Research

Original Investigation

Long-term Outcome of Airway Stenosis in Granulomatosis

With Polyangiitis (Wegener Granulomatosis)
An Observational Study
Marcos Martinez Del Pero, MD, FRCS (ORL-HNS); David Jayne, MD, FRCP; Afzal Chaudhry, PhD, FRCP;
Pasupathy Sivasothy, FRCP; Piyush Jani, FRCS (ORL-HNS)

IMPORTANCE Airway stenosis occurs in patients with granulomatosis with polyangiitis (GPA
or Wegener granulomatosis). It produces significant morbidity and contributes to mortality.

OBJECTIVE To investigate the frequency and distribution of airway stenoses in GPA and
evaluate the efficacy of local interventions in maintaining airway patency.

DESIGN, SETTING, AND PARTICIPANTS A retrospective single-center study of 44 patients with

GPA and airway stenosis assessed and treated as needed by a multidisciplinary team at a
university medical center between 1997 and 2012. The median duration of observation for
each patient from the time of diagnosis was 146 months.

INTERVENTIONS Patients who had critical stenoses underwent either dilatation or laser radial
cuts to the lesion. In some cases, intralesional administration of steroids or topical mitomycin
C was used.

MAIN OUTCOMES AND MEASURES The main outcome measure was airway patency for at least
12 months and the number of interventions required to achieve this end point. Details of
patients and interventions were recorded at baseline and at each treatment.

RESULTS The median age at diagnosis was 37.6 years; 73% of patients were women (n = 34).
The median follow-up after the initial intervention was 62.5 months. Subglottic stenosis was
found in 36 patients, lower airway stenosis in 30. There were 213 interventions in 39 patients,
including balloon and bougie dilatation and laser treatment. Adjuvant local treatment was
used in 71 interventions. A 12-month period of airway stability was achieved in 34 of 36 cases
(97%) (5 had no procedures and 3 had follow-up shorter than 12 months). The median
interval between procedures was 4.9 months, and after the last intervention recorded,
patients had at least 27 months of airway stability. Fourteen adverse events were recorded
(6.6%).

Author Affiliations: Department of

CONCLUSIONS AND RELEVANCE The frequency and distribution of airway stenoses in 44
Otolaryngology, Addenbrooke’s
patients with GPA has been described. In the 39 patients who required intervention, multiple Hospital, Cambridge University
procedures were required, but 97% then achieved a prolonged period of airway patency. The Hospitals NHS Foundation Trust,
procedures and adjuvant treatments were found to be safe. Our experience with a variety of Cambridge, England (Martinez Del
Pero, Jani); Department of
techniques in this rare presentation has permitted design of a structured approach and an Nephrology and Vasculitis,
algorithm to manage and evaluate airway stenosis in GPA. Addenbrooke’s Hospital, Cambridge
University Hospitals NHS Foundation
Trust, Cambridge, England (Jayne,
Chaudhry); Department of
Respiratory Medicine, Addenbrooke’s
Hospital, Cambridge University
Hospitals NHS Foundation Trust,
Cambridge, England (Sivasothy).
Corresponding Author: Marcos
Martinez Del Pero, MD,
FRCS (ORL-HNS), Department of
Otolaryngology, Box 48,
Addenbrooke’s Hospital, Hills Road,
JAMA Otolaryngol Head Neck Surg. 2014;140(11):1038-1044. doi:10.1001/jamaoto.2014.2430 Cambridge, CB2 0QQ, England
Published online October 16, 2014. (marcos@doctors.org.uk).

