Sassoon, Catherine S

Younes, Magdy

English

eScholarship - University of California

UC IrvineUC Irvine Previously Published WorksTitleAirway Occlusion Pressure RevisitedPermalinkhttps://escholarship.org/uc/item/35w0j26jJournalAmerican Journal of Respiratory and Critical Care Medicine, 201(9)ISSN1073-449XAuthorsSassoon, Catherine SYounes, MagdyPublication Date2020-05-01DOI10.1164/rccm.202003-0585ed Peer reviewedeScholarship.org Powered by the California Digital LibraryUniversity of Californiasamples, and with a high prevalence of bronchiectasis–the latterproving to be a major predictor of CBI. These factors may limit thegeneralizability of the results and call for them to be validated.Lastly, the definition of CBI was not based on a single baselineassessment but on repeated sampling over time, which complicatesits clinical utility as a risk prediction tool and may haveconfounded the observed relationship between CBI andpneumonia.The results of this study are biologically plausible andlogically appealing. The presence of low blood eosinophil countsand/or CBI appear to be risk factors that increase pneumonia riskand, therefore, influence the benefit–risk calculation for the useof ICS in COPD. That said, large-scale, routine, and repeatedsputum collection and analysis poses logistic and implementationchallenges, particularly in primary care. Unless this practical hurdleis overcome, it seems likely that decisions about ICS use willremain part science, part art. nAuthor disclosures are available with the text of this article atwww.atsjournals.org.Mark T. Dransfield, M.D.Division of Pulmonary, Allergy, and Critical CareUniversity of Alabama at BirminghamBirmingham, AlabamaandBirmingham VA Medical CenterBirmingham, AlabamaDave Singh, M.D.Manchester Academic Health Science CentreThe University of ManchesterManchester, United KingdomandMedicines Evaluation UnitManchester University NHS Foundation TrustManchester, United KingdomReferences1. Kew KM, Seniukovich A. Inhaled steroids and risk of pneumonia forchronic obstructive pulmonary disease. Cochrane Database Syst Rev2014; (3):CD010115.2. Agusti A, Fabbri LM, Singh D, Vestbo J, Celli B, Franssen FME, et al.Inhaled corticosteroids in COPD: friend or foe? Eur Respir J 2018;52:1801219.3. Pascoe S, Barnes N, Brusselle G, Compton C, Criner GJ, Dransfield MT,et al. Blood eosinophils and treatment response with triple and dualcombination therapy in chronic obstructive pulmonary disease:analysis of the IMPACT trial. Lancet Respir Med 2019;7:745–756.4. Singh D. Predicting corticosteroid response in chronic obstructivepulmonary disease: blood eosinophils gain momentum. Am J RespirCrit Care Med 2017;196:1098–1100.5. Singh D, Agusti A, Anzueto A, Barnes PJ, Bourbeau J, Celli BR, et al.Global strategy for the diagnosis, management, and prevention ofchronic obstructive lung disease: the GOLD science committee report2019. Eur Respir J 2019;53:1900164.6. Martinez-Garcia MA, Faner R, Oscullo G, de la Rosa D, Soler-CataluñaJ-J, Ballester M, et al. Inhaled steroids, circulating eosinophils, chronicairway infection, and pneumonia risk in chronic obstructive pulmonarydisease: a network analysis. Am J Respir Crit Care Med 2020;201:1078–1085.7. Crim C, Calverley PM, Anderson JA, Celli B, Ferguson GT, Jenkins C,et al. Pneumonia risk in COPD patients receiving inhaledcorticosteroids alone or in combination: TORCH study results. EurRespir J 2009;34:641–647.8. Crim C, Dransfield MT, Bourbeau J, Jones PW, Hanania NA, Mahler DA,et al. Pneumonia risk with inhaled fluticasone furoate and vilanterolcompared with vilanterol alone in patients with COPD. Ann Am ThoracSoc 2015;12:27–34.9. Agusti A, Fabbri LM, Singh D, Vestbo J, Celli B, Franssen FME, et al.Inhaled corticosteroids in COPD: friend or foe? Eur Respir J 2018;52:1801219.10. Pavord ID, Lettis S, Anzueto A, Barnes N. Blood eosinophil count andpneumonia risk in patients with chronic obstructive pulmonary disease:a patient-level meta-analysis. Lancet Respir Med 2016;4:731–741.11. Vestbo J, Anderson JA, Brook RD, Calverley PM, Celli BR, Crim C,et al.; SUMMIT Investigators. Fluticasone furoate and vilanterol andsurvival in chronic obstructive pulmonary disease with heightenedcardiovascular risk (SUMMIT): a double-blind randomised controlledtrial. Lancet 2016;387:1817–1826.12. Papi A, Vestbo J, Fabbri L, Corradi M, Prunier H, Cohuet G, et al. Extrafineinhaled triple therapy versus dual bronchodilator therapy in chronicobstructive pulmonary disease (TRIBUTE): a double-blind, parallelgroup, randomised controlled trial. Lancet 2018;391:1076–1084.13. Kolsum U, Donaldson