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Should We Get Sniffy About Maximal Inspiratory Pressure?
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Editorial
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Should We Get Sniffy About Maximal Inspiratory Pressure? Michael I. Polkey, PhD William D-C. Man, PhD London, England
Respiratory muscle weakness either occurs in isolation or as part of a more generalized neuromuscular process. In the former case, this is very often self-limiting as, for example, after iatrogenic damage to the phrenic nerve or in the case of neuralgic amyotrophy. In the latter case, patients will usually have evidence of limb muscle involvement and or a known diagnosis (notable exceptions, however, being Pompe disease and about 3% of amyotrophic lateral sclerosis [ALS] presentations). From this conjecture follow the two main reasons why clinicians request evaluation of inspiratory muscle strength—either to rule in or rule out inspiratory muscle weakness as a cause of symptoms or to predict prognosis (or the need for noninvasive ventilation). Maximal inspiratory pressure (MIP) has also frequently been used as an outcome measure for trials of inspiratory muscle training. Having requested the test, the clinician has then to decide what to do with the result, and here the process becomes much more difficult for several reasons, which include the following: First the test is difficult for some FOR RELATED ARTICLE SEE PAGE 32
AFFILIATIONS: NIHR Respiratory Biomedical Research Unit at the Royal Brompton & Harefield Foundation NHS Trust and Imperial College. FINANCIAL/NONFINANCIAL DISCLOSURES: The authors have reported to CHEST the following: M. I. P. discloses having received institutional and personal money for research, consultancy, and lecturing from Biomarin and Genzyme Sanofi. W. D-C. is supported by the NIHR Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for northwest London. CORRESPONDENCE TO: Michael I. Polkey, PhD, NIHR Respiratory Biomedical Research Unit at the Royal Brompton & Harefield Foundation NHS Trust and Imperial College, Fulham Rd, London SW3 6NP, UK; e-mail: [email protected] Copyright Ó 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved. DOI: http://dx.doi.org/10.1016/j.chest.2017.01.015
6 Editorial
patients to perform, requiring good technique from both the physiologist and the patient, who has to exhale to residual volume and then inspire against a closed glottis without air leakage. Furthermore, for those with facial weakness, forming a good seal while using a flanged mouthpiece is particularly troublesome. Second, the value can be slightly reduced by a variety of factors, including age, comorbid disease, and hyperinflation. Third, the normal range is quite wide. In our own laboratory, as a rule of thumb we have historically considered an MIP > 80 cm H2O (or 70 cm H2O for women) to be normal, but it is quite common to record values significantly in excess of 120 cm H2O in healthy adults. However, an additional problem with interpreting MIP data is that several normal ranges have been reported. The data reported by Rodrigues et al1 in the current issue of the Journal go some way to address this. They used a novel approach by identifying a cluster of factors that indicate respiratory muscle weakness; these were suspected (or, one assumes, known) neuromuscular or diaphragmatic disease as the reason for the request, breathlessness as judged by the medical research council dyspnea score, a restrictive defect judged by vital capacity or total lung capacity or a supine drop in vital capacity of > 20%. These criteria are termed in the paper a “higher pretest possibility” of inspiratory muscle weakness. Although each of these may be debated in isolation (eg, patients with heart failure may be breathless, whereas patients with ALS may have normal respiratory muscle strength), the concept is highly original, because it made an attempt to define normality in a way that was not simply based on defining the ends of a Gaussian distribution. The study, of course, has other caveats acknowledged by the authors, including its single-center nature and that the participants were not chosen at random; it might also have been helpful to factor either discrepancies between the carbon monoxide gas transfer coefficient and factor (KCO/TLCO)2 or radiographic appearance into the process that decided the probability of inspiratory muscle weakness, although the latter is certainly not infallible.3 With this approach, they found that three of six commonly used reference equations defined some participants who most likely had inspiratory muscle
