Lung Function Reduced in LOPD Despite Long-term Myozyme Use
Despite treatment for years with Myozyme (alglucosidase alfa) — marketed in the U.S. as Lumizyme — people with late-onset Pompe disease (LOPD) still develop airway abnormalities and experience reduced lung function, a small Taiwanese retrospective study shows.
While none of the five patients in the study required a ventilator or feeding tube, all developed respiratory complications to include sleep disorder breathing.
According to the researchers, regular monitoring of pulmonary function, including visualization of the deep airways using a flexible bronchoscope, may allow for early diagnosis and intervention to lessen lung function decline.
The study, “Airway abnormalities and pulmonary complications in long-term treated late-onset Pompe disease: Diagnostic and interventional by flexible bronchoscopy,” was published in the journal Pediatric Pulmonology.
Pompe disease is characterized by the excessive accumulation of glycogen, a sugar molecule, inside cells. This buildup is caused by the lack of an enzyme called acid alpha-glucosidase (GAA).
Late-onset Pompe, a form of the disorder that develops during childhood or adulthood, is usually linked with breathing problems as the disease progresses.
People with LOPD may be treated with Sanofi Genzyme’s Myozyme, an enzyme replacement therapy (ERT) approved for Pompe in the EU and other countries. ERT provides patients a form of the GAA enzyme they are missing and is currently the standard treatment for the disease.
However, according to prior studies, abnormalities in the airways are still seen in LOPD patients receiving long-term treatment with Myozyme.
Now, in a retrospective study, researchers in Taiwan evaluated airway abnormalities in such patients using a bronchoscope — a long, thin tube enclosing a fiber optic system and a light source that is used to examine the breathing passages.
In total, the team tested five LOPD patients — three males and two females, whose mean age at diagnosis was 12.7 years — followed at the Taipei Veterans General Hospital, in Taiwan. The patients had been treated with Myozyme since 2012 and were followed for a mean of six years (range from three to 8.5 years).
All patients were evaluated using a flexible bronchoscope. Lung function tests and sleep evaluations were performed either every six months or annually, depending on the individual patient’s respiratory status, to evaluate the degree of respiratory compromise.
Data showed that while no patient required respiratory assistance with invasive ventilators or feeding tubes through the end of the study, all of them developed respiratory complications, including respiratory distress and sleep disorder breathing. One patient required a wheelchair for daily life.
Lung function for all of the patients was stable during the first five years following Myozyme treatment, but function did deteriorate after that point for two patients. All patients showed signs of decreased or inadequate breathing (hypoventilation) during sleep.
The evaluations using the bronchoscope showed all five had narrowed nasal tracts and an oral cavity with a compromised oropharynx — the middle part of the throat. Also present was mild tracheomalacia, a rare condition characterized by the softening of the cartilage of the windpipe. The five also had a mild reduction in the cartilage support of the smaller airways, which is a condition called bronchomalacia.
Thick sputum was found for one patient, with further analysis proving positive for infection with the bacteria Klebsiella pneumoniae, known to cause pneumonia, among other conditions.
Overall, all patients in the study had varying degrees of airway collapsibility, pulmonary complications, and sleep apnea syndrome despite years of Myozyme treatment, the researchers found.
Based on these findings, the team concluded that “LOPD patients who have received long‐term and regular treatment still presented with different severities of airway abnormalities and pulmonary complications,” they wrote, noting that “the respiratory condition continued to deteriorate along the time.”
Furthermore, compared with patients with infantile-onset Pompe — whose disease manifests and is diagnosed in the first few months of life — LOPD patients had worse airway and pulmonary complications.
“The pulmonary complications seem more obvious than those observed in patients with infantile-onset Pompe disease, which might be related to the late diagnosis and treatment,” the team wrote.
On average, the data show, it took more than three years, on average, from symptoms onset to a confirmed diagnosis for each of the patients.
“For Pompe patients, it is important to regularly follow‐up on the respiratory conditions, which are better evaluated by dynamic imaging studies or functional tests,” the researchers wrote, suggesting that a flexible bronchoscope “could be an effective tool for early diagnosing and doing interventions at the same time.”
“Early diagnosis of respiratory dysfunction is a critical prognostic factor of the longterm outcome of treated LOPD patients,” the team concluded.
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