The Clinical Features of Otitis Media with Antineutrophil Cytoplasmic Antibody-Associated Vasculitis and the Role of Routine Blood Tests in Its Diagnosis

Abstract

Background:

To study the clinical features of otitis media with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (OMAAV) and its differences with other forms of ANCA-associated vasculitis (non-OMAAV) and to explore whether routine blood tests could be beneficial to diagnosing OMAAV.

Methods:

A retrospective study was conducted on 18 patients with OMAAV, 15 patients with non-OMAAV, and 23 patients with otitis media with effusion (OME). Basic and clinical information, laboratory data, and treatment outcomes were collected. The differences in the clinical characteristics between OMAAV and non-OMAAV patients were explored. Furthermore, the red cell distribution width (RDW), mean platelet volume (MPV), platelet-to-lymphocyte ratio (PLR), and neutrophil-to-lymphocyte ratio (NLR) were compared between OME and OMAAV patients. The optimal cutoff values for the routine blood indicators were estimated via receiver operating characteristic (ROC) curve analysis.

Results:

All eighteen OMAAV patients (100%) were initially misdiagnosed. Compared with non-OMAAV patients, involvement of nose, throat, and facial nerve was more common in OMAAV patients, whereas kidney damage was less common. However, neither of these differences was statistically significant. Relapse and disease-related death rates did not differ between the OMAAV and non-OMAAV groups. OMAAV patients presented with a lower MPV but a higher PLR and NLR than OME patients (P < 0.05).

Conclusion:

OMAAV is often misdiagnosed as OME in elderly patients, but unlike OME, OMAAV is characterized by mixed hearing loss over its course. Low-cost routine blood tests may help otolaryngologists distinguish OMAAV from OME in the early stage. An abnormal middle ear condition with mixed hearing loss and a PLR ≥ 203.3 or NLR ≥ 4.7 may suggest a potential OMAAV diagnosis.

Keywords

otitis media with antineutrophil cytoplasmic antibody-associated vasculitis red cell distribution width mean platelet volume platelet-to-lymphocyte ratio neutrophil-to-lymphocyte ratio

Introduction

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is characterized by necrotizing inflammation and predominantly affects small- to medium-sized blood vessels.¹ In general, it is a rare systemic autoimmune disease associated with significant mortality. If untreated, AAV patients have an average survival time of 5 months and a mortality rate of 80% to 82% within 1 year.^2,3 The duration from AAV onset to diagnosis can range from 3 to 9 months, and in some cases, it can take up to 8 years.^4,5 Efforts to reduce mortality rates and major organ damage are primarily focused on early diagnosis of the disease. The initial manifestations of AAV include otologic symptoms, such as adult otitis media refractory to conventional treatments like antibiotics, tympanocentesis, and myringotomy tubes. Therefore, the study group of the Japan Otologic Society proposed the concept of otitis media with AAV (OMAAV) to facilitate early diagnosis and management.^6,7 However, immunological tests for identifying patients with suspected OMAAV are expensive and time-consuming. In addition, nearly 15% of patients with OMAAV have negative results for both ANCAs and histopathological examinations, and no other organ involvement is evident at the initial visit.⁷ A retrospective study revealed that 56% of OMAAV patients who were initially misdiagnosed had previously visited an ear, nose, and throat (ENT) clinic.⁸ Therefore, distinguishing OMAAV from recurrent otitis media with effusion (OME) in the early stage is highly important but can sometimes be challenging.

