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. 2021 May 8;159(6):2373–2383. doi: 10.1016/j.chest.2021.01.055

Pleural Pressure Targeted Positive Airway Pressure Improves Cardiopulmonary Function in Spontaneously Breathing Patients With Obesity

Gaetano Florio a, Roberta Ribeiro De Santis Santiago a, Jacopo Fumagalli a, David A Imber a, Francesco Marrazzo a, Abraham Sonny a, Aranya Bagchi a, Angela K Fitch b, Chika V Anekwe b, Marcelo Britto Passos Amato d, Pankaj Arora e, Robert M Kacmarek a,c, Lorenzo Berra a,c,∗
PMCID: PMC8579318  PMID: 34099131

Abstract

Background

Increased pleural pressure affects the mechanics of breathing of people with class III obesity (BMI > 40 kg/m2).

Research Question

What are the acute effects of CPAP titrated to match pleural pressure on cardiopulmonary function in spontaneously breathing patients with class III obesity?

Study design and Methods

We enrolled six participants with BMI within normal range (control participants, group I) and 12 patients with class III obesity (group II) divided into subgroups: IIa, BMI of 40 to 50 kg/m2; and IIb, BMI of ≥ 50 kg/m2. The study was performed in two phases: in phase 1, participants were supine and breathing spontaneously at atmospheric pressure, and in phase 2, participants were supine and breathing with CPAP titrated to match their end-expiratory esophageal pressure in the absence of CPAP. Respiratory mechanics, esophageal pressure, and hemodynamic data were collected, and right heart function was evaluated by transthoracic echocardiography.

Results

The levels of CPAP titrated to match pleural pressure in group I, subgroup IIa, and subgroup IIb were 6 ± 2 cmH2O, 12 ± 3 cmH2O, and 18 ± 4 cmH2O, respectively. In both subgroups IIa and IIb, CPAP titrated to match pleural pressure decreased minute ventilation (IIa, P = .03; IIb, P = .03), improved peripheral oxygen saturation (IIa, P = .04; IIb, P = .02), improved homogeneity of tidal volume distribution between ventral and dorsal lung regions (IIa, P = .22; IIb, P = .03), and decreased work of breathing (IIa, P < .001; IIb, P = .003) with a reduction in both the work spent to initiate inspiratory flow as well as tidal ventilation. In five hypertensive participants with obesity, BP decreased to normal range, without impairment of right heart function.

Interpretation

In ambulatory patients with class III obesity, CPAP titrated to match pleural pressure decreased work of breathing and improved respiratory mechanics while maintaining hemodynamic stability, without impairing right heart function.

Trial Registry

ClinicalTrials.gov; No.: NCT02523352; URL: www.clinicaltrials.gov

Key Words: CPAP, hypertension, obesity, pleural pressure

Abbreviations: EPE0, esophageal pressure at the end of exhalation during spontaneous breathing; PTP, pressure time product

FOR EDITORIAL COMMENT, SEE PAGE 2145

CPAP is used commonly in individuals with obesity as a treatment for OSA.1 As a result of providing a patent upper airway, CPAP improves oxygenation, decreases systemic hypertension, and improves quality of life.2, 3, 4, 5 In mechanically ventilated critically ill patients with obesity, elevated values of positive end-expiratory pressure have been shown to improve gas exchange and lung mechanics.6

A measurement that reflects cardiac function and pulmonary collapse is pleural pressure, which is markedly elevated in mechanically ventilated patients with obesity.7,8 The cephalad displacement of the abdominal girth on the diaphragm is thought to increase pleural pressure in these patients.

In critically ill mechanically ventilated patients with or without acute respiratory failure and with class III obesity, increasing positive end-expiratory pressure to overcome pleural pressure (achieving a positive value of end-expiratory transpulmonary pressure, defined as the difference between airway pressure and pleural pressure) decreases lung collapse and thus improves lung compliance, oxygenation, and hemodynamic stability and is associated with improved survival.6,9, 10, 11, 12

To date, it is not clear whether the elevated pleural pressures that are observed in patients with obesity during general anesthesia or critical illness exist also in awake, spontaneously breathing patients with obesity who otherwise are healthy. Furthermore, the effect of positive end-expiratory transpulmonary pressure on cardiopulmonary function in the absence of sedation and paralysis has not been explored.

