Application of respiratory function tests in patients with neurological diseases

Article information

Ann Clin Neurophysiol. 2023;25(1):1-9
Publication date (electronic) : 2023 April 28
doi :
1Department of Neurology, Nowon Eulji Medical Center, Eulji University School of Medicine, Seoul, Korea
2Department of Neurology, Seoul National University Hospital, Seoul, Korea
3Center for Hospital Medicine, Seoul National University Hospital, Seoul, Korea
4Neuroscience Research Institute, Seoul National University College of Medicine, Seoul, Korea
Correspondence to Jung-Joon Sung Department of Neurology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea Tel: +82-2-2072-2820 Fax: +82-2-3672-7553 E-mail:
Received 2022 August 30; Revised 2022 October 17; Accepted 2022 October 18.


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.1,2 Moreover, breathing is resulting from the contraction of inspiratory and expiratory muscles under the control of respiratory neurons in the brainstem and the ventral horn of the upper cervical spinal cord.3 Respiratory distress conditions such as dyspnea, orthopnea, and central and obstructive sleep apnea can be attributed to diseases that impair the functions of respiratory neurons, the respiratory center, and inspiratory and expiratory muscles.1,2,4-11 Neuromuscular diseases, stroke, Parkinson’s disease, and multiple system atrophy predispose patients to dysfunction of either the respiratory neuron or respiratory muscles and manifests alongside nocturnal hypoventilation and pneumonia, thereby shortening the survival duration of patients and reducing their quality of life.5-11 Respiratory function tests should be considered for identifying respiratory dysfunction and determining whether assisted devices are required for patients with neurological diseases that involve the respiratory system. Herein we review the characteristics and clinical applications of respiratory function tests.



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.12 The test involves repeatedly inhaling for as long as possible and exhaling for 6-15 seconds with maximal effort at least three times, with the obtained results interpreted using the following three variables: vital capacity (VC), forced expiratory volume in 1 second (FEV1), and FEV1/VC% (i.e., FEV1/VC×100). For reproducibility, tests are repeated until the difference between the maximum values of forced VC (FVC) and FEV1 is within 5% or 0.1 L.

A decreased FEV1 /VC% indicates airway obstruction, whereas a decreased total lung capacity and a normal FEV1/VC% indicates restrictive pulmonary disease.12 Restrictive patterns may not be fully revealed through spirometry alone when there is moderate-to-severe airway obstruction. The VC is divided into the following two types according to the test procedure: (1) FVC involves the patient inhaling maximally and exhaling as fast as possible in a sitting or supine position, whereas (2) slow VC involves the patient inhaling maximally and exhaling slowly. FVC is usually measured in a sitting position, but occasionally in the supine position. Spirometry it easy to perform, but it has the disadvantage of requiring the orofacial muscle to be strong enough to hold the mouthpiece during the test.13,14

Blood gas measurements

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.15 They are sometimes performed to confirm the therapeutic effect of mechanical ventilation or O2 supplementation or to determine intubation timing. Arterial blood is often sampled, but venous blood may be used instead to evaluate goal-directed therapy for septic shock, or where perform an arterial puncture is difficult in patients with acute illness.16,17 Results may be imprecise if the storage time is prolonged at room temperature, and so the test should be performed within 30 minutes of blood collection. In blood samples from patients with remarkably increased leukocytes, PaO2 could decrease rapidly due to O2 consumption by leukocytes (i.e., leukocyte larceny) after blood collection.18-20 The sample may also be contaminated by the anticoagulant, air, or saline, leading to erroneous results.15

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.21

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.22 The results obtained using a divided nasal cannula have the advantage of a smaller difference in blood CO2 concentration than for those obtained using a face mask. However, a method that uses a divided nasal cannula cannot detect air that is breathed through the mouth, and the tube can sometimes become clogged by water vapor or mucus.21,23

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.21,24

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.25,26

Peak cough expiratory flow measurement

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.10 A value higher than 400 L/min are considered normal and one lower than 270 L/min could indicate a risk of pneumonia.27

Measurements of maximal inspiratory pressure, maximal expiratory pressure, and sniff nasal inspiratory pressure

