Variability in CF lung function may predict disease outcome: Study
Function varies more in men, patients diagnosed earlier
Men and patients diagnosed with cystic fibrosis (CF) earlier in life have higher lung function and greater lung function variability, according an analysis spanning over 20 years of data from the U.K. Cystic Fibrosis Registry.
Lung function variability increased in men and women with CF after age 40, a time when their forced expiratory volume in one second (FEV1), a standard measure of lung function, was lower. According to the researchers, this suggests that higher lung function variability might be linked to disease severity or more negative outcomes.
“This work opens new avenues to understand the role played by lung function variability in disease progression and its utility in predicting key outcomes such as mortality,” the scientists wrote.
The study, “Demographic factors associated with within-individual variability of lung function for adults with cystic fibrosis: A UK registry study,” was published in the Journal of Cystic Fibrosis.
CF is caused by mutations in the CFTR gene, leading to no or faulty production of the CFTR protein. This results in the accumulation of thick and sticky mucus, particularly in the lungs and in the digestive system.
Variability within individuals
Lung function assessments are paramount to tracking disease progression in CF. However, lung function within each patient can vary with time, a phenomenon known as within-individual variability.
CF researchers have debated whether within-individual variability could be linked with steeper lung function decline and thus be a better reflector of lung capacity than pulmonary exacerbations, episodes characterized by rapid disease worsening.
However, the association of within-individual variability with patients’ demographics, such as age and sex, and their genetic profile remains unknown.
To answer this, a team led researchers in the U.K. analyzed data from 7,099 adults with CF, ages 18-49, followed from 1996 to 2020 in the U.K. CF Registry. This corresponded to 65,522 annual reviews.
To build a statistical model for the assessment of long-term variability in lung function, the team collected information about participants’ sex, age at each yearly assessment, age at diagnosis, date of birth, and whether they were homozygous for the F508del mutation, the most common CF-causing mutation. In this context, being homozygous means having that mutation in both CFTR gene copies.
Patients diagnosed after the first year of life showed a tendency for higher FEV 1 (by 0.05 liters) and lower lung function variability than those diagnosed before reaching age 1. In addition, participants homozygous for the F508del mutation tended to have lower FEV1 but slightly higher lung function variability.
The researchers then analyzed how lung function varied with age in men versus women. The analysis showed that mean FEV1 was always higher in men than in women, though it decreased with age in both sexes. Lung function variability tended to decrease, in both men and women, until age 30. But while it remained relatively flat in the next decade in women, men still showed a decline, albeit at a lower rate.
“Further work is needed to determine whether this relates to the lower life expectancy, which is observed in the female UK CF population, and whether it could play a role in survival prediction,” the investigators wrote.
Patients born around 1960 showed, on average, a higher FEV1 than those born before or after that year. Patients born between 1980 and 1985 tended to have lower FEV1 than younger patients, again if all other parameters were comparable.
The researchers then modeled how lung function varied within each individual across time. The model indicated that for both men and women, lung function variability increases after they reach age 40, despite lower mean FEV1.
Patients who died during follow-up had, on average, higher lung function variability than those who survived. The study did not account for age at death, thus requiring confirmation of this result, according to the scientists.
A predictive model taking into account genetic profile and age at diagnosis found that patients who are not homozygous for the F508del mutation had lower lung function variability.
Overall, the findings suggest that “within-individual variability could lead to a better characterisation of individual lung function decline in adults with cystic fibrosis and potentially to improved prediction of disease outcomes,” the team concluded.
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