of asthma (5). These mechanisms are likely to contribute to the frequent occurrence of ACO.
Airway allergy driven by allergen-induced type 2 inflammation is a major cause of eosinophilic airway inflammation in asthma. This mechanism might also contribute to the asthmatic features of COPD. Indeed, allergic sensitization in COPD has been associated with symptoms such as wheezing, nocturnal cough, and frequent exacerbations, which resemble those of asthma (6,7). Among various allergens, fungal sensitization is a known risk factor for severe asthma (8). Moreover, fungal sensitization has been reported to be prevalent in COPD and it is associated with a higher frequency of acute exacerbations (9,10). Furthermore, chronic structural and immunological alterations in the COPD airways may impair the epithelial defense functions and facilitate the access of airborne fungal components to the lower airways. These findings raise the possibility that fungal sensitization may contribute to the manifestation of asthmatic features in COPD and they may explain, in part, the relatively high frequency of ACO observed in clinical settings. However, no study has comprehensively evaluated fungal sensitization in comparison with other common inhalant allergens regarding the asthmatic features that form the diagnostic basis for ACO in COPD.
Although several definitions of ACO have been proposed (4,11,12), the absence of universally accepted criteria makes an ACO diagnosis challenging and it also complicates the investigation of its biological mechanisms. The diagnosis of ACO generally relies on a comprehensive assessment of asthmatic features such as elevated blood eosinophil counts and recurrent wheezing. In particular, in the management of COPD, an elevated blood eosinophil count has been clinically applied not only as a diagnostic marker of ACO, but also as a predictor of inhaled corticosteroid (ICS) responsiveness, with a threshold generally reported at 300-400 cells/mm3 (13,14). Focusing on these individual features rather than the composite diagnosis of ACO may provide more clinically applicable insights and help clarify the contribution of specific factors, such as fungal sensitization, to the asthmatic manifestations in COPD.
This study aimed to investigate whether fungal sensitization contributes to the development of asthmatic features in patients with COPD, with a particular focus on elevated blood eosinophil counts and recurrent wheezing. By focusing on these key features rather than relying on a composite diagnosis of ACO, our study sought to elucidate whether fungal sensitization could serve as a biological link underlying the emergence of the ACO phenotype in COPD. This approach allowed us to assess the clinical and biological significance of fungal sensitization across the real-world spectrum of COPD without being constrained by the heterogeneity and uncertainty of current ACO definitions.
Materials and Methods
Patients and study design
Data from patients diagnosed with COPD according to the Global Initiative for Chronic Obstructive Lung Disease criteria (15), who visited the COPD specialty clinic at Tokyo Medical University Hospital (Tokyo, Japan) and had their specific immunoglobulin E (IgE) levels measured between October 2019 and January 2024, were included in this study and then were retrospectively analyzed. The inclusion criteria were as follows: post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio ＜0.7; age ≥40 years; smoking history ≥10 pack-years; and measurement of specific IgE antibodies for mites, house dust, cedar, moth, Aspergillus, Candida, Alternaria, Cladosporium, and Trichophyton. Patients with allergic bronchopulmonary mycosis were excluded from this study. This study was approved by the Ethics Committee of Tokyo Medical University Hospital (approval number: T2024-0045; approval date: March 26th, 2024). The requirement for informed consent was waived. However, we provided the opportunity to refuse participation in this study by using the opt-out method. The association between specific IgE positivity and clinical parameters, including blood eosinophil count, was evaluated retrospectively. Specific IgE levels were measured using a fluorescent enzyme immunoassay, and a positive result was defined as class 1 or higher. The association between specific IgE positivity and the blood eosinophil count was assessed using laboratory results obtained on the same day. Pulmonary function test results were recorded from the date nearest to the date of the laboratory investigation. Recurrent wheezing episodes were confirmed using medical records. The data of patients other than those in the study population were recorded from the test performed on the date closest to the beginning of the study period. ACO was diagnosed on the basis of the clinical judgment of the attending physician. The diagnosis was made with reference to the key diagnostic elements proposed by the Japanese Respiratory Society (12). The distinction between ACO and non-ACO was used as supplementary stratification rather than as the main analytical framework.
