Annals of Otology, Rhinology & Laryngology 1 –6© The Author(s) 2015Reprints and permissions: sagepub.com/journalsPermissions.navDOI: 10.1177/0003489415582255aor.sagepub.com

Original Article

IntroductionAcquired subglottic stenosis (AS) may be attributable to a multitude of etiologies, including systemic inflamma-tory conditions, trauma, prolonged intubation, or prior tracheostomy. In contrast, idiopathic subglottic and tra-cheal stenosis (ISTS) has no attributable cause and is a diagnosis of exclusion after other etiologies have been ruled out. Although it has been suggested to be associated with gastroesophageal reflux disease (GERD), hormonal influences, respiratory tract infection, cough, and autoim-mune disease, there is limited research to delineate a clear etiology; its pathogenesis is solely speculative and likely multifactorial.1-9

ISTS is a rare, slowly progressive inflammatory condi-tion affecting the subglottis and first 2 tracheal rings.8,10 It is predominately diagnosed in otherwise healthy women in the third to fifth decade of life.5,8,11 Symptomatically, patients present with dyspnea on exertion, shortness of breath,

hoarseness, stridor, or chronic cough. Frequently, patients are treated for asthma without benefit prior to diagnosis.1,4,8 In a prior series, 33% to 37% of subglottic stenosis patients were previously misdiagnosed with asthma.12,13 Identification of the stenosis can be made via flexible laryngoscopy, surgi-cal endoscopy, or imaging studies. Initial treatment may be conservative, including observation.5 Surgical treatment typically consists of serial incision and dilations, mucosal rotational flaps, and/or tracheal resection and reanastomo-sis.3,5,8,10-15 Adjuvant therapies may include mitomycin C

582255 AORXXX10.1177/0003489415582255Annals of Otology, Rhinology & LaryngologyGnagi et alresearch-article2015

1Department of Otolaryngology–Head and Neck Surgery, Mayo Clinic Arizona, Phoenix, Arizona, USA2Inside Story, Sydney, NSW, Australia

Corresponding Author:David G. Lott, Department of Otolaryngology–Head and Neck Surgery, Mayo Clinic Arizona, 5777 East Mayo Boulevard, Phoenix, AZ 85054, USA. Email: lott.david@mayo.edu

Idiopathic Subglottic and Tracheal Stenosis: A Survey of the Patient Experience

Sharon H. Gnagi, MD1, Brittany E. Howard, MD1, Catherine Anderson, BA, PGDip, QPMR2, and David G. Lott, MD1

AbstractObjectives: To report and compare patients’ experiences with acquired subglottic stenosis (AS) versus idiopathic subglottic and tracheal stenosis (ISTS).Methods: A survey was made available to patients with AS and ISTS. Results were analyzed for inter- and intragroup differences using a 2-tailed t test.Results: The study included 160 survey participants (AS n = 28; ISTS n = 132), with a predominance of female participants (82% AS, 98% ISTS). Acid reflux was the most prevalent comorbidity across groups (42%-43%). A significant difference in time to diagnosis was found between groups, with 32% of AS patients diagnosed within 3 months of symptom onset, compared to 2% with ISTS. A diagnosis delay greater than 18 months occurred for 58% of ISTS patients. There was no difference in treatment approach, with the most common treatment being balloon dilation, followed by laser dilation. Tracheal resection was performed in 36% of patients in both groups. Patient satisfaction with surgical outcomes was significantly higher after tracheal resection (76%) compared to other treatment modalities (39%).Conclusions: ISTS remains a diagnostic challenge as highlighted by the delay in diagnosis compared to AS. There appears to be no historical or symptomatic factors specific to ISTS. Additionally, patients report increased satisfaction and symptom resolution after tracheal resection.

