This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Search for Related Content PubMed PubMed Citation

ATS/ERS Statement on Respiratory Muscle Testing

	INTRODUCTION

TOP INTRODUCTION Introduction 1. Tests of Overall... REFERENCES 2. Tests of Respiratory... REFERENCES  3. Electrophysiologic Techniques... REFERENCES   4. Tests of Respiratory... REFERENCES    5. Assessment of Respiratory... REFERENCES     6. Assessment of Chest... REFERENCES     8. Tests of Upper... REFERENCES     9. Tests of Respiratory... REFERENCES     10. Assessment of Respiratory... REFERENCES

Introduction, 520

1. Tests of Overall Respiratory Function

G. John Gibson, William Whitelaw, Nikolaos Siafakas

Static Lung Volumes, 521

Dynamic Spirometry and Maximum Flow, 521

Maximum Voluntary Ventilation, 522

Arterial Blood Gases: Awake, 522

Measurements during Sleep, 523

Tests of Respiratory Control, 524

Carbon Monoxide Transfer, 525

Exercise Testing, 526

Conclusion, 526

2. Tests of Respiratory Muscle Strength

Malcolm Green, Jeremy Road, Gary C. Sieck, Thomas Similowski

Pressure Measurements, 528

Devices for Measuring Pressures, 528

Techniques for Pressure Measurement, 530

Volitional Tests of Respiratory Muscle Strength, 531

Pressures Obtained via Phrenic Nerve Stimulation, 535

Abdominal Muscle Stimulation, 542

Conclusion, 542

3. Electrophysiologic Techniques for the Assessment of Respiratory Muscle Function

Thomas K. Aldrich, Christer Sinderby, David K. McKenzie, Marc Estenne, Simon C. Gandevia

Electromyography, 548

Stimulation Tests, 554

Conclusion, 556

Summary, 557

4. Tests of Respiratory Muscle Endurance

Thomas Clanton, Peter M. Calverly, Bartolome R. Celli

Measures of Respiratory Muscle Activity Used in Endurance Testing, 559

Ventilatory Endurance Tests, 562

Endurance to External Loads, 564

Endurance of the Diaphragm, 568

Conclusion, 569

5. Assessment of Respiratory Muscle Fatigue

Gerald S. Supinski, Jean Will Fitting, François Bellemare

Types of Fatigue, 571

Tests of Respiratory Muscle Fatigue, 572

Conclusion, 578

6. Assessment of Chest Wall Function

Stephen H. Loring, Andre de Troyer, Alex E. Grassino

Pressures in the Chest Wall, 580

Assessment of the Properties of the Relaxed Human Chest Wall: Rahn Diagram, 580

Assessment of the Function of the Active Chest Wall: Campbell Diagram, 581

Estimation of Ventilation Based on Chest Wall Motion: Konno-Mead Diagram, 582

Devices Used to Monitor Breathing: Pneumograph, Magnetometer, and Respiratory Inductive Plethysmograph, 583

Optical Devices Used to Measure Chest Wall Motion, 584

Inferring Respiratory Muscle Contribution to Breathing from Chest Wall Motion, 584

Inferring Respiratory Muscle Contribution to Breathing from the Esophageal–Gastric Pressure Relationship: Macklem Diagram, 585

Inferring Respiratory Muscle Contribution to Breathing from Pressure–Volume Relationships, 585

Inferring Diaphragm Activation and Electromechanical Effectiveness from EMG, 585

Conclusion, 586

7. Imaging Respiratory Muscle Function

Neil B. Pride, Joseph R. Rodarte

Transmission Radiography, 588

Ultrasound, 589

Volumetric Imaging, 591

Nuclear Medicine, 591

Summary, 591

8. Tests of Upper Airway Function

Neil J. Douglas, Samuel T. Kuna

Electromyography, 593

Upper Airway Resistance, 594

Indirect Laryngoscopy, 596

Fiberoptic Imaging, 596

Computed Tomographic Scanning, 596

Magnetic Resonance Imaging, 597

Acoustic Reflection, 597

Flow–Volume Loops, 597

Polysomnography, 597

Muscle Biopsy, 598

Strength, Fatigue, and Endurance of Upper Airway Muscles, 598

Site of Pharyngeal Airway Closure during Sleep, 598

Conclusion, 598

9. Tests of Respiratory Muscle Function in Children

Claude Gaultier, Julian Allen, Sandra England

Physiology of the Developing Respiratory Pump, 601

Tests of Respiratory Function, 601

Conclusion, 607

10. Assessment of Respiratory Muscle Function in the Intensive Care Unit

Martin J. Tobin, Laurent Brochard, Andrea Rossi

Breathing Pattern, 610

Lung Volumes, 611

Pressure Measurements, 611

Prediction of Weaning, 617

Conclusion, 619

	INTRODUCTION

TOP INTRODUCTION Introduction 1. Tests of Overall... REFERENCES 2. Tests of Respiratory... REFERENCES  3. Electrophysiologic Techniques... REFERENCES   4. Tests of Respiratory... REFERENCES    5. Assessment of Respiratory... REFERENCES     6. Assessment of Chest... REFERENCES     8. Tests of Upper... REFERENCES     9. Tests of Respiratory... REFERENCES     10. Assessment of Respiratory... REFERENCES

This official joint statement represents the work of an expert ATS/ERS committee, which reviewed the merits of currently known techniques available to evaluate respiratory muscle function. The statement consists of 10 sections, each addressing a major aspect of muscle function or a particular field of application. Each section addresses the rationale for the techniques, their scientific basis, the equipment required, and, when pertinent, provides values obtained in healthy subjects or in patients. Some of the techniques reviewed in this statement have thus far been used primarily in clinical research and their full potential has not yet been established; however, they are mentioned for the purpose of stimulating their further development.

Through continued efforts in the area of respiratory muscle testing, it is anticipated that there will be further enhancement of diagnostic and treatment capabilities in specialties such as intensive care, sleep medicine, pediatrics, neurology, rehabilitation, sports medicine, speech therapy, and respiratory medicine.

	1. Tests of Overall Respiratory Function

TOP INTRODUCTION Introduction 1. Tests of Overall... REFERENCES 2. Tests of Respiratory... REFERENCES  3. Electrophysiologic Techniques... REFERENCES   4. Tests of Respiratory... REFERENCES    5. Assessment of Respiratory... REFERENCES     6. Assessment of Chest... REFERENCES     8. Tests of Upper... REFERENCES     9. Tests of Respiratory... REFERENCES     10. Assessment of Respiratory... REFERENCES

STATIC LUNG VOLUMES
Rationale and Scientific Basis
The most frequently noted abnormality of lung volumes in patients with respiratory muscle weakness is a reduction in vital capacity (VC). The pattern of abnormality of other subdivisions of lung volume is less consistent. Residual volume (RV) is usually normal or increased, the latter particularly with marked expiratory weakness (1). Consequently, total lung capacity (TLC) is less markedly reduced than VC, and the RV/TLC and FRC/TLC ratios are often increased without necessarily implying airway obstruction.