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 Granulomatosis With Polyangiitis (Wegener’s) Original Investigation Research

G
ranulomatosis with polyangiitis (GPA or Wegener infection distal to the stenosis) and the presence of active vas-
granulomatosis) is a primary systemic vasculitis syn- culitis. Medical treatment was attempted in all patients be-
drome that predominantly affects the lungs, kidneys, fore local intervention unless they had critical stenoses.
and otorhinolaryngologic (ENT) system. More than 70% of pa- Beginning in 2007, stenoses in the distal main bronchi
tients with GPA have ENT involvement at follow-up.1-4 Sub- and their divisions were treated with balloon dilatation
glottic stenosis (SGS) is a less common, but serious, manifes- under sedation, and laser and bougies were used for proxi-
tation of ENT disease,5 and it is different from other ENT mal stenoses (subglottis, trachea, and main bronchi). A
manifestations in that it can present at any time regardless of combination of general anesthesia or sedation was used
disease activity; it is the most common manifestation of ENT between 1997 and 2007. Currently, intralesional glucocorti-
disease in children6,7; and it follows a relapsing course often coid administration is used as an adjuvant therapy in active
refractory to standard medical therapy. stenoses, and mitomycin C in fibrosed recurrent stenoses.
Subglottic stenosis can also present as part of more exten- Active stenosis is diagnosed clinically in the presence of fri-
sive airway stenosis affecting the lower airways. Other pulmo- able irregular tissue, and scarred, pale, nonfriable lesions
nary manifestations of GPA include lung nodules, cavities, and are considered fibrosed stenoses.
hemorrhagic alveolitis.8 In a large case series, Cordier et al9 found Pulmonary function was assessed using the Empey in-
that 17% of patients had endobronchial stenosis. dex, calculated as the forced expiratory volume in 1 second
Traditionally, airway stenoses in GPA are treated with im- (FEV1) (milliliters per second) divided by the peak expiratory
munosuppression followed by local interventions for persis- flow rate (PEFR) (liters per minute), and the incremental shuttle
tent symptomatic stenoses. Some authors have suggested that walk test. An Empey index greater than 10 is considered ab-
stenoses should be treated during active disease with dilata- normal. The walking test assesses the distance a patient walks
tion and intralesional glucocorticoids.10 Other local interven- with incremental speed between 2 fixed points, and an in-
tions include dilatation with balloons or bougies 11 ; laser crease of 47.5 m is considered symptomatically significant.19
resection,12 cryotherapy, or Argon-plasma coagulation. Topi- The aim of therapy was to achieve a 12-month period of stable
cal mitomycin C has been used to reduce recurrence rates.13,14 airway patency defined by stability on direct visualization and
Prompt medical therapy combined with local interventions has clinically.
reduced the need for tracheostomies and stents.10,15 Stents are
generally avoided because they contribute to persistent in- Analysis
flammation and disease reactivation.16 Sleeve excision of Continuous data are summarized by medians and interquar-
the stenosis and end-to-end tracheal repair has also been tile ranges (IQRs), while categorical and nominal data are sum-
reported7,12,17 but is uncommonly performed. marized using percentages. Stable airway patency was de-
The purpose of this study was to determine whether patients fined as a period of 12 months or more of follow-up without
with airway stenosis and GPA reach complete airway stability and intervention. Patients were subcategorized according to the
to use the data from the disease course as well as published data sites affected: subglottic stenosis (SGS) only; main airways (SGS
to establish a strategy for the management of this condition. and/or trachea and main bronchi); secondary bronchi only; and
widespread (main airways and secondary bronchi affected).
Despite the large sample size compared with previous
cohorts,10,15,20 the data were considered too heterogeneous for
Methods meaningful statistical analysis of outcomes.
Addenbrooke’s Hospital registered this retrospective cohort
study project in the research and development department and
decided that it did not require ethical approval.
Results
Patients Patient Characteristics and Disease Manifestations
The medical records were evaluated for all patients with air- Forty-four (17.5%) of 251 patients with GPA seen at our insti-
way stenosis and a diagnosis of GPA treated between 1997 and tution had airway stenosis. The median age at diagnosis of air-
May 2012 by a multidisciplinary team in our tertiary referral way stenosis was 37.6 years, and 73% were women (n = 34)
center. The diagnosis of GPA was applied according to cur- (Table 2).21
rent classification guidelines.18 The demographic data of the Over half of the patients had localized disease (ENT and/or
patients were recorded, and a database was designed to record lower airway stenosis only), and a quarter had renal involve-
the distribution of the lesions, intervention details, and pul- ment. Four of 5 myeloperoxidase–antineutrophil cytoplas-
monary function test results. mic antibody (MPO-ANCA)–positive patients had localized dis-
ease and almost all ANCA-negative patients (10 of 11) had lower
Data Collected airway involvement and constitutional symptoms without re-
The data collected encompassed all interventions from diag- nal disease. Only 1 of the ANCA-negative patients presented
nosis until May 2012. The general management of these pa- with isolated SGS and constitutional symptoms, and the di-
tients is detailed in Table 1. The decision for active local inter- agnosis was made by clinical assessment and biopsy.
vention was based on the patients’ clinical progress (ie, The median time from diagnosis of GPA to diagnosis of en-
breathlessness, reduced lung capacity or walking distance, and dobronchial disease was 23 months (IQR, 0-69 months), with