We hypothesized that in ambulatory people with class III obesity based on BMI, defined as the body mass divided by the square of the body height and expressed in kilograms per square meter, counterbalancing the increased level of pleural pressure by applying titrated CPAP would decrease work of breathing and would improve oxygenation without altering cardiovascular function. To test our hypothesis, we designed a physiologic study comparing patients with class III obesity with a control group of healthy participants with normal BMI.

Methods

This case-control, physiologic study was approved by the Massachusetts General Hospital Institutional Review Board (Identifier: 2015P001770) and is registered on ClinicalTrials.gov (Identifier: NCT02523352).

Study Population

The study enrolled adult participants in two groups. Group I included those with BMI within the normal range (BMI, 19-24 kg/m2). Group II included participants with class III obesity (BMI ≥ 40 kg/m2). Based on our prior findings6,10 that patients with a BMI of ≥ 50 kg/m2 generally have a pleural pressure close to 20 cmH2O (which may limit the use of noninvasive CPAP), we divided participants with class III obesity into two subgroups: subgroup IIa included those with BMI of 40 to 49 kg/m2; subgroup IIb included participants with BMI of ≥ 50 kg/m2.

Study Procedure

The study was divided into two phases. In phase 1, the participant was supine and breathing spontaneously at atmospheric pressure. In phase 2, the participant was supine and breathing room air with CPAP. Esophageal manometry was used to monitor pleural pressure in both phases. The level of CPAP used for each participant was determined through the analysis of the esophageal pressure tracing, as explained below. Transthoracic echocardiography measurement of left (aortic velocity-time integral) and right (tricuspid annular plane systolic excursion and peak systolic velocity) ventricular function were performed at the end of each phase to define the impact of CPAP on cardiac function. Pulmonary artery pressure was estimated by pulmonary artery acceleration time analysis. Measurements of respiratory physiologic features (tidal volume, respiratory rate, minute ventilation, peak pressure, mean airway pressure, and arterial oxygen saturation) were noted. Noninvasive BP was measured every 5 min, whereas heart rate and arterial oxygen saturation were monitored continuously throughout the study. Data were recorded 30 minutes after the start of each phase.

Analysis of Esophageal Pressure Tracings

The level of CPAP used in the second phase of the study was determined by analysis of the esophageal pressure tracing while the participant was supine and breathing spontaneously at atmospheric pressure. We determined in participants with normal BMI that the level of esophageal pressure at functional residual capacity is equal to the value recorded while the glottis is open at the end of exhalation (without any respiratory muscular effort) while breathing at atmospheric pressure (e-Fig 1). The level of CPAP applied in the study was set equal to this value of esophageal pressure at the end of exhalation during spontaneous breathing (EPE0). Pressure time product (PTP) per breath and per minute was calculated as an estimate of participants’ work of breathing.13

Analysis of Electrical Impedance Tomography

To obtain a direct visualization of the tidal distribution of ventilation at atmospheric pressure and at titrated CPAP levels, electric impedance tomography (Enlight 1800, Timpel) was applied. The lung image was divided into two isovolumetric regions each covering 50% of the ventrodorsal lung area, and homogeneity of ventilation was expressed as percentage of tidal variation of impedance directed to each region of interest.