A decrease in VC indicates either restrictive pulmonary disease or inspiratory muscle weakness.28 Decreased FEV1 or FEV1/VC% indicates airway obstruction or expiratory muscle weakness. The maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), and sniff nasal inspiratory pressure (SNIP) are often tested when the results of respiratory tests are abnormal in the absence of obstructive airway and respiratory pulmonary disease, or when the following diseases that involve respiratory muscles are suspected: respiratory muscle weakness associated with malnutrition, myasthenia gravis, Guillain-Barré syndrome, spinal cord injury, amyotrophic lateral sclerosis (ALS), stroke, and muscular dystrophy.11,29-31 These tests are often performed in a sitting position and have advantages of being relatively simple to measure and noninvasive (Fig. 1).28

Fig. 1.

Apparatus for measuring maximal inspiratory pressure, maximal expiratory pressure, and sniff nasal inspiratory pressure.

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. 11,28 Patients with generalized muscle weakness present with decreases in both MIP and MEP, whereas those with only diaphragm weakness only present with a decrease in MIP.

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.11,14 SNIP measures global inspiratory muscle strength more accurately and has the advantage of less variability than MIP, whereas MIP measures diaphragm strength more specifically than does SNIP.11,32-35

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.

Transdiaphragmatic pressure measurement

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.36

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.11

Phrenic nerve stimulation

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.37-40 The normal value of the transdiaphragmatic pressure measured using phrenic nerve stimulation is 25-35 cmH2O.

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.11 Third, it should be avoided in patients in the intensive care unit (ICU) with an external pacemaker, and should be carefully considered in those with an internal jugular catheter or cardiac pacemaker.40

Diaphragm imaging

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.11

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.11 Ultrasonography also allows real-time measurements of the diaphragmatic thickness (which indirectly reflects diaphragm strength) at the end of expiration using a transducer placed in the midaxillary line at the intercostal space level between the seventh and ninth ribs.11 The diaphragm is a hypoechoic structure seen between the peritoneal and diaphragmatic pleurae that appear as hyperechoic lines, and it is normally thinner than 2 mm. Patients are considered to have diaphragmatic weakness if the diaphragm does not thicken during inspiration.11,41

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.11 However, both tests have limitations. The result may be a false negative if the breathing of a patient with neuromuscular disease is reliant on abdominal muscle contraction, or a false positive if the anterior diaphragm performs paradoxical cephalad movement during inspiration.11


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.1-11 Based on these features, neurological diseases that exhibit respiratory dysfunction are categorized according to whether the lesion is in the brain, spinal cord, motor neuron, nerve, neuromuscular junction, or muscles.

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.9,42-46 Examples of diseases that involve motor neurons, nerves, neuromuscular junctions, and muscles include spinal muscular atrophy (SMA) types 1c, 2, and 3a, spinal and bulbar muscular atrophy, ALS, Guillain-Barré syndrome, critical-illness polyneuropathy, myasthenia gravis, Lambert-Eaton syndrome, botulism, organophosphate poisoning, Duchenne muscular dystrophy, myotonic dystrophy, Pompe disease, periodic paralysis, and inflammatory myopathy.47-59 Diseases such as myotonic dystrophy and Duchenne muscular dystrophy may also cause conditions associated with sleep-disordered breathing such as obstructive and central sleep apnea in addition to respiratory muscle weakness. Multiple sclerosis also manifests as respiration dysfunction due to certain causes such as respiratory muscle weakness, respiratory control impairment, sleep-disordered breathing, and neurogenic pulmonary edema.60 Parkinson’s disease and multiple-system atrophy present restrictive and peripheral obstructive patterns on spirometry, and respiratory muscle weakness induces decreases in MIP and MEP that are negatively correlated with the disease severity.9,42

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.61,62 Guidelines on the management of ALS, SMA, Guillain-Barré syndrome, and Pompe disease recommend that patients are monitored. 59,63-66 The values of MIP and SNIP are also related to the prognosis. When the MIP is reduced to less than 60 cmH2O, the survival duration and quality of life of a patient with ALS deteriorates, and when SNIP is reduced to lower than 40 cmH2O, patients with ALS are more likely to die within 6 months.14,67,68