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 Research Original Investigation Granulomatosis With Polyangiitis (Wegener’s)

Table 1. Overview of the Management Strategy for Airway Stenosis in Granulomatosis With Polyangiitisa

Local Interventions
Physical Medical Anti-infective Therapy Systemic Therapy
Balloon dilatation with Glucocorticoids Prolonged antibiotic therapy Standard therapy:
or without cutting for recurrent or persisting
Mitomycin C bacterial infections guided by Induction
Bougie antibiotic sensitivities Cyclophosphamide and
Alemtuzumab glucocorticoids
Laser Topical antibiotics if recurrent
crusting Maintenance
Cryotherapy Azathioprine and/or
Antifungal agents only if methotrexate and
Diathermy positive culture glucocorticoids

Argon-plasma Lavage Refractory

coagulation Rituximab and glucocorticoids a
All the treatments run in parallel.

ticularly among the 16 patients with only 1 lesion (n = 14).

Table 2. Characteristics of Patients With Airway Stenosis
The remaining 2 patients with single lesions had tracheal
Characteristic Measured Valuea and left upper lobe stenosis. Conversely, 14 of 15 patients
Women 32 (73)
with main bronchi involvement had more than 2 lesions,
Demography, median (IQR)
and 5 had bilateral stenoses of the main bronchi. There were
Age at GPA diagnosis, y 30.1 (19.9-43.2)
23 patients with lesions in the secondary bronchi: 9 were
Age at airway stenosis diagnosis, y 37.6 (26.6-46.8)
bilateral, and two-thirds of the lesions (15 of 23) presented
Disease duration, mo 146.1 (91.4-228.8)
in the left upper lobe. Eight patients had lesions in the sub-
Immunosuppressants tried, No. 4 (3-5)
glottis, with more severe lesions in the secondary bronchi
CYC exposure, mg/kg 140 (76-199)
Treated with antibiotics 18 (41)
sparing the main bronchi.
Distribution
Interventions
ENT system 43 (98)
During the follow-up period, 213 interventions were recorded
Lungs 25 (73)
(Table 3). The most common procedure overall was balloon
Kidneys 11 (34)
dilatation without adjuvant local treatment, but patients with
Other 16 (36)
SGS only were treated with carbon dioxide laser and mitomy-
Localizedb 23 (52)
cin C. Five (11.4%) did not require intervention, and 4 of these
Early systemicc 10 (23)
had only SGS (median follow-up, 69.1 months; IQR, 33.0-87.7
Generalizedd 10 (23)
Severee 1 (2)
months). Three-quarters of the lesions in the subglottis (26 of
Serologic findings 36), two-thirds of the lesions affecting the trachea or main bron-
PR3-ANCA positive 27 (61) chi (18 of 28), and half of the lesions in the secondary bronchi
MPO-ANCA positive 4 (9) (23 of 46) received local treatment.
PR3 and MPO-ANCA positive 1 (2) The median number of interventions per patient was 2,
ANCA negative 11 (25) and only 3 patients had a single procedure (Table 3). Forty-
three interventions (20.2%) were performed for critical ste-
Abbreviations: ANCA, antineutrophil cytoplasmic antibody;
CYC, cyclophosphamide; ENT, otorhinolaryngologic; GPA, granulomatosis with noses during active GPA, with a median interval before the
polyangiitis; IQR, interquartile range; MPO, myeloperoxidase; PR3, proteinase 3. next intervention of 4.4 months (IQR, 2.4-11.5 months), and
a
Unless otherwise indicated, data are reported as number (percentage) of the the median interval of those performed during remission of
44 included patients. GPA was 5.2 months (IQR, 2.4-14.4 months). Following the
b
Affecting the upper or lower airways. last planned intervention, the median follow-up period was
c
Any organ except renal or imminent vital organ failure. 27 months. Thirteen patients (30%) required tracheostomies
d
End-organ involvement, but creatinine level less than 500 μmol/L or other during the follow-up period, and 7 of these were subse-
vital organ failure.
e
quently decannulated. After the change in management
Renal disease (creatinine level >500 μmol/L).21
strategy in 2007, 1 patient had a temporary tracheostomy
and was decannulated within 22 days.
the longest being 239 months. Twelve patients had airway ste- All but 1 patient reached at least 1 period of airway sta-
nosis at the time of diagnosis, of whom 4 had renal disease, bility (≥12 months between treatments). The median time
and 2had ENT involvement only. Ten of these patients were patients spent without interventions was 27.6 months (IQR,
women. 17.2-46.3 months), and overall, patients spent 45.7% of the
follow-up time with a stable patent airway (IQR, 28.5-84.3
Distribution of Lesions months). Five patients without interventions and 3 with
Bronchoscopic examination of the 44 patients revealed 110 short follow-up were excluded from this calculation. Most
lesions with the distribution shown in Figure 1. The median of the patients who required further treatment after more
number of lesions per patient was 2 (IQR, 1-4). Subglottic than 2 years of disease control presented with airway diffi-
stenosis was the most prevalent lesion (36 of 44, 82%), par- culties but no evident reactivation of GPA (11 patients, 12 of