The VC is limited by weakness of both the inspiratory muscles, preventing full inflation, and expiratory muscles, inhibiting full expiration. In addition to the direct effect of loss of muscle force, reductions in compliance of both the lungs (2) and chest wall (3) also contribute to the reduction of VC in patients with chronic respiratory muscle weakness. In severe weakness, the TLC and VC relate more closely to lung compliance than to the distending force (4, 5) (Figure 1) . The mechanism of reduced lung compliance is unclear. Contrary to earlier suggestions, it is probably not simply due to widespread microatelectasis (6). Static lung volumes may also be affected in some patients by coexistent lung or airway disease. Vital capacity, thus, reflects the combined effect of weakness and the static mechanical load on the respiratory muscles.

View larger version (18K): [in this window] [in a new window]   Figure 1. Relation between static lung compliance and total lung capacity in 25 patients with chronic respiratory muscle weakness of varying severity. Dashed line is regression line. Reprinted by permission from Reference 5.

View larger version (23K): [in this window] [in a new window]   Figure 2. Curvilinear relation of maximum static inspiratory pressure (inspiratory muscle strength) to vital capacity in 25 patients with chronic weakness of varying severity. Dashed line and statistics relate to logarithmic regression. Solid line represents relationship calculated from a standard maximal static pressure–volume diagram assuming normal elastic properties of the respiratory system. The greater than expected reduction in VC is due to reduced compliance of the lungs and chest wall. Reprinted by permission from Reference 5.

Methodology and Equipment
Recommendations and requirements for the measurement of VC and other lung volumes are covered in detail elsewhere (9, 10).

Advantages
VC has excellent standardization, high reproducibility and well-established reference values. It is easily performed, widely available, and economical. It is quite sensitive for assessing progress in moderate to severe respiratory muscle weakness. The rate of decline has been shown to predict survival in both amyotrophic lateral sclerosis (11) and Duchenne muscular dystrophy (12).

Disadvantages
VC has poor specificity for the diagnosis of respiratory muscle weakness. In mild weakness, it is generally less sensitive to changes than are maximum pressures (13).

Applications
Serial measurements of VC should be routine in monitoring progress of patients with acute and chronic respiratory muscle weakness.

Measurement of postural change of VC gives a simple index of weakness of the diaphragm relative to the other inspiratory muscles.

DYNAMIC SPIROMETRY AND MAXIMUM FLOW
Rationale and Scientific Basis
Airway resistance is normal in uncomplicated respiratory muscle weakness (14). Airway function may appear to be supernormal when volume-corrected indices such as FEV₁/VC or specific airway conductance are used (2).

The maximum expiratory and maximum inspiratory flow–volume curves characteristically show a reduction in those flows that are most effort dependent, that is, maximum expiratory flow at large lung volumes (including peak expiratory flow) and maximum inspiratory flow at all lung volumes (2, 5) (Figure 3) . The descending limb of the maximum expiratory flow–volume curve may suggest supernormal expiratory flow when this is related to absolute volume (2, 3). With severe expiratory weakness, an abrupt fall in maximum expiratory flow is seen immediately before RV is reached (1). In health the FEV₁ is usually less than the forced inspiratory volume in 1 second. Reversal of this ratio is seen with upper (extrathoracic) airway obstruction, as well as in respiratory muscle weakness, and may give a pointer to these diagnoses during routine testing.

View larger version (15K): [in this window] [in a new window]   Figure 3. Schematic maximum expiratory and inspiratory flow–volume curves in a patient with severe respiratory muscle weakness (solid line) compared with predicted (dotted line). Volume is expressed in absolute terms (i.e., percent predicted). Note marked reductions in FVC, V·Emax at higher volumes, and V·Imax at all volumes. Note also the blunted contour of the expiratory curve and the abrupt cessation of V·Emax at RV. In the midvolume range, V·Emax exceeds that predicted for the absolute lung volume.

Oscillations of maximum expiratory and/or inspiratory flow—the so-called sawtooth appearance—are seen particularly when the upper airway muscles are weak and in patients with extrapyramidal disorders (17) (Figure 4) .

View larger version (13K): [in this window] [in a new window]   Figure 4. Maximum expiratory and inspiratory flow–volume curves, showing "sawtooth" oscillations of flow.

Advantages
Maximum flow–volume curves are easily performed, widely available, and economical. Peak expiratory flow can be obtained with simple portable devices.

Disadvantages
Intersubject variability is greater than for VC. Reference values for _V^·Emax at standard percentages of FVC may present problems of interpretation.

Applications
Visual inspection may suggest the likelihood of weakness.

The sawtooth appearance in an appropriate context may suggest weakness or dyscoordination of upper airway muscles. However, this appearance is nonspecific and is seen also in some subjects with obstructive sleep apnea, nonapneic snoring, and thermal injury of the upper airway.

MAXIMUM VOLUNTARY VENTILATION
Rationale and Scientific Basis
The maximum voluntary ventilation was formerly recommended as a more specific test for muscle weakness than volume measurements but, in practice, the proportionate reduction is usually similar to that of VC (18, 19). Disproportionate reductions may be seen in Parkinson's disease (20), in which the ability to perform frequent alternating movements is impaired.

Methodology and Equipment
Recommendations and requirements are covered elsewhere (10).

Advantages
No advantages are perceived in most situations.

Disadvantages
The test depends on motivation and is tiring for the subject.

Applications
Maximum voluntary ventilation is not generally recommended for patients with known or suspected respiratory muscle weakness but may be helpful in the assessment and monitoring of patients with extrapyramidal disorders.

ARTERIAL BLOOD GASES: AWAKE
Rationale and Scientific Basis
In chronic muscle weakness, even when quite severe, Pa_O2 and the alveolar–arterial PO₂ difference are usually only mildly abnormal (2, 21). In acute muscle weakness, Pa_O2 may be more markedly reduced, but the picture may be complicated by atelectasis or respiratory infection (22).

With mild weakness, Pa_CO2 is usually less than normal (19, 22), implying alveolar hyperventilation. In the absence of primary pulmonary disease, daytime hypercapnia is unlikely unless respiratory muscle strength is reduced to < 40% of predicted and VC is reduced to < 50% of predicted (19) (Figures 5 and 6) . Elevation of venous bicarbonate concentration occasionally gives an important clue to otherwise unsuspected hypercapnia. Patients with muscle weakness are less able than normal subjects to compensate for minor changes in respiratory function. If hypercapnia is established or incipient, even minor infections may cause a further rise in Pa_CO2, as also may injudicious use of sedative drugs or uncontrolled oxygen.

