Modeling Recurrence in Idiopathic Subglottic Stenosis With Mobile Peak Expiratory Flow

Abstract

Objectives/hypothesis: We sought to establish normative peak expiratory flow (PEF) data for patients with idiopathic subglottic stenosis (iSGS), evaluate whether immediate changes in PEF after a procedure predict long-term treatment response, and test if a decline in longitudinal PEF is associated with disease recurrence.

Study design: International, prospective, 3-year multicenter cohort study of 810 patients with untreated, newly diagnosed, or previously treated iSGS.

Methods: iSGS patients consented and enrolled in the North American Airway Collaborative (NoAAC) iSGS¹⁰⁰⁰ cohort recorded PEF data on a mobile smartphone app. Cox regression tested the associations between the magnitude of postoperative PEF improvement and longitudinal 90-day PEF decline with the risk of disease recurrence.

Results: Within the NoAAC iSGS¹⁰⁰⁰ cohort, 810 patients participated in a 3-year prospective study comparing surgical treatment efficacy and 385 had appropriate PEF measurements and follow-up data. Of those patients, 42% (161/385) required at least one operation during study follow-up. The mean PEF preceding operative intervention was 241 L/min (95% confidence interval [CI]: 120-380) corresponding to a predicted PEF of 52%. The mean increase in PEF following a procedure was 111 L/min (95% CI: 96-125 L/min). Interestingly, the magnitude of immediate PEF improvement was not predictive of disease recurrence (hazard ratio [HR] for 100 L/min increase = 0.90, 95% CI: 0.60-1.00). However, recurrence was associated with the magnitude of PEF decline over 90 days (30% vs. 10% decline, HR = 2.2, 95% CI: 1.5-3.0).

Conclusions: We provide normative PEF data on a large iSGS patient cohort. The degree of PEF improvement immediately after surgery was not associated with a longer procedure-free interval. However, a 30% decline in PEF over 90 days was associated with elevated risk of disease recurrence.

Level of evidence: 2 Laryngoscope, 131:E2841-E2848, 2021.

Keywords: Idiopathic subglottic stenosis; disease-free interval; expiratory flow; peak expiratory flow.

Figure 1.

Patient inclusion flowsheet.

Figure 2.

A) Distribution of PEF_PRE and PEF_POST B) Distributions of relative PEF_PRE (% predicted) and PEF_POST. C) Individual treatment responses after surgical procedure for 137 patients with one or more operations after trial enrollment.

Figure 3.

Kaplan-Meier curves by stratum of ΔPEF (ΔPEF = PEF_POST - PEF_PRE) in L/min.

Figure 4.

Estimated relationship between longitudinal PEF decline and recurrent procedure free survival. The % decline in PEF over 90 days was utilized as a continuous variable in Cox regression analysis estimating probability of operative procedure. Patients with a 30% decline in PEF were more than twice as likely to require an operative procedure when compared with patients that only experienced a 10% decline (HR: 2.2, 95% CI: 1.5–3.0).

Figure 5.

Predictions of exact PEF_NADIR date based on slope derived from different amount of PEF data after a highest PEF (such as after an operation). The y axis represents the difference (in days) between the predicted date of PEF_NADIR and observed date of PEF_NADIR (the larger the absolute value of the number, the worse the prediction).

Figure 6.

Distinct patterns of PEF decline in iSGS patients: “sawtooth” (left) and “flatline” (right).