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 Granulomatosis With Polyangiitis (Wegener’s) Original Investigation Research

Figure 1. Distribution of Stenotic Lesions in the Airways of 44 Patients

(n=44)

36 (82)

7 (16)

8 (18)
6 (14) 12 (28) 3 (7)
15 (34)

9 (20)

4 (9)

3 (7)
6 (14)

Data are reported as number

(percentage) of patients with lesions
in the indicated areas; numbers sum
to more than 100% because patients
presented with multiple lesions.

13 procedures). In addition, in 6 of these 11 patients, the tance was 395 m (IQR, 285-445 m). After treatment, there was
lesion requiring further treatment changed over time. Four improvement in all the values (Table 5). The greatest increase
of 5 patients who had 2 to 4 intralesional injections with in PEFR and greatest reduction in Empey index were seen in
alemtuzumab in clinically fibrotic scars had a median patients with SGS. The median change in walking distance was
intervention-free period of 42.5 months. an improvement of 25 m (16.5%) in the 6 patients who had data
The results for each subgroup are listed in Table 4. before and after interventions.
Patients in the bronchi group had a more refractory course.
This is also seen in patients in the widespread group with a Adverse Events
stenotic lesion in each anatomical area of the bronchial tree Major adverse events included postoperative hemorrhages
(n = 9; median time with airway stability, 55.7 months; IQR, in 2 patients and self-limiting perforation of the airway due
46.9-98.7 months) and in those with SGS and stenosis in the to trauma from the bougie dilatation in 2 patients (Table 6).
secondary bronchi only (n = 8; median time with airway sta- Two patients developed chest infections after intralesional
bility, 95.7 months; IQR, 83.8-98.2 months). injections of alemtuzumab, although they were also receiv-
ing this medication systemically. One patient developed
Pulmonary Function Tests polypoidal granulation tissue in the area treated with topi-
Twenty patients had pretreatment assessments, and 26 had cal mitomycin C, which caused mild breathlessness and
data available for comparison before and after treatment. Data required excision using a flexible bronchoscope. One
for pretreatment walking tests were present in 9 patients, and patient had stents inserted in the main bronchi in another
there were data for progress assessment for 19 patients. Be- hospital, and these subsequently required surgical removal
fore interventions, the median percentage of predicted FEV1 after failed attempts at controlling restenosis with systemic
was 74.5% (IQR, 52.6%-83.2%); the median percentage of pre- treatment. Another patient died 5 months after a dilatation
dicted PEFR was 45.8% (IQR, 37.1%-76.4%); the median Empey with no adjuvant treatment from respiratory and renal fail-
index was 9.89 (IQR, 8.0-11.4); and the median walking dis- ure secondary to refractory active vasculitis. This patient