GC, Singh R, Barker BL, Gupta V, George L,et al. Blood and sputum eosinophils in COPD; relationship withbacterial load. Respir Res 2017;18:88.14. Garnacho-Montero J, Huici-Moreno MJ, Gutiérrez-Pizarraya A, López I,Márquez-Vácaro JA, Macher H, et al. Prognostic and diagnosticvalue of eosinopenia, C-reactive protein, procalcitonin, andcirculating cell-free DNA in critically ill patients admitted withsuspicion of sepsis. Crit Care 2014;18:R116.15. George L, Wright A, Mistry V, Sutcliffe A, Chachi L, Haldar K, et al.Sputum Streptococcus pneumoniae is reduced in COPD followingtreatment with benralizumab. Int J Chron Obstruct Pulmon Dis 2019;14:1177–1185.Copyright © 2020 by the American Thoracic SocietyAirway Occlusion Pressure RevisitedThe use of airway occlusion pressure (P0.1) as a measure of respiratorydrive was introduced by Whitelaw and colleagues 45 years ago based ontwo basic assumptions (1). First, in the absence of flow or volumechange during the occlusion, pressure generated by the inspiratorymuscles is transmitted directly (1:1 ratio) to the external airway. Second,if the occlusion is brief (i.e., 0.1 s), there is no time for behavioralresponses to influence the pressure output of the inspiratory muscles.Hence, the change in airway pressure during a constant brief timereflects the rate of rise of inspiratory muscle pressure at the beginning ofspontaneous inspiration, which has been shown to correlate well withthe rate of rise of inspiratory muscle activity, at least in normal subjects.This article is open access and distributed under the terms of the CreativeCommons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/). For commercial usage andreprints, please contact Diane Gern (dgern@thoracic.org).Originally Published in Press as DOI: 10.1164/rccm.202003-0585ED onMarch 23, 2020EDITORIALSEditorials 1027 Although the second tenet still holds true, several factors weresubsequently identified that can alter the relation between P0.1and inspiratory muscle pressure or electrical diaphragm muscle outputin the absence of volume changes or behavioral responses. As noted byWhitelaw and Derenne in 1993, these factors include the presence ofdynamic hyperinflation, expiratory muscle activity, chest walldistortion, respiratory muscle weakness, neuromuscular junctionblockade, and the shape of the inspiratory pressure waveform (2). All ofthese modifiers apply to critically ill patients. In addition, the methodused to measure P0.1 in such patients is of critical importancedepending on whether a true occlusion is implemented, whethermeasurements are made close to the patient or remotely in theventilator, what type of triggering is used, and other technical factors.Almost certainly, because of the numerous variables that modify therelation between P0.1 and inspiratory muscle pressure output or drive,the results of P0.1 in weaning assessments, even when measuredproperly with specialized equipment, have been variable and generallynot impressive. There is, however, evidence that an excessively highor excessively low respiratory drive in patients is an importantrisk factor for continued ventilator dependence (3, 4). Identifying suchpatients would be of clinical value because this might spare them frombeing subjected to unsuccessful weaning trials and point to theabnormality that needs to be addressed.The use of specialized equipment to measure P0.1 in the ICUis a major deterrent to such studies because the setup, properapplication of occlusion, and assessment of the quality of theresults require considerable expertise. Several commerciallyavailable ventilators measure P0.1 and display the results onthe ventilator screen. The methods used by these ventilatorsvary but do not include the desirable application of occlusionnear the patient’s airway, and some ventilators do not even applya true occlusion. An important practical question, therefore,is whether the ventilator-generated P0.1 is an adequate surrogatefor the more complex and demanding use of specialized equipment.In a study presented in this issue of the Journal, Teliasand colleagues (pp. 1086–1098) compared P0.1 estimated by differentcommercial ventilators (P0.1vent) with values obtained in the properway (P0.1ref) in critically ill patients and in a bench test using asimulator (5). In addition, they determined the relation between P0.1and the pressure–time product of the inspiratory muscles. Notsurprisingly, there were good correlations between P0.1 and pressureoutput in individual patients, consistent with the fact that airwaypressure is directly related to respiratory muscle output