Statistical Analysis

We enrolled 12 patients with class III obesity and six participants with normal BMI in this physiologic study. The sample size of the study was determined based on our prior studies evaluating esophageal pressure measurement. In prior studies, we observed that esophageal pressure patients with a BMI of more than 40 kg/m2, but lower than 50 kg/m2, is higher than 10 cmH2O and approximates to 20 cmH2O when BMI is higher than 50 kg/m2. For this physiologic study assessing the effects of CPAP on transpulmonary pressure, we arbitrarily decided to study 12 participants with class III obesity: six participants with a BMI from 40 to 49 kg/m2, and the remaining six participants with a BMI of more than 50 kg/m2. To describe respiratory mechanics in those with normal BMI, we enrolled six individuals as control participants (BMI, 20-24 kg/m2). The Shapiro-Wilk test was used to assess normality of continuous variables. Data were expressed as median (range). The Wilcoxon signed-rank test was used for intergroup comparison. Statistical significance was defined as P < .05 (two-tailed). Additional information regarding study population, sample size, study procedures, data recording, and statistical analysis have been included in e-Appendix 1.

Results

A total of 18 participants were enrolled in the study. The first group included six participants with a BMI of 22 ± 2.5 kg/m2 (abdominal circumference, 85 ± 5 cm). The second group included 12 participants with class III obesity; six participants with BMI of 42 ± 2.0 kg/m2 (abdominal circumference, 123±13 cm) were included in subgroup IIa and six participants with BMI of 56 ± 5.0 kg/m2 (abdominal circumference, 153 ± 14 cm) were included in subgroup IIb.

Esophageal Pressure and Airways Opening Pressure Are Increased in Participants With Class III Obesity Compared With Participants With Normal Body Habitus

The median esophageal pressure was 5 cmH2O (range, 4-8 cmH2O) in group I, 12.5 cmH2O (range, 8-16 cmH2O) in group IIa, and 18 cmH2O (range, 17-23 cmH2O) in group IIb. Esophageal pressure swings were broken down into two components: the first component represents the work needed to overcome the airways opening pressure, as measured by the esophageal pressure change preceding inspiratory flow. We intend airways opening pressure as the pressure at which closed airways reopen. The second component of the esophageal pressure swing corresponded to the pressure change during generation of tidal volume (Fig 1). The median value of esophageal pressure swing preceding inspiratory flow was 0 cmH2O in group I, 3.5 cmH2O (range, 1-6 cmH2O) in group IIa, and 7.2 cmH2O (range, 1-13 cmH2O) in group IIb (e-Tables 1-3). Our measurements suggest that, compared with participants with normal body habitus (Fig 1A), elevated pleural pressure in participants with class III obesity causes high levels of airways opening pressure during spontaneous breathing that must be overcome to initiate inspiratory flow (Fig 1B).

Figure 1.

Figure 1

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A, B, Graphs showing analyses of tracings of airway pressure, EP, and airflow during titration of CPAP in a participant with normal BMI (A) and BMI of > 50 kg/m2 (B). The orange dotted line indicates the zero-flow level. SwingAOP is defined as the difference EPE0 – EPS0 at atmospheric pressure and as the difference EPECPAP – EPSCPAP while undergoing CPAP. SwingTV is defined as the difference EPS0 – EPI0 at atmospheric pressure and as the difference EPSCPAP – EPICPAP while breathing with CPAP. SwingTOT is the sum of the two previous components. Please see the text for details. EP = esophageal pressure; EPE0 = esophageal pressure at the end of exhalation during spontaneous breathing; EPECPAP = esophageal pressure at the end of exhalation during CPAP; EPI0 = esophageal pressure at the end of inspiration during spontaneous breathing; EPICPAP = esophageal pressure at the end of inspiration during CPAP; EPS0 = esophageal pressure at the start of inspiration during spontaneous breathing; EPSCPAP = esophageal pressure at the start of inspiration during CPAP; SwingAOP = swing needed to reach the opening airway pressure, ie, the onset of inspiratory flow; SwingTOT = total swing; SwingTV = esophageal pressure change during the generation of a tidal volume.