Statistical analysis
Data are expressed as the median and interquartile range (IQR). Differences were considered statistically significant at p＜0.05. Categorical variables were compared using Fisher's exact test. Differences between the groups were analyzed using the Mann-Whitney U test. Correlations were evaluated using Spearman's correlation analysis. A multivariate logistic regression analysis and Firth's penalized logistic regression analysis were performed using the EZR software program (Saitama Medical Center, Jichi Medical University, Saitama, Japan). All other statistical analyses were performed using the Prism software program (GraphPad, San Diego, USA).
Results
Patient characteristics
During the study period, 166 patients with COPD visited a COPD specialty clinic. Of these, 72 had specific IgE levels. Data from these 72 patients [median age, 73.5 years (IQR, 68-79 years); 78% male] with COPD were analyzed. There was no significant difference in the clinical characteristics between the study COPD population and the entire COPD population, as shown in Supplementary material 1.
The median number of pack-years was 54.4 (IQR, 32.8-87.5); and the proportion of current and former smokers was 24% and 76%, respectively. The median FEV1/FVC ratio and FEV1 % predicted were 54.8% (IQR, 41.4-63.7%) and 75.4% (IQR, 58.2-93.8%), respectively. The median blood eosinophil count was 233/mm3 (IQR, 119-425/mm3) and the median proportion of eosinophils was 3.4% (IQR, 1.8-6.1%). Twenty-eight patients had a blood eosinophil count ≥300 cells/mm3. The median IgE level was 125 IU/mL (IQR, 39.9-506.3 IU/mL). Sixty percent of patients tested positive for specific IgE. The antigen with the highest positivity rate was the cedar antigen. Thirty-eight percent of the patients exhibited specific IgE positivity for any fungus. The proportion of patients who were clinically diagnosed with ACO was 33%. The proportion of patients who received ICS on the day of the blood test was 38%. The patient characteristics are summarized in Table 1.
Table 1.
Characteristics of Patients Enrolled in This Study (n=72).
| Age, years | 73.5 (68.0-79.0) |
| Sex, n (%) | |
| Male | 56 (78%) |
| Female | 16 (22%) |
| BMI, kg/m2 | 23.5 (21.2-26.5) |
| Smoking status | |
| Current smoker, n (%) | 17 (24%) |
| Ex-smoker, n (%) | 55 (76%) |
| Number of pack-years | 53.4 (32.8-87.5) |
| Pulmonary function | |
| FEV1/FVC (%) | 54.8 (41.4-63.7) |
| FEV1 %predicted (%) | 75.4 (58.2-93.8) |
| FVC %predicted (%) | 101.9 (86.0-115.2) |
| Blood test | |
| White blood cell count (/mm3) | 6,550 (5,800-8,400) |
| Eosinophil proportion (%) | 3.4 (1.8-6.1) |
| Eosinophil count (/mm3) | 233 (119-425) |
| IgE (IU/mL) | 125 (39.9-506.3) |
| Positive results of specific IgE, n (%) | |
| House dust | 16 (22%) |
| Mite | 19 (26%) |
| Cedar | 26 (36%) |
| Moth | 22 (31%) |
| Aspergillus | 10 (14%) |
| Alternaria | 1 (1%) |
| Cladosporium | 3 (4%) |
| Candida | 15 (21%) |
| Trichophyton | 15 (21%) |
| Clinically diagnosed ACO, n (%) | 24 (33%) |
| Treatment on the day of blood test | |
| ICS, n (%) | 27 (38%) |
| Bronchodilator, n (%) | 53 (74%) |
| OCS, n (%) | 0 (0%) |
ACO: asthma-COPD overlap, BMI: body mass index, FEV1: forced expiratory volume in 1 s, FVC: forced vital capacity, ICS: inhaled corticosteroid, IgE: immunoglobulin E, OCS: oral corticosteroid. Data are presented as median and interquartile range when appropriate.
