Pei-Wen Wu,1– 3 Po-Hung Chang,1 Chi-Che Huang,1,2 Ta-Jen Lee,1,2,4 Chien-Chia Huang1– 3

1Division of Rhinology, Department of Otolaryngology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan; 2School of Medicine, Chang Gung University, Taoyuan, Taiwan; 3Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 4Department of Otolaryngology, Xiamen Chang Gung Hospital, Xiamen, People’s Republic of China

Correspondence: Chien-Chia Huang, Division of Rhinology, Department of Otolaryngology, Chang Gung Memorial Hospital, LinKou Branch, No. 5, Fu-Shin Street, Kweishan, Taoyuan, 333, Taiwan, Tel +886-3-3281200ext.8466, Fax +886-3-3979361, Email [email protected]

Purpose: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a persistent inflammation of the sinuses accompanied by the formation of obstructive nasal polyps, which may lead to symptoms of common mental disorders, including anxiety and depression, as a result of long-term discomfort. This study aimed to investigate the associations of severe CRSwNP, with anxiety and depression.
Methods: Adult patients with severe primary diffuse CRSwNP scheduled to undergo sinus surgery and healthy control participants were prospectively enrolled. Clinical data were collected and the Sinonasal Outcome Test-22 (SNOT-22), Beck Depression Inventory-II (BDI-II), and Beck Anxiety Inventory (BAI) were used to evaluate quality of life.
Results: Ninety-six patients with CRSwNP and 40 controls were enrolled in this study. Patients with CRSwNP exhibited significantly higher BAI scores than controls. However, BDI-II scores were not significantly different. Among the patients with CRSwNP, 32.3% exhibited possible anxiety, defined as a BAI score > 7. Comorbid asthma, SNOT-22 score, and blood eosinophil percentage were significant factors associated with anxiety in patients with CRSwNP in univariate logistic regression analysis and comorbid asthma and SNOT-22 remained statistically significant in multivariable analysis. An SNOT-22 score > 57 was the optimal cutoff value for identifying patients with possible anxiety.
Conclusion: A significant proportion of patients with CRSwNP exhibited anxiety symptoms. Comorbid asthma, SNOT-22 score, and blood eosinophil percentage were significant factors associated with the presence of anxiety. These findings emphasize the importance of screening for psychological symptoms and potentially integrating psychological assessments and interventions in the care of high-risk patients.

Keywords: anxiety, beck anxiety inventory, beck depression inventory II, chronic rhinosinusitis with nasal polyp, emotion, function, 22-item sino-nasal outcome test

Introduction

Chronic rhinosinusitis (CRS) is one of the most common chronic diseases, characterized by persistent inflammation of the sinuses and nasal mucosa for more than three months.1 CRS is classified into two main phenotypes: CRS with (CRSwNP) and without nasal polyps (CRSsNP).2 CRSwNP account for approximately one-fifth of all CRS cases.2,3 Patients with CRSwNP tend to experience a high symptom burden, reduced quality of life, poor response to treatment, and a high rate of postoperative recurrence.1–3

Depression and anxiety are the two most common mental health conditions in clinical practice.4,5 Previous studies have reported that the prevalence of anxiety and depression may rise to 20–36% in patients with CRS.6–9 Furthermore, comorbid depression and anxiety in CRS may seriously affect daily quality of life, work productivity, social functioning,10 and treatment response in these patients.11,12 The influence of mental health conditions on disease burden and therapeutic outcomes may explain the poor correlation between objective measures, such as nasal endoscopy and sinus computed tomography (CT) scores, and subjective patient-reported sinus symptoms.13

Most previous studies on mental health conditions in patients with CRS have focused on the prevalence of anxiety and depression.8 Few have explored risk factors for anxiety and depression or evaluated the possible interaction between different subdomains of quality of life in patients with CRS.9 Furthermore, the disease burden in patients with CRSwNP has been considered greater than that in patients with CRSsNP.3 Comprehensive evaluation of subjective symptoms and quality of life in patients with CRSwNP has become increasingly important, particularly in an era when an increasing number of biological agents are being introduced for CRSwNP treatment.14

In the present study, we aimed to evaluate the prevalence of possible anxiety and depression, examine the association between these psychiatric measurements and quality of life, and identify risk factors for possible anxiety in patients with CRSwNP. This approach may help clinicians better evaluate subjective symptoms to determine the severity of sinonasal inflammation in patients with CRSwNP and provide optimal therapeutic strategies.