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 Research Original Investigation Granulomatosis With Polyangiitis (Wegener’s)

had had a limited response to the dilatation, which suggests (28%-62.5%)10,17,22 and may reflect the focus on SGS in other
that there was alveolar disease. series. As in previous reports, patients with airway stenosis pre-
sented at an earlier mean age (37.6 years) (published range,
26-40 years10,12,15,17) than the general GPA population (pub-
lished range, 53-55 years23,24). However, the female predomi-
Discussion nance (73%) in our cohort is mirrored only by McDonald et al.4
This medical record review is one of the largest published se- The area most affected was the subglottis (36 of 44, 81.8%),
ries describing the airway management in GPA. The preva- and most patients with a single lesion had SGS (14 of 16). It is
lence of airway stenosis among patients with GPA in our in- not clear whether stenoses with the appearance of mature scar
stitution was 17.5% (44 of 251), similar to that reported in other tissue in GPA are fibrotic or whether there is an underlying in-
publications (12%-50%).2-4,9,15,22 Lower-airway involvement (30 flammatory process.15,25 Our results with alemtuzumab sug-
of 44, 68.2%) was higher than figures quoted in the literature gest that even in fibrotic-looking lesions there may be an un-
derlying inflammatory process.
Table 3. Characteristics of Procedures The proportion of patients who required only 1 proce-
dure was at the lower end of published data (11%-35%).10,12,15
Characteristic Measured Valuea
Continuous data, median No. (IQR) This may be explained by the long follow-up period in this study
Lesions per patient 2 (1-4) and the refractory nature of the condition. The number of pro-
Interventions per patient 3 (1-8) cedures performed (n = 213) and the fact that patients spent
Interval between procedures (median-IQR), mo 4.9 (2.3-14.1) just under half (45.7%) of their follow-up time with a stable pat-
Follow-up duration after last procedure, mo 27 (6.2-47.5) ent airway illustrates the refractory nature of the condition.
Procedures during active endobronchial diseaseb 43 (20.1) Patients with lower airway stenoses had the most refractory
Procedures during lung infectionb 66 (30.4) course (Table 4).
Methods of dilatation (n = 213)c,d The median interval between procedures was the same
Balloon dilatation 130 (60.8) whether patients were treated during disease activity or not.
Bougie dilatation 34 (15.9) Topical mitomycin C showed some benefit in patients treated
Laser dissection 24 (11.2) with thermal techniques or persistent stenoses. Our experi-
Diathermy dissection 5 (2.34) ence using carbon dioxide laser was favorable and without
Argon-plasma coagulation 5 (2.34) long-lasting adverse events. Although there are no good com-
Cryotherapy 9 (4.21)
parative trials, most authors advocate the use of mechanical
Adjuvant therapy
techniques of dilatations and/or radial incisions with intral-
Intralesional glucocorticoids 24 (9.3)
esional corticosteroid or topical mitomycin C.11,13,14,26 Initial
Topical mitomycin C 38 (14.7)
pulmonary function test results were consistent with airway
Intralesional alemtuzumab 9 (3.5)
obstruction, but 3 patients requiring treatment for symptoms
None 142 (55.0)
had normal pulmonary function findings. Pulmonary func-
Abbreviation: IQR, interquartile range. tion test results showed an improvement over time in objec-
a
Unless otherwise indicated, data are reported as number (percentage) of tive and functional measures, but more consistent data are re-
procedures.
b
quired to confirm these findings.
Infection was defined as positive cultures of bronchial lavage or sputum.
c
The incidence of adverse events was 9%, and the inci-
Six patients treated with only glucocorticoids or alemtuzumab.
d
dence of adverse events directly related to endoscopy was 5%.
A total of 53 dilatations (24.8%) were performed under general anesthesia.
The rate of airway perforations (1.3%) was comparable to other