View larger version (16K): [in this window] [in a new window]   Figure 5. Relation of daytime PaCO2 to "respiratory muscle strength" (RMS = arithmetic mean of PImax and PEmax) in 33 patients with "uncomplicated" chronic myopathy (closed circles, regression lines) and 14 patients with myopathy plus chronic lung disease (open circles). Note that in uncomplicated myopathy, PaCO2 is reduced (< 40 mm Hg) in most patients with mild weakness and is likely to be elevated only when RMS < 40% predicted. Reprinted by permission from Reference 19.

View larger version (16K): [in this window] [in a new window]   Figure 6. Relation of daytime PaCO2 to VC in 37 patients with uncomplicated chronic myopathy (closed circles, regression line) and 16 with myopathy plus chronic lung disease (open circles). Reprinted by permission from Reference 19.

Disadvantages
Definitely abnormal arterial blood gases usually imply late and severe impairment of respiratory muscles and therefore their measurement is neither sensitive nor specific. Daytime values may underestimate the severity of abnormal gas exchange.

Applications
Measurement of arterial blood gases is routinely performed to assess the consequences of respiratory muscle weakness.

MEASUREMENTS DURING SLEEP
Rationale and Scientific Basis
Patients with moderate or severe respiratory muscle weakness characteristically show dips in oxygen saturation (Sa_O2) related to periods of rapid eye movement (REM) sleep (23, 24) (Figure 7) . The episodic desaturation is usually due to hypopnea and less often to apnea and is associated particularly with phasic REM sleep, when brief periods of rapid, irregular eye movements are accompanied by reduced activity of skeletal muscles (24) (Figure 8) . The hypopneas and/or apneas may appear to be either "central" (Figure 8) or "obstructive," or sometimes a mixture of both. The precise pattern of such events depends on the relative activation of the respiratory pump and upper airway dilator muscles (24). Obstructive apneas are more likely in weak patients who are also overweight (25). In patients with severe respiratory muscle weakness, some apneas that appear to be central may in fact be obstructive, incorrect classification being due to failure of external sensors to detect chest wall movements of reduced amplitude (26).

View larger version (17K): [in this window] [in a new window]   Figure 7. Section of sleep recording of SaO2 and transcutaneous PCO2 (TcCO2) in a patient with chronic myopathy, showing mild desaturation (SaO2 90%) in non-REM sleep and frequent periodic dips in SaO2 in REM sleep. The PCO2 shows progressive elevation during REM periods. Reprinted by permission from Reference 23.

View larger version (25K): [in this window] [in a new window]   Figure 8. Brief ( 2 minute) polysomnographic recording in REM sleep in a patient with chronic myopathy. The signals are as follows: SaO2, airflow (V·), posteroanterior motion of rib cage (RCPA) and abdomen (ABPA), electro-oculogram (EOG), and integrated surface electromyograms from inspiratory intercostals (EMGint) and diaphragm (EMGdi) (the ECG is superimposed on EMG signals). A–D, Periods of REM sleep. During periods A and C, marked irregular eye movements ("phasic" REM) are accompanied by reduced EMG activity and consequently reduced motion and flow with subsequent desaturation; rib cage and abdominal motion remain in phase, indicating central hypopneas. During periods B and D, eye movements are relatively quiescent and EMG activity increases with consequent increased motion and flow and subsequent recovery of SaO2 (increasing SaO2 during period C reflects the increased ventilation in period B). Reprinted by permission from Reference 24.

The timescale of progression from nocturnal to persistent diurnal hypercapnia in patients with chronic respiratory muscle weakness is not known.

Methodology
Polysomnographic techniques are described in detail elsewhere (28). To assess whether upper airway narrowing is a contributing cause of apneas or hypopneas may require use of a supraglottic or esophageal pressure sensor. Interpretation of recordings obtained by inductance plethysmography or other devices that measure rib cage and abdominal expansion is problematic in patients with quadriplegic or diaphragm paralysis. It is essential to check the polarity of the tracings and to compare phase relations awake and asleep.

Reliability of the devices for monitoring PCO₂ in sleep is currently doubtful and requires more study.

Advantages
Overnight oximetry is simple to perform.

Nocturnal measurements are more sensitive for detection of abnormal pulmonary gas exchange than daytime blood gases.

Disadvantages
Polysomnography is labor-intensive and relatively expensive. Current evidence suggests that nocturnal hypoxemia is a less good prognostic indicator than either vital capacity or awake Pa_CO2 (12, 29).

Applications
The role of sleep measurements in patients with respiratory muscle weakness is currently uncertain. Polysomnography may be useful in patients with daytime sleepiness and suspected nocturnal hypoventilation, perhaps especially if awake Pa_CO2 is borderline or only mildly elevated.

Marked REM-related desaturation is seen occasionally in patients with relatively normal daytime Sa_O2 (26). More typically, however, the severity of nocturnal desaturation is predictable from daytime measurements, with more marked desaturation in patients with lower daytime Pa_O2, higher Pa_CO2, and lower VC (23) (Figure 9) .

View larger version (20K): [in this window] [in a new window]   Figure 9. Relation of sleep hypoxemia to daytime blood gases and VC in 20 patients with chronic myopathy (regression line [solid line] ± 95% confidence limits [dashed lines]). The abscissa in each panel shows the nadir SaO2 in REM sleep. More severe REM desaturation occurs with lower awake PaO2 (top panel), higher awake PaCO2 (middle panel), and lower VC (lower panel). Reprinted by permission from Reference 23.

TESTS OF RESPIRATORY CONTROL
Rationale and Scientific Basis
The respiratory control system may be considered to have three functional components: (1) sensory receptors that provide information about the status of the respiratory system (only chemoreceptors that measure arterial PCO₂, PO₂, and pH are usually considered or tested, but there are many other sensory inputs of importance); (2) the central integrating circuits; and (3) the motor output to the respiratory muscles. The tests available are stimulus response tests, in which a receptor is stimulated and the motor output or a downstream mechanical effect of motor output, is measured. It is important to recognize that these tests are generally unable to separate the three functional components of the control system.

Minute ventilation and arterial PCO₂ are maintained at normal levels even with quite marked weakness of the respiratory muscles, implying that the control system compensates for the weakness by driving the respiratory muscles harder than normal. The mechanism by which the control system identifies muscle weakness and adjusts its motor output is unknown. The increased motor output is difficult to appreciate because it succeeds in generating only normal pressures, volumes, and flows. It is most readily apparent when accessory muscles or abdominal muscles are more active than normal during quiet breathing. If phasic contraction of scalenes, sternocleidomastoids, pectoral muscles, or abdominal muscles can be palpated, it is safe to conclude that respiratory motor output is above normal.

When respiratory muscles are chronically severely weak and arterial PCO₂ begins to rise, two explanations are possible. The muscles may be so weak that they cannot continually generate sufficient alveolar ventilation. Otherwise, an abnormality of the ventilatory control system may be allowing the PCO₂ to rise even though the muscles themselves are quite capable of keeping it normal. A gradual shift in the PCO₂ "set point" of the controller does seem to occur in some patients with muscle disease, as it does in some cases of sleep apnea and chronic obstructive pulmonary disease.

