Breathing is controlled by complex interactions between the central and peripheral nervous systems in conjunction with the respiratory system. Neurological diseases predispose patients to nocturnal desaturation and pneumonia due to respiratory dysfunction, which increases mortality, daytime sleepiness and fatigue, and reduces the quality of life. Respiratory function tests are required to identify respiratory function decline and to consider compensatory management. This review summarizes the characteristics of several respiratory function tests and their applications to neurological diseases.
Respiration is controlled by the cerebral cortex and respiratory center that is constituted by neuron networks in the pons and medulla.
Spirometry is performed to differentiate between airway obstruction and restrictive pulmonary disease in order to assess whether the patient has a chronic obstructive disease (e.g., asthma) and to evaluate a patient with dyspnea or wheezing.
A decreased FEV1 /VC% indicates airway obstruction, whereas a decreased total lung capacity and a normal FEV1/VC% indicates restrictive pulmonary disease.
Blood gas measurements include arterial and venous blood gas analyses such as pulse oximetry, end-tidal oxygen (O2) and end-tidal carbon dioxide (CO2) measurements, and transcutaneous CO2 measurement. These measure O2 saturation, O2, and CO2 concentrations in exhaled air, and the concentration of blood gas through the skin, respectively. These measurements have the advantage of noninvasive monitoring of hypercapnia and hypoxemia in the presence of respiratory dysfunction.
Arterial blood gas analyses are performed to determine the oxygenation, ventilation, acid-base status, and O2-carrying capacity of the subject, which are measured using the O2 pressure and oxyhemoglobin saturation; CO2 pressure; pH; and partial pressure of oxygen (PaO2), oxyhemoglobin saturation, total hemoglobin, and dyshemoglobin saturation; respectively.
Pulse oximetry has some limitations. It can only detect hypoxemia early and cannot detect hypercapnia. When a patient presents with apnea, there might be a delay before this is reflected in the results due to significant O2 reserves in the blood.
End-tidal CO2 measurement is useful when there is no abnormality in O2 saturation and only in hypercapnia due to a high O2 concentration in inhaled air. The results of end-tidal CO2 measurement are sometimes not strongly correlated with the actual arterial blood concentration due to alterations by various physiological and pathological conditions such as cyanotic heart disease, airway obstruction, mouth breathing, and O2 supplementation.
Impairment of alveolar ventilation results is relative small changes in the CO2 concentration due to CO2 buffering, whereas O2 concentration more accurately reflects the apnea in that condition. Moreover, if alveolar hypoventilation induces hypoxemia, O2 saturation is hardly altered due to considerable O2 reserves in the blood; instead, hypoxemia is reflected more promptly by end-tidal O2 concentration.
Measuring the transcutaneous CO2 only roughly represents the arterial CO2 concentration and is affected by skin thickness, age, cardiac function, local metabolism, and peripheral perfusion.
Coughing plays an important role in airway protection by removing pathogens from and maintaining the airway, and involves the glottis first closing and the expiratory muscle contracting, and the glottis then reopens to exhale air and other substances from the airway. Peak cough expiratory flow is measured by blocking the nose with a clip and inhaling maximally to total lung capacity, and then coughing.
A decrease in VC indicates either restrictive pulmonary disease or inspiratory muscle weakness.
MIP is determined by the peak pressure while performing maximal and static inspiration (Muller’s maneuver) that starts from functional residual capacity after full expiration. MEP is determined by the peak pressure while performing maximal and static expiration (Valsalva maneuver) that starts from the total lung capacity after full inspiration. Both MIP and MEP are measured three times, and the largest value is selected.
Sniff inspiratory pressure is determined by the inspiration pressure during the maximal sniff maneuver, which starts from the forced residual capacity after full expiration to minimize the residual volume and is divided into transesophageal, esophageal, and nasal pressures based on the measurement method. Among them, SNIP is widely used because it is less invasive. SNIP measures the peak inspiratory pressure five times with a nasal plug in one nostril and the other one occluded, and is determined as the highest value among them.
MIP and MEP are difficult to measure when the patient has a significant orofacial weakness, and MIP, MEP, and SNIP are more difficult to perform when patients have cognitive impairment.