Table 4. Patient Phenotype and Outcome According to Disease Distribution

Patients, No. (%) Local Median Proportion

Localized Disease PR3-ANCA–Positive Interventions, Follow-up, of Time With
Lesion Distributiona (n = 23) (n = 27) Median No. mo Stable Airway, %a
SGS only 4 (17.4) 11 (78.6) 1 38.8 87.1b
(n = 14)
SGS, trachea, and/or main bronchi 5 (21.7) 5 (71.4) 10 88.1 78.3
(n = 7)
Bronchi only 3 (13.0) 3 (50.0) 3.5 44.9 36.7c
(n = 6)
Widespread diseased 11(47.8) 3 (33.3) 4 83.9 94.7
(n = 17)
c
Abbreviations: ANCA, antineutrophil cytoplasmic antibody; PR3, proteinase 3; Two patients excluded: 1 had no interventions, and 1 had follow-up shorter
SGS, subglottic stenosis. than 12 months.
a d
Calculated from the sum of months with airway stability over total follow-up Any combination of main airways and secondary bronchi.
period.
b
Six patients excluded: 4 had no interventions, and 2 had follow-up shorter
than 12 months.

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 Granulomatosis With Polyangiitis (Wegener’s) Original Investigation Research

reports (0%-4%).10,11,15,26 One patient had a complication di-

Table 5. Pulmonary Function Testsa
rectly attributable to mitomycin C (1 of 213, 0.5%) and re-
quired further intervention. Mitomycin C carries a risk of Difference From
Predicted Change, % Change
scarring,10,13,27-29 but our results show that the risks can be re- in Empey
Lesion Distribution FEV1 PEFR Index, %
duced when this treatment is used with caution, ie, no more SGS only 8.5 64.31 −28.72
than 4 applications of 0.5 mg each for less than 60 seconds. (n = 8)
Seven of 13 patients who required tracheostomies were de- Main airways 5.67 10.16 −11.30
(n = 6)
cannulated. This compares favorably with other published co-
SGS, trachea, and/or 29.32 21.00 −13.38
horts where the tracheostomy rates vary from 0% to 42%, of main bronchi
which 2.3% to 100% are permanent.10,12,15,26 (n = 4)
The long follow-up in the present study allows the Widespread diseaseb 4.11 15.17 −13.53
(n = 12)
authors to draw useful conclusions on the course of the dis-
Abbreviations: FEV1, forced expiratory volume in 1 second; IQR, interquartile
ease. However, a larger sample to enable comparison
range; PEFR, peak expiratory flow rate.
between treatment groups would have been advantageous, a
Change measured as initial test result minus the last test result. The median
and more complete data on pulmonary function tests to (IQR) time from procedure was 13.57 (IQR, 3.07-43.6) months.
assess functional outcomes would be desirable. The man- b
Any combination of main airways and secondary bronchi.
agement and outcome analysis of airway stenosis in GPA is
complex, as demonstrated by the fact that recurrence of
Table 6. Adverse Events and Outcomes
stenosis is independent of disease activity and that over
time the site of stenosis requiring treatment may change. Adverse Event Outcome
Different outcome measures such as airway diameter, func- Infection Treated successfully; 1 mucus plug removed
(n = 5) endoscopically; 1 lung infection after
tional and symptomatic assessments, and intervals between alemtuzumab treatment; 3 chronic lung
procedures are not entirely satisfactory. Airway diameter infections following several courses of treatment
and functional and symptomatic assessments lack consis- Polyps after treatment Excised with flexible bronchoscope
(n = 1)
tency, and interprocedure interval measurements are Bleeding Self-limiting
blurred in those patients who have staged procedures (eg, (n = 2)
the overall median interval in the present study was 4.9 Perforation Healed spontaneously
(n = 2)
months, while the median intervention-free period after the
Allergy to fentanyl No severe effects
last planned procedure was 27 months). Using 12-month air- (n = 1)
way stability as the outcome seemed sensible for this data Stent complications Both stents were removed; 1 of the patients later
set, but the addition of a patient-reported outcome measure (granulation and developed bronchopleural fistula
displacement)
would be useful. Using our data and those of previous (n = 2)
reports,10,14,15,30 we developed an algorithm for the assess- Death Patient died of pneumonia and active pulmonary
(n = 1) vasculitis 5 months after last intervention
ment and management of these patients (Figure 2).