Laboratory tests of overall respiration that have been used to try to assess the control system include inhalation of hypercapnic or hypoxic gas mixtures to stimulate chemoreceptors, with measurements of ventilation or occlusion pressure to assess motor output, and sleep studies to monitor behavior of the control system during sleep.

In patients with weak muscles, interpretation of slopes of conventional ventilatory curves is clouded for several reasons.

• The output of the controller is abnormally high when ventilation is normal. The controller may therefore be on the nonlinear part of its normal response curve.

• The high motor neuron output cannot be measured directly and its mechanical effect (e.g., ventilation) is reduced in the presence of weakness.

• The response will become flat if ventilation nears the limit of respiratory muscle endurance and that limit may be only a short distance above resting ventilation.

Abnormal central control of respiration is well documented in bulbar poliomyelitis and other conditions affecting the central nervous system, presumably because of direct involvement of medullary respiratory centers. It has been suggested that certain muscle diseases are also associated with primary abnormalities of central respiratory control; these conditions include myotonic dystrophy, acid maltase deficiency, and other congenital myopathies. Impaired ventilatory responses to CO₂ and/or hypoxia have frequently been described, but in many cases, respiratory muscle function was assessed inadequately. In myotonic dystrophy it has been shown that the relations between hypercapnia and both maximum respiratory pressures and VC are similar to those in nonmyotonic diseases (30).

Occlusion pressure is the pressure generated in the airway (and by inference the pressure generated in the pleural space) by contraction of inspiratory muscles when the airway has been occluded at end expiration. It was introduced to separate hypoventilation due to high pulmonary resistance or elastance from hypoventilation due to a failure of the respiratory pump apparatus (i.e., the muscles, passive components of the chest wall, and the control system) (31, 32). Occlusion pressure amplitude does not directly assess either the degree of muscle weakness or the degree of neuronal adjustment to the weakness. P_0.1 is the pressure generated in the first 100 milliseconds of inspiration against an occluded airway. Its timing is such that it is not influenced by the conscious response to occlusion and as an index of ventilatory drive it has the advantage over ventilation of being independent of the mechanical properties of the lung (31). It is, however, dependent on the contractile state and function of the respiratory muscles and consequently on the lung volume at which it is measured. For example, because of the length–tension relationship of the muscles, a reduced value for a given neural output would be expected with pulmonary hyperinflation and an elevated FRC. On the other hand, if inspiration starts below equilibrium lung volume the value of P_0.1 recorded depends on relaxation of the expiratory muscles.

Values of P_0.1 are around 1 cm H₂O in normal subjects at rest, around 3 cm H₂O in patients with stable chronic obstructive pulmonary disease, and may be 10 cm H₂O or more in acute respiratory failure due to chronic obstructive pulmonary disease or acute respiratory distress syndrome. Such values reflect a high ventilatory drive consequent on a greatly increased mechanical load. Some, although not all, studies have suggested that in patients with chronic obstructive pulmonary disease receiving ventilatory support values greater than 4–6 cm H₂O are associated with failure to wean (33).

In patients with weak muscles, resting P_0.1 tends to be normal or slightly increased (34). In the model of acute respiratory muscle weakness provided by partial curarization of healthy subjects, the slope of P_0.1 response to CO₂ is increased even though the ventilatory response is reduced (35). However, in patients with chronic weakness the ventilatory and P_0.1 slopes are both diminished (even though resting P_0.1 is normal or increased). Hence, a reduced response in such individuals does not necessarily imply impaired ventilatory drive (30).

Methodology and Equipment
For assessment of ventilatory responses to hypercapnia or hypoxia (36), the subject inhales a gas mixture that causes a change in either arterial PO₂ or PCO₂. A plot of PO₂ (or PCO₂) against ventilation (or, for PO₂ response the algebraic constants describing a hyperbola) are compared with normal values. The induced change in blood gases may be continuous (rebreathing methods) or a few discrete points (steady state methods). Usually PCO₂ is held constant while PO₂ is changed and vice versa. Standard methods are available for measuring ventilatory responses during rebreathing (37, 38).

Steady state or quasi-steady state tests (39) are done simply by having the subject inhale a prepared mixture of gases, usually for 5 minutes (40). Judgments about the safety of inducing hypoxemia or acidosis are made clinically for individual patients. In chronically hypoxemic patients, transient responses to inhalation of pure oxygen may be useful and are safe (40).

For the measurement of P_0.1, it is essential to close the airway exactly at the point of zero flow. This is usually done by separating the inspiratory and expiratory lines with one-way valves and then closing the inspiratory line while the subject is exhaling. Conscious subjects must be unable to anticipate occlusions, which must be done silently and unexpectedly. Obstruction can be simply performed by inflating a balloon within the lumen of the inspired line or by closing a valve. A sensitive transducer and timer are used to record pressure at 0.1 second.

Advantages
A completely flat ventilatory response may identify defective chemoreceptor or brainstem function, but lesser abnormalities are difficult to interpret.

Occlusion pressure (P_0.1) is relatively easy to measure. Marked discrepancies between occlusion pressure and minute ventilation point to a lung disease causing substantial increase in airway resistance or lung elastance. Usually, however, such a problem is clinically evident and better evaluated by spirometry.

Disadvantages
Indices of ventilatory control have a wide normal range and are subject to overinterpretation.

Occlusion pressures in general, and P_0.1 in particular, are difficult to interpret without additional measurements of mechanics and control events through the whole respiratory cycle, which are usually not available. P_0.1 is a valid index of neural output only at FRC. Breath-to-breath scatter in the data requires averaging of many breaths to obtain precise results. The theoretical issues regarding measurement and interpretation have been reviewed (41).

Clinical Applications
These tests are seldom used in routine clinical assessment of stable patients. In acute respiratory failure, mouth occlusion pressure during unstimulated breathing may be of value in assessing respiratory drive and the likelihood of successful weaning.

Occlusion pressure has no proven clinical value in respiratory muscle disease but may occasionally be helpful by pointing to an unsuspected mechanical problem.

If a patient is known to have a mixed problem of muscle weakness and a lung disease (e.g., polymyositis plus interstitial pulmonary fibrosis) and the response of the controller to CO₂ or O₂ is being studied, P_0.1 can be measured in conjunction with ventilation as the response and may be a more reliable way of comparing the result with normal values.

CARBON MONOXIDE TRANSFER
Rationale and Scientific Basis
Single-breath CO diffusing capacity (transfer factor) (DL_CO) in patients with muscle weakness is usually normal or mildly reduced. Reduction is due to inability to achieve full distension of the lungs at TLC and consequent failure to expose all the alveolar surface to carbon monoxide. As with other extrapulmonary causes of lung volume restriction, the transfer coefficient (KCO) is often supernormal.

