Problems with Diaphragm Evident in Lung Function Tests of LOPD Patients, Study Reports

People with late-onset Pompe disease (LOPD) have lower dynamic diaphragm function and altered endurance and strength during inhalation, but they show some compensatory mechanisms to preserve air volume, according to a recent study.

These findings, which were achieved using dynamic — rather than the standard, static — lung function tests, provide additional information on the disease’s impact. Researchers noted that these tests may help to understand patients’ respiratory adaptation mechanisms to disease.

The study, “Dynamic respiratory muscle function in late-onset Pompe disease,” was published in the journal Scientific Reports.

People with LOPD start experiencing disease symptoms in early childhood (more than 1 year old) or later in life. While the late-onset form is associated with milder symptoms, muscles of the respiratory system (mainly the diaphragm and intercostal muscles) are often affected, leading to problems with breathing during sleep, ineffective airway clearance, and progressive lung insufficiency.

As in most neuromuscular diseases, lung insufficiency is the main cause of death in LOPD patients, with respiratory failure estimated to be responsible for early death in 70% of these patients.

Despite the frequency of lung problems in people with LOPD, “there are limited methods to comprehensively and objectively evaluate changes in respiratory muscle function,” the researchers wrote.

Maximal inspiratory pressure (MIP) is a standard lung function test used to assess inspiratory muscle strength at a static breath-hold. Despite being non-invasive and inexpensive, MIP does not reflect the dynamic properties of the respiratory muscles and may not reveal specific respiratory muscle adaptations to breathing disruptions associated with disease.

Dynamic lung function tests incorporate changes in respiratory pressure or volume over a precise period of time, such as when inhaling and exhaling a normal breath, and have the potential to detect respiratory muscle adaptations to disease.

Researchers at University of Florida evaluated LOPD patients’ lung function using two dynamic respiratory muscle function tests — inspiratory load compensation (ILC), and dynamic magnetic resonance imaging (MRI) of the thorax — and whether these tests revealed lung compensations in these patients.

ILC assesses changes in ventilatory timing, flow, pressure, and volume in response to mechanical disturbances in breathing, and may offer insight into compensatory changes in breathing patterns in disease progression or in response to exercise training.

Dynamic MRI does not require static breath-holds, and allows the capturing of multiple breaths over a short period of time, while detecting changes in chest configuration related to respiratory muscle movements.

Seven people with LOPD (five women and two men; ages 29 to 63) and seven age- and gender-matched healthy individuals underwent a battery of standard (including MIP) and dynamic (ILC and dynamic MRI) lung function tests.

Results showed that LOPD patients had significantly poorer static and dynamic lung function compared with healthy people.

Additionally, the dynamic tests revealed that these patients had evidence of early diaphragm dysfunction, along with impaired inspiratory endurance and strength. ILC testing also showed a compensatory prolongation of the inspiratory time (the time taken for inhalation) that helped to preserve air volume during the loaded breath.

These findings highlighted that diaphragm dysfunction in LOPD patients affects both static and dynamic features of lung function.

This impaired inspiratory endurance and strength “may ultimately affect a patient’s ability to resist physiological stressors such as … a narrowed airway during sleep, placing them at higher risk for failure,” the researchers wrote.

“While likely more useful as research tools than in daily clinical practice, these tests appear to capture distinct aspects of dynamic respiratory muscle function beyond standard pulmonary function tests, which could help clarify how patients maintain minute ventilation [the amount of air a patient moves in one minute] despite gradual LOPD disease progression,” they added.

The team noted that future studies are required to assess how dynamic respiratory muscle function changes with disease progression in LOPD patients.