Figure 2. Algorithm for Managing Patients With Granulomatosis With Polyangiitis

and Suspected Airway Stenosis

Assessment
Symptoms and disease activity
Dynamic spirometry and incremental shuttle test
Nasendoscopy and bronchoscopy
Microbiology of nose, throat, BAL, and brushings
Chest CT scan

Local intervention Antimicrobial therapy Systemic vasculitis therapy

Subglottic, tracheal, or Secondary bronchi or

severe and/or recurrent moderate and/or unilateral
main bronchial stenosis main bronchial stenosis

Laser and/or bougie Balloon dilatation

dilatation cryotherapy

Chronic and/or fibrotic Active lesion,

lesion, topical mitomycin C intralesional glucocorticoid

No Yes
Reassess Improvement Periodic reassessment
BAL indicates bronchoalveolar
lavage; CT, computed tomography.

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 Research Original Investigation Granulomatosis With Polyangiitis (Wegener’s)

longed airway stability periods were achieved in most

Conclusions patients, but stenosis of the airways often recurred. A multi-
disciplinary team comprising an ENT surgeon, respiratory
The frequency, distribution, and management of subglottic, physician, and vasculitis physician was assembled. 31 We
tracheal, and bronchial stenoses occurring in patients with suggest tight control of infection and immunomodulatory
GPA has been described. Patients underwent various inter- therapy, lifelong follow-up, and an algorithm to structure
ventions, and multiple procedures were needed before a the approach to these patients to assess the effect of each
period of stable airway patency could be achieved. Pro- treatment modality.

ARTICLE INFORMATION 5. Suresh E, Wong D, Kamali S, Hall C, Luqmani R. 19. Singh SJ, Jones PW, Evans R, Morgan MD.
Submitted for Publication: March 31, 2014; final An unusual cause of death in Wegener’s Minimum clinically important improvement for the
revision received June 9, 2014; accepted August granulomatosis. Ann Rheum Dis. 2006;65(5):698. incremental shuttle walking test. Thorax. 2008;
29, 2014. 6. Belostotsky VM, Shah V, Dillon MJ. Clinical 63(9):775-777.

