Discussion

Relapsing polychondritis is a rare autoimmune disease that influences both males and females,^{Reference Smylie, Malhotra and Brassard6} but has a higher prevalence in middle-aged individuals. Our research included 16 males and 12 females, with age of disease onset ranging from 18 to 68 years. No obvious differences were observed between patients with and without airway involvement regarding gender and age.

The annual incidence of relapsing polychondritis ranges from 0.71 to 3.5 per million people,^{Reference McAdam, O'Hanlan, Bluestone and Pearson4} and 18–26 per cent of relapsing polychondritis patients present with respiratory involvement.^{Reference Eng and Sabanathan7} Approximately half of relapsing polychondritis patients experience different degrees of airway involvement during disease progression.^{Reference de Montmollin, Dusser, Lorut, Dion, Costedoat-Chalumeau and Mouthon8} A retrospective analysis of 142 relapsing polychondritis patients in France found that 43 per cent of the patients had laryngeal involvement and 22 per cent had tracheal involvement.^{Reference Dion, Costedoat-Chalumeau, Sène, Cohen-Bittan, Leroux and Dion9} Furthermore, a retrospective analysis of 239 patients found that airway involvement occurred in 50 per cent of relapsing polychondritis patients.^{Reference Shimizu, Yamano, Kawahata and Suzuki10} Two large-sample studies conducted in China reported that approximately 69–81.7 per cent of relapsing polychondritis patients had airway involvement.^{Reference Zhang, Wang, Yan, Yang, Wu and Wu11,Reference Lin, Yang, Zhang, Lv, Jin and Gu12} Wang et al. performed a prospective study, and reported that approximately 81.5 per cent of relapsing polychondritis patients had airway involvement.^{Reference Wang, Chen, Cui, Gao and Wang13}

In the current study, a retrospective case comparative analysis was conducted, and the findings revealed that patients with airway involvement accounted for 50 per cent of all relapsing polychondritis patients. Of note, the clinical misdiagnosis rate for relapsing polychondritis patients with airway involvement was high, at 85.7 per cent, suggesting a high incidence of relapsing polychondritis patients with airway involvement. However, laboratory and pathological auxiliary examinations are ineffective for diagnosis, as atypical clinical symptoms contribute to a high rate of misdiagnosis.

Clinical typing of relapsing polychondritis is critical to improve diagnostic rates. A previous study categorised relapsing polychondritis into three types based on the affected sites: ‘R’ type, characterised by airway involvement; ‘A’ type, characterised by ear involvement; and ‘O’ type, characterised by airway and ear involvement. These types were analysed, and it was discovered that there were conspicuous differences in the incidence, clinical diagnosis and treatment of patients with different types of relapsing polychondritis.^{Reference Shimizu, Yamano, Kawahata and Suzuki10} Additionally, a French study revealed that although airway involvement is the major cause of death in relapsing polychondritis patients, airway involvement is not highly correlated with heart involvement.^{Reference Dion, Costedoat-Chalumeau, Sène, Cohen-Bittan, Leroux and Dion9} Research conducted in China classified relapsing polychondritis into four types based on the affected organs, as follows: ‘A’ type, characterised by airway involvement; ‘B’ type, characterised by ear involvement; ‘C’ type, characterised by overlapping involvements; and ‘D’ type, in which the airway and ear are unaffected. The results revealed noticeable differences in the clinical diagnosis and prognosis among the types. Patients with subtype A relapsing polychondritis had a greater risk of nasal cartilage involvement, and those with subtype B disease had a higher risk of eye involvement and a better prognosis than patients with the other subtypes.^{Reference Zhang, Yun, Wu, He, Guo and Han14}

In this study, relapsing polychondritis patients were assigned to two groups based on the presence or absence of airway involvement. Patients with airway involvement were less likely to develop ear and eye involvement than those without airway involvement. Additionally, airway involvement was difficult to diagnose, with higher rates of misdiagnosis and missed diagnosis in this group, triggering a protracted disease course, increased re-hospitalisation rates and a poor prognosis (Tables 1 and 2).

Table 2. Comparison of time-to-diagnosis between relapsing polychondritis patients with or without airway involvement

RP = relapsing polychondritis; SD = standard deviation

Airway involvement is the main risk factor for death in relapsing polychondritis patients.^{Reference Ernst, Rafeq, Boiselle, Sung, Reddy and Michaud15} Early and timely diagnosis and treatment can substantially improve the prognosis of relapsing polychondritis patients with airway involvement.^{Reference Wang, Chen, Cui, Gao and Wang13} However, the existing diagnostic criteria are mainly based on the clinical characteristics of patients, and are ineffective for the early diagnosis of relapsing polychondritis. Prior reports revealed that additional investigations, such as CT and endoscopy of the neck and chest, can be applied for the early diagnosis and differential diagnosis of relapsing polychondritis.^{Reference Dubey, Gelder, Pink, Ali, Taylor and Shakespeare16–Reference Thaiss, Nikolaou, Spengler, Spira, Xenitidis and Henes18} In our study, the rate of positive chest CT examination findings, namely varying degrees of airway thickening, stenosis and calcification, was 88.9 per cent in airway-affected patients. The predominant symptom was thickening of the main bronchial wall, which is concordant with the findings of Wang et al.^{Reference Wang, Chen, Cui, Gao and Wang13} Bronchoscopy exhibited findings that were positive for airway involvement in 85.7 per cent of patients. The findings demonstrated varying degrees of tracheal mucosal thickening, stenosis and oedema in relapsing polychondritis patients. Multiple mucosal lesions appeared in 66.7 per cent of patients, as determined by laryngoscopy analysis. In patients with laryngeal involvement, the neck CT results were concurrent with the laryngoscopy results.