There was no statistically significant difference in the blood eosinophil count between ICS users [259/mm3 (IQR, 103-450)] and non-users [218/mm3 (IQR, 119-369); p=0.329]. Similarly, the proportion of patients with a blood eosinophil count ≥300 cells/mm3 did not differ significantly between ICS users and non-users (44% vs. 36%, p=0.467). In contrast, patients receiving ICS had a significantly higher frequency of recurrent wheezing (59% vs. 16%, p＜0.001), suggesting that recurrent wheezing is an important feature associated with the clinical diagnosis of ACO and initiation of ICS therapy. Patients with clinically diagnosed ACO experienced recurrent wheezing more frequently than did those without ACO (79% vs. 8%, p＜0.001). However, there was no significant difference in blood eosinophil counts between patients with and without clinically diagnosed ACO [246 cells/mm3 (IQR, 119-541) vs. 221 cells/mm3 (IQR, 120-355), p=0.235]. The detailed characteristics of the patients with and without clinically diagnosed ACO are presented in Supplementary material 2.
Association between positivity for specific IgE and the blood eosinophil level
The total IgE level tended to correlate with both the blood eosinophil count (r=0.217, p=0.067) and proportion (r=0.219, p=0.064). However, the correlation coefficients were not statistically significant. An analysis of the differences in blood eosinophil count and proportion between the patients with and without specific IgE positivity for various antigens revealed that both eosinophil count and proportion were significantly higher in the patients with specific IgE positivity for any fungus, namely Aspergillus, or Trichophyton. However, there were no significant differences in the blood eosinophil counts or proportions between patients with and without specific IgE positivity for house dust, mites, cedar pollen, moths, or Candida spp. (Table 2).
Table 2.
Difference in Blood Eosinophil Levels between Patients with and without Positive Specific IgE Results.
| Blood eosinophil proportion (%) | Blood eosinophil count (/mm3) | ||||||
|---|---|---|---|---|---|---|---|
| Positive | Negative | p value | Positive | Negative | p value | ||
| Any allergen | 3.4 (2.1-6.1) | 2.9 (1.5-5.6) | 0.527 | 241.5 (96.35-429.8) | 226.8 (122.4-366.0) | 0.833 | |
| House dust | 4.0 (2.3-6.8) | 3.2 (1.5-5.6) | 0.280 | 376.4 (150.0-430.5) | 224.5 (112.1-359.9) | 0.166 | |
| Mite | 3.7 (2.2-6.8) | 3.3 (1.5-5.6) | 0.256 | 350.2 (102.5-431.2) | 225.0 (119.2-353.8) | 0.246 | |
| Cedar | 3.6 (2.0-6.8) | 3.2 (1.7-5.1) | 0.367 | 269.3 (114.4-435.9) | 225.4 (116.3-354.2) | 0.368 | |
| Moth | 4.4 (2.1-6.8) | 3.1 (1.6-5.1) | 0.236 | 376.4 (121.1-453.8) | 214.7 (116.3-319.4) | 0.102 | |
| Any fungus | 4.3 (2.4-6.9) | 2.9 (1.5-4.7) | 0.042* | 350.2 (132.0-465.0) | 218.4 (110.5-332.6) | 0.045* | |
| Aspergillus | 6.5 (3.2-8.8) | 3.2 (1.6-4.9) | 0.017* | 412.9 (244.9-668.2) | 221.2 (108.1-373.6) | 0.019* | |
| Candida | 3.5 (2.4-7.7) | 3.3 (1.5-5.6) | 0.287 | 241.5 (132.0-503.2) | 226.8 (110.5-381.3) | 0.380 | |
| Trichophyton | 5.0 (3.1-6.9) | 3.1 (1.5-5.2) | 0.036* | 423.2 (179.8-465.0) | 218.4 (106.3-338.6) | 0.023* | |
| IgE: immunoglobulin E. Data are presented as median and interquartile range when appropriate. *Significant, p<0.05. | |||||||
A multivariate logistic regression model was constructed to assess the confounding effects of age, sex, and current smoking on the relationship between fungal sensitization and blood eosinophil count (≥300 cells/mm3), which has been reported to be the threshold for response to ICS (13,14). After adjusting for these variables, fungal sensitization was independently associated with a blood eosinophil count of ≥300 cells/mm3 [odds ratio (OR): 3.51 (95% confidence interval (CI): 1.21-10.20)] (Table 3). To account for the potential instability of the model due to the limited sample size and number of covariates, we additionally performed Firth's penalized logistic regression analysis, which demonstrated that fungal sensitization remained independently associated with a blood eosinophil count ≥300 cells/mm3 [OR: 3.22 (95% CI: 1.18-9.32)] (Supplementary material 3).
