Geographic Clustering of Idiopathic Subglottic Stenosis in North America: An Ecological Cohort Study

Idiopathic subglottic stenosis (iSGS) is a recurrent fibroinflammatory narrowing of the subglottis, typically affecting White pre- and perimenopausal women. While its etiology remains uncertain, inflammatory signaling, reflux, hormonal influences, and mycobacterial factors have been proposed. This study evaluated geographic variability in survey-ascertained iSGS prevalence, exploring potential environmental correlates associated with regional disease distribution.

A retrospective ecological analysis of self-reported demographic and clinical data from members of an international iSGS online support group was performed. Responses were analyzed by continent, country, and US state or Canadian province. Estimated prevalence per 1,000,000 White females was calculated using census data and examined in relation to environmental and access-related factors, including temperature, humidity, and particulate matter.

Among 4450 survey respondents, 99.3% were female and 83.8% reported symptom onset after age 30. Survey-ascertained prevalence was highest in Wyoming (18.1), Utah (17.4), Iowa (15.3), Colorado (13.9), and Minnesota (12.1), and lowest in New Hampshire (1.2), Montana (1.5), Alaska (2.3), and Indiana (2.3). In Canada, survey-ascertained prevalence was highest in Alberta (85.4) and Saskatchewan (65.3), and lowest in Quebec (2.9). Higher prevalence regions were geographically clustered in areas sharing dry or semi-arid climates, higher elevation, higher temperature and lower humidity. PM2.5 modified the association between elevation and survey-ascertained prevalence but was not independently associated with prevalence.

iSGS demonstrated geographic clustering in North America associated with higher altitude, lower humidity and higher temperatures; however, these ecological findings should be considered hypothesis-generating and warrant further investigation using patient-level exposure and biologic data.

This study represents Level 4 evidence given its ecological, cross-sectional design.