Routine blood tests are performed in daily medical practice and can yield abundant information. Two routine blood parameters include the red cell distribution width (RDW), which estimates the variability in red blood cell size, and the mean platelet volume (MPV), which represents the the average size of platelets generated in the bone marrow.⁹ RDW and MPV alterations can reflect not only hematological disorders but also general patient health, inflammatory conditions, and autoimmune diseases. Many studies have reported that the RDW and MPV are significantly increased in rheumatoid arthritis patients.^10,11 In addition, the platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) have also been used to reflect vasculitis activity and predict relapse in AAV patients.^12,13 Nevertheless, no research on the disease status and outcomes of OMAAV patients has been conducted with these indicators. In this study, we hypothesized that these serological indicators, obtained from routine blood tests, could help to identify and diagnose patients with OMAAV. OME patients served as controls, and the RDW, MPV, PLR, and NLR were compared between OME patients and OMAAV patients. Furthermore, the effectiveness of a threshold value was also tested that could assist in diagnosing OMAAV. If this hypothesis were confirmed, early identification and proper management of OMAAV would be extremely feasible, as the relevant tests for obtaining these laboratory data are inexpensive. In addition, a comparison of the clinical features of OMAAV and other forms of AAV (non-OMAAV) was conducted to better understand OMAAV.

Patients and Methods

A retrospective study was conducted on 18 patients with OMAAV who were treated between September 2015 and September 2022 at the ENT department of Xijing Hospital (Air Force Military Medical University), a tertiary referral center. The diagnosis of OMAAV was made according to the diagnostic criteria proposed by the Japan Otological Society (Table 1).⁷ Twenty-three patients with OME and 15 patients with non-OMAAV who were treated during the same period were randomly selected and, after age- and sex-matching to the OMAAV group, were included in the control group. Initially, all OME and non-OMAAV patients who met the inclusion criteria were listed. Random selection was performed using a computer-generated random number sequence, which ensured that the patients selected for the control group were chosen in an unbiased manner. Second, age- and sex matching was carried out by an independent researcher. Then, the allocation sequence was concealed until the matching process was completed. Finally, these processes ensured that there was no significant difference in basic information among these groups. Patients with hematological illness, malignancies, serious infections, or inflammatory diseases were excluded. In addition, none of the enrolled patients had previously received immunosuppressive treatment. This study was approved by the Medical Ethics Committee of the First Affiliated Hospital of the Air Force Medical University (No. KY20242022-C-1). Informed consent was obtained from the patients enrolled in the study.

Table 1.

Diagnostic Criteria of OMAAV. (The 7th in References list).

OMAAV is diagnosed, if the three criteria (A, B, C) were fulfilled.
(A) Disease onset with initial signs/symptoms due to intractable otitis media with effusion or granulation, which was resistant to antibiotics and insertion of a tympanic ventilation tube.
(B) At least one of the following three findings:
1. Positivity for serum MPO- or PR3-ANCA.
2. Histopathology consistent with AAV, ie, necrotizing vasculitis predominantly affecting small vessels with or without granulomatous extravascular inflammation.
3. At least one accompanying sign/symptom of AAV-related involvement other than the ear (eye, nose, pharynx/larynx, lung, kidney, facial palsy, hypertrophic pachymeningitis, and others).
(C) Exclusion of the other types of intractable otitis media, such as bacterial otitis media, cholesterol granuloma, cholesteatoma, malignant osteomyelitis, tuberculosis, neoplasm, and eosinophilic otitis media, as well as the exclusion of other autoimmune diseases and vasculitis diseases other than AAV, such as Cogan’s syndrome and polyarteritis nodosa among others.

Abbreviations: AAV, ANCA-associated vasculitis; MPO, myeloperoxidase; OMAAV, otitis media with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis; PR3, proteinase 3.

Basic information, including age, sex, affected ear, and medical and family history, as well as the duration from onset to diagnosis and details regarding the involved organs, were collected. For OMAAV patients, the initial symptoms and audiometric results before and after treatment were recorded. Indirect immunofluorescence was conducted to identify cytoplasmic ANCAs (c-ANCAs) and perinuclear ANCAs (p-ANCAs), and an enzyme-linked immunosorbent assay (ELISA) was performed for detecting myeloperoxidase (MPO) and proteinase 3 (PR3) ANCAs. The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, serum creatinine level, and relevant blood parameters were determined. RDW and MPV data were collected. The NLR was defined as the ratio of the neutrophil count to the lymphocyte count. The PLR was defined as the ratio of the platelet count to the lymphocyte count.