Table 3.
Results from Multivariate Logistic Regression Model for Blood Eosinophil Count ≥300 cells/mm3.
| Variables | OR (95% CI) | p value |
|---|---|---|
| Age | 1.00 (0.95-1.06) | 0.971 |
| Female | 1.18 (0.34-4.12) | 0.796 |
| Current smoking | 1.59 (0.46-5.47) | 0.460 |
| Fungal sensitization | 3.51 (1.21-10.20) | 0.021* |
CI: confidence interval, OR: odds ratio. *Significant, p<0.05.
We also examined the associations between fungal sensitization and the blood eosinophil counts separately in the clinically diagnosed ACO and non-ACO subgroups. In both subgroups, there were no statistically significant differences in the blood eosinophil counts between the patients with and without fungal sensitization [445 (IQR, 203-668) vs. 218 (IQR, 119-279) cells/mm3 in ACO, p=0.204; 259 (IQR, 156-426) vs. 218 (IQR, 118-330) cells/mm3 in non-ACO, p=0.238].
Association between fungal sensitization and recurrent wheezing
Patients with recurrent wheezing episodes were more likely to have specific IgE to at least one allergen (78% vs. 51%, p=0.039). Among the evaluated specific IgE levels, the proportion of patients with positive specific IgE for any fungus was significantly higher in those with recurrent wheezing episodes than in those without (57% vs. 29%, p=0.036) (Table 4).
Table 4.
The Difference of Allergic Sensitization between Patients with and without Recurrent Wheezing.
| Episodes of recurrent wheezing | p value | ||
|---|---|---|---|
| + (n=23) | - (n=49) | ||
| Any allergen, n (%) | 18 (78%) | 25 (51%) | 0.039* |
| House dust, n (%) | 6 (26%) | 10 (20%) | 0.762 |
| Mite, n (%) | 8 (35%) | 11 (22%) | 0.390 |
| Cedar, n (%) | 9 (39%) | 17 (35%) | 0.795 |
| Moth, n (%) | 8 (35%) | 14 (29%) | 0.596 |
| Any fungus, n (%) | 13 (57%) | 14 (29%) | 0.036* |
| Aspergillus, n (%) | 6 (26%) | 4 (8%) | 0.065 |
| Candida, n (%) | 7 (30%) | 8 (16%) | 0.217 |
| Trichophyton, n (%) | 6 (26%) | 9 (18%) | 0.537 |
*Significant, p<0.05.
A multivariate logistic regression model was constructed to assess the confounding effects of age, sex, and current smoking status on the relationship between fungal sensitization and recurrent wheezing. After adjusting for these variables, fungal sensitization and female sex were independently and positively associated with recurrent wheezing [OR: 6.93 (95% CI: 1.86-25.80) and OR: 4.11 (95% CI: 1.03-16.40), respectively] (Table 5). Firth's penalized logistic regression analysis also demonstrated that fungal sensitization and female sex were independently associated with recurrent wheezing [OR: 5.78 (95% CI: 1.80-22.02) and OR: 3.63 (95% CI: 1.01-14.16), respectively] (Supplementary material 3).
Table 5.
Results from Multivariate Logistic Regression Model for Recurrent Wheezing.
| Variables | OR (95% CI) | p value |
|---|---|---|
| Age | 0.97 (0.91-1.03) | 0.280 |
| Female | 4.11 (1.03-16.40) | 0.045* |
| Current smoking | 2.15 (0.55-8.38) | 0.271 |
| Fungal sensitization | 6.93 (1.86-25.80) | 0.004* |
| CI: confidence interval, OR: odds ratio. *Significant, p<0.05. | ||
We further examined the associations between fungal sensitization and recurrent wheezing separately in clinically diagnosed ACO and non-ACO subgroups. Recurrent wheezing was significantly more frequent in the fungal-sensitized patients in the ACO subgroup (100% vs. 58%, p=0.037), whereas no difference was observed in the non-ACO subgroup (6% vs. 7%, p=1.000).