duringoccluded breaths. Also, as expected from the various known modifiersof the relationship between P0.1 and inspiratory muscle pressure,there was much scatter in this relationship among patients. There areseveral important novel findings from this study. First, P0.1 measuredby ventilators that apply a true end-expiratory occlusion accuratelyreflects P0.1ref in bench testing, whereas ventilators that do not applyocclusion are inaccurate. Second, on average, P0.1 measured by themore accurate ventilators in patients has little systematic error(minimal bias), and therefore these average values can be used toevaluate the impact of P0.1 on outcomes in group comparisons. Third,having defined a high respiratory output as P0.1.4.0 cm H2O and alow output as,1.1 cm H2O measured by P0.1ref, and notwithstandingthe large differences between P0.1vent and P0.1ref in individual patients,P0.1vent could identify patients above and below these thresholds withreasonable accuracy. A limitation exists in that although the thresholdsof P0.1ref have been validated, those of P0.1vent have not.These results are encouraging in that they suggest that P0.1displayed in select ventilators can be used to identify patients withabnormally high and low values. Some caveats remain, however. First,as the authors acknowledge, the thresholds used to set limits on highrisk are derived from retrospective analyses of patients with weaningfailure. It is not clear whether respiratory muscle output in thesepatients was the only or main reason for weaning failure. Second, thethresholds selected here apply to only a small fraction of the patientsstudied; in most patients, P0.1 was between the high and lowthresholds, and in such patients the P0.1 results would be equivocal.Knowledge in physiology in the interpretation of P0.1 isindispensable. In the extremes, as mentioned above, variables thatmodify P0.1 measurements may create conflicting results regarding therelationship between P0.1 (as an estimate of respiratory drive) andinspiratorymuscle pressure output. In the presence ofmuscle weakness,high chest wall elastance, dynamic hyperinflation, or chestwall–abdominal paradox, a high respiratory drive associated withrespiratory distress may yield low inspiratory muscle effort and P0.1(6). Conversely, a low respiratory drive is not inevitably associatedwith low inspiratory muscle effort and low P0.1. For example,expiratory muscle recruitment in response to external positive end-expiratory pressure may be associated with high P0.1 despite a weakinspiratory effort (2). Important questions remain: 1) what is thethreshold of inspiratory muscle effort–induced injury, and 2) doesmonitoring of P0.1 and inspiratory muscle efforts in critically illpatients receiving mechanical ventilation alter clinical outcomes?Future prospective studies will need to address these questions. nAuthor disclosures are available with the text of this article atwww.atsjournals.org.Catherine S. Sassoon, M.D.Department of MedicineUniversity of California, IrvineIrvine, CaliforniaMagdy Younes, M.D., Ph.D.Department of MedicineUniversity of ManitobaWinnipeg, Manitoba, CanadaReferences1. Whitelaw WA, Derenne JP, Milic-Emili J. Occlusion pressureas a measure of respiratory center output in conscious man. RespirPhysiol 1975;23:181–199.2. Whitelaw WA, Derenne JP. Airway occlusion pressure. J Appl Physiol(1985) 1993;74:1475–1483.3. Vaporidi K, Akoumianaki E, Telias I, Goligher EC, Brochard L, GeorgopoulosD. Respiratory drive in critically ill patients. Pathophysiology and clinicalimplications. Am J Respir Crit Care Med 2020;201:20–32.4. Goligher EC, Dres M, Fan E, Rubenfeld GD, Scales DC, Herridge MS, et al.Mechanical ventilation-induced diaphragm atrophy strongly impactsclinical outcomes. Am J Respir Crit Care Med 2018;197:204–213.5. Telias I, Junhasavasdikul D, Rittayamai N, Piquilloud L, Chen L,Ferguson ND, et al. Airway occlusion pressure as an estimate ofrespiratory drive and inspiratory effort during assisted ventilation.Am J Respir Crit Care Med 2020;201:1086–1098.6. Spinelli E, Mauri T, Beitler JR, Pesenti A, Brodie D. Respiratory drivein the acute respiratory distress syndrome: pathophysiology,monitoring, and therapeutic interventions. Intensive Care Med 2020;46:606–618.Copyright © 2020 by the American Thoracic SocietyEDITORIALS1028 American Journal of Respiratory and Critical Care Medicine Volume 201 Number 9 | May 1 2020 

Airway Occlusion Pressure Revisited

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Airway Occlusion Pressure Revisited.

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