Background/Purpose:

Damage to the large airways is a devastating complication of granulomatosis with polyangiitis (GPA).  Identification of patient subsets at particular risk for airway disease and development of non-invasive screening methods to detect tracheobronchial disease is an unmet need in GPA.  This study aimed to characterize patients with subglottic stenosis (SGS) and bronchial disease and test whether dynamic expiratory-phase CT is useful to detect airway damage in patients with GPA.

Methods: i) A retrospective analysis of a multi-center cohort of patients with GPA identified demographic and clinical features associated with the presence of SGS or endobronchial involvement; ii) A subset of patients with GPA underwent a dynamic chest CT at a single center, assessed by a central reader blinded to clinical status.  Differences were assessed by the chi square test and ANOVA with post-hoc Tukey test to account for multiple comparisons.

Results:

Data from 962 patients with GPA from 9 centers were used for the initial phase analyses.  As outlined in Table 1, SGS was identified in 95 (10%) patients with no differences in ANCA subtype in patients with SGS compared to the overall cohort.  Patients with SGS were more likely to be female (72% vs 53%, P < 0.01), younger at time of diagnosis (36 vs 49 years, p < 0.01), and less likely to have constitutional, cardiovascular, renal, or nervous system involvement.  Among 95 patients in the cohort with nasal septal perforation and saddle nose deformities, 28 (29%) and 27 (30%), respectively, also had SGS. 

Endobronchial disease was seen in 59 (6%) patients.  Compared to the full cohort, patients with endobronchial involvement were younger at time of diagnosis, more likely to have ENT involvement and be PR3-ANCA positive (78% vs 63%, p=0.02), but less likely to be ANCA-negative (0% vs 9%, p = 0.02) or have renal disease. There was no association between endobronchial involvement and sex. Patients with SGS were more likely to have endobronchial involvement.  Concomitant SGS and endobronchial involvement (25 patients) was not associated with sex (60% vs 55% female, p = 0.60).

Six of ten patients screened by dynamic chest CT had large-airway pathology.  Isolated SGS was confirmed by imaging in two female patients.  Previously unknown tracheobronchomalacia was discovered in 4 patients, including one male patient thought to have isolated SGS.

Conclusion:

Both SGS and endobronchial disease are moderately common in GPA and each manifestation is associated with various other aspects of GPA.  SGS is more commonly seen in female patients with GPA, whereas bronchial involvement is not associated with sex.  There should be a low threshold to evaluate airway disease in GPA, especially in younger patients, and those with destructive sinonasal disease.  Dynamic expiratory phase chest CT is a potential non-invasive screening test for tracheobronchial disease in GPA.