Advantages
The measurement is easily performed and well standardized.

Disadvantages
A reduced DL_CO is a nonspecific finding (but if accompanied by elevation of KCO it suggests extrapulmonary volume restriction). Any effects of respiratory muscle weakness on the measurements are indirect.

Clinical Applications
The pattern of normal or mildly reduced DL_CO and raised KCO directs attention to extrapulmonary conditions, that is, respiratory muscle weakness, pleural disease or rib cage abnormalities. Otherwise, the main role of measurement of CO uptake is in the recognition or exclusion of coexistent lung disease.

EXERCISE TESTING
In many patients with muscle weakness, exercise is limited, and therefore, maximum oxygen consumption is reduced because of weakness of the leg muscles rather than cardiorespiratory factors. The limited available data suggest that the relation of workload to oxygen consumption is normal, as also are indices of submaximal exercise performance (42).

Advantages
Formal testing allows confirmation and quantification of exercise incapacity and may aid elucidation of its mechanism.

Disadvantages
Exercise is limited by weakness of nonrespiratory muscles in many patients with neuromuscular disease. Exercise testing is poorly standardized in this patient population.

Clinical Applications
Exercise testing may help determine the main factor(s) limiting exercise capacity, especially if related or coexistent cardiac or pulmonary disease is present or suspected.

CONCLUSION
This Section of the Statement has explored the usefulness of analyzing the results of pulmonary function tests to infer alterations in respiratory muscle function. Some such inferences are as follows:

1. Respiratory muscle weakness reduces VC.
   
2. Expiratory muscle weakness can increase RV.
   
3. Reduction in chest wall and lung compliance, as a consequence of muscle weakness, reduces lung volumes, notably VC.
   
4. A fall in VC in the supine position, compared with when upright, suggests severe diaphragm weakness or paralysis.
   
5. With respiratory muscle weakness the maximal expiratory and inspiratory flow–volume loops show a reduction in effort-dependent flows (peak flows) and a sharp fall in end-expiratory flow.
   
6. Reduced maximal flows in neuromuscular disease may reflect poor respiratory muscle coordination.
   
7. Maximum inspiratory and expiratory flow–volume curves showing sawtooth oscillations are seen when the upper airway muscles are weak and also in patients with extrapyramidal disorders (e.g., Parkinson's disease).
   
8. Pa_O2 and Pa_CO2 are affected by muscle weakness. Mild weakness causes slight hypoxemia and hypocapnia; severe weakness causes hypercapnia, but only when strength is < 40% predicted. A raised bicarbonate level may suggest muscle weakness.
   
9. Respiratory muscle weakness may cause desaturation and hypercapnia during REM sleep.
   
10. CO transfer (DL_CO) in patients with muscle weakness is normal or mildly reduced but, as with other causes of extrapulmonary lung volume restriction, the transfer coefficient (KCO) is often raised.
    

	REFERENCES

TOP INTRODUCTION Introduction 1. Tests of Overall... REFERENCES 2. Tests of Respiratory... REFERENCES  3. Electrophysiologic Techniques... REFERENCES   4. Tests of Respiratory... REFERENCES    5. Assessment of Respiratory... REFERENCES     6. Assessment of Chest... REFERENCES     8. Tests of Upper... REFERENCES     9. Tests of Respiratory... REFERENCES     10. Assessment of Respiratory... REFERENCES

 