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.63,64,69 A mechanical insufflation/exsufflation device can be considered for reducing the risk of pneumonia related to expiratory muscle weakness based on the following criteria: peak cough expiratory flow <160 L/min and MEP <60 cmH2O.21,69,70 Diaphragmatic strength can also be evaluated using slow VC or the difference between the FVC values measured in supine and sitting positions in situations where the above-mentioned tests for evaluating diaphragm strength are not available or where patients with neurological disease present with significant orofacial weakness.71-73

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%.74 Respiratory function tests are also considered for weaning off mechanical ventilation. MEP, MIP, and rapid shallow breathing index calculated as the tidal volume divided by the respiratory rate of higher than 30 cmH2O, higher than 36 cmH2O, and lower than 105 breaths/min/L, respectively, probably indicate successful weaning.75-77 The characteristics and clinical applications of respiratory function tests are summarized in Table 1.

Summary of respiratory function tests


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.


Conflicts of Interest

The authors declare no conflicts of interest.


1. Vaporidi K, Akoumianaki E, Telias I, Goligher EC, Brochard L, Georgopoulos D. Respiratory drive in critically ill patients. Pathophysiology and clinical implications. Am J Respir Crit Care Med 2020;201:20–32.
2. Ikeda K, Kawakami K, Onimaru H, Okada Y, Yokota S, Koshiya N, et al. The respiratory control mechanisms in the brainstem and spinal cord: integrative views of the neuroanatomy and neurophysiology. J Physiol Sci 2017;67:45–62.
3. Routal RV, Pal GP. Location of the phrenic nucleus in the human spinal cord. J Anat 1999;195:617–621.
4. Polkey MI, Lyall RA, Moxham J, Leigh PN. Respiratory aspects of neurological disease. J Neurol Neurosurg Psychiatry 1999;66:5–15.
5. Mellies U, Dohna-Schwake C, Voit T. Respiratory function assessment and intervention in neuromuscular disorders. Curr Opin Neurol 2005;18:543–547.
6. Howard RS. Respiratory failure because of neuromuscular disease. Curr Opin Neurol 2016;29:592–601.
7. Diebold D. Management of respiratory complications in neuromuscular weakness. Clin Pulm Med 2011;18:175–180.
8. Boentert M, Wenninger S, Sansone VA. Respiratory involvement in neuromuscular disorders. Curr Opin Neurol 2017;30:529–537.
9. Polatli M, Akyol A, Cildag O, Bayülkem K. Pulmonary function tests in Parkinson’s disease. Eur J Neurol 2001;8:341–345.
10. Chiang J, Mehta K, Amin R. Respiratory diagnostic tools in neuromuscular disease. Children (Basel) 2018;5:78.
11. DePalo VA, McCool FD. Respiratory muscle evaluation of the patient with neuromuscular disease. Semin Respir Crit Care Med 2002;23:201–209.
12. Crapo RO. Pulmonary-function testing. N Engl J Med 1994;331:25–30.
13. Lyall RA, Donaldson N, Polkey MI, Leigh PN, Moxham J. Respiratory muscle strength and ventilatory failure in amyotrophic lateral sclerosis. Brain 2001;124:2000–2013.
14. Morgan RK, McNally S, Alexander M, Conroy R, Hardiman O, Costello RW. Use of sniff nasal-inspiratory force to predict survival in amyotrophic lateral sclerosis. Am J Respir Crit Care Med 2005;171:269–274.
15. Davis MD, Walsh BK, Sittig SE, Restrepo RD. AARC clinical practice guideline: blood gas analysis and hemoximetry: 2013. Respir Care 2013;58:1694–1703.
16. Ak A, Ogun CO, Bayir A, Kayis SA, Koylu R. Prediction of arterial blood gas values from venous blood gas values in patients with acute exacerbation of chronic obstructive pulmonary disease. Tohoku J Exp Med 2006;210:285–290.