Prior studies have shown that ¹⁸F-fluoro-2-deoxyglucose positron emission tomography (FDG-PET)/CT images exhibited the characteristic features of relapsing polychondritis.^{Reference Kubota, Yamashita and Mimori19,Reference Kamada, Takanami, Toyama, Saito and Takase20} Chen et al. conducted a review of 28 relapsing polychondritis patients with airway involvement, all of whom underwent PET/CT examination.^{Reference Chen, Pan, Guan, Yang, Liu and Chen21} Twenty-four PET/CT scans of the tracheal and bronchial trachea revealed augmented density, tube wall oedema, thickening and calcification, and limited stenosis. Furthermore, four patients had increased density and tube wall thickening, and oedema in laryngeal cartilage. Intriguingly, PET/CT assumes a pivotal role in guiding biopsy, because of the high metabolic rate at the affected site. Biopsy performed at sites with hypermetabolic activity according to PET/CT was associated with positive results in 93.3 per cent of cases, illustrating that this imaging is effective for the diagnosis of relapsing polychondritis.^{Reference Lei, Zeng, Zeng, Zhang, Zhu and Jiang22} In our study, one patient was diagnosed with relapsing polychondritis following PET-CT examination. However, the role of PET-CT in the diagnosis and prognosis of relapsing polychondritis should be further explored.

The findings showed that glucocorticoids and immunosuppressants were ineffective in relapsing polychondritis patients with airway involvement, emphasising that early pharmacological management is necessary to prevent relapsing polychondritis progression. Patients with dyspnoea should have their treatment plans adjusted to their condition, and effective surgical intervention should be implemented when appropriate.^{Reference Guo, Zhao, Xing, Liang, Yang and Zhao23}

At present, tracheostomy and endotracheal stent implantation are the only surgical options for the short-term relief of dyspnoea. Oryoji et al.^{Reference Oryoji, Ono, Himeji, Yoshihiro, Kai and Matsuda24} successfully resuscitated a 73-year-old man who had suffered acute respiratory failure due to relapsing polychondritis with airway involvement, through metal stent implantation and tracheostomy. In the present study, five patients underwent a tracheostomy in addition to receiving glucocorticoid and immunosuppressants; effective airway management was achieved in four of these patients.

Stent placement is prone to complications such as stent fracture, pulmonary artery or airway erosion, bleeding, or granulation tissue ingrowth.^{Reference Wu, Zhang, Zhang, Huang and Li25} In light of this, and because complications including respiratory infection and airway obstruction usually occur four to six weeks following surgery, some scholars suggest an initial review period of two to four weeks, followed by review every three months.^{Reference Wang26} In a study by Guo et al.,^{Reference Guo, Zhao, Xing, Liang, Yang and Zhao23} a patient implanted with membrane-covered stents for half a year developed extensive granulation tissue growth and mucosal destruction, as observed at follow up, necessitating removal of the stents. In this study, one patient with central airway involvement suffered granulation tissue hyperplasia at the stent – a post-stenting complication; this patient eventually died after developing pulmonary infection and dyspnoea.

For long-term treatment, the surgical treatment regimens include: tracheobronchial external fixation, laryngeal tracheal reconstruction, tracheal sleeve resection, and balloon dilatation with adjustable pressure and security performance.^{Reference Oryoji, Ono, Himeji, Yoshihiro, Kai and Matsuda24,Reference Li, He and Zhang27,Reference Xie, Shah, Shah and Sandhu28} Tracheobronchial external fixation, in which the collapsed trachea is sutured and suspended over autologous tissues or grafts to open the airway, is suitable for patients with extensive airway softening and collapse. Laryngeal tracheal reconstruction is indicated for patients with limited stenosis of the trachea or subglottis. It utilises a sternocleidomastoid muscle flap or costal cartilage to broaden the laryngeal tracheal reconstruction. Xie et al.^{Reference Xie, Shah, Shah and Sandhu28} reported a successful tracheal restoration using thymus lingual muscle, in a patient with laryngeal stenosis induced by relapsing polychondritis. Tracheal sleeve resection, which is suitable for limited airway stenosis, requires long-term drug treatment and a T-type tube following surgery. Balloon dilatation with adjustable pressure and security performance is suitable for relapsing polychondritis induced laryngeal and tracheal stenosis.

One retrospective study enrolled 11 patients with different degrees of airway stenosis caused by relapsing polychondritis, in which: 9 patients underwent laryngotracheal reconstruction surgery with a sternohyoid myocutaneous flap or costal cartilage to widen laryngeal tracheal reconstruction, 1 patient underwent long-term T-tube placement, and 1 patient underwent routine balloon dilatation. All patients had complete recovery of respiratory and swallowing functions after two to seven years.^{Reference Guo, Zhao, Xing, Liang, Yang and Zhao23}

In addition to the surgery itself, we should calm patients’ emotions prior to treatment, administer anaesthesia, and adequately absorb and discharge sputum, all of which should be supported by hormone therapy pre- and post-operatively.

Biological medication has revolutionised the management of refractory relapsing polychondritis. For instance, tumour necrosis factor-α and interleukin-6 receptor antagonists are effective in the treatment of relapsing polychondritis cases.^{Reference Lekpa and Chevalier29} However, randomised double-blind experiments with large samples are required to verify their effectiveness. In the current study, two patients received adalimumab injections; the results indicated that this treatment was effective in one patient. Bronchial involvement causes diffuse airway stenosis in patients, with the majority of these lesions occurring in the thoracic segment, for which nasal positive pressure ventilation is recommended.^{Reference Yu and Joosten30} Patients who require urgent surgical treatment should be counselled before treatment and administered adequate anaesthesia. Additionally, complete sputum suction and hormone treatment may be employed as adjunctive therapies.