1. Kreitzer SM, Saunders NA, Tyler HR, Ingram RH. Respiratory muscle function in amyotrophic lateral sclerosis. Am Rev Respir Dis 1978;117: 437–447.[Medline]
2. Gibson GJ, Pride NB, Newsom Davis J, Loh C. Pulmonary mechanics in patients with respiratory muscle weakness. Am Rev Respir Dis 1977; 115:389–395.[Medline]
3. Estenne M, Heilporn A, Delhez L, Yernault J-C, De Troyer A. Chest wall stiffness in patients with chronic respiratory muscle weakness. Am Rev Respir Dis 1983;128:1002–1007.[Medline]
4. Gibson GJ, Pride NB. Lung mechanics in diaphragmatic paralysis. Am Rev Respir Dis 1979;119:119–120.[Medline]
5. De Troyer A, Borenstein S, Cordier R. Analysis of lung volume restriction in patients with respiratory muscle weakness. Thorax 1980;35:603–610.[Abstract]
6. Estenne M, Gevenois PA, Kinnear W, Soudon P, Heilporn A, De Troyer A. Lung volume restriction in patients with chronic respiratory muscle weakness: the role of microatelectasis. Thorax 1993;48:698–701.[Abstract]
7. Allen SM, Hunt B, Green M. Fall in vital capacity with weakness. Br J Dis Chest 1985;79:267–271.[Medline]
8. Laroche CM, Carroll N, Moxham J, Green M. Clinical significance of severe isolated diaphragm weakness. Am Rev Respir Dis 1988;138:862–866.[Medline]
9. Quanjer PH. Standardised lung function testing. Eur Respir J 1993; 6(Suppl 16):3S–102S.
10. American Thoracic Society. Standardisation of spirometry: 1987 update. Am Rev Respir Dis 1987;136:1285–1298.[Medline]
11. Fallat RJ, Jewitt B, Bass M, Kamm B, Norris FH. Spirometry in amyotrophic lateral sclerosis. Arch Neurol 1979;36:74–80.[Abstract]
12. Phillips M, Smith PEM, Carroll N, Edwards RHT, Calverley PMA. Does nocturnal oxygen desaturation predict survival in childhood onset muscular dystrophy? Thorax 1997;52:A18.
13. Black LF, Hyatt RE. Maximal static respiratory pressures in generalised neuromuscular disease. Am Rev Respir Dis 1971;103:641–650.[Medline]
14. Wesseling G, Quaedvlieg FCM, Wouters EFM. Oscillatory mechanics of the respiratory system in neuromuscular disease. Chest 1992;102:1752–1757.[Abstract/Free Full Text]
15. Polkey MI, Lyall RA, Green M, Leigh PN, Moxham J. Expiratory muscle function in amyotrophic lateral sclerosis. Am J Respir Crit Care Med 1998;158:734–741.[Abstract/Free Full Text]
16. Estenne M, van Muylem A, Gorini M, Kinnear W, Heilporn A, de Troyer A. Effects of abdominal strapping on forced expiration in tetraplegic patients. Am J Respir Crit Care Med 1998;157:95–98.[Free Full Text]
17. Vincken WG, Cosio MG. Flow oscillations on the flow–volume loop: clinical and physiological implications. Eur Respir J 1989;2:543–549.[Medline]
18. Serisier DE, Mastaglia FL, Gibson GJ. Respiratory muscle function and ventilatory control. I. In patients with motor neurone disease; II. In patients with myotonic dystrophy. Q J Med 1982;51:205–226.[Abstract/Free Full Text]
19. Braun NMT, Arora NS, Rochester DF. Respiratory muscle and pulmonary function in polymyositis and other proximal myopathies. Thorax 1983;38:616–623.[Abstract]
20. Tzelepis GE, McCool FD, Friedman JH, Hoppin FG. Respiratory muscle dysfunction in Parkinson's disease. Am Rev Respir Dis 1988;138: 266–271.[Medline]
21. Lane DJ, Hazleman B, Nichols PJR. Late onset respiratory failure in patients with previous poliomyelitis. Q J Med 1974;43:551–568.[Abstract/Free Full Text]
22. Harrison BDW, Collins JV, Brown KGE, Clark TJH. Respiratory failure in neuromuscular diseases. Thorax 1971;26:579–584.[Medline]
23. Bye PTP, Ellis ER, Issa FG, Donnelly PM, Sullivan CE. Respiratory failure and sleep in neuromuscular disease. Thorax 1990;45:241–247.[Abstract]
24. White JES, Drinnan MJ, Smithson AJ, Griffiths CJ, Gibson GJ. Respiratory muscle activity and oxygenation during sleep in patients with muscle weakness. Eur Respir J 1995;8:807–814.[Abstract]
25. Labanowski M, Schmidt-Nowara W, Guilleminault C. Sleep and neuromuscular disease: frequency of sleep-disordered breathing in a neuromuscular disease clinic population. Neurology 1996;47:1173–1180.[Abstract/Free Full Text]
26. Smith PEM, Calverley PMA, Edwards RHT. Hypoxaemia during sleep in Duchenne muscular dystrophy. Am Rev Respir Dis 1988;137:884–888.[Medline]
27. Gilmartin JJ, Cooper BG, Griffiths DJ, Walls TJ, Veale D, Stone TN, Osselton JW, Hudgson P, Gibson GJ. Breathing during sleep in patients with myotonic dystrophy and non-myotonic respiratory muscle weakness. Q J Med 1991;78:21–31.
28. American Thoracic Society. Indications and standards for cardio-pulmonary sleep studies. Am Rev Respir Dis 1989;139:559–568.[Medline]
29. 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.[Medline]
30. Gibson GJ, Gilmartin JJ, Veale D, Walls TJ, Serisier DE. Respiratory muscle function in neuromuscular disease. In: Jones NL, Killian KJ, editors. Breathlessness. Hamilton, Canada: CME; 1992. p. 66–71.
31. Whitelaw WA, Derenne JP, Milic-Emili J. Occlusion pressure as a measure of respiratory center output in conscious man. Respir Physiol 1975;23:181–199.[CrossRef][Medline]
32. Matthews AW, Howell JBL. The rate of isometric inspiratory pressure development as a measure of responsiveness to carbon dioxide in man. Clin Sci Mol Med 1975;49:57–68.[Medline]
33. Sassoon CSH, Te TT, Mahutte CK, Light RW. Airway occlusion pressure: an important indicator for successful weaning in patients with chronic obstructive pulmonary disease. Am Rev Respir Dis 1987;135:107–113.[Medline]
34. Baydur A. Respiratory muscle strength and control of ventilation in patients with neuromuscular disease. Chest 1991;99:330–338.[Abstract/Free Full Text]
35. Holle RHO, Schoene RB, Pavlin EJ. Effect of respiratory muscle weakness on P0.1 induced by partial curarization. J Appl Physiol 1984;57: 1150–1157.[Abstract/Free Full Text]
36. Cherniack NS, Dempsey J, Fencl V, Fitzgerald RS, Lourenco RV, Rebuck AS, Rigg J, Severinghaus JW, Weil JW, Whitelaw WA, et al. Workshop on assessment of respiratory control in humans. I. Methods of measurement of ventilatory responses to hypoxia and hypercapnia. Am Rev Respir Dis 1977;115:177–181.[Medline]
37. Read DJC. A clinical method for assessing the ventilatory response to CO₂. Australas Ann Med 1967;16:20.[Medline]
38. Rebuck AS, Campbell EJM. A clinical method for assessing the ventilatory response to hypoxia. Am Rev Respir Dis 1974;109:345.[Medline]
39. Weil JW, Byrne-Quinn E, Sodal JE, Filey GF, Grover RF. Acquired attenuation of chemoreceptor function in chronically hypoxic man at altitude. J Clin Invest 1971;50:186.
40. Cunningham DJC, Cormack RS, O'Riordan JLH, Jukes MGM, Lloyd BB. An arrangement for studying the respiratory effects in man of various factors. Q J Exp Physiol 1957;42:294.
41. Whitelaw WA, Derenne J-P. Airway occlusion pressure. J Appl Physiol 1995;74:1475–1483.[Abstract/Free Full Text]
42. Carroll JE, Hagberg JM, Brooks MH, Shumate JB. Bicycle ergometry and gas exchange measurements in neuromuscular disease. Arch Neurol 1979;36:457–461.[Abstract]

	2. Tests of Respiratory Muscle Strength

TOP INTRODUCTION Introduction 1. Tests of Overall... REFERENCES 2. Tests of Respiratory... REFERENCES  3. Electrophysiologic Techniques... REFERENCES   4. Tests of Respiratory... REFERENCES    5. Assessment of Respiratory... REFERENCES     6. Assessment of Chest... REFERENCES     8. Tests of Upper... REFERENCES     9. Tests of Respiratory... REFERENCES     10. Assessment of Respiratory... REFERENCES

PRESSURE MEASUREMENTS
Muscles have two functions: to develop force and to shorten. In the respiratory system, force is usually estimated as pressure and shortening as lung volume change or displacement of chest wall structures. Thus, quantitative characterization of the respiratory muscles has usually relied on measurements of volumes, displacements, pressures, and the rates of change of these variables with time.

Several important considerations have to be kept in mind:

1. Pressures at a given point are usually measured as a difference from barometric pressure.
   
2. Pressures measured at a point are taken to be representative of the pressure in that space. Differences in pressure at different locations in normal subjects can arise from two causes: gravity and shear stress (1). Gravity causes vertical pressure gradients related to the density of the contents of the space. In the thorax this gradient is 0.2 cm H₂O · cm^-1 height and is related to lung density. In the abdomen, this gradient is nearly 1 cm H₂O · cm^-1 height. Pressure fluctuations are usually little affected by gravitational gradients. Deformation of shape-stable organs can cause local variations in pressure, such as those that occur when the diaphragm displaces the liver during a large forceful diaphragmatic contraction (2). Pleural pressure may not be uniform in patients with disordered lung architecture, particularly emphysema. The schematic drawing in Figure 1 shows relationships between pressures and intervening respiratory structures and equipment.
   
3. Pressure differences across structures are usually the relevant "pressures" for characterizing those structures. Table 1 lists pressures measured at a point and pressure differences across structures, which are usually taken in a direction such that positive pressure differences inflate the structure or lung.
   