Materials and Methods

The research team continued enrolling adult patients (aged ≥18 years) with diffuse primary CRSwNP who were scheduled for endoscopic sinus surgery between January 2020 and April 2023 for clinical and laboratory analysis. CRSwNP was diagnosed according to the European Position Paper on Rhinosinusitis and Nasal Polyps 2020 (EPOS2020) criteria.1 Patients had previously failed conservative medical therapy, including intranasal corticosteroids and nasal douches. Patients with (1) sinonasal neoplasms, (2) concomitant immunological disorders or mucociliary dysfunction, or (3) a history of immunosuppressive treatment before recruitment were excluded. Patients who visited the otolaryngology outpatient clinic for follow-up of a completely resolved nasal problem, such as those three months after surgery for nasal septal deviation, were recruited as the control group after evaluation using a nasal symptom questionnaire and endoscopic examination. The Institutional Review Board of Chang Gung Memorial Hospital approved this study (IRB numbers: 202002219A3, 202102257A3, 202202075A3, and 202400485A3) and all participants provided informed consent prior to enrollment. All research was performed in accordance with the relevant guidelines and regulations of the Institutional Review Board and the Declaration of Helsinki. This study uses and adherences to RECORD guidelines. Previous studies determined the minimal clinically important difference of Taiwan Smell Test and risk factors of postoperative residual sinus inflammation in patients with CRSwNP.15,16 The current study would like to evaluate anxiety and depression in patients with CRSwNP.

Clinical characteristics and demographic data of the participants were collected. Laboratory data, including peripheral blood eosinophil percentages, total serum immunoglobulin E levels, and serum eosinophil cationic protein (ECP) levels, were collected. Nasal polyp size was assessed using the nasal polyp scoring system, with scores ranging from 0 to 4 for each side of the nasal cavity, as previously described.17 The Lund-Mackay score was used to quantify radiological severity on CT images in patients with CRSwNP.18

Nasal symptoms and quality of life were evaluated using the 22-item sinonasal outcome test (SNOT-22) questionnaire. The SNOT-22 was further categorized into five domains, including nasal, ear/facial, sleep, functional, and emotional symptoms, as described in a previous study (Table S1 in Supplementary Material).19 Validated instruments, including the Beck Depression Inventory-II (BDI-II)20 and Beck Anxiety Inventory (BAI),21 were used to evaluate the symptoms of anxiety and depression in the participants. Both BDI-II and BAI consist of 21 items, each scored from 0 to 3, corresponding to the absence of symptoms and presence of severe symptoms, with a total score ranging from 0 to 63. A total BDI-II score ≤ 13 and BAI score ≤ 7 were considered indicative of normal.22,23

Statistical Analysis

Data are presented as the mean ± standard deviation (SD). GraphPad Prism 5 (GraphPad Software, San Diego, CA, USA) and SPSS Statistics v27.0 (IBM Corp., Armonk, NY, USA) were used for the statistical analyses. Categorical variables were compared using the χ2 test, whereas continuous variables were compared using the Mann–Whitney U-test. Correlations between questionnaire scores were determined using Spearman correlation coefficient (rs). Logistic regression analyses were performed to evaluate the association between anxiety and clinical variables. Receiver operating characteristic (ROC) curves were generated, and the area under the ROC curve (AUC) was calculated to determine the cutoff value for predicting possible anxiety. Statistical significance was set at p < 0.05.