Discussion
Our findings revealed that fungal sensitization was independently associated with an elevated blood eosinophil count and recurrent wheezing episodes in the patients diagnosed with COPD. In contrast, sensitization to non-fungal allergens showed no significant association with either outcome, suggesting that the effect of allergic sensitization varies across allergens, with fungal sensitization exerting a particularly strong influence. This selective association suggests that fungal sensitization may contribute to the manifestation of asthmatic features in COPD through mechanisms that are different from those of other common aeroallergens.
The prevalence of specific IgE positivity for inhaled allergens has been reported to be higher in the patients with COPD than that in healthy controls (9,16). Interestingly, the prevalence and pattern of allergic sensitization to inhaled allergens in patients with COPD have been found to be similar to those in patients with asthma (16). Several genetic and environmental factors contribute to the development of COPD, but not all smokers necessarily develop the disease. Atopy is a known risk factor for COPD (17). The total IgE levels have been shown to be associated with a longitudinal decline in FEV/FVC irrespective of smoking status and asthma (18). Moreover, airway epithelial cell function is impaired in patients with COPD (19). This dysfunction may facilitate the penetration of inhaled allergens through the epithelial layer, thereby contributing to allergic sensitization (20,21). These factors are believed to contribute to the increased prevalence of allergic sensitization to inhaled allergens in COPD patients.
Previous studies have classified pure COPD and ACO and investigated the relationship between allergic sensitization and ACO. It has been reported that patients with ACO have higher total IgE levels and a greater number of patients sensitized to at least one allergen than patients with pure COPD (22). Additionally, a study that more rigorously defined ACO and examined a wider range of allergens found that many patients with ACO were sensitized to mites, suggesting their involvement in the diagnosis and pathophysiology (23).
Fungal sensitization is prevalent in both asthma and COPD patients and it contributes to disease severity in both conditions (8,10,24). Several studies have demonstrated that fungi, particularly Aspergillus species, are frequently isolated from the sputum of patients, even in the absence of overt infections (25,26). These findings suggest that structural and immunological alterations in the COPD airways, including epithelial barrier damage, reduced mucociliary clearance, and impaired innate immunity, may facilitate the entry and persistence of fungal antigens into the lower airways, thereby increasing the likelihood of fungal sensitization. Sensitization to Aspergillus has been reported to be 8.5% in patients with COPD, in contrast to 0% in healthy individuals (24). In one study, Aspergillus sensitization was observed in 18% of patients with COPD, with a higher prevalence among males and a greater frequency of bronchiectasis (27). Furthermore, patients with COPD and Aspergillus sensitization experience more frequent exacerbations, a poorer respiratory function, and a worse prognosis (10). In a study involving a larger population, fungal sensitization was detected in 55.8% of patients with COPD, and patients sensitized to Aspergillus or Penicillium frequently experienced acute exacerbations (9). Although the prevalence of fungal sensitization in this study was higher than that in previous reports, the research was conducted in Southeast Asia, a region with a hot and humid climate, suggesting that the prevalence of fungal sensitization may vary according to the geographical region. Given that the environmental abundance of fungal allergens is influenced by temperature and humidity, the clinical impact of fungal sensitization may differ across regions. Therefore, the prevalence and clinical impact of fungal sensitization should be further investigated in different regions.
In our study, fungal sensitization was uniquely associated with an elevated blood eosinophil count and higher frequency of recurrent wheezing episodes. This finding suggests that fungal allergens may exert a stronger ability to drive type 2 airway inflammation than other inhalant allergens do. Previous experimental studies have demonstrated that fungal components, particularly Alternaria and Aspergillus spp., possess unique immunostimulatory properties that can amplify type 2 airway inflammation. Beyond simply acting as allergens, these fungi release proteases that disrupt epithelial barrier integrity and trigger the rapid release of epithelial-derived alarmins such as interleukin (IL)-33, IL-25, and thymic stromal lymphopoietin (28,29). In parallel, fungal extracts have been shown to function as potent adjuvants, suppressing IL-12 production by dendritic cells while enhancing OX40 L expression, thereby promoting a Th2-skewed immune response (30). Through these combined mechanisms, fungal allergens drive a more vigorous eosinophilic and Th2-polarized response than non-fungal aeroallergens.