Published Online: October 16, 2014. features in 17 paediatric patients with Wegener 20. Hoare TJ, Jayne D, Rhys Evans P, Croft CB,
doi:10.1001/jamaoto.2014.2430. granulomatosis. Pediatr Nephrol. 2002;17(9):754- Howard DJ. Wegener’s granulomatosis, subglottic
761. stenosis and antineutrophil cytoplasm antibodies.
Author Contributions: Dr Martinez Del Pero had J Laryngol Otol. 1989;103(12):1187-1191.
full access to all of the data in the study and takes 7. Rottem M, Fauci AS, Hallahan CW, et al. Wegener
responsibility for the integrity of the data and the granulomatosis in children and adolescents: clinical 21. European Community Study Group on Clinical
accuracy of the data analysis. presentation and outcome. J Pediatr. 1993;122(1): Trials in Systemic Vasculitis ECSYSVASTRIAL.
Study concept and design: Martinez Del Pero, Jayne, 26-31. European therapeutic trials in ANCA-associated
Sivasothy, Jani. 8. Brown KK. Pulmonary vasculitis. Proc Am Thorac systemic vasculitis: disease scoring, consensus
Acquisition, analysis, or interpretation of data: Soc. 2006;3(1):48-57. regimens and proposed clinical trials. Clin Exp
Martinez Del Pero, Chaudhry, Sivasothy, Jani. Immunol. 1995;101(suppl 1):29-34.
9. Cordier JF, Valeyre D, Guillevin L, Loire R,
Drafting of the manuscript: Martinez Del Pero, Brechot JM. Pulmonary Wegener’s granulomatosis. 22. Rosenberg DM, Weinberger SE, Fulmer JD, Flye
Jayne, Sivasothy. A clinical and imaging study of 77 cases. Chest. MW, Fauci AS, Crystal RG. Functional correlates of
Critical revision of the manuscript for important 1990;97(4):906-912. lung involvement in Wegener’s granulomatosis. Use
intellectual content: Chaudhry, Sivasothy, Jani. of pulmonary function tests in staging and
Statistical analysis: Martinez Del Pero, Jayne, 10. Nouraei SA, Obholzer R, Ind PW, et al. Results follow-up. Am J Med. 1980;69(3):387-394.
Chaudhry, Sivasothy. of endoscopic surgery and intralesional steroid
therapy for airway compromise due to 23. Holle JU, Gross WL, Latza U, et al. Improved
Administrative, technical, or material support: outcome of 445 Wegener's granulomatosis patients
Sivasothy, Jani. tracheobronchial Wegener’s granulomatosis. Thorax.
2008;63(1):49-52. in a German vasculitis center over four decades.
Study supervision: Chaudhry, Sivasothy, Jani. Arthritis Rheum. 2010.
Conflict of Interest Disclosures: None reported. 11. Hoffman GS, Thomas-Golbanov CK, Chan J, Akst
LM, Eliachar I. Treatment of subglottic stenosis, due 24. Takala JH, Kautiainen H, Malmberg H,
Funding/Support: This project was supported by to Wegener’s granulomatosis, with intralesional Leirisalo-Repo M. Wegener’s granulomatosis in
the Cambridge Biomedical Research Centre. corticosteroids and dilation. J Rheumatol. 2003;30 Finland in 1981-2000: clinical presentation and
Role of the Sponsor: The Cambridge Biomedical (5):1017-1021. diagnostic delay. Scand J Rheumatol. 2008;37(6):
Research Centre had no role in the design and 435-438.
12. Gluth MB, Shinners PA, Kasperbauer JL.
conduct of the study; collection, management, Subglottic stenosis associated with Wegener’s 25. Daum TE, Specks U, Colby TV, et al.
analysis, and interpretation of the data; granulomatosis. Laryngoscope. 2003;113(8):1304- Tracheobronchial involvement in Wegener’s
preparation, review, or approval of the manuscript; 1307. granulomatosis. Am J Respir Crit Care Med. 1995;151
and decision to submit the manuscript for (2 Pt 1):522-526.
publication. 13. Roediger FC, Orloff LA, Courey MS. Adult
subglottic stenosis: management with laser 26. Eliachar I, Chan J, Akst L. New approaches to
Previous Presentation: Data reported herein were incisions and mitomycin-C. Laryngoscope. 2008;118 the management of subglottic stenosis in
presented as an oral presentation at the (9):1542-1546. Wegener’s granulomatosis. Cleve Clin J Med. 2002;
Laryngology and Rhinology Free Paper Session of 69(suppl 2):SII149-SII151.
the Royal Society of Medicine; February 1, 2013; 14. Arebro J, Henriksson G, Macchiarini P, Juto JE.
New treatment of subglottic stenosis due to 27. Roh JL, Kim DH, Rha KS, Sung MW, Kim KH,
London, England. Park CI. Benefits and risks of mitomycin use in the
Wegener’s granulomatosis. Acta Otolaryngol. 2012;
132(9):995-1001. traumatized tracheal mucosa. Otolaryngol Head
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