Keywordsidiopathic subglottic stenosis, laryngotracheal stenosis, patient experience

2 Annals of Otology, Rhinology & Laryngology

application,8,12,15-17 intralesional steroid injection,8,12,13 cryo-therapy,18 proton pump inhibitors,1,8,12,19 trimethoprim-sulfa-methoxazole,12 or postoperative inhaled steroid use.12

Airway stenosis can be a significantly debilitating disease. Patients often find themselves living life from breath to breath, wondering when they will need to undergo their next treatment. Studies on the disease to this point have been from the physician/scientist perspective and have not been defini-tive. We postulated that a survey of patients with airway ste-nosis might discover new points that could further guide investigation or treatment. This article reviews the patients’ perspectives of their disease process and experiences with treatment. The primary intent is to present a patient-centered survey designed by a patient to seek commonalities in the largest multinational cohort ever studied for this disease. The manuscript is not meant to define causative factors for idio-pathic subglottic stenosis but rather to elucidate any trends that can be further investigated and provide clinicians with the patients’ perspectives of their disease.

MethodsA survey was made available to patients internationally with either acquired or idiopathic subglottic stenosis via the Internet. Treating clinicians and institutions were purposefully not involved in the administration or collection of the survey other than to notify patients it was available in an attempt not to bias the results. The goal of the survey was to provide phy-sicians with the patient’s perspective of this condition as well as contribute to the body of knowledge of this disease. This research was Institutional Review Board exempt.

The survey was developed by a patient with subglottic stenosis and encompassed questions regarding demograph-ics, symptomatology, diagnosis, associated conditions, treatment, and response to treatment. Given the various backgrounds and cultures of the study subjects, questions were created to allow for a broad range of answers so any

potential association would not be missed. Results were ana-lyzed for inter- and intragroup differences using a 2-tailed t test. A P value <.05 was considered statistically significant.

Results

DemographicsA total of 160 people participated in the study. The ISTS group consisted of 132 people. There were 28 people in the AS group. More than 95% of the participants completed the survey via referral from various Internet-based support groups, with less than 5% completing the survey as a result of a referral from a treating clinician. Most participants were from North America (83%) but included Europe (13%), Australia/Oceania (3%), and South America (1%). The ISTS group was comprised of 98% women and 2% men. The AS group included 82% women and 18% men. The most common age at diagnosis for ISTS was between 41 and 50 (28%), followed by 21 to 30 (26%). The most common age at diagnosis for the AS patients was between 31 and 40 (32%) (Table 1).

Associated SymptomsFluctuations in difficulty breathing are not consistent across patients. Twenty-one percent state that the morning is worse. However, 37% describe no change in respiratory symptoms over the course of a day. Coughing and mucus is the most common associated symptom, with 91% com-plaining of this.

Comorbid ConditionsAllowing for a write-in response in the survey, no comorbid conditions or familial diseases were significantly more prominent in either group (Figure 1). These were defined as

Table 1. Demographics for Patients With Acquired Subglottic Stenosis (AS) and Idiopathic Subglottic And Tracheal Stenosis (ISTS).

Gender (%)

Male Female

ISTS 2 98AS 18 82

Age at Survey (%) Under 20 21-30 31-40 41-50 51-60 61-70 Over 70ISTS 1 14 19 33 23 9 1AS 0 11 25 18 25 11 4 Age at Diagnosis (%) Under 20 21-30 31-40 41-50 51-60 61-70 Over 70ISTS 2 26 23 28 18 2 1AS 7 4 32 29 7 7 0

Gnagi et al 3

either patient perception of symptoms or clinical diagnosis. Acid reflux was the most common comorbid condition in each group but was not significantly different between the groups (43% ISTS, 42% AS). The majority of patients did not have allergies or intolerances (63% ISTS, 57% AS). Specific allergy differences did not achieve significance (Figure 2).

Hormonal AlterationOverall, more ISTS patients have had some sort of hormone therapy and have used oral contraceptives more frequently than AS (Figure 3). However, once the number of males in the AS group were taken into account, there was no signifi-cant difference. There was no difference between the type of hormone replacement or length of treatment.

DiagnosisOne in 3 patients (32%) with AS were diagnosed within 3 months of symptom onset, compared to 2% in the ISTS group (P < .05). A majority of the ISTS patients (58%) were not diagnosed for more than 18 months, with 45% not diag-nosed for more than 2 years after symptom onset (Figure 4).