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152#1 CHEST JULY 2017
]
weakness as “normal individuals”; the remaining three4-6 that generated higher numeric predicted values were less likely to do so and also better agreed with each other. The authors, therefore, advocate using one of these equations for the diagnosis of inspiratory muscle weakness. In addition, in Table 2 of their study, they present cutoffs identified from receiver operating characteristic curve analysis as a function of age and sex, which clinicians may find useful. Although these data are helpful, it is crucial to remember that as with any clinical measurement, MIP values themselves should not be interpreted in isolation. Also, for monitoring disease progression, we lack meaningful data on the minimal clinically important difference for MIP or the magnitude of learning effects, although we noted previously that regimens involving inspiratory muscle training in particular may lead to a larger MIP without change in diaphragm strength assessed nonvolitionally.7 In that context, it may well be wiser to focus attention on investigating the corollaries of inspiratory muscle weakness, such as the presence of nocturnal hypercapnia. Where then does this leave clinicians? Rodrigues et al’s1 data certainly allow clinicians to say with greater confidence which MIP values are likely to be associated with clinical features of respiratory muscle weakness. Additional strategies that should be considered are the use of a complementary test of inspiratory muscle function, which, if dramatically higher than the MIP, may indicate a technical rather than a pathologic reason for a low MIP. In context, the most useful candidate test would be the maximal sniff nasal inspiratory pressure (SNIP), which is also simple to undertake and acceptable to patients. We previously evaluated this approach directly in a small study8; despite using a high threshold of normality (> 80 cm H2O for men and > 70 cm H2O for women) seven of 17 patients who had been defined
chestjournal.org
as weak judged by the MIP were considered normal using the SNIP. Two large studies have subsequently shown that the use of both MIP and SNIP reduces the “prevalence” of weakness.9,10 Moreover, the biological relevance of SNIP has recently been confirmed by the demonstration in patients with ALS that compared with the MIP, the SNIP has equivalent specificity and slightly greater sensitivity for the prediction of ventilation-free survival.11 Since the SNIP test is also simple and inexpensive, we therefore suggest that this investigation should be considered a first-line additional test when equivocal or low MIP results are obtained.
References 1. Rodrigues A, Da Silva ML, Berton DC, et al. Maximal inspiratory pressure: does the choice of reference values actually matter? Chest. 2017;152(1):32-39. 2. Hart N, Cramer D, Ward SP, et al. Effect of pattern and severity of respiratory muscle weakness on carbon monoxide gas transfer and lung volumes. Eur Respir J. 2002;20:996-1002. 3. Chetta A, Rehman AK, Moxham J, et al. Chest radiography cannot predict diaphragm function. Respir Med. 2005;99:39-44. 4. Black LF, Hyatt RE. Maximal respiratory pressures: normal values and relationships to age and sex. Am Rev Respir Dis. 1969;99: 696-702. 5. Bruschi C, Cerveri I, Zoia MC, et al. Reference values of maximal respiratory mouth pressures: a population-based study. Am Rev Respir Dis. 1992;146:790-793. 6. Neder JA, Andreoni S, Lerario MC, et al. Reference values for lung function tests. II. Maximal respiratory pressures and voluntary ventilation. Braz J Med Biol Res. 1999;32:719-727. 7. Hart N, Sylvester K, Ward S, et al. Evaluation of an inspiratory muscle trainer in healthy humans. Respir Med. 2001;95:526-531. 8. Hughes PD, Polkey MI, Kyroussis D, et al. Measurement of sniff nasal and diaphragm twitch mouth pressure in patients. Thorax. 1998;53:96-100. 9. Steier J, Kaul S, Seymour J, et al. The value of multiple tests of respiratory muscle strength. Thorax. 2007;62:975-980. 10. Hart N, Polkey MI, Sharshar T, et al. Limitations of sniff nasal pressure in patients with severe neuromuscular weakness. J Neurol Neurosurg Psychiatry. 2003;74:1685-1687. 11. Polkey MI, Lyall RA, Yang K, et al. Respiratory muscle strength as a predictive biomarker for survival in amyotrophic lateral sclerosis. Am J Respir Crit Care Med. 2017;195:86-95.