The intrathoracic pressure decreases and the intra-abdominal pressure increases when the diaphragm contracts during respiration. The transdiaphragmatic pressure is calculated by subtracting the esophageal pressure measured using a catheter placed in the stomach from the gastric pressure measured using a catheter placed in the esophagus, and this indirectly indicates diaphragm strength. The transdiaphragmatic pressure is normally 10 cmH2O during small breaths and increases to 150 cmH2O during inspiration with maximal effort, which is less varied and a far higher value than the former.
The transdiaphragmatic pressure can specifically reflect the diaphragm strength, but its measurement has some limitations: it is invasive, can be painful for the patient, is risky if a patient has dysphagia, and measurements are complicated. It may also be difficult to place the catheter into the stomach if the patient has severe respiratory muscle weakness.
The phrenic nerve that controls the diaphragm originate from the C3–C5 spinal roots and descend along the neck to allow direct stimulation to the neck. Phrenic nerve stimulation measures the diaphragmatic twitch magnitude using surface and reference electrodes placed in the seventh or eighth intercostal spaces and on the ipsilateral arm, respectively. It is performed using electrical or magnetic transcutaneous stimulation from the posterolateral side of the sternocleidomastoid muscle at the cricoid cartilage level.
Because this measurement method does not require patient effort, it is valuable for those with impaired consciousness or cognitive impairment, but it has the following limitations: first, the transdiaphragmatic pressure is affected by the impedances of the abdomen and rib cage, and increases when the abdominal fat is thick. Second, the transdiaphragmatic pressure could be altered by diaphragmatic contraction just before the measurement due to twitch potentiation.
Diaphragm abnormalities can be identified via chest X-rays, fluoroscopy, and ultrasonography. Chest X-rays can confirm abnormalities such as hemidiaphragm elevation, but they are mostly taken to confirm pulmonary disease rather than diaphragm strength.
Fluoroscopy and ultrasonography are performed instead of chest X-rays to evaluate diaphragm strength. Fluoroscopy allows the real-time evaluation of diaphragm strength by measuring the excursion of the diaphragm dome during inhalation and exhalation with maximal effort, but it has the limitation that it exposes the patient to radiation.
Fluoroscopy and ultrasonography can be applied to patients in the ICU because they can be performed with a portable device, and have the advantages of being noninvasive and can be carried out without a mouthpiece, and hence are applicable to patients with significant orofacial weakness.
Respiration is regulated by the cerebral cortex and brainstem and occurs through contraction of the inspiratory and expiratory muscles that are innervated by the phrenic nerve, motor neurons, and phrenic nucleus in the upper cervical spinal cord; respiratory distress is therefore induced by abnormalities in one or more lesions in those areas.
Respiratory abnormalities in stroke differ depending on the stroke location. Cerebral hemispheric lesions manifest with decreased strengths of the chest wall and diaphragm on the side opposite the stroke, bilateral hemispheric lesions induce Cheyne-Stokes respiration or apnea due to periodic palsy of the vocal cord, and brainstem lesions induce central sleep apnea, obstructive sleep apnea, and alteration in respiration rhythm. Conditions such as spinal cord injury and postpolio syndrome manifest respiratory distress due to abnormalities in the spinal cord.
Patients with respiratory dysfunction are predisposed to respiratory complications, which consequently lead to increased mortality, pneumonia, and reduced quality of life due to daytime sleepiness or fatigue. Respiratory function tests are therefore required to identify respiratory dysfunction before such conditions appear, and several assistant devices are used according to the obtained results. Respiratory function tests including MIP, MEP, phrenic nerve conduction study, nocturnal O2 saturation, and CO2 concentration are recommended for patients with stroke.
Noninvasive ventilation is found to be assistant device to ameliorate respiratory distress and improve survival in neurological diseases such as ALS, and it can also be considered in conditions such as nocturnal hypoventilation associated with inspiratory muscle weakness based on the following criteria: the presence of orthopnea, MIP <40 cm-H2O or <60 cmH2O, SNIP <40 cmH2O, VC <50% predicted or 80%, daytime hypercapnia of partial pressure of carbon dioxide >45 mmHg, nocturnal hypoxemia, or symptomatic sleep-disordered breathing.
VC, MIP, and MEP can also be used to predict the need for endotracheal intubation and mechanical ventilation by applying the following criteria: VC, MIP, and MEP <20 mL/kg, 30 cmH2O, and 40 cmH2O, respectively, or decreases by more than 30%.