17. Herrington WG, Nye HJ, Hammersley MS, Watkinson PJ. Are arterial and venous samples clinically equivalent for the estimation of pH, serum bicarbonate and potassium concentration in critically ill patients? Diabet Med 2012;29:32–35.
18. Deane JC, Dagleish MP, Benamou AE, Wolf BT, Marlin D. Effects of syringe material and temperature and duration of storage on the stability of equine arterial blood gas variables. Vet Anaesth Analg 2004;31:250–257.
19. Fox MJ, Brody JS, Weintraub LR. Leukocyte larceny: a cause of spurious hypoxemia. Am J Med 1979;67:742–746.
20. Woolley A, Hickling K. Errors in measuring blood gases in the intensive care unit: effect of delay in estimation. J Crit Care 2003;18:31–37.
21. Folke M, Cernerud L, Ekström M, Hök B. Critical review of non-invasive respiratory monitoring in medical care. Med Biol Eng Comput 2003;41:377–383.
22. Friesen RH, Alswang M. End-tidal PCO2 monitoring via nasal cannulae in pediatric patients: accuracy and sources of error. J Clin Monit 1996;12:155–159.
23. Loughnan TE, Monagle J, Copland JM, Ranjan P, Chen MF. A comparison of carbon dioxide monitoring and oxygenation between facemask and divided nasal cannula. Anaesth Intensive Care 2000;28:151–154.
24. Linko K, Paloheimo M. Monitoring of the inspired and end-tidal oxygen, carbon dioxide, and nitrous oxide concentrations: clinical applications during anesthesia and recovery. J Clin Monit 1989;5:149–156.
25. Kavanagh BP, Sandler AN, Turner KE, Wick V, Lawson S. Use of end-tidal PCO2 and transcutaneous PCO2 as noninvasive measurement of arterial PCO2 in extubated patients recovering from general anesthesia. J Clin Monit 1992;8:226–230.
26. Santos LJ, Varon J, Pic-Aluas L, Combs AH. Practical uses of end-tidal carbon dioxide monitoring in the emergency department. J Emerg Med 1994;12:633–644.
27. Bach JR, Saporito LR. Criteria for extubation and tracheostomy tube removal for patients with ventilatory failure. A different approach to weaning. Chest 1996;110:1566–1571.
28. Evans JA, Whitelaw WA. The assessment of maximal respiratory mouth pressures in adults. Respir Care 2009;54:1348–1359.
29. De Troyer A, Borenstein S, Cordier R. Analysis of lung volume restriction in patients with respiratory muscle weakness. Thorax 1980;35:603–610.
30. Tully K, Koke K, Garshick E, Lieberman SL, Tun CG, Brown R. Maximal expiratory pressures in spinal cord injury using two mouthpieces. Chest 1997;112:113–116.
31. Arora NS, Rochester DF. Respiratory muscle strength and maximal voluntary ventilation in undernourished patients. Am Rev Respir Dis 1982;126:5–8.
32. Stefanutti D, Benoist MR, Scheinmann P, Chaussain M, Fitting JW. Usefulness of sniff nasal pressure in patients with neuromuscular or skeletal disorders. Am J Respir Crit Care Med 2000;162:1507–1511.
33. Mier-Jedrzejowicz A, Brophy C, Moxham J, Green M. Assessment of diaphragm weakness. Am Rev Respir Dis 1988;137:877–883.
34. Koulouris N, Mulvey DA, Laroche CM, Sawicka EH, Green M, Moxham J. The measurement of inspiratory muscle strength by sniff esophageal, nasopharyngeal, and mouth pressures. Am Rev Respir Dis 1989;139:641–646.
35. Laroche CM, Mier AK, Moxham J, Green M. The value of sniff esophageal pressures in the assessment of global inspiratory muscle strength. Am Rev Respir Dis 1988;138:598–603.
36. Miller JM, Moxham J, Green M. The maximal sniff in the assessment of diaphragm function in man. Clin Sci (Lond) 1985;69:91–96.
37. Mier A, Brophy C, Moxham J, Green M. Twitch pressures in the assessment of diaphragm weakness. Thorax 1989;44:990–996.
38. Polkey MI, Duguet A, Luo Y, Hughes PD, Hart N, Hamnegård CH, et al. Anterior magnetic phrenic nerve stimulation: laboratory and clinical evaluation. Intensive Care Med 2000;26:1065–1075.