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Editorial
]
Should We Get Sniffy About Maximal Inspiratory Pressure? Michael I. Polkey, PhD William D-C. Man, PhD London, England
Respiratory muscle weakness either occurs in isolation or as part of a more generalized neuromuscular process. In the former case, this is very often self-limiting as, for example, after iatrogenic damage to the phrenic nerve or in the case of neuralgic amyotrophy. In the latter case, patients will usually have evidence of limb muscle involvement and or a known diagnosis (notable exceptions, however, being Pompe disease and about 3% of amyotrophic lateral sclerosis [ALS] presentations). From this conjecture follow the two main reasons why clinicians request evaluation of inspiratory muscle strength—either to rule in or rule out inspiratory muscle weakness as a cause of symptoms or to predict prognosis (or the need for noninvasive ventilation). Maximal inspiratory pressure (MIP) has also frequently been used as an outcome measure for trials of inspiratory muscle training. Having requested the test, the clinician has then to decide what to do with the result, and here the process becomes much more difficult for several reasons, which include the following: First the test is difficult for some FOR RELATED ARTICLE SEE PAGE 32
AFFILIATIONS: NIHR Respiratory Biomedical Research Unit at the Royal Brompton & Harefield Foundation NHS Trust and Imperial College. FINANCIAL/NONFINANCIAL DISCLOSURES: The authors have reported to CHEST the following: M. I. P. discloses having received institutional and personal money for research, consultancy, and lecturing from Biomarin and Genzyme Sanofi. W. D-C. is supported by the NIHR Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for northwest London. CORRESPONDENCE TO: Michael I. Polkey, PhD, NIHR Respiratory Biomedical Research Unit at the Royal Brompton & Harefield Foundation NHS Trust and Imperial College, Fulham Rd, London SW3 6NP, UK; e-mail: [email protected] Copyright Ó 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved. DOI: http://dx.doi.org/10.1016/j.chest.2017.01.015
6 Editorial
patients to perform, requiring good technique from both the physiologist and the patient, who has to exhale to residual volume and then inspire against a closed glottis without air leakage. Furthermore, for those with facial weakness, forming a good seal while using a flanged mouthpiece is particularly troublesome. Second, the value can be slightly reduced by a variety of factors, including age, comorbid disease, and hyperinflation. Third, the normal range is quite wide. In our own laboratory, as a rule of thumb we have historically considered an MIP > 80 cm H2O (or 70 cm H2O for women) to be normal, but it is quite common to record values significantly in excess of 120 cm H2O in healthy adults. However, an additional problem with interpreting MIP data is that several normal ranges have been reported. The data reported by Rodrigues et al1 in the current issue of the Journal go some way to address this. They used a novel approach by identifying a cluster of factors that indicate respiratory muscle weakness; these were suspected (or, one assumes, known) neuromuscular or diaphragmatic disease as the reason for the request, breathlessness as judged by the medical research council dyspnea score, a restrictive defect judged by vital capacity or total lung capacity or a supine drop in vital capacity of > 20%. These criteria are termed in the paper a “higher pretest possibility” of inspiratory muscle weakness. Although each of these may be debated in isolation (eg, patients with heart failure may be breathless, whereas patients with ALS may have normal respiratory muscle strength), the concept is highly original, because it made an attempt to define normality in a way that was not simply based on defining the ends of a Gaussian distribution. The study, of course, has other caveats acknowledged by the authors, including its single-center nature and that the participants were not chosen at random; it might also have been helpful to factor either discrepancies between the carbon monoxide gas transfer coefficient and factor (KCO/TLCO)2 or radiographic appearance into the process that decided the probability of inspiratory muscle weakness, although the latter is certainly not infallible.3 With this approach, they found that three of six commonly used reference equations defined some participants who most likely had inspiratory muscle
