Respiratory Muscle Paralysis Clinical Trial
Official title:
Multimodal Measurement of Respiratory Muscle Strength and Function: Validation of Volitional and Non-volitional Tests With Regard to Nocturnal Hypoventilation in Patients With Neuromuscular Disorders and Chronic Obstructive Pulmonary Disease
Using an extensive set of both volitional and non-volitional tests of respiratory muscle
function and strength it is the aim of this study to
- identify disease-specific patterns of respiratory muscle impairment in different NMD
and COPD
- establish which set of tests is predictive of sleep-disordered breathing or daytime
hypercapnia in patients with NMD or COPD, respectively.
- to investigate the decline of respiratory muscle function in patients with progressive
NMD and COPD along with sleep studies and capnography
Numerous neuromuscular disorders (NMD) are characterized not only by weakness of axial and
limb muscles but also by respiratory muscle and upper airway involvement. Respiratory muscle
weakness first manifests as sleep-disordered breathing (SDB). SDB in neuromuscular disease
mainly comprises alveolar hypoventilation but upper airway collapse may also occur because
pharyngeal muscle tone is impaired by both neuromuscular weakness and sleep.
Diaphragmatic weakness and myopathy are hallmarks of advanced obstructive pulmonary disease
leading to even greater impairment of gas exchange in affected patients.
Non-invasive ventilation (NIV) should be initiated in patients with diaphragm weakness if
significant SDB or hypercapnic respiratory failure is present. Indication criteria for NIV
include measurement of spiromanometric parameters such as forced vital capacity (FVC),
maximum inspiratory pressure (MIP), or sniff nasal inspiratory pressure (SNIP). These
measurements are volitional, i. e. test results are dependent on individual patient effort
and may show intraindividual variance which may not properly reflect disease progression or
treatment effects, respectively. Associations between volitional and non-volitional methods
of respiratory muscle strength testing have been reported mainly for healthy individuals but
only scarcely in patients with specific NMD.
Non-volitional tests of respiratory muscle strength include phrenic nerve conduction
studies, diaphragmatic ultrasound, and magnetic stimulation of the phrenic nerves in
particular. Magnetic stimulation is usually combined with esophageal and gastric manometry
yielding the twitch transdiaphragmatic pressure which closely reflects diaphragmatic
strength.
It is desirable to obtain validated data on both volitional and non-volitional tests of
respiratory muscle strength in various NMD. Validation has to be carried out with regard to
both daytime hypercapnia and nocturnal retention of carbon dioxide because the latter often
represents the earliest manifestation of respiratory muscle weakness. SDB often starts long
before exertional dyspnea or orthopnea develop. Since NIV is one of the mainstays of
symptomatic treatment in both NMD and advanced obstructive lung disease, early recognition
of SDB is crucial for optimal patient care, and in many conditions, life expectancy and
quality of life may be substantially increased by NIV. In this study, FVC, MIP, MEP and SNIP
testing along with non-volitional methods and diaphragmatic ultrasound will be applied in
order to establish a protocol which may help to reliably predict SDB or need for ventilatory
support, respectively.
Patients with chronic obstructive pulmonary disease (COPD) develop flattening, shortening,
and weakness of the diaphragm. This is not only due to downward dislocation of the diaphragm
but also to impairment of contractile function, tissue structure, and intracellular
biochemistry. Respiratory muscle weakness in COPD is of major clinical relevance since
maximum inspiratory pressure is an independent predictor of survival in severely affected
patients. In addition, hypercapnic respiratory failure due to inspiratory muscle weakness is
associated with morbidity and mortality in COPD.
Direct comparison of both volitional and non-volitional measures of respiratory muscle
function between patients with diaphragmatic weakness due to neuromuscular disease and
patients with COPD is desirable. This approach may allow for further characterization of
"impairment patterns" probably specific to either COPD or certain neuromuscular disease,
respectively.
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