CPAP Decreased Esophageal Pressure Swing Needed to Generate Inspiratory Flow, Decreased Work of Breathing, and Improved Oxygenation and Homogeneity of Ventilation in Participants With Class III Obesity

During spontaneous breathing at atmospheric pressure in groups IIa and IIb, the median of the total swing of esophageal pressures (EPE0 – EPI0 [esophageal pressure at the end of inspiration during spontaneous breathing]) was 15 cmH2O (range, 11-19 cmH2O) and 20.5 cmH2O (range, 19-31 cmH2O), respectively. This was far greater than that observed in participants with normal habitus (3.5 cmH2O; range, 2-6 cmH2O).

To reach zero end-expiratory transpulmonary pressure in the supine position, CPAP was set to match the level of esophageal pressure measured before the onset of inspiratory effort. The median CPAP setting was 5 cmH2O (range, 4-8 cmH2O) in participants with normal body weight, 12.5 cmH2O (range, 8-16 cmH2O) in group IIa, and 18 cmH2O (range, 17-23 cmH2O) in group IIb. All 18 participants tolerated CPAP well for the entire period of the study.

CPAP eliminated the first component of esophageal pressure swing and greatly reduced the second (Figs 1, 2 and e-Tables 2-5) in both groups IIa and IIb, whereas, as expected, CPAP did not reduce esophageal pressure swings in group I. In all study groups immediately after titrating CPAP according to EPE0, tidal PTP decreased (Fig 3): the degree of work of breathing reduction was inversely proportional to the class of BMI. Thirty minutes after beginning CPAP, minute ventilation decreased in groups IIa and IIb, which further reduced work of breathing (PTP per minute). Although the application of CPAP led to an improvement in peripheral oxygen saturation in groups IIa and IIb, peripheral saturation of oxygen remained unchanged in group I (Fig 4, e-Table 1). Compared with group I, among participants with morbid obesity in supine position breathing at atmospheric pressure, tidal ventilation distributes predominantly to the most ventral lung regions, and more so with the more severe degree of obesity (Fig 5, e-Table 6). Titrating CPAP according to EPE0 leads to a more homogeneous distribution of ventilation by increasing the amount of tidal volume directed to the dorsal gravity-dependent lung areas.

Figure 2.

Figure 2

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A, B, Graphs showing EP swings during spontaneous breathing at atmospheric pressure and with CPAP in participants with normal BMI (group I, red), BMI of 41 to 49 kg/m2 (group IIa, blue), and BMI of > 50 kg/m2 (group IIb, gray). Data are shown as median and range. A, Total EP swing. B, EP swing needed to reach opening airway pressure. C, EP swing during tidal ventilation. Atm P = atmospheric pressure; AOP = airway opening pressure; EP = esophageal pressure.

Figure 3.

Figure 3

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A, B, Graphs showing analyses of changes in airway pressure (blue trace) and EP (red trace) when titrated CPAP was applied in participant 6 (A) and participant 3 (B). Within a few seconds of CPAP initiation, a decrease in EP swing was detected. Work of breathing, calculated as pressure-time product (see text and e-Appendix 1 for details) and highlighted in gray in the figures, decreased as well. EP = esophageal pressure.

Figure 4.

Figure 4

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Graph showing effects of CPAP on respiratory pressures and volumes during spontaneous breathing in participants with normal BMI (group I, red), BMI of 41 to 49 kg/m2 (group IIa, blue), and BMI of > 50 kg/m2 (group IIb, gray). Data are shown as median and range. Atm P = atmospheric pressure; PTP = pressure-time product; SB = spontaneous breathing; SpO2 = peripheral saturation of oxygen; VE = minute ventilation.

Figure 5.

Figure 5

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Analysis of tidal ventilation distribution by electrical impedance tomography (EIT) during spontaneous breathing at Atm P and with CPAP. EIT shows that at Atm P in patients with class III obesity, ventilation distributes predominantly to the most ventral lung regions. Titrating CPAP according to end-expiratory esophageal pressure leads to a more homogeneous distribution of ventilation by increasing the amount of tidal volume directed to the dorsal, gravity-dependent lung areas (group I, P = .22; group IIa, P = .22; and group IIb, P = .03). Atm P = atmospheric pressure.