[
152#1 CHEST JULY 2017
]
weakness as “normal individuals”; the remaining three4-6 that generated higher numeric predicted values were less likely to do so and also better agreed with each other. The authors, therefore, advocate using one of these equations for the diagnosis of inspiratory muscle weakness. In addition, in Table 2 of their study, they present cutoffs identified from receiver operating characteristic curve analysis as a function of age and sex, which clinicians may find useful. Although these data are helpful, it is crucial to remember that as with any clinical measurement, MIP values themselves should not be interpreted in isolation. Also, for monitoring disease progression, we lack meaningful data on the minimal clinically important difference for MIP or the magnitude of learning effects, although we noted previously that regimens involving inspiratory muscle training in particular may lead to a larger MIP without change in diaphragm strength assessed nonvolitionally.7 In that context, it may well be wiser to focus attention on investigating the corollaries of inspiratory muscle weakness, such as the presence of nocturnal hypercapnia. Where then does this leave clinicians? Rodrigues et al’s1 data certainly allow clinicians to say with greater confidence which MIP values are likely to be associated with clinical features of respiratory muscle weakness. Additional strategies that should be considered are the use of a complementary test of inspiratory muscle function, which, if dramatically higher than the MIP, may indicate a technical rather than a pathologic reason for a low MIP. In context, the most useful candidate test would be the maximal sniff nasal inspiratory pressure (SNIP), which is also simple to undertake and acceptable to patients. We previously evaluated this approach directly in a small study8; despite using a high threshold of normality (> 80 cm H2O for men and > 70 cm H2O for women) seven of 17 patients who had been defined
chestjournal.org
as weak judged by the MIP were considered normal using the SNIP. Two large studies have subsequently shown that the use of both MIP and SNIP reduces the “prevalence” of weakness.9,10 Moreover, the biological relevance of SNIP has recently been confirmed by the demonstration in patients with ALS that compared with the MIP, the SNIP has equivalent specificity and slightly greater sensitivity for the prediction of ventilation-free survival.11 Since the SNIP test is also simple and inexpensive, we therefore suggest that this investigation should be considered a first-line additional test when equivocal or low MIP results are obtained.
References 1. Rodrigues A, Da Silva ML, Berton DC, et al. Maximal inspiratory pressure: does the choice of reference values actually matter? Chest. 2017;152(1):32-39. 2. Hart N, Cramer D, Ward SP, et al. Effect of pattern and severity of respiratory muscle weakness on carbon monoxide gas transfer and lung volumes. Eur Respir J. 2002;20:996-1002. 3. Chetta A, Rehman AK, Moxham J, et al. Chest radiography cannot predict diaphragm function. Respir Med. 2005;99:39-44. 4. Black LF, Hyatt RE. Maximal respiratory pressures: normal values and relationships to age and sex. Am Rev Respir Dis. 1969;99: 696-702. 5. Bruschi C, Cerveri I, Zoia MC, et al. Reference values of maximal respiratory mouth pressures: a population-based study. Am Rev Respir Dis. 1992;146:790-793. 6. Neder JA, Andreoni S, Lerario MC, et al. Reference values for lung function tests. II. Maximal respiratory pressures and voluntary ventilation. Braz J Med Biol Res. 1999;32:719-727. 7. Hart N, Sylvester K, Ward S, et al. Evaluation of an inspiratory muscle trainer in healthy humans. Respir Med. 2001;95:526-531. 8. Hughes PD, Polkey MI, Kyroussis D, et al. Measurement of sniff nasal and diaphragm twitch mouth pressure in patients. Thorax. 1998;53:96-100. 9. Steier J, Kaul S, Seymour J, et al. The value of multiple tests of respiratory muscle strength. Thorax. 2007;62:975-980. 10. Hart N, Polkey MI, Sharshar T, et al. Limitations of sniff nasal pressure in patients with severe neuromuscular weakness. J Neurol Neurosurg Psychiatry. 2003;74:1685-1687. 11. Polkey MI, Lyall RA, Yang K, et al. Respiratory muscle strength as a predictive biomarker for survival in amyotrophic lateral sclerosis. Am J Respir Crit Care Med. 2017;195:86-95.
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