39. De Carvalho M. Electrodiagnostic assessment of respiratory dysfunction in motor neuron disease. Handbook of Clinical Neurophysiology 2004;4:513–528.
40. Preston DC, Shapiro BE. Electromyography and neuromuscular disorders e-book: clinical-electrophysiologic-ultrasound correlations 4th edth ed. Philadelphia: Elsevier Health Sciences; 2020. p. 713–728.
41. Gottesman E, McCool FD. Ultrasound evaluation of the paralyzed diaphragm. Am J Respir Crit Care Med 1997;155:1570–1574.
42. Wang Y, Shao WB, Gao L, Lu J, Gu H, Sun LH, et al. Abnormal pulmonary function and respiratory muscle strength findings in Chinese patients with Parkinson’s disease and multiple system atrophy--comparison with normal elderly. PLoS One 2014;9e116123.
43. Howard RS, Rudd AG, Wolfe CD, Williams AJ. Pathophysiological and clinical aspects of breathing after stroke. Postgrad Med J 2001;77:700–702.
44. Houston JG, Morris AD, Grosset DG, Lees KR, McMillan N, Bone I. Ultrasonic evaluation of movement of the diaphragm after acute cerebral infarction. J Neurol Neurosurg Psychiatry 1995;58:738–741.
45. Cohen E, Mier A, Heywood P, Murphy K, Boultbee J, Guz A. Diaphragmatic movement in hemiplegic patients measured by ultrasonography. Thorax 1994;49:890–895.
46. Zimmer MB, Nantwi K, Goshgarian HG. Effect of spinal cord injury on the respiratory system: basic research and current clinical treatment options. J Spinal Cord Med 2007;30:319–330.
47. Hughes RA, Bihari D. Acute neuromuscular respiratory paralysis. J Neurol Neurosurg Psychiatry 1993;56:334–343.
48. Laroche CM, Mier AK, Spiro SG, Newsom-Davis J, Moxham J, Green M. Respiratory muscle weakness in the Lambert-Eaton myasthenic syndrome. Thorax 1989;44:913–918.
49. Wilcox P, Andolfatto G, Fairbarn MS, Pardy RL. Long-term follow-up of symptoms, pulmonary function, respiratory muscle strength, and exercise performance after botulism. Am Rev Respir Dis 1989;139:157–163.
50. Tsao TC, Juang YC, Lan RS, Shieh WB, Lee CH. Respiratory failure of acute organophosphate and carbamate poisoning. Chest 1990;98:631–636.
51. Howard RS, Wiles CM, Hirsch NP, Spencer GT. Respiratory involvement in primary muscle disorders: assessment and management. Q J Med 1993;86:175–189.
52. Shahrizaila N, Kinnear WJ, Wills AJ. Respiratory involvement in inherited primary muscle conditions. J Neurol Neurosurg Psychiatry 2006;77:1108–1115.
53. Rimmer KP, Golar SD, Lee MA, Whitelaw WA. Myotonia of the respiratory muscles in myotonic dystrophy. Am Rev Respir Dis 1993;148:1018–1022.
54. Howard RS, Russell S, Losseff N, Harding AE, Hughes JM, Wiles CM, et al. Management of mitochondrial disease on an intensive care unit. QJM 1995;88:197–207.
55. Braun NM, Arora NS, Rochester DF. Respiratory muscle and pulmonary function in polymyositis and other proximal myopathies. Thorax 1983;38:616–623.
56. Niedermeyer S, Murn M, Choi PJ. Respiratory failure in amyotrophic lateral sclerosis. Chest 2019;155:401–408.
57. Atsuta N, Watanabe H, Ito M, Banno H, Suzuki K, Katsuno M, et al. Natural history of spinal and bulbar muscular atrophy (SBMA): a study of 223 Japanese patients. Brain 2006;129:1446–1455.
58. Wijngaarde CA, Veldhoen ES, van Eijk RPA, Stam M, Otto LAM, Asselman FL, et al. Natural history of lung function in spinal muscular atrophy. Orphanet J Rare Dis 2020;15:88.
59. Finkel RS, Mercuri E, Meyer OH, Simonds AK, Schroth MK, Graham RJ, et al. Diagnosis and management of spinal muscular atrophy: part 2: pulmonary and acute care; medications, supplements and immunizations; other organ systems; and ethics. Neuromuscul Disord 2018;28:197–207.
60. Tzelepis GE, McCool FD. Respiratory dysfunction in multiple sclerosis. Respir Med 2015;109:671–679.