ResultsClinical Characteristics of Participants

A total of 96 adult patients with bilateral CRSwNP (66 males, 30 females) and 40 controls were enrolled in this study. The demographic characteristics of patients with CRSwNP and controls are presented in Table 1 and Table S2 in Supplementary Material, respectively. Among the patients with CRSwNP, 20 (20.8%) had comorbid asthma and 26 (27.1%) had a history of previous sinus surgery. The mean nasal polyp, Lund-Mackay, and SNOT-22 scores of patients with CRSwNP were 5.6 ± 1.6, 17.3 ± 4.0, and 49.3 ± 20.7, respectively. There was no significant difference between patients with CRSwNP and the control group in terms of age and sex (p = 0.539 and 0.693, respectively). There were 31 (32.3%) and 8 (20%) individuals who experienced possible anxiety, defined as a BAI score >7, in the CRSwNP and the control groups, respectively (p = 0.047). Additionally, 12 (12.5%) and 2 (5.0%) individuals experienced possible depression, defined as a BDI-II score >13, in the CRSwNP and control groups, respectively (p = 0.232).

Table 1 Clinical Characteristics of Participants with Chronic Rhinosinusitis and Nasal Polyp

Comparison of Depression and Anxiety Between CRSwNP Patients and Controls

The total BAI score was significantly higher in patients with CRSwNP than in controls, whereas the BDI-II scores did not differ significantly between the two groups (Figure 1a). Specifically, patients with CRSwNP had significantly higher scores on the BAI items assessing fear of the worst happening, dizziness, lightheadedness, feeling of choking, and difficulty breathing than the controls (Table 2). In addition, patients with CRSwNP had significantly higher scores on the BDI-II terms assessing loss of energy, changes in sleeping patterns, concentration difficulties, tiredness or fatigue, and loss of interest in sex than the controls (Table 3).

Table 2 The BAI Item Score in Participants

Table 3 The BDI-II Item Score in Participants

Figure 1 Patients with CRSwNP exhibited significantly higher total scores on the Beck Anxiety Inventory (BAI) compared to control subjects (p = 0.020). However, the Beck Depression Inventory II (BDI-II) scores did not differ significantly between the two groups (a). The receiver operating characteristic (ROC) curve for the SNOT-22 score showed an area under the curve (AUC) significantly greater than 0.5 (AUC = 0.786, p < 0.001). The optimal cut-off value for the 22-Item Sino-Nasal Outcome Test (SNOT-22), which maximizes the sum of sensitivity and specificity, is indicated (b). *p < 0.05, ***p < 0.001.

Comparison of Clinical Characteristics Between CRSwNP Patients with and without Possible Anxiety

As patients with CRSwNP had significantly higher total BAI scores than controls, CRSwNP patients with possible anxiety (n = 31), defined as a BAI score >7, were compared to those without anxiety (n = 65) (Table 1). The prevalence of comorbid asthma, SNOT-22 scores, serum ECP levels, and blood eosinophil percentages was significantly higher in patients with CRSwNP and possible anxiety than in those without anxiety.

Logistic regression analysis identified comorbid asthma, SNOT-22 score, and blood eosinophil percentage as significant factors associated with anxiety in patients with CRSwNP. Comorbid asthma and SNOT-22 remained statistically significant in multivariable analysis (Table 4).

Table 4 Logistic Regression Analyses of Clinical Variables for Possible Anxiety in Participants

ROC curve analysis of the SNOT-22 score for predicting the presence of possible anxiety in patients with CRSwNP showed an AUCs significantly greater than 0.5 (AUC = 0.786, p < 0.001). The optimal cutoff value was 57 (maximizing the sum of sensitivity and specificity), with a sensitivity of 71.0% and specificity of 76.9% (Figure 1b).

SNOT-22 Subdomain Analysis

To evaluate the interaction between these psychiatric measurements and different subdomains of quality of life in the SNOT-22, comparisons of item and subdomain scores between CRSwNP patients with and without possible anxiety showed that scores in the ear/face, sleep, functional, and emotional subdomains, but not in the nasal symptom subdomain, were significantly higher in patients with possible anxiety (Table 5). The BAI score was significantly correlated with scores in the ear/face, sleep, functional, and emotional subdomains of the SNOT-22, whereas no significant correlations were found with the nasal subdomain (Figure 2). ROC curve analysis of the SNOT-22 subdomains showed AUC values significantly greater than 0.5 for all subdomains except the nasal subdomain (Figure S in Supplementary Material).

Table 5 SNOT-22 Item Score in Participants

Figure 2 The BAI scores were significantly correlated with the total score (a), ear/facial (c), sleep (d), function (e), and emotion (f) domains of the 22-Item Sino-Nasal Outcome Test (SNOT-22), but not with the nasal (b) domain scores. ***p < 0.001.