Titrated CPAP Did Not Impair Hemodynamics in Participants With Class III Obesity

In three of six participants in group IIa and in five of six participants in group IIb, systemic hypertension was detected, as defined by the American Heart Association definition,14 as shown in Figure 6. Overall, CPAP did not alter BP in the two groups. BP decreased slightly only in patients with baseline systemic hypertension (Fig 6).

Figure 6.

Figure 6

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Diagram showing BP during spontaneous breathing at Atm P and with CPAP in each participant. Colors in the cells are consistent with the hypertension classification according to the American Heart Association.14 Atm P = atmospheric pressure.

Furthermore, hemodynamics did not deteriorate in groups I and IIb, whereas hemodynamics actually improved in group IIa. Indeed, in group IIa, CPAP resulted in a decrease in heart rate and an increase in pulmonary artery acceleration time 30 min after starting CPAP, suggesting a decreased pulmonary artery pressure (e-Tables 7-8).

In both groups IIa and IIb, no differences were detected in velocity time integral at the left ventricular outflow tract, suggesting that the left ventricle stroke volume was unchanged. Also, in groups IIa and IIb, systolic right heart function (assessed by tricuspid annular plane systolic excursion and peak systolic velocity) also was unchanged (e-Tables 7-8), suggesting that right heart function was not impaired during CPAP.

Discussion

In this study, we tested whether CPAP targeted to match pleural pressure would reduce work of breathing and improve respiratory mechanics and not impair cardiovascular function in participants with class III obesity. Our findings can be summarized as follows. First, in the supine position at atmospheric pressure, the pleural pressure (estimated by esophageal pressure) and work of breathing (estimated by PTP) are increased in patients with class III obesity compared with lean individuals. Second, CPAP titrated according to pleural pressure dramatically decreased the work needed to overcome airways opening pressure and initiate inspiratory flow and also greatly diminished work of breathing during tidal ventilation. A reduction in minute ventilation and improvements in oxygen saturation and the homogeneity of tidal ventilation distribution also were observed. Third, high levels of CPAP were well-tolerated hemodynamically throughout the study.

In anesthetized and paralyzed patients with class III obesity in the operating room, Behazin et al7 found that the absolute value of pleural pressure is higher than what is generally observed in patients with normal BMI. In a physiological study, Tharp et al15 also demonstrated that increased levels of pleural pressure in people with obesity during laparoscopic surgery contribute to airway closure occurrence. Underestimation of baseline pleural pressure and airways closure in class III obesity may lead to suboptimal ventilation strategies, atelectasis, and increased shunt that could result in misdiagnosis (ie, ARDS) and prolonged mechanical ventilation. Anesthesiologists and critical care physicians6,10,16, 17, 18 have started to appreciate that positive end-expiratory pressure and recruitment maneuvers must be titrated to individual patient physiologic features,19 rather than to generic or universal protocolized values.20 We have been interested in understanding lower respiratory tract physiology in critically ill mechanically ventilated patients with obesity. We expanded on findings from prior investigators7 and demonstrated in the ICU setting that when airway pressure is titrated to counterbalance increased pleural pressure, oxygenation and lung compliance are improved while avoiding regional overdistension.6,9,10,12,21

Far less has been described about lung mechanics in spontaneously breathing patients with class III obesity using traditional physiologic monitoring techniques, such as esophageal manometry. Our present study demonstrates that nonsedated, spontaneously breathing participants with class III obesity have elevated pleural pressure at end-expiration and must use large swings in pleural pressure to generate tidal ventilation. We observed that the initial portion of these pleural pressure swings do not generate inspiratory flow, representing an occlusion to airways opening. CPAP matching baseline pleural pressure ameliorated both the elevated work of breathing and pleural pressure swings and eliminated, almost entirely, airways opening occlusion. These findings complement ongoing hypotheses regarding late-onset nonallergic asthma in obesity and research that has shown airway occlusion of even the central tracheobronchial tree.22, 23, 24

