External validation of predictive equations for determining the need for in-flight oxygen supplementation in patients with respiratory disease

Rationale Patients with chronic respiratory diseases may develop clinically significant hypoxemia during commercial air travel because of reduced cabin pressure. In-flight oxygen prescription is typically guided by hypoxic challenge testing (HCT), a procedure that is time-consuming, costly, and not universally available. Several predictive equations based on sea-level physiological measurements have been proposed as alternatives. We aimed to externally validate six published predictive equations by comparing their performance with HCT in a large, heterogeneous cohort of patients with chronic respiratory diseases. Methods We retrospectively analyzed all patients who underwent HCT at our center between 2016 and 2026. Sea-level arterial blood gases, pulmonary function tests, and relevant clinical data were collected. Six published predictive equations (E1–E6) were used to estimate in-flight PaO 2 and compared with PaO 2 measured during HCT. Results A total of 177 patients were included: 39 (22%) with COPD, 64 (36%) with ILD, 34 (19%) with cystic fibrosis, and 40 (23%) with other chronic respiratory diseases. Significant correlations between predicted in-flight PaO 2 and HCT PaO 2 were observed (ρ = 0.48 for E1 and E2 to 0.84 for E5; all p ≤ 0.001), but diagnostic performance remained limited. Across all patients, predictive equations demonstrated high specificity (76% for E2 to 98% for E6) but inadequate sensitivity (11% for E6 to 67% for E2) for identifying patients requiring supplemental oxygen. Cohen’s κ coefficients ranged from 0.07 (95% CI, −0.06 to 0.20) for E4 to 0.43 (95% CI, 0.27–0.59) for E2. Areas under the ROC curve ranged from 0.71 (95% CI, 0.62–0.81) for E4 to 0.79 (95% CI, 0.70–0.88) for E1. Conclusions In this large external validation study, currently available predictive equations demonstrated insufficient diagnostic performance to safely replace HCT for determining the need for in-flight oxygen supplementation. Although several equations showed moderate to strong agreement with measured HCT PaO 2 , inadequate sensitivity resulted in clinically important misclassification of patients requiring supplemental oxygen. HCT should remain the reference standard for evaluating patients in whom the need for in-flight oxygen supplementation is uncertain.