Standard induction treatment with a combination of glucocorticoids and either rituximab or cyclophosphamide is recommended, and plasma exchange is applied when necessary for patients with severe renal dysfunction. Remission was evaluated as the absence of AAV-related symptoms for 3 months. Relapse was defined as the appearance of new involvement or the recurrence or exacerbation of the preexisting symptoms after remission.

Statistical Analysis

Data analyses were performed with SPSS 26.0 software (SPSS Inc., Chicago, IL). Fisher’s exact tests and ANOVA were applied to assess the differences in clinical features between OMAAV and non-OMAAV patients. The Mann‒Whitney U test and ANOVA were conducted to compare the laboratory parameter levels between OMAAV and OME patients at diagnosis. Receiver operating characteristic (ROC) curve analysis was conducted to investigate the diagnostic capabilities of the different parameters in distinguishing OMAAV from OME. Analysis of the routine blood indicators was carried out to determine the optimal cutoff values and sensitivity and specificity. The diagnostic cutoff values for the NLR and PLR values were defined as the points on their ROC curves that maximized Youden’s index, which is calculated as the difference between the sensitivity and the value of 1 minus the specificity. The independent predictive value of PLR for OMAAV diagnosis was investigated by multivariable logistic regression analysis. MedCalc (version 20.0.22) was used for comparisons of the ROC curves. P < .05 was considered to indicate statistical significance.

Results

Eighteen patients (10 males, 55.6%) with OMAAV with a mean age of 61.3 ± 10.4 (46 to 72) years, were included. The majority of patients (13, 72.2%) had bilateral ear involvement. The initial otologic symptoms included hearing loss (10, 55.6%), otorrhea (6, 33.3%), otalgia (3, 16.7%), facial paralysis (3, 16.7%), and dizziness (1, 5.6%). Patients presented with mixed hearing loss and middle ear abnormalities (Figure 1A and B). All OMAAV patients had previously been misdiagnosed; among them, 10 patients (55.6%) misdiagnosed with OME had undergone myringotomy and ventilation tube placement (Figure 1C). The hearing levels were improved after immunosuppressive intervention in nine patients (50%) (Table 2).

Figure 1.

(A) Thickening and vasodilation in the pars tensa and pars flaccida of the TM. (B) Swelling and granulation in the posterior wall and the TM. (C) Persistent otorrhea did not improve after pharmacotherapy and thickening of the wall of the external auditory canal was observed. TM, tympanic membrane.

Table 2.

Clinical Features of OMAAV at Diagnosis and Hearing Outcomes.

Clinical features	OMAAV(n = 18)
Demographic information
Age (years)	61.3 ± 10.4
Male	10 (55.6%)
Affected ear
Left	3 (16.7%)
Right	2 (11.1%)
Bilateral	13 (72.2%)
Initial otological symptoms
Hearing loss	10 (55.6%)
Otalgia	3 (16.7%)
Otorrhea	6 (33.3%)
Facial paralysis	3 (16.7%)
Vestibular symptom	1 (5.6%)
Middle ear conditions
Perforation	3 (16.7%)
Effusion	3 (16.7%)
Myringotomy	5 (27.8%)
Inflammatory or thicken of TM	7 (38.9%)
Hearing loss types
Mixed hearing loss	18 (100%)
Initial diagnosis
OME	10 (55.6%)
COM	7 (38.9%)
AOM	1 (5.6%)
Previous myringotomies	10 (55.6%)
Onset to diagnosis: median (Q25 to Q75) months	6.5 (3.0, 12.0)
Hearing outcomes
Improved	9 (50.0%)
Worsen	2 (11.1%)
No alteration	2 (11.1%)
Dropout	5 (27.8%)

Abbreviations: AOM, acute otitis media; COM, chronic otitis media; OMAAV, otitis media with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis; OME, otitis media with effusion; Q, percentile; TM, tympanic membrane.