It has been proposed that large swings in esophageal pressure should be monitored in respiratory failure,25,26 and elevated values are significant for high levels of parenchymal lung stress that could cause patient self-inflicted lung injury.27, 28, 29 Based on our investigation, it seems that patients with class III obesity without respiratory failure constantly are exposed to elevated swings of pleural pressure (up to 31 cmH2O). However, this ventilation pattern in patients with obesity does not seem to cause acute lung injury, although subclinical lung injury resulting from opening and closing of airways (atelectrauma) cannot be excluded. Two features distinguish the ventilatory effort in spontaneously breathing patients with class III obesity compared with patients at risk for acute lung injury resulting from spontaneous effort: pleural pressure swings in participants with class III obesity exist almost entirely above atmospheric pressure (thus yielding modest transpulmonary forces) and do not produce excessively large tidal volumes, because a portion of the swing is “wasted” on the occlusion to airways opening.30, 31, 32

As described previously,33 participants with class III obesity show an extremely high level of work of breathing (PTP > 300 cmH2O × s/min) when lying supine and breathing at atmospheric pressure, similar to the values described for patients failing a spontaneous breathing trial. Mahul et al34 described the successful extubation of 16 critically ill patients with obesity (BMI, 44 kg/m2; range, 35-67 kg/m2), despite these patients having a PTP in the range of 300 to 400 cmH2O × s/min both before and after endotracheal tube removal. Our findings in spontaneously breathing volunteers expand on these findings,34 suggesting that patients with class III obesity, even outside of critical illness, have an increased work of breathing that may not predict extubation success or failure.

However, the incidence of extubation failure in patients with obesity in fact is high (10%-20%).35 Although, as mentioned, the exact degree of elevated work of breathing after extubation may not predict success or failure for patients with obesity, it is reasonable to presume that a method to improve work of breathing would be beneficial in this vulnerable setting. Herein, we observed that when applying CPAP targeted to a participant’s baseline end-expiratory pleural pressure, the effort performed per breath and the minute ventilation were reduced by approximately half, with work of breathing reduced to levels comparable with those in lean participants (PTP < 200 cmH2O × s/min).

A few physiologic hypotheses could be considered when explaining the improvement in peripheral oxygen saturation seen in our participants with class III obesity after initiation of CPAP. Based on our prior studies in mechanically ventilated patients with obesity and on results by Bates et al23 in seated spontaneously breathing participants using measurement of respiratory of respiratory system impedance by oscillometry, the first mechanism to consider would be alveolar recruitment.6,10,21 However, without more advanced imaging or more precise measurements of lung volume and compliance, this conclusion cannot be drawn confidently at present from this study. Another mechanism that can be considered is improved ventilation-perfusion coupling. We observed in this study through electric impedance tomography that after initiating CPAP, an improvement in the homogeneity of the distribution of tidal ventilation occurs, with more volume being redistributed to the posterior thorax. Whether this marks actual recruitment of previously atelectatic alveoli is unclear. At the very least, more aeration of the more perfused, posterior portions of the lung occurs, which should improve ventilation-perfusion matching and oxygenation. Finally, the reduction in work of breathing after starting CPAP could reduce aerobic work that, in the setting of intrapulmonary shunt from atelectasis, could improve peripheral arterial oxygen saturation.

As expected, we observed a high prevalence of systemic hypertension14 in patients with obesity: hypertension was detected in 8 of 12 participants. CPAP targeted to match pleural pressure did not cause hypotension. In participants with systemic hypertension at baseline, especially in subgroup IIb with BMI of > 50 kg/m2, a slight decrease in these hypertensive values of BP after CPAP initiation were found. Although a prior randomized control trial36 demonstrated an improvement in BP when chronic use of CPAP is combined with pharmacotherapy, no study to date has evaluated the acute impact of CPAP in participants with class III obesity. Despite concerns regarding cardiac function classically associated with high levels of positive airway pressure, transthoracic echocardiography in our study demonstrated no deleterious changes in the parameters commonly used to evaluate right heart function. In fact, pulmonary artery acceleration time actually increased in group IIa, suggesting a decrease in pulmonary vascular resistance. There are several hypotheses that could explain these findings,21 and we believe one possible explanation is a restoration of lung volumes closer to physiologic functional residual capacity.37, 38, 39 Another possible explanation could be that the elevated BP in these participants is not simply hydrodynamic, but rather represents a persistent change in BP control (eg, autonomic elevation in peripheral resistance).