TreatmentOtolaryngology physicians are by far the most common physicians treating this disorder for both groups (61% ISTS,

67% AS). Thoracic surgeons managed 26% of ISTS and 23% of AS patients in this survey. Balloon dilation is the most common treatment, followed by laser dilation in both groups (Figure 5). Tracheal resection was performed in 36% of both ISTS and AS patients. More AS patients (21%) had received no treatment at the time of the survey com-pared to the ISTS group (6%).

0 10 20 30 40 50

Thyroid condition

Heart condition

Diabetes

Hypercholesterolemia

Hiatal hernia

Acid Reflux

None

Other

Percentage of Patients

Idiopathic Subglottic Stenosis

Acquired Subglottic Stenosis

Figure 1. Comorbid conditions.

0 10 20 30 40 50 60 70

Dairy intolerance

Gluten intolerance

Lactose intolerance

Soy intolerance

Dairy allergy

Egg allergy

Other

Unsure

No

Yes

Percentage of Patients

Idiopathic Subglottic Stenosis

Acquired Subglottic Stenosis

Figure 2. Allergies/intolerances.

0 10 20 30 40 50 60 70

Oral Contraceptive

Hormone Replacement Therapy

Estrogen for Postmenopausal Therapy

Contraceptive Skin Implant

None

Other

Percentage of Patients

Idiopathic Subglottic Stenosis

Acquired Subglottic Stenosis

Figure 3. Hormonal alteration.

4 Annals of Otology, Rhinology & Laryngology

Tracheal Resection OutcomesWithin the ISTS group, 34 patients had a tracheal resection. Following resection, 47% of ISTS patients had complete resolution of respiratory symptoms at the time of the survey (Figure 6). Length of time after resection was not taken into account. An additional 29% classified their breathing as mostly normal. Therefore, 76% of patients classified their breathing as essentially normal following resection. When compared to ISTS patients who have not had a resection, this demonstrated a significant improvement in respiratory symptoms (resection 76%, no resection 39%). This benefit decreases as exercise becomes more strenuous. Forty-seven percent of patients classify themselves as essentially normal with strenuous exercise after resection.

DiscussionThe management of ISTS can be frustrating for both patients and physicians. Compounding this frustration is the lack of significant research findings that elucidate any

potential etiologies. This survey was created to seek com-monalities in the largest multinational cohort ever studied for this disease. The intent of the study was not to define causative factors for idiopathic subglottic stenosis but rather to collect a broad, inclusive experience from a large and diverse patient cohort. As such, specificity was sacri-ficed for inclusivity. These findings may then be used to further investigate potential trends, provide clinicians with insight into the patient’s perspective, or council new patients based on shared experiences with others suffering from this disease.

The survey method of data collection subjects the data in this study to voluntary and nonresponse biases. Patient self-reporting may lead to inconsistencies in terminology and misunderstanding of diagnoses or treatment modalities. Idiopathic cases may be overrepresented secondary to undi-agnosed conditions, such as limited Wegener’s granuloma-tosis. In addition, all respondents were at different stages of treatment and follow-up, potentially misrepresenting the efficacy of various treatments. Similarly, the methodology of treatments, degree of stenosis at time of treatment, and adjuvant therapies may not have been accurately reported, thus further complicating the interpretation of treatment response. The multinational nature of this patient cohort may cause further misrepresentations of the reported data due to cultural and medical management differences. Despite these potential inconsistencies, the data presented from this survey do contribute to the fund of knowledge of this rare and minimally studied disease and did reveal some trends that may warrant further investigation.

Demographically, this survey is consistent with prior studies that demonstrate a female predominance among patients with ISTS in a similar age group. Interestingly, the AS group had a higher proportion of females than what is typically reported. We postulate that this is likely secondary to the higher female involvement in online support groups for these conditions.

0

10

20

30

40

50

60

Perc

enta

ge o

f Pat

ient

s

Acquired Subglottic Stenosis

Idiopathic Subglottic Stenosis

Figure 5. Treatments received.

0 to 1 No to slight stridor; mostly to completely normal breathing2 to 3 More to regular stridor and cough4 to 5 Regular to constant stridor and cough

0

20

40

60

80

100

0 to 1 2 to 3 4 to 5

Perc

enta

ge o

f Pat

ient

s

Self Rating

Resection

No Resection

Figure 6. Response to treatment.