Table 3 shows the comparison of the clinical characteristics between OMAAV and non-OMAAV patients. Age, sex distribution, and baseline ANCA status did not differ between the two groups (P > .05). Lung involvement was common in both the OMAAV and non-OMAAV groups. Nose, throat, and facial nerve damage and hypertrophic pachymeningitis were more common in OMAAV patients, and renal dysfunction was more common in non-OMAAV patients; however, these differences were not statistically significant (P > .05). Furthermore, in patients with OMAAV, the mean value of serum creatinine fluctuated within the normal range, but it was significantly elevated in patients with non-OMAAV (P < .05). The CRP level and ESR were elevated in both groups, but the differences were not statistically significant (P > .05). The follow-up durations were 29.6 ± 15.3 months and 33.9 ± 13.4 months for the OMAAV and non-OMAAV groups, respectively, but the differences were not statistically significant (P > .05). Neither the relapse rate nor the disease-related death rate differed between the two groups (P > .05).

Table 3.

Basic Information in OMAAV and Non-OMAAV at Diagnosis and the Prognosis of Them.

Clinical features	OMAAV(n = 18)	Non-OMAAV(n = 15)	P value
Demographic information
Age (years)	61.3 ± 10.4	61.3 ± 7.8	.984
Male	10 (55.6%)	7 (46.7%)	.056
ANCA status
MPO-ANCA (or p-ANCA)	8 (44.4%)	11(73.3%)	.158
PR3-ANCA (or c-ANCA)	10 (55.6%)	4 (26.7%)	.158
Double positive	0	1 (6.7%)	.455
Involved organs
Lung	11 (61.1%)	12 (80.0%)	.283
Kidney	4 (22.2%)	8 (53.3%)	.083
Nose/throat	10 (55.5%)	3 (20.0%)	.072
Facial nerve	3 (16.7%)	1 (6.7%)	.607
Hypertrophic pachymeningitis	3 (16.7%)	2 (13.1%)	.59
Serum creatinine (μmol/L)	68 (55.5, 82.0)	100 (75, 193)	.003
CRP (mg/L)	20.3 ± 33.1	10.1 ± 18.1	.293
ESR (mm/h)	52.1 ± 32.5	57.2 ± 35.1	.669
Follow-up (months)	29.6 ± 15.3	33.9 ± 13.4	.4
Relapse	7 (33.8%)	5 (33.3%)	.52
Disease-related death	3 (16.7%)	2 (13.1%)	.59

Abbreviations: CRP, C-reactive protein; ESR, erythrocyte sedimentation rate.

Table 4 shows the details of the 23 patients with OME selected to explore the importance of routine blood tests for diagnosing OMAAV. The two groups were matched for age and sex (P > .05). The serum creatinine level did not differ between the two groups (P > .05). The hemoglobin level was notably lower in patients with OMAAV than in patients with OME (P < .05). The MPV decreased substantially (P < .05), whereas the RDW showed little change in the OMAAV group (P > .05). The platelet and neutrophil counts were significantly greater in patients with OMAAV than in those with OME (P < .05). The lymphocyte counts were significantly lower in patients with OMAAV than in patients with OME (P < .05). The NLR and PLR values calculated from the lymphocyte counts, neutrophil counts and platelet counts were both significantly greater in the OMAAV group (P < .05).

Table 4.

Laboratory Data at Diagnosis and Possible Predictors in OMAVV Diagnosis.

Laboratory data	OMAAV(n = 18)	OME(n = 23)	P value
Age (years)	62.5 (51, 71.3)	54.0 (52, 64)	0.184
Sex (Male)	10 (55.6%)	11 (47.8%)	0.623
Serum creatinine (μmol/L)	85.3 ± 65.6	79.7 ± 18.1	0.695
Hemoglobin (g/L)	115 ± 16.6	145.5 ± 16.5	<0.01
MPV (fl)	10.4 ± 0.9	11.4 ± 1.6	<0.05
RDW (fl)	45.3 ± 7.1	43.2 ± 3.6	0.225
Platelet count (10⁹/L)	274.8 ± 68.3	200.4 ± 39.7	<0.01
Neutrophil count (10⁹/L)	7.4 ± 3.4	3.7 ± 1.0	<0.05
Lymphocyte count (10⁹/L)	1.2 ± 0.6	1.6 ± 0.5	<0.05
NLR	7.9 ± 4.8	2.9 ± 2.7	<0.05
PLR	275.5 ± 126.9	160.2 ± 169.8	<0.05

Abbreviations: MPV, mean platelet volume; NLR, neutrophil-to-lymphocyte ratio; OME, otitis media with effusion; PLR, platelet-to-lymphocyte ratio; RDW, red cell distribution width.