Study Limitations

First, this was an interventional physiologic study of short duration with the goal of determining the acute effects of pleural pressure-guided CPAP titration on the lower respiratory tract and on the cardiovascular system in a limited number of participants (12 participants with class III obesity and six control participants) evaluated in the supine position (no other positions were evaluated in this study). The present study did not directly compare with the gold standard method (ie, standard polysomnography) for the titration of CPAP in participants with OSA. We did not evaluate the long-term effects of CPAP titrated by our method. Future studies should investigate whether CPAP targeting pleural pressure would benefit patients with obesity without sleep apnea syndrome and without pulmonary diseases. Second, transpulmonary pressure measured by esophageal manometry does not consider the gravitational pleural pressure gradient and the horizontal pleural pressure gradient. Body position also may change the pleural pressure gradient according to the caudal-cephalad displacement of the diaphragm and of the abdomen. The present investigation assessed esophageal manometry only in the supine position (no other positions were evaluated in this study). Third, a limitation of our approach is the use of noninvasive transthoracic echocardiography Doppler-based measurements. We minimized error in the following ways. The same echocardiographer obtained all images in a single participant. All images were assessed by a cardiologist. Another potential source of error that may affect Doppler-based measurements is angle error resulting from challenges with Doppler alignment. Because the same anatomic challenges in Doppler alignment exist in all measurements from a single participant, it will affect only absolute values and will not the change within a participant. Because our analysis used the Wilcoxon signed-rank test, which looks at within-patient differences, this should not have affected our results.

Interpretation

Our study demonstrated that spontaneously breathing participants with class III obesity who are not in respiratory failure have greatly elevated resting pleural pressures and must generate large swings in pleural pressure to achieve tidal ventilation, with a resultant increased work of breathing compared with lean control participants. CPAP titrated to match pleural pressure greatly decreases the effort necessary to overcome airways opening occlusion and leads to a reduction of both minute ventilation and work of breathing to a range similar to that of lean participants. Pleural pressure-targeted CPAP is hemodynamically tolerated without compromising right heart function.

Take-home Points.

Study Question: What are the acute effects of pleural pressure-targeted CPAP on cardiopulmonary function in spontaneously breathing participants with class III obesity?

Results: In the absence of respiratory failure, spontaneous breathing participants with class III obesity have greatly elevated resting pleural pressures and must generate large swings in pleural pressure to achieve tidal ventilation, with a resultant increased work of breathing compared with lean control participants. CPAP titrated to match pleural pressure strongly decreases the work of breathing, improves peripheral oxygen saturation, and homogeneity of tidal volume distribution without impairment of right heart function.

Interpretation: In spontaneously breathing participants with class III obesity, CPAP titrated to match pleural pressure greatly decreases the effort necessary to overcome airways opening occlusion and leads to a reduction of both minute ventilation and work of breathing to a range similar to lean participants. Pleural pressure-targeted CPAP is hemodynamically tolerated without compromising right heart function.

Acknowledgments

Author contributions: G. F., J. F., R. M. K., and L. B. conceived and designed the study. G. F., R. R. D., and F. M. collected and analyzed data. A. B. and A. S. performed transthoracic echocardiography. G. F., R. M. K., and L. B. performed the statistical analysis and interpreted the data. G. F., R. M. K., D. A. I., and L. B. wrote the manuscript. All authors revised the manuscript for important intellectual content and approved the final version.

Financial/nonfinancial disclosures: The authors have reported to CHEST the following: M. B. P. A. reports that his research laboratory has received grants from Covidien/Medtronics (research on mechanical ventilation), Orange Med, and Timpel S.A