As a supplementary analysis, we evaluated the associations separately in clinically diagnosed ACO and non-ACO subgroups. In both subgroups, there were no statistically significant differences in the blood eosinophil counts between the patients with and without fungal sensitization. In contrast, the frequency of recurrent wheezing was significantly higher among the fungal-sensitized patients in the ACO subgroup. This finding indicates that fungal sensitization is associated with recurrent wheezing, even in clinically diagnosed ACO, a condition in which asthmatic features are already prominent, suggesting that fungal sensitization may contribute to the severity of asthma-related symptoms within this phenotype, as observed in typical asthma.
The present study is associated with several limitations. First, its retrospective, single-center design and small sample size may have influenced our results. Second, this study enrolled COPD patients who underwent specific IgE level measurements. In addition, because the study was conducted at a tertiary care facility, the COPD cohort in this study may differ from the general COPD population. However, the proportion of patients clinically diagnosed with ACO was 33% in this study, whereas a meta-analysis investigating the global prevalence of COPD reported that 29.6% of patients with COPD had ACO (2). Regarding asthmatic features, there was likely no significant difference between the general COPD population and the cohort in this study. Third, the number of events per variable (EPV) in the multivariate logistic regression analysis was low, which may compromise the stability of the logistic regression estimates. Nevertheless, our supplementary analysis using Firth's penalized logistic regression analysis yielded consistent results, thereby supporting the reliability of our findings, despite the limited EPV. Finally, because this study included only patients with COPD, we could not directly compare the association between fungal sensitization and asthmatic features with that observed in non-COPD populations, such as smoking asthmatics, healthy smokers, or non-smokers. Therefore, it remains uncertain whether the relationship between fungal sensitization and eosinophilic or asthmatic manifestations observed in this study reflects a COPD-specific mechanism or a general phenomenon of fungal allergies. However, previous studies have shown that fungal sensitization is more prevalent in COPD patients than in the general population, and fungi are potent inducers of type 2 inflammation. These findings suggest that fungal sensitization may exert a particularly strong biological influence on the development of asthmatic features in COPD patients.
This study showed that fungal sensitization is independently associated with specific asthmatic features, namely elevated blood eosinophil counts and recurrent wheezing, in patients with COPD. Given that COPD provides an airway environment that facilitates the entry of fungi into the lower respiratory tract, fungi, which are potent inducers of type 2 inflammation, may therefore have a particularly strong impact on the development of asthmatic features within this population. These findings support a trait-based approach, in which fungal sensitization is considered to be a potentially treatable trait. Future prospective studies should evaluate whether targeting fungal sensitization as a distinct treatable trait with anti-inflammatory therapies, including ICS or biologics, has the potential to improve the clinical outcomes in COPD.
The authors state that they have no Conflict of Interest (COI).
Supplementary Material
This supplementary table compares the clinical characteristics of the analyzed study population with those of the entire COPD population who visited the COPD specialty clinic during the study period.
This supplementary table shows the differences in clinical characteristics between patients with and without clinically diagnosed asthma-COPD overlap.
This supplementary table presents the results of Firth’s penalized logistic regression analyses evaluating factors associated with blood eosinophil count ≥300 cells/mm3 and recurrent wheezing.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
This supplementary table compares the clinical characteristics of the analyzed study population with those of the entire COPD population who visited the COPD specialty clinic during the study period.
This supplementary table shows the differences in clinical characteristics between patients with and without clinically diagnosed asthma-COPD overlap.
This supplementary table presents the results of Firth’s penalized logistic regression analyses evaluating factors associated with blood eosinophil count ≥300 cells/mm3 and recurrent wheezing.