Arterialized oxygen tension and unfavorable clinical outcomes in pediatric cystic fibrosis

Abstract

Introduction: Maintaining good lung function is a primary goal in managing Cystic Fibrosis (CF). As spirometry lacks sensitivity for detecting mild lung disease, early progression often remains unrecognized. To overcome this limitation, more sensitive monitoring tools are needed. We evaluated arterialized oxygen tension (pO₂) as an easily accessible, and widely applicable surveillance method.

Methods: In this retrospective observational single-center cohort study, arterialized gas exchange was assessed in 103 young people with CF (47 females, 56 males, aged 5-18 years). Trends from baseline (age 5 years) to early adulthood and performance relative to annual best pulmonary function (FEV1) and lung clearance index were examined, along with baseline oxygen tension's predictive value on future FEV1 decline and the occurrence of CF-related complications.

Results: pO₂ correlated significantly with FEV1 (p < 0.001) and inversely with lung clearance index (p < 0.001). Higher pO₂ was associated with pancreatic sufficiency (p = 0.069) and dual CFTR modulator use (p < 0.05), with no differences by sex or chronic Pseudomonas aeruginosa infection. By age 5, 19.8% of young individuals with CF had pO₂ below 80 mmHg (5th percentile), of whom 73.7% had normal FEV1. A linear mixed model showed a steeper FEV1 decline in those with abnormal pO₂ at baseline [estimate = 0.06 (Z-score*year^-1), p < 0.001]. Early low pO₂ was significantly associated with a higher probability of allergic bronchopulmonary aspergillosis (HR = 7.69, p = 0.016) and a trend towards early CF-related diabetes (HR = 2.78, p = 0.06) and early chronic Pseudomonas aeruginosa infection (HR = 2.38, p = 0.09).

Conclusions: Early abnormal pO₂ at age 5 significantly correlated with accelerated FEV1 decline and a greater probability for CF-related complications. Implementing arterialized oxygen tension may offer valuable insights beyond spirometry alone in identifying high-risk patients.

Keywords: blood gas monitoring; disease progression; respiratory function test; risk stratification; secondary prevention.

Figure 1

Progression of arterialized oxygen tension (pO₂) and FEV1 during childhood and adolescence. Mean values (points) and standard deviations (vertical lines) for FEV1 (A), and pO₂ (B) are shown across age groups for all patients (grey) and stratified by whether the corresponding pO₂ (A) or FEV1 (B) falls above (light grey) or below (black) −1.64 Z-scores. Mean values were calculated based on the actual number of patients in each age group. The number of patients is detailed in Supplementary Table 1 in the online supplement.

Figure 2

Association of corresponding LCI_2.5, pO₂, and FEV1 values. Distribution of LCI_2.5 and pO₂ values from a total of 188 N₂BMW maneuvers and corresponding blood gas analyses from 85 PwCF aged 6 to 18 years (see Supplementary Table 1 in the online supplement for age distribution). Black triangles represent individuals with poor pulmonary function (FEV1 Z-scores <−1.64), whereas the grey circles indicate individuals with normal FEV1 at the time of assessment. The grey rectangle indicates a pathologically high LCI_2.5 (>7.91) combined with a concurrently low pO₂ Z-score (<−1.64). FEV1, forced expiratory volume in the first second; LCI_2.5, lung clearance index; N₂MBW, nitrogen multiple breath washout; pO₂, arterialized oxygen tension; PwCF, people with CF.

Figure 3

FEV1 and pO₂ at the age of 5 years. pO₂ and FEV1 Z-scores at the age of 5 years are shown. The black lines represent the lower limits of normal (LLN) for both pO₂ and FEV1 Z-scores. The grey rectangle indicates hypoxemic 5-year-olds (pO₂ Z-score <−1.64, equivalent to 80 mmHg). Abbreviations used: FEV1 (forced expiratory volume in the first second), N (number of patients), pO₂ (arterialized oxygen tension), PwCF (people with CF).

Figure 4

FEV1 and pO₂ trend relative to CFTR modulator introduction. Progression of FEV1 (A) and pO₂ (B) relative to CFTR modulator introduction, expressed in years before (−) and after () initiation. Shown are mean values (black points) and standard deviations (black vertical lines) for all individuals on ivacaftor/lumacaftor or ivacaftor/tezacaftor. Individual trajectories are shown separately for each person with CF (PwCF) on ivacaftor/lumacaftor or ivacaftor/tezacaftor (grey, n = 26), ivacaftor monotherapy (blue, n = 2), and the triple combination of elexacaftor/tezacaftor/ivacaftor (red, n = 1).

Figure 5

Trajectory of FEV1 in relation to pO₂ at 5 years (baseline). Mean values (points) and standard deviations (vertical lines) for FEV1 progression from ages 6 to 18 years are shown separately for individuals with abnormal pO₂ Z-score (<−1.64, black line) and those with normal pO₂ Z-score (≥−1.64, grey line) at baseline (age 5). At age 5, a pO₂ Z-score of −1.64 corresponds to 80 mmHg. FEV1 (forced expiratory volume in the first second), pO₂ (arterialized oxygen tension).