4. A pressure difference between two points is always the pressure difference across two or more structures or groups of structures. For example, the pressure difference between the pleural space and the body surface in a breathing person is both the trans-chest wall (transthoracic) and the transpulmonary pressure.
   

View larger version (43K): [in this window] [in a new window]   Figure 1. Locations at which pressures can be measured, and pressure differences derived from them (see also Table 1). AbW = abdominal wall; aw = airway; Di = diaphragm; Eq = equipment; Lt = lung tissue; Pab = abdominal pressure; Palv = alveolar pressure; Pao = pressure at airway opening; Pbs = body surface pressure; Ppl = pleural pressure; rc = rib cage.

To test respiratory muscle properties, pressures can be measured either during voluntary maneuvers (see subsequent section) or during involuntary contractions, notably in response to phrenic nerve stimulation (see subsequent section). In the former, the synergistic action of several inspiratory or expiratory muscle groups is tested. In the latter, the pressure developed is specific to the contracting muscle(s).

The purpose of this article is to describe the methodology used to measure the various pressures for the assessment of respiratory muscle strength.

DEVICES FOR MEASURING PRESSURES
A comprehensive review of the techniques for measurement of pressures in respiratory physiology and of the associated problems was presented by Milic-Emili (6) in 1984.

Pressure Transducers
As for most pressure measurements of respiratory events, a frequency response flat up to 10–15 Hz is adequate to measure both dynamic and static pressures related to contractions of respiratory muscles. The frequency response of a transducer can be much altered by the characteristics of the systems attached to it, including balloons, tubing, and interconnecting fittings (7) (see subsequent section). Thus, testing the response characteristics of any transducer with the specific connectors and fittings that are to be used to make the measurements of pressure is highly recommended (7).

When differential pressure transducers are used, care must be taken that their two sides have identical frequency responses. Calibration is best made with water manometers. Electrical calibration is acceptable, but should be checked regularly with a water manometer.

The required range and sensitivity of the transducers depends on the test in question. Phrenic nerve stimulation in disease may develop pressures as low as a few centimeters of water, whereas maximal static maneuvers in healthy subjects can be associated with positive and negative pressures exceeding 200 cm H₂O. It may be possible to use a single type of transducer for all respiratory muscles tests, provided that it is sufficiently sensitive, with a resolution of approximately 0.5 cm H₂O and a range ± 200 cm H₂O. Pressure differences between two points can be measured directly with two catheters connected to a single differential pressure transducer.

Excellent pressure transducers, with such characteristics, are commercially available, including devices based on a metal "membrane." More recently, other types of transducer that provide good results (e.g., piezoelectric transducers) have been made available at lower cost.

Probes for "Internal" Pressures
Balloon catheter systems.
The balloon catheter system is the most widely used method for recording esophageal pressure (Pes, Poes; see APPENDIX for a list of abbreviations) as a reflection of pleural pressure (Ppl), and gastric pressure (Pga) as a reflection of abdominal pressure (Pab) (8). Air-containing latex balloons are sealed over catheters, which in turn transmit pressures to the transducers. Single- and double-balloon catheter systems are commercially available, but can be made in-house at low cost. Double-balloon catheters associated with an electromyograph (EMG) electrode have been used (9–11). When choosing or preparing a balloon catheter system, careful attention must be given to its physical characteristics. Indeed, the volume of the balloon, its volume–pressure characteristics, and the dimensions of the catheter can influence the measurement of pressure and introduce major errors. Standardization has been proposed (12).

For the measurement of Pes, good results have been provided by latex balloons 5–10 cm long, 3.5–5 cm in perimeter, and with a thin wall (8, 13, 14). For accurate transmission of pressure, air should be introduced into the balloon until it is fully distended to smooth out folds, and then most of the air removed so that a volume is retained at which the rubber is unstretched without distending the esophagus significantly. A volume of 0.5 ml is adequate for balloons with these characteristics. The volume displacement coefficient of the balloon catheter–transducer system should be measured, particularly if the balloon will measure positive pressures, to ensure that the pressure level to be measured does not completely empty the balloon into the catheter and transducer. Thus, if high positive pressures are to be measured (e.g., for Pes during maximal expiratory maneuvers) a volume of 0.5 ml may be inadequate (6). Balloon volumes should be checked repeatedly during measurements.

For the measurement of Pga, balloon volume is less crucial and measurements can be made with a balloon volume of 1–2 ml, given that this remains within the range of volume over which the rubber is unstretched. If studies of relatively long duration are planned, the walls of the gastric balloon should be thicker than those of esophageal balloons to increase resilience to gastric secretions.

Respiratory muscle studies can involve dynamic maneuvers with high rates of change in pressure (e.g., sniffs and twitches) resulting in a significant risk of a damped signal if the frequency response of the measuring system is inadequate, as may occur if the internal diameter of the catheter is too small or the gas volume too large. Polyethylene catheters with an internal diameter 1.4–1.7 mm and 70–100 cm in length provide, when associated with adequate transducers, an appropriate frequency response (6).

The catheter should be reasonably stiff, with a series of holes arranged in a spiral pattern over the entire portion of the catheter covered by the balloon, because the gas in the balloon tends to shift to the point where the pressure surrounding it is most negative, i.e., the top of the balloon in upright subjects.

Liquid-filled catheters.
Fluid-filled catheter systems have been employed, mainly in neonates and small animals for study of respiratory mechanics. Their advantage is that the transmission of pressure involving a noncompressible fluid (usually water) gives a high-frequency response. The catheters can, thus, be thinner than for balloons, theoretically reducing discomfort. An important practical difficulty is the need for regular flushing of the catheter, to avoid plugging of distal holes and to keep the catheter–manometer system free of air bubbles, which may dampen the measured pressure. Another drawback is that while the gas bubble in the balloon migrates to the point where the pressure is least (which is thought to minimize artifacts in the esophagus and to locate pressure at the surface of the gastric air bubble in the stomach) in a liquid-filled catheter, pressure is always measured at the end of the catheter, which may not be the optimal site. Respiratory muscle studies in adult humans with this technique are limited or not described, and its place in this context is probably limited.

Catheter-mounted microtransducers.
Catheter-mounted microtransducers, often referred to as Millar catheters (15, 16), have a level of performance comparable to that of balloon catheters (17, 18). Their management during long studies is probably easier, with a lower risk of technical problems (e.g., leaking balloons), and they may be easier to tolerate for the subject. Their frequency response is high, which may eliminate the phase lag sometimes seen with balloon catheters during extremely rapid pressure changes. However, catheter-mounted microtransducers record pressure at a single focused point so that the measured Pes may not be as representative of Ppl as balloon catheters, which sample pressure at the point where it is most negative. They are also much more expensive than balloon catheter systems, and may be difficult to sterilize and reuse with confidence.

