What Are Pulmonary Function Testing Options in Neuromuscular Diseases Like SMA?

Muscle weakness or failure leading to loss of pulmonary function is a hallmark of progressive neuromuscular diseases, and with various options for measuring pulmonary function in these diseases, such as spinal muscular atrophy (SMA), a pair of researchers has reviewed the most commonly used measures.

These measures span 4 categories—volume, flow, pressure, and gas exchange—and each offer their own specificity in describing respiratory muscle dysfunction and in the practicality of use as measured by the complexity of the testing, the availability of a patient to perform it, and in having the normative data to use.

Volume

Because its measure of both inspiratory and expiratory muscle output, forced vital capacity (FVC) has long been used as a global assessment of neuromuscular impairments for pediatric patients. In SMA specifically, FVC is useful for measuring the progression of respiratory muscle weakness over time, and widely available data via spirometry supports its use.

For example, research has shown that compared with SMA type 3, baseline absolute FVC and FVC% predicted is lower among patients with SMA type 2. Data from a large, comprehensive study of treatment-naïve patients with SMA showed that the average change in VC% predicted dropped by 1.57% and 1.65% annually for patients with type 2a and 2b, respectively, compared with 1.06% in type 3a SMA.

The measure has also been used to differentiate SMA types and functional status, according to the researchers, who detailed a study in which differences in baseline FVC% predicted between functional status were observed among patients with SMA types 2 and 3.

Flow

Peak expiratory flow (PEF), typically used as a marker of disease severity, can also be leveraged to measure respiratory muscle strength, specifically expiratory output and with longitudinal data available specifically for patients with DMD aged at least 3 years.

“PEF has been proposed as a useful pulmonary outcome measure in DMD and has been used to assess treatment efficacy,” wrote the pair. “Interestingly, it is less variable than the more conventional measure of expiratory muscle function, that is, maximal expiratory pressed (MEP), and as a result, PEF is potentially better for assessing changes in expiratory muscle strength over time, and treatment effects.”

However, the researchers noted that more data on PEF as an outcome measure, especially relative to well-studied measures like FVC.

Another measure, peak cough flow, can determine airway clearance capability and can be measured easily in the office with a peak flow meter or spirometer in patients aged older than 6 years, although there is currently no available longitudinal data. Inspiratory flow reserve has also been proposed as a measure of inspiratory function, as reported in a pharmacotherapy intervention trial. According to the researchers, the measure has been included as an outcome measure in several additional ongoing trials.

Pressure

Both maximal inspiratory (MIP) and expiratory (MEP) static pressures are both commonly used to measure muscle function for patients aged at least 6 years, although the researchers note there are challenges in performing the measures in patients with progressive muscular disease, including that the test requires a maximal sustained effort for at least 1 second, which is a challenge, especially in patients with progressive respiratory weakness. There is longitudinal data available for both SMA and DMD.

Sniff nasal inspiratory pressure has been used as a more natural alternative to MIP and according to the researchers is a highly reproducible, volitional, and easily performed in children at least 6 years of age; however, there are some limitations to the accuracy of the measure.

Gas exchange

The “gold standard” for assessment of chronic respiratory failure is polysomnography with continuous capnography and pulse oximetry coupled with standard thoracoabdominal motion, respiratory rate, and heart rate. According to the researchers, conventional pulmonary function testing can be used to identify which patients are at risk for hypoventilation and should get a polysomnogram, which could be particularly important outside of large medical centers where polysomnography with continuous capnography may not be available.

Reference

Miller K, Hayer O. Pulmonary function testing in patients with neuromuscular disease. Pediatr Pulmonol. Published online December 8, 2020. doi:10.1002/ppul.25182