0

10

20

30

40

50

0-3 mo 4-6 mo 7-12 mo 12-18 mo 18-24 mo Over 2 yrs

Perc

enta

ge o

f Pat

ient

s Acquired Subglottic Stenosis

Idiopathic Subglottic Stenosis

Figure 4. Time to diagnosis.

Gnagi et al 5

The higher female predominance in the ISTS group continues to question the possible hormonal role or estro-gen effect in the etiology of ISTS. Although prior studies have failed to demonstrate estrogen receptors in stenotic lesions,8,10,11 the role of estrogen in wound healing draws attention to its questionable contribution in this dis-ease.8,20 In this survey, both acquired and idiopathic patients were equally likely to have taken hormones, sug-gesting that supplemental hormone usage does not play a role in ISTS. However, the specifics of hormonal altera-tion were not addressed and may be an area to further investigate. It is important to highlight that this study only asked about supplemental hormone usage, and the fact that there was not a significant difference between the ISTS and the AS groups does not exclude the role of other hormonal or autoimmune causes. Fourteen percent of patients stated that their physician had tested their hor-mone levels in relation to their ISTS. Perhaps this shows an increased awareness of the need for further investiga-tion in this regard.

There was no statistically significant difference in his-torical or symptomatic factors specific to ISTS when com-pared to AS, including other medical conditions, allergies, or intolerances. Both groups had a similar incidence of self-reported or diagnosed GERD, which may suggest a poten-tial role in the development of both ISTS and AS. However, secondary to its equal presence in both disease states, it decreases the likelihood that it is an inciting factor specific to ISTS.

The nonspecific presentation of symptoms without a his-tory of possible airway trauma likely explains the delay in diagnosis of over 18 months for the majority of ISTS patients, in comparison to a less than 3-month diagnosis in a third of AS patients. This finding is consistent with prior reports showing duration of symptoms ranging from an average of 10 to 31 months prior to diagnosis.4,5,11 In fact, Loutsidis et al21 proposed an average duration of symptoms of 2 years as useful criteria in diagnosis. This highlights the importance of ruling out subglottic stenosis in any middle-aged woman with complaints of wheezing, chronic cough, dyspnea on exertion, or shortness of breath.

Most patients were treated with either serial dilations or tracheal resection. When treatment is necessary, dila-tion is convenient, may be performed in an outpatient set-ting, and avoids a skin incision. However, dilation is typically associated with short-term improvement and a recurrence rate of at least 60% in 5 years.12 An average of approximately 1 to 2 procedures per patient per year has been previously reported.13 Given the need for multiple anesthetics and repeated dilation procedures, a tracheal resection should be a serious and possibly earlier consid-eration in patients presenting with ISTS. While open resection and reanastamosis has a higher risk, longer hos-pitalization, and longer recovery, it has been shown to be

a more definitive treatment with excellent long-term results.22-24 In our study, when compared to patients treated with dilations, patients receiving tracheal resec-tion reported significantly improved breathing. Seventy-six percent of resection patients rated their breathing as mostly normal or better.

ConclusionISTS remains a diagnostic and therapeutic challenge for physicians as highlighted by a significant delay in diagno-sis. It is an important consideration in the differential diag-nosis of chronic cough or dyspnea, especially in young to middle-aged women. Little is known about the etiology of ISTS, and this study did not reveal any statistically signifi-cant differences between historical or symptomatic factors specific to ISTS or AS. Etiologic factors previously pro-posed, including GERD and hormonal influences, have not been proven, and further research in this field is needed to elucidate causative factors and potential targeted therapies. Additionally, patients report increased satisfaction and symptom resolution after tracheal resection when com-pared to serial dilations. Therefore, it might be prudent to make resection an earlier consideration in ISTS patients as they often require multiple operative procedures over their lifetimes.

Authors’ NoteThis was a poster presentation at the American Bronchoesoph- agological Association at the Combined Otolaryngology Spring Meeting April 11, 2013, in Orlando, Florida.

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

FundingThe author(s) received no financial support for the research, authorship, and/or publication of this article.

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