Other systems.
Other systems exist to measure pressures in humans, including fiberoptic sensors. Fiberoptic sensors have long been used for measurement of intracerebral pressures in neurosurgery (19) (for review, see Yellowlees [20] and Shapiro and coworkers [21]). They are probably adequate to measure respiratory pressures (22), and may offer advantages over other devices, including decreased chance of false measurements due to occlusion with water or mucus, less chance of kinking, and, possibly, more rapid response to pressure changes. This remains to be precisely established, and, apparently, no study of fiberoptic systems in respiratory muscle tests is available.

Devices for Measurement of Airway Opening Pressure
Air-filled catheter systems are commonly used to measure pressures in airways and at the mouth. Airway opening pressure (Pao) is usually sampled from a side tap (lateral pressure) in a mouthpiece (Pmo), tracheal tube (Ptr), face mask (Pmask), or from a nostril plug (Pnas) (23). For nasal pressure to reflect airway pressure there must be free communication between the nostrils and mouth, with nasal flows. If Pao is measured from a side tap of a mouthpiece or a tracheal tube during a maneuver that involves gas flow, the cross-section of the device through which the subject breathes must be large enough to avoid measurement errors due to the Bernoulli effect (24). In some cases, Pao serves to estimate alveolar pressure (PA, Palv) during dynamic respiratory efforts made against an obstructed airway (e.g., mouth pressure response to phrenic nerve stimulation). For Pao to reflect PA accurately the transmission of pressure from the alveoli to the airway has to be very fast. The time constant of transmission is the product of the flow resistance offered by the airways (Raw) and the compliance of the extrathoracic airways (Cuaw) including the mouth, cheeks, and equipment. In practice the internal volume of the measuring equipment (mouthpiece, face mask, tracheal tube) contributes negligibly to the time constant (6), but should be minimized in patients with an already increased time constant, such as patients with chronic obstructive pulmonary disease (COPD). The compliance of the cheeks can be minimized by holding them rigid with the hands.

TECHNIQUES FOR PRESSURE MEASUREMENT
Esophageal, Gastric, and Transdiaphragmatic Pressures
Scientific basis.
Transdiaphragmatic pressure (Pdi) is defined as the difference between Ppl and Pab (13) and, in practice, is generally equated to the difference between Pes and Pga, so that Pdi = Pga - Pes (where Pes is usually, but not always, negative). This is contrary to most pressures across a structure, which are taken at a direction such that positive pressures inflate (e.g., positive transpulmonary pressures inflate the lung). For this reason Pdi is also sometimes defined as Pdi = Pes - Pga. As the diaphragm is the only muscle in which contraction simultaneously lowers Pes and increases Pga, an increase in Pdi is, in principle, the result of diaphragmatic contraction unless there is passive stretching. An inspiratory effort produced with a completely passive unstretched diaphragm is associated with a negative change in Pes and Pga but no change in Pdi. This assumes that changes in Pes or Pga induced by mechanisms other than diaphragm contraction are uniformly transmitted across the diaphragm from one compartment to the other. This is probably true when the diaphragm is relaxed (6, 13) at functional residual capacity (FRC), but may be modified when the diaphragm is stretched, as at low lung volumes.

Methodology.
Pes and Pga are most often measured by passing a pair of probes, generally balloon catheters (see previous passages), through the nose, following local anesthesia of the nasal mucosa and pharynx. Their position is usually assessed by asking the subject to perform sharp sniff maneuvers while monitoring the signal on an oscilloscope or computer screen. A simple technique is to advance both probes well into the stomach, as judged by a positive deflection during a sniff and then to withdraw one of them until the sniff-related pressure deflection first becomes negative, indicating that the balloon has entered the esophagus. It is then withdrawn a further 10 cm. The validity of the Pes measurement can be checked by matching Pes to Pao during static Mueller (inspiratory) maneuvers (the dynamic occlusion test) (6, 12, 14). Displacement of balloons is minimized by taping the catheters to the nose. The distance between the nostril and the tip of the balloons varies with the size of the subject, but is usually 35–40 cm for Pes and 50–60 cm for Pga in adults.

Placing the probes becomes more difficult when the subject cannot perform voluntary inspiration (e.g., with anesthetized patients, diaphragmatic paralysis, cognitive impairment, or muscle incoordination). The pressure signals during a swallow can then be useful: A balloon is positioned in the esophagus if swallowing is associated with a slow, powerful rise in pressure, whereas if this does not occur the balloon is likely to be in the stomach. Measurement of balloon distance from the nostril can be a useful indication of its position.

It is advisable to measure Pes and Pga separately by using two pressure transducers, with Pdi derived from a third differential pressure transducer or reconstructed electronically offline. This allows the investigator to monitor balloon position and detect confounding events such as esophageal spasms, as well as recording the three pressures independently. Resting Pga is usually positive with respect to atmosphere due to hydrostatic pressure in the abdomen. For respiratory muscle measurements Pga is conventionally taken as zero at resting end expiration.

Advantages.
Pdi is specific for diaphragm contraction (see previous passages). Separate measurements of Pes and Pga provide information on the components of this contraction and Pes on the inspiratory driving pressure (Pes/Pdi ratio).

Disadvantages.
The procedures require the subject's co-operation and occasionally untrained healthy volunteers can fail to increase Pdi because of lack of coordination, in the absence of any diaphragmatic abnormality (25). This is, however, unusual during the inspiratory phase of quiet breathing at rest. The measurements are mildly uncomfortable, both initially (when swallowing the catheters) and during studies. However, the discomfort of swallowing a thin catheter is small compared with other established medical procedures and scarcely "invasive." Good-quality equipment and adequate practice minimize the discomfort, but some skill is necessary and passing the probes can be time-consuming. Particular care must be taken in patients with impaired swallowing, as well as esophageal diseases, or disorders at the level of the gastroesophageal sphincter.

Mouth Pressure and Nostril Pressure
Scientific basis.
Pmo is easy to measure and changes may give a reasonable approximation of change in alveolar pressure and thus Pes, providing there is relatively little pressure loss down the airways, or across the lungs. This may be realistic with normal lungs, particularly when changes in lung volume are small, but is unlikely to be fulfilled in patients with severe lung or airway disease. When used in combination with voluntary static and dynamic maneuvers at FRC, Pmo provides a global index of the action of synergistic respiratory muscles. When the diaphragm contracts in isolation against a closed airway, as with phrenic nerve stimulation, Pmo may be a useful reflection of Pdi.

Pnas is also easy to measure (see VOLITIONAL TESTS OF RESPIRATORY MUSCLE STRENGTH) but has the same caveats as Pmo.

Methodology.
Pmo is measured at the side port of a mouthpiece. It should be possible to occlude the mouthpiece at the distal end and a small leak should be incorporated to prevent glottic closure during inspiratory or expiratory maneuvers (26). The type of mouthpiece used can significantly influence the results (27). The i