61. Askenasy JJ, Goldhammer I. Sleep apnea as a feature of bulbar stroke. Stroke 1988;19:637–639.
62. Devereaux MW, Keane JR, Davis RL. Automatic respiratory failure associated with infarction of the medulla. Report of two cases with pathologic study of one. Arch Neurol 1973;29:46–52.
63. Andersen PM, Abrahams S, Borasio GD, de Carvalho M, Chio A, Van Damme P, et al. EFNS guidelines on the clinical management of amyotrophic lateral sclerosis (MALS)--revised report of an EFNS task force. Eur J Neurol 2012;19:360–375.
64. Shoesmith C, Abrahao A, Benstead T, Chum M, Dupre N, Izenberg A, et al. Canadian best practice recommendations for the management of amyotrophic lateral sclerosis. CMAJ 2020;192:E1453–E1468.
65. Leonhard SE, Mandarakas MR, Gondim FAA, Bateman K, Ferreira MLB, Cornblath DR, et al. Diagnosis and management of Guillain-Barré syndrome in ten steps. Nat Rev Neurol 2019;15:671–683.
66. Kishnani PS, Steiner RD, Bali D, Berger K, Byrne BJ, Case LE, et al. Pompe disease diagnosis and management guideline. Genet Med 2006;8:267–288.
67. Schmidt EP, Drachman DB, Wiener CM, Clawson L, Kimball R, Lechtzin N. Pulmonary predictors of survival in amyotrophic lateral sclerosis: use in clinical trial design. Muscle Nerve 2006;33:127–132.
68. Gay PC, Westbrook PR, Daube JR, Litchy WJ, Windebank AJ, Iverson R. Effects of alterations in pulmonary function and sleep variables on survival in patients with amyotrophic lateral sclerosis. Mayo Clin Proc 1991;66:686–694.
69. Miller RG, Jackson CE, Kasarskis EJ, England JD, Forshew D, Johnston W, et al. Practice parameter update: the care of the patient with amyotrophic lateral sclerosis: drug, nutritional, and respiratory therapies (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2009;73:1218–1226.
70. Finder JD, Birnkrant D, Carl J, Farber HJ, Gozal D, Iannaccone ST, et al. Respiratory care of the patient with Duchenne muscular dystrophy: ATS consensus statement. Am J Respir Crit Care Med 2004;170:456–465.
71. Fromageot C, Lofaso F, Annane D, Falaize L, Lejaille M, Clair B, et al. Supine fall in lung volumes in the assessment of diaphragmatic weakness in neuromuscular disorders. Arch Phys Med Rehabil 2001;82:123–128.
72. Andrews JA, Meng L, Kulke SF, Rudnicki SA, Wolff AA, Bozik ME, et al. Association between decline in slow vital capacity and respiratory insufficiency, use of assisted ventilation, tracheostomy, or death in patients with amyotrophic lateral sclerosis. JAMA Neurol 2018;75:58–64.
73. Huang X, Du C, Yang Q, Fan D. Comparison of slow and forced vital capacity on ability to evaluate respiratory function in bulbar-involved amyotrophic lateral sclerosis. Front Neurol 2022;13:938256.
74. Lawn ND, Fletcher DD, Henderson RD, Wolter TD, Wijdicks EF. Anticipating mechanical ventilation in Guillain-Barré syndrome. Arch Neurol 2001;58:893–898.
75. Tzanis G, Vasileiadis I, Zervakis D, Karatzanos E, Dimopoulos S, Pitsolis T, et al. Maximum inspiratory pressure, a surrogate parameter for the assessment of ICU-acquired weakness. BMC Anesthesiol 2011;11:14.
76. Karthika M, Al Enezi FA, Pillai LV, Arabi YM. Rapid shallow breathing index. Ann Thorac Med 2016;11:167–176.
77. Lin SJ, Jerng JS, Kuo YW, Wu CL, Ku SC, Wu HD. Maximal expiratory pressure is associated with reinstitution of mechanical ventilation after successful unassisted breathing trials in tracheostomized patients with prolonged mechanical ventilation. PLoS One 2020;15e0229935.

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Fig. 1.

Apparatus for measuring maximal inspiratory pressure, maximal expiratory pressure, and sniff nasal inspiratory pressure.

Table 1.

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.