Discussion

CRS is a persistent inflammatory disease of the sinonasal tract, and depression and anxiety are common psychological disorders, both of which can seriously affect the physical and mental health of patients and impose a significant socioeconomic burden.1,5,6 The results of the current study showed that patients with CRSwNP had higher levels of anxiety symptoms than controls. Overall, 32.3% of the patients exhibited possible anxiety, defined as a BAI score > 7. These findings are consistent with a recent meta-analysis that reported an estimated prevalence of anxiety symptoms of 29.7%.9 Patients with CRSwNP and possible anxiety exhibited a significantly higher prevalence of comorbid asthma, as well as higher SNOT-22 scores, serum ECP levels, and blood eosinophil percentages than those without possible anxiety. Similarly, comorbid asthma, SNOT-22 score, and blood eosinophil percentage were significantly associated with anxiety symptoms in regression analysis. Based on the ROC analysis, the optimal cutoff value for predicting the presence of possible anxiety in patients with CRSwNP was an SNOT-22 score > 57. These findings indicate that eosinophilic inflammation, rather than the objective extent of disease burden, such as nasal polyps and CT scores, is more closely related to anxiety symptoms in patients with CRSwNP. Subjective evaluation of symptoms and quality of life may be affected by comorbid psychological symptoms, which may not be improved with standard CRSwNP treatments, including medical and surgical therapies.24 In addition, comorbid psychological disorders may adversely affect treatment outcomes in patients with CRS.25 These findings may help clinicians better evaluate subjective symptoms when assessing the severity of sinonasal inflammation in patients with CRSwNP and provide optimal therapeutic strategies, particularly in an era when an increasing number of biological agents are being introduced for CRSwNP treatment.

However, our results revealed no significant differences in depression scores assessed using the BDI-II between patients with CRSwNP and the controls. The prevalence of possible depression, defined as a BDI-II score > 13, was 12.5%, which was lower than the 20% reported in a previous study.9 Nevertheless, previous studies have also demonstrated that the prevalence of depression symptoms is lower in patients with CRSwNP than in those with CRSsNP.9,26 One plausible explanation is that patients with CRSwNP may experience more severe nasal congestion and anosmia, whereas patients with CRSsNP may experience more severe pain.1,2,27 Chronic pain is associated with a 5–10 times greater prevalence of clinically significant depressive symptoms.28 Previous study also reported that patients with CRSsNP have been reported to experience a greater burden of disease and worse general health-related quality of life than those with CRSwNP.27 This may explain the lower prevalence of depression symptoms in patients with CRSwNP than in those with CRSsNP.

Most studies have only reported the number of depression cases in patients with CRS,9 without providing sufficient data to support analyses of the relative risk associated with accompanying conditions, such as nasal polyps, comorbid asthma, and allergies. Additionally, these studies have mainly focused on depression, with limited data on anxiety. In the current study, a significant proportion of patients with CRSwNP exhibited anxiety symptoms, regardless of nasal polyp size and CT score. In contrast, comorbid asthma and elevated blood eosinophil percentage were associated with anxiety symptoms. Comorbid asthma has been associated with more severe type 2 eosinophilic inflammation and a significant impact on the rhinologic and sleep-related symptoms in patients with CRSwNP.29 Nevertheless, poorer sleep quality has been reported to be closely associated with higher levels of depression, anxiety, and stress.30,31 Sleep disturbances can cause significant distress, impair quality of life, and increase the risk of suicidal ideation.32 Taken together, patients with CRSwNP and comorbid asthma may experience systemic eosinophilic airway inflammation and significantly impaired sleep quality, which may contribute to increased susceptibility to anxiety symptoms. These factors may further deteriorate the quality of life and compromise therapeutic outcomes in patients with CRSwNP. Thus, early identification of patients with possible psychological disorders, such as anxiety and depression, along with appropriate treatment, is critical for the management of severe CRSwNP.