Table 5 and Figure 2 present the area under the curve (AUC) and optimal cutoff values of the routine blood indicators in diagnosing OMAAV. Neutrophil count (AUC = 0.796, 95% CI: 0.632-0.96, P = .001), NLR (AUC = 0.778, 95% CI: 0.606-0.949, P = .003), PLR (AUC = 0.824, 95% CI: 0.692-0.955, P < .001), and PLT (AUC = 0.814, 95% CI: 0.674-0.954, P = .001) all demonstrated high predictive value for OMAAV diagnosis (all P < .05). Among these, PLR exhibited the highest AUC (0.824), indicating superior diagnostic performance. By contrast, hemoglobin (AUC = 0.099, P < .001), lymphocyte count (AUC = 0.245, P = .006), and MPV (AUC = 0.278, P = .016) all showed AUC values significantly below 0.5, suggesting limited discriminative ability for OMAAV.

Table 5.

The Area Under Curve and Optimal Cutoff of the Routine Blood Indicators for OMAAV Diagnosis.

Routine blood indicators	AUC	P value	95% CI
Hemoglobin	0.099	.000	0.003-0.195
Neutrophil count	0.796	.001	0.632-0.96
Lymphocyte count	0.245	.006	0.086-0.404
PLT	0.814	.001	0.674-0.954
MPV	0.278	.016	0.122-0.434
NLR	0.778	.003	0.606-0.949
PLR	0.824	.000	0.692-0.955

Abbreviations: AUC, area under curve; CI, confidence interval.

Figure 2.

ROC curve for discriminating OMAAV from OME.

The independent predictive value of PLR for OMAAV diagnosis was investigated by multivariable logistic regression analysis (Table 6). After adjusting for confounding factors, age and sex, PLR (OR = 1.006, 95% CI: 1.052-1.962, P = .046) was an independent predictor of OMAAV diagnosis.

Table 6.

The Independent Predictive Value of PLR for OMAAV Diagnosis.

Variable	β coefficient	Standard error	OR (95% CI)	P value
PLR	10.802	0.023	1.006 (1.052-1.962)	.046
Age	0.05	0.02	1.05 (1.01-1.09)	.012
Sex (male)	0.42	0.21	1.52 (1.01-2.29)	.045

Abbreviation: CI, confidence interval; OR, odds ratio.

Discussion

According to previous studies, both OMAAV and non-OMAAV patients are predominantly female and older individuals.^7,14 However, males (55.6%) were slightly more likely to have OMAAV in this study, perhaps due to the small sample size. In this study, the bilateral ears of 13 (72.2%) patients were affected, and 10 (55.6%) patients with mixed hearing loss were misdiagnosed with OME, consistent with previous findings that showed that OMAAV frequently affects both ears and that misdiagnosis is very common.¹⁵ In this study, the initial signs also included facial paralysis (16.7%) and vestibular symptoms (5.6%). Bilateral or unilateral facial paralysis has been reported in 5% to 22% of OMAAV patients, and bilateral involvement could aid in early diagnosis.^4,16 Vestibular symptoms rarely present as initial signs of OMAAV and are frequently accompanied by sudden hearing loss.^16,17 The average duration from onset to diagnosis in this study was 6.5 months, which is consistent with the findings of previous reports.^18,19 After immunosuppressant treatment, hearing levels improved in nine patients (50%), and no alterations or deterioration of hearing conditions occurred in two patients (11.1%). It was assumed that delay in treatment could not reverse immune complex deposition or the toxic impact on the inner ear.^20-22

