A novel, noninvasive assay shows that distal airway oxygen tension is low in cystic fibrosis, but not in primary ciliary dyskinesia

Abstract

Objectives Oxygen tension affects the biology of aerobic and denitrifying organisms. Using a novel, fast‐response sensor, we developed a noninvasive procedure to measure pO2 in distal human airways. We hypothesized that distal pO2 would be low in cystic fibrosis (CF) airways. Materials and Methods We measured the fraction of expired oxygen (FEO2) in real time using a fast laser diode analyzer in healthy subjects and in patients with CF, asthma, and primary ciliary dyskinesia (PCD). Subjects slowly exhaled to residual volume (RV), where the nadir of FEO2 (NFO) was recorded. Values were compared to peripheral oxygen saturation (SaO2), expired CO2 at RV, FEV1, FEV1/FVC, and FEF25‐75. We also measured the effect of supplemental oxygen on FEO2. Results Seventy‐four subjects completed the study. Seven additional subjects could not perform the maneuver. Mean (±SD) NFO values for controls (n = 29), CF patients (n = 23), asthma patients (n = 15), and PCD patients (n = 7) were 13.4 ± 1.1%, 12.4 ± 1.2%, 13.3 ± 1.1%, 14.4 ± 0.6%, respectively. NFO in CF was lower than in controls (P = 0.0162), and NFO in PCD was higher than in CF (P = 0.0007). Asthma results were heterogeneous. Oxygen caused a dose‐dependent increase in NFO (P < 0.0005; n = 3; r2 = 0.91). NFO values were positively associated with FEV1 (P = 0.0009), FEV1/FVC (P = 0.0019) and FEF25‐75 (P = 0.0155), but there was no association with SaO2. Conclusions Distal airway pO2 is lower in CF than in controls. This may reflect absorption of oxygen in partially plugged acinar units, and/or increased epithelial oxygen consumption. Distal airway pO2 can be precisely titrated to treat infections.

Mitochondrial uncoupling proteins protect human airway epithelial ciliated cells from oxidative damage

“…An advantage is that we used primary cultures of differentiated human airway epithelia at the air–liquid interface; they closely mimic in vivo human airway epithelia. In addition, the percentage of O 2 in the cell culture incubator (18.5%) † matches well with in vivo human data where humidified inspired air has 19.7% O 2 , with 5% CO 2 it has 18.5% O 2 , and at the end of a complete slow expiration to residual volume, it can fall as low as 13.5% O 2 ( 64 ). A limitation of the in vitro model may be lack of exposure to sheer stress/air flow, submucosal gland secretions, and disease-associated inflammatory changes that could alter airway ciliation and/or ROS generation.…”

Non-cystic fibrosis bronchiectasis in children and adolescents: Neglected and emerging issues

“…Finally, fraction of end-expiratory oxygen (F EO2 ) measured by a fastresponse analyzer connected to a pneumotachometer was recently proposed as a non-invasive test to evaluate O 2 tension of distal airways. 28 The F EO2 in CF was found to be significantly lower than in PCD, possibly given the thinner PCD airways secretions compared to CF mucus plugs, supporting a potential application of this procedure for screening PCD in cases with bronchiectasis.…”

A Universal Stress Protein upregulated by hypoxia may contribute to chronic lung colonisation and intramacrophage survival in cystic fibrosis

“…To elucidate the role that both USPs play in Bcc chronic infection, we examined a series of phenotypes associated with environmental pressures experienced during chronic infection or associated with Bcc virulence. The CF lung has profoundly low pO2 due to a combination of disease associated issues including mucous plugging, constant neutrophilic inflammation and increased epithelial oxygen consumption [17,26]. Oxidative stress in the CF lung contributes to the cycle of inflammation and is an inherent feature of CF [27].…”