Lung Clearance Index Best Judge of Nighttime Hypoxemia, Study Suggests

A measure called the lung clearance index (LCI) can predict low blood oxygen levels during sleep in people with cystic fibrosis (CF) better than conventional assessments of lung function, a study suggests.

The study, “Lung clearance index evaluation in detecting nocturnal hypoxemia in cystic fibrosis patients: Toward a new diagnostic tool,” was published in the journal Respiratory Medicine.

Nocturnal hypoxemia refers to abnormally low levels of oxygen in the blood during sleep. This symptom commonly occurs in people with lung diseases like CF, and it can lead to problems including disturbed sleep, pulmonary hypertension, and heart failure. As such, there is a need to identify people who experience nocturnal hypoxemia, particularly in early stages of disease.

Finding predictors of nocturnal hypoxemia, however, has proved challenging. Blood oxygen levels during the day are not always reflective of those while asleep — people can have normal daytime oxygen levels and still experience nocturnal hypoxemia.

Moreover, measurements of lung function — mostly through forced expiratory volume (FEV), which assesses the amount of air a person can exhale in a given length of time — have been found to be poorly predictive of nighttime oxygen levels.

A team led by researchers at the University of Catania, in Italy, tested whether LCI could predict nocturnal hypoxemia.

“The Lung Clearance Index (LCI) is a measure of lung ventilation distribution obtained from a multiple-breath washout technique,” the researchers wrote.

Essentially, LCI is assessed by having a person inhale a ‘tracer gas,’ and then seeing how long it takes for that person to ‘clear’ the tracer gas from their lungs. LCI is generally measured in the number of ‘turnovers’ needed for clearance; a value above seven is typically considered outside of normal.

Researchers evaluated 31 people with stable CF (16 females, 15 males, age range 10–27, all Caucasian) who were being treated at the Cystic Fibrosis Unit of the University of Catania. All had mild to moderate disease, and underwent a battery of assessments, including LCI, FEV, and measures of oxygen levels during the day and at night.

Results showed that, in general, all participants had normal daytime oxygen levels, but mild-to-moderate nocturnal hypoxemia. This was reflected by mean SpO₂ scores — a measure of oxygen saturation, the amount of oxygen in the blood based on the percentage of oxygenated hemoglobin, the oxygen-carrying molecule in red blood cells. Patients’ mean daytime SpO₂ was 97%, and mean nighttime SpO₂ was 93%.

There was a significant negative correlation between LCI and nighttime SpO_2. That is, individuals with higher LCI values tended to have lower SpO₂ (i.e., worse nocturnal hypoxemia).

The ability of LCI to predict nocturnal hypoxemia was assessed by calculating the area under the receiver operating characteristics curve (AUC) — a measure of how well a given criteria (in this case, LCI) can distinguish between groups (in this case, those with and without nocturnal hypoxemia). An AUC of 1.0 is considered a ‘perfect’ score.

Results showed that the AUC of LCI as a predictor of nocturnal hypoxemia was 0.96 (high predictive accuracy). In contrast, the AUC of FEV was 0.71 (moderate degree of accuracy).

“LCI showed a high effectiveness in predicting nocturnal hypoxemia in stable patients with CF, particularly when compared with a traditional parameter of lung function such as FEV1,” the researchers wrote.

However, “the mechanism linking changes in LCI and nocturnal desaturation remains to be cleared,” they added, noting that no standardized protocols cover the use of LCI in people with CF. Further research is needed to validate the findings of the study.