Furthermore, this study investigated the correlations between anxiety measurements and different subdomains of quality of life in the SNOT-22.19 The results found that scores in the ear/facial, sleep, functional, and emotional subdomains, but not the nasal subdomains, were significantly higher in patients with possible anxiety. In addition, the BAI score was significantly correlated with the ear/facial, sleep, functional, and emotional subdomains of SNOT-22, whereas no significant correlation was found with the nasal subdomain. These findings emphasize the importance of psychological evaluations in the management of patients with CRSwNP. As psychological symptoms may not improve with treatment primarily targeting nasal symptoms,24 clinicians should proceed with caution when assessing the subjective disease burden and therapeutic response in patients with CRSwNP. The current study sheds light on the interaction between the different dimensions of quality of life in patients with CRSwNP. An improved understanding of these associations may help clinicians better evaluate disease burden and treatment outcomes to guide optimal interventions. However, further investigation of the role of psychological interventions in CRS patients with anxiety or depressive symptoms is warranted.

This study had several limitations that warrant consideration. First, patients who underwent sinus surgery at a tertiary referral medical center were enrolled, which may have introduced selection bias. Disease severity in the study cohort may be greater than that in the general population with CRSwNP. Our study focused on patients with severe CRSwNP requiring surgery, a condition associated with severe symptoms and an economic burden. These patients often require multiple treatment modalities, including surgery, systemic glucocorticoids, and biologics.1,2,33 Given the high risk of poor treatment response and disease recurrence, patients with severe CRSwNP warrant comprehensive evaluation. As a result, thorough evaluation of disease burden, including psychological symptoms, is particularly important in the era of biologic therapies for CRSwNP.14 Second, patients with CRSsNP were not included in this study. Future research investigating the use of psychological questionnaires in patients with CRSsNP, unilateral lesions, and those treated non-surgically or with biological agents is necessary to validate the findings of the current study across other CRS populations. Third, the use of self-reported questionnaires is susceptible to response biases, such as changes in internal standards, priorities, and interpretation of the instrument, although these measures have been validated in previous studies.17,34,35 Fourth, the relatively smaller sample size of the control group compared to the CRSwNP group may have resulted in insufficient statistical power. Additionally, the control group consisted of patients who had previously undergone surgery and may have experienced prior sinonasal symptoms, which could have influenced psychological outcomes such as anxiety and depression. However, a post-hoc power analysis was conducted and demonstrated 76% power based on the BAI score. The prevalence of possible anxiety in the control group was 20%, which is similar to that reported in the general population.36 Future studies with larger patient cohorts and comprehensive objective and subjective evaluations before and after treatment are necessary to validate the findings of the present study.

Conclusion

A significant proportion of patients with CRSwNP exhibit anxiety symptoms. Comorbid asthma, SNOT-22 score, and blood eosinophil percentage were significantly associated with the presence of anxiety. These findings highlight the importance of screening for psychological symptoms and potentially integrating psychological assessments and interventions into the care of high-risk patients.

Abbreviations

CRSwNP, chronic rhinosinusitis with nasal polyp; SNOT-22, Sinonasal Outcome Test-22; BDI-II, Beck Depression Inventory-II (BDI-II); BAI, Beck Anxiety Inventory; CRS, chronic rhinosinusitis; CRSsNP, chronic rhinosinusitis without nasal polyps; CT, computed tomography; EPOS2020: the European Position Paper on Rhinosinusitis and Nasal Polyps 2020; ECP, eosinophil cationic protein; SD, standard deviation; rs, Spearman correlation coefficient; ROC curve, receiver operating characteristic curve; AUC, area under the curve; WBC, white blood cell; IgE, immunoglobulin E; CI, confidence interval.

Data Sharing Statement

The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Author Contributions

Chien-Chia H Conceptualization, data curation, formal analysis, funding acquisition, and writing – review and editing. PWW: Data curation, formal analysis, and writing – original draft. PHC: Data curation, supervision and writing – review and editing; Chi-Che H: Data curation, supervision and writing – review and editing. TJL: Data curation, supervision, review and editing. All authors gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Funding

The authors received research grants from the Chang Gung Memorial Hospital (CMRPG3P0572 and CMRPG3Q0541) and the Taiwan National Science and Technology Council (114-2314-B-182 −031 -MY2). The funder played no role in study design, data collection and analysis, decision to publish, or manuscript preparation.

Disclosure

The authors declare no conflicts of interest.

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