In various neurological diseases, respiratory dysfunction caused by various conditions such as central and obstructive sleep apnea, inspiratory and expiratory muscle weakness, and lung volume loss may lead to increases in the risks of mortality and pneumonia. Respiratory function tests should therefore be considered at an appropriate time to detect respiratory dysfunction and to allow for the application of auxiliary devices.
The authors declare no conflicts of interest.
Apparatus for measuring maximal inspiratory pressure, maximal expiratory pressure, and sniff nasal inspiratory pressure.
Summary of respiratory function tests
Test | Advantage | Disadvantage | Applications in neurological diseases |
---|---|---|---|
Spirometry | Noninvasive, widely applicable, performed easily | Not applicable in orofacial muscle weakness or cognitive impairment | Discerns between airway obstruction and restrictive pulmonary disease, the difference between supine and sitting forced VC, slow VC indicate diaphragmatic weakness, consider NIV as a result of VC <50% predicted |
Blood gas analysis | Transcutaneous CO2 measurement and pulse oximetry are noninvasive and can be performed in any setting using portable devices | Transcutaneous CO2 measurement: affected by skin thickness, age | Measurement during sleep can detect nocturnal hypoventilation as follows: CO2 >55 mmHg for more than 10 min in arterial blood gas measurement or transcutaneous or end-tidal CO2 measurement; increase in CO2 of 10 mmHg compared with the value in the supine position during wakefulness and CO2 higher than 50 mmHg for 10 min |
Pulse oximetry: only detects hypoxemia | |||
AVBGA: invasive | Considers NIV in patients with daytime hypercapnia CO2 >45 mmHg during wakefulness or symptomatic nocturnal hypoventilation as mentioned above | ||
PCEF | Noninvasive, performed easily | Not applicable in cognitive impairment | Values lower than 270 and 160 L/min indicate pneumonia risk, and the need for a mechanical insufflation/exsufflation device, respectively |
MIP, MEP, SNIP | Noninvasive and allows early detection of diaphragm weakness | Not applicable in orofacial muscle weakness or cognitive impairment | Specifically enable assessments of inspiratory and expiratory muscles strengths (e.g., ALS, Duchenne muscular dystrophy, and stroke) |
Probable criteria for considering endotracheal intubation and weaning are the following values: MIP <30 cmH2O, MEP <40 cmH2O or decreases by more than 30%; MIP >36 cmH2O, MEP >30 cmH2O | |||
Consider NIV and mechanical insufflation/exsufflation device for patients with ALS with results of MIP <40-60 cmH2O, SNIP <40 cmH2O, and MEP <60 cmH2O, respectively | |||
TP | Relatively accurate evaluations of diaphragm muscle strength | Invasive, painful, risky in presence of dysphagia, and difficult to perform | Specifically enable for assessment of diaphragm strength in patients with neuromuscular disease (e.g., amyotrophic lateral sclerosis, Guillain-Barré syndrome, etc.) |
Consider mechanical ventilation for patients with Guillain-Barré syndrome in results of diaphragmatic weakness | |||
PNS | Applicable in cognitive impairment and impaired consciousness | Affected by impedances of abdomen and rib cage, and not applicable in presence of external pacemaker | Specifically enable for assessment of diaphragm strength in patients with neuromuscular disease (e.g., amyotrophic lateral sclerosis, Guillain-Barré syndrome, etc.) |
Consider mechanical ventilation for patients with Guillain-Barré syndrome in results of the decreased action potential of the diaphragm | |||
Diaphragm imaging | Noninvasive, assessment possible in any setting using portable devices, and applicable in orofacial weakness, cognitive impairment, and impaired consciousness | Inaccurate in the following instances: false negative if patient breathing is reliant on abdominal muscle contraction, and false positive if the anterior diaphragm performs paradoxical cephalad movement during inspiration | Specifically enable for assessment of diaphragm strength in patients with neuromuscular disease (e.g., amyotrophic lateral sclerosis, Guillain-Barré syndrome, etc.) |
VC, vital capacity; NIV, noninvasive ventilation; CO2, carbon dioxide; AVBGA, arterial and venous blood gas analyses; PCEF, peak cough expiratory flow; MIP, maximal inspiratory pressure; MEP, maximal expiratory pressure; SNIP, sniff nasal inspiratory pressure; ALS, amyotrophic lateral sclerosis; TP, transdiaphragmatic pressure; PNS, phrenic nerve stimulation.