A third of Fabry patients in study found to have poor lung function
Obstructive airflow limitation most common with smokers, severe disease
Nearly one-third of Danish patients in Fabry disease registries were found to have poor lung function, with obstructive airflow limitation most common among those with severe disease and smokers, a study found.
People with Fabry “frequently develop an obstructive airflow limitation,” which is found “not only in smokers, but also in never smokers,” researchers wrote. They urged caregivers to “be aware of the development of respiratory illness as part of the disease.”
The study, “Respiratory impairments in patients suffering from Fabry disease – A cross-sectional study,” was published in Chronic Respiratory Disease.
Fabry disease is caused by mutations in the GLA gene, which codes for an enzyme called alpha-galactosidase A (Gal A). A faulty alpha-Gal A enzyme leads to a toxic buildup of fatty molecules in the body’s organs, including the lungs. This can affect how well the lungs work over time.
The researchers looked at the lung function of 86 adults with Fabry disease in Denmark who were enrolled in one or both of two international patient databases for Fabry disease, the Fabry Registry (NCT00196742) by Sanofi and FollowME by Amicus Therapeutics.
Most in study had classic Fabry mutations
All patients (54 women and 32 men) had at least one lung function test to measure how well their lungs were working. Half were on enzyme replacement therapy at the time of the first lung function test, while the other half were not, either by indication or their own choice.
Most (92%) patients had mutations linked to classic Fabry disease, a more severe type of the disease. Two (2%) had mutations linked to late-onset Fabry disease, and five (6%) had previously unreported disease-causing mutations. In all men and in 35 (65%) of the women, alpha-Gal A enzyme activity was below normal.
On average, patients scored 23.4 points on the Mainz Severity Score Index (MSSI), a measure of the severity of symptoms of Fabry disease. Higher scores indicate more severe symptoms, with those falling in the range of 20–40 points being moderate.
Percent predicted forced expiratory volume in the first second (FEV1), a measure of the amount of air that can be forced out of the lungs in one second, averaged 88.1%. Forced vital capacity (FVC), which measures the amount of air that can be forced out in a full breath, averaged 98.6%.
Almost a third of patients had some degree of lung function limitation.
Based on an FEV1/FVC ratio equal to or less than 70%, 17 (20%) patients had an obstructive airflow limitation, which occurs when the airways become narrowed or blocked, making it harder to breathe out air from the lungs. Seven (8%) patients had an FEV1/FVC ratio equal to or higher than 90%, indicating a restrictive airflow limitation, often due to stiffening, which makes it harder to fully expand and fill the lungs with air when breathing in.
More severe symptoms based on MSSI scores greater than 40 points were linked to a lower FEV1/FVC ratio, and “cigarette smoking strengthened this association,” the researchers wrote. Nearly one-third (31%) of patients were current smokers, whereas the remaining two-thirds were either former or never smokers.
The researchers said their study was the first “to show that patients with Fabry disease frequently develop an obstructive lung function defect regardless of their smoking status being current, former, or never smoker.”
The use of certain medications, such as inhaled corticosteroids, was also linked to a lower FEV1/FVC ratio. Nighttime breathing difficulties and shortness of breath were linked to heart problems, but not to poor lung function.
The study is “important” for clinicians who might look to “measure FEV1 in patients with respiratory symptoms, whereas a screening approach might be suggested based on our findings,” the researchers wrote.
“Further studies with more late-onset patients, are needed to confirm a broader disease spectrum of these findings,” the researchers wrote.
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