Some studies have focused on the clinical features of OMAAV and non-OMAAV.^19,23 Two types of ANCAs are commonly tested in patients with AVV: MPO and PR3 ANCAs. Two studies based on 235 and 39 OMAAV patients in Japan reported 60% and 75.0% positivity, respectively, for the MPO-ANCA complex, suggesting that MPO-ANCA was more common in patients with ear involvement.⁷ However, in this study, the percentage of PR3-ANCA positivity was slightly higher in OMAAV patients, but the difference was not statistically significant, again likely due to the small sample size. Hosokawa also reported that compared with non-OMAAV patients, OMAAV patients were more likely to present with simultaneous facial palsy and hypertrophic pachymeningitis and less likely to demonstrate kidney involvement.¹⁹ In this study, the patients also presented with these clinical characteristics, but there was no significant difference between the two groups. However, the serum creatinine level was significantly higher in the non-OMAAV group than in the OMAAV group. Moreover, the CRP level and the ESR were increased in both OMAAV patients and non-OMAAV patients, but the differences between the groups were not significant. These findings suggest that immune activity increases similarly in both groups. Hence, Okada suggested that OMAAV management should be equivalent to non-OMAAV management.²³ Studies have shown that OMAAV patients are more likely to experience relapse and have worse remission.^19,23 Moreover, Morita detected MPO-DNA in the middle ear fluid of OMAAV patients and suggested that this complex may suggest the emergence of OMAAV.²⁴ A study analyzing the data of 235 OMAAV patients in Japan reported that four factors, namely, facial palsy, hypertrophic pachymeningitis, the two ANCA-negative phenotypes, and disease relapse, are adversely associated with disease mortality.⁷ The present study revealed no significant differences in relapse or disease-related mortality rates between the two groups at similar follow-up periods. These findings suggest that both OMAAV and non-OMAAV should be followed up for similar durations and treated with similar drug products.

Routine blood tests are common laboratory examinations in clinical practice and can provide abundant information. Anemia was previously reported to be responsible for increases in RDW.²⁵ The platelet count is an important indicator of proinflammatory elements, and the MPV is associated with platelet activation.⁹ Currently, the RDW and MPV are widely employed to assess the severity and prognosis of several autoimmune disorders.^11,26 Several underlying mechanisms explain the changes in RDW and MPV in illness, including telomere length, oxidative stress, and inflammation.²⁷ One study concluded that the RDW is closely related to the levels of inflammatory factors and autoantibodies in rheumatoid arthritis patients.²⁸ Another report suggested that changes in RDW were due to hemoglobin reduction.²⁹ OMAAV, which is associated with antineutrophil cytoplasm, principally affects small- to medium-sized blood vessels, leading to increased inflammatory activation and vascular permeability; this pathological state accounts for the impairment of erythrocyte maturation.²⁸ In this study, the RDW was greater in OMAAV patients, but the difference was not statistically significant, which may be attributed to the small sample size. Although some studies have shown that the MPV is not related to disease severity,⁹ several reports have suggested that the MPV is either positively or negatively associated with inflammatory conditions.^30-32 These inconsistent conclusions may stem from the different sizes of platelet fragments involved in different diseases.³² This study revealed that the MPV was negatively associated with OMAAV, suggesting that small platelets are primarily involved in the development of this condition.

Some studies have recently suggested that the NLR and PLR are linked to AAV and even reflect the severity of the disease and disease-related mortality.^12,13,33 The neutrophil count proportionally increases with increasing AAV severity because the high abundance of such cells is the primary pathophysiology of this disease.¹² However, lymphocyte count reduction frequently occurs in response to autoimmune disease.³⁴ Cumulative evidence suggests that the platelet count is elevated since it is involved in vascular and endothelial injury in patients with advanced AAV.^12,35 The increases in the neutrophil count and platelet count and the reduction in the lymphocyte count in this study are in accordance with findings from the literature.^12,13 The NLR and PLR are overwhelmingly effective in diagnosing AAV and predicting patient outcomes. The potential reasons are as follows: first, the NLR represents two types of immune responses: rapid responses, produced by neutrophils, and a relatively slow response, linked to lymphocytes.³⁶ Second, the PLR represents two cell lineages and highly reflects disease severity.¹² Reports have shown that either a PLR ≥ 272.0 or an NLR ≥ 5.9 at diagnosis are highly indicative of AAV.^12,37 Huang et al. investigated 188 Chinese patients with MPO-AAV and concluded that patients with an NLR ≥ 9.53 may have a greater likelihood of mortality than those with NLR < 9.53.³³ In this study, the mean values of the PLR and NLR in OMAAV patients were 275.5 and 7.9, respectively. These findings suggest that the NLR and PLR may contribute to diagnosing OMAAV and help ENT surgeons distinguish it from OME at an early stage. In addition, the AUC and optimal cutoff values of the routine blood indicators for diagnosing OMAAV were also investigated, and the results revealed that a PLR ≥ 203.3 or an NLR ≥ 4.7 may be suitable cutoff values. Furthermore, after adjusting for confounding factors, age and sex, PLR has superior diagnostic performance. However, these cutoff values had relatively low specificity, which may be due to the small number of subjects in this single-center study. Hence, a larger-scale multicenter sample size would be beneficial for determining more accurate cutoff values of the NLR and PLR in diagnosing OMAAV.

A scoring system for the tympanic membrane (TM) has been proposed as a method for diagnosing OMAAV.³⁸ Precise microscopic identification of changes in the TM, such as thickening or vasodilation of the pars tensa, and swelling of the posterior wall would be helpful for discriminating OMAAV from repetitive OME.³⁸ Thus, combining with these core otologic features with serological indicators such as the PLR and NLR could also contribute to training artificial intelligence (AI) programs for promptly diagnosing and systematically evaluating disease status.

Some limitations of this study should be mentioned. Some clinical indicators were not available in the retrospective study. For example, the Birmingham Vasculitis Activity Score (BVAS), which is widely applied in therapeutic studies of systemic vasculitis, was not assessed in every patient. It is impossible to further explore the relationships between disease severity (using the BVAS) and the PLR and NLR in OMAAV.

Conclusion

OMAAV is often characterized by mixed hearing loss and abnormal middle ear conditions at diagnosis, and is easily misdiagnosed as OME in elderly patients. There was no significant difference in ANCA positivity or organ involvement at diagnosis between the OMAAV group and the non-OMAAV group. However, the serum creatinine level was lower in OMAAV patients than in non-OMAAV patients. Compared with the OME group, the MPV in OMAAV patients was lower, and the NLR and PLR were greater. In addition, a PLR ≥ 203.3 or an NLR ≥ 4.7 may suggest a potential OMAAV diagnosis, and the PLR has superior diagnostic performance. These low-cost and convenient predictors, obtained from routine blood tests, may help otolaryngologists differentiate OMAAV from OME. A large-scale multicenter study would be indispensable for further validating these results and aiding in promptly diagnosing and treating OMAAV.

Footnotes

Acknowledgements

None.

ORCID iDs

Runqin Yang

Zhuo Xu

Xingchen He

Dingjun Zha

Ethical Considerations and Consent to Participate

This research was approved by the Medical Ethics Committee of the First Affiliated Hospital of the Air Force Medical University (No. KY20242022-C-1).

Author Contributions

The study was designed by DJ Z. RQ Y and ZX collected data, performed statistical analysis, and wrote this manuscript. XC H and ZH G participated in the patient follow-up. The revision work was conducted by DJ Z and YL. All authors performed data interpretation and approved the manuscript.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by grants from the Innovation Team of Shaanxi Province (2023-CX-TD-70) and Key Industrial Chain of Shaanxi Province (2022ZDLSF02-10 and 2024SF-ZDCYL-01-16). This project’s recipient is Dingjun Zha.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Data Availability Statement

The datasets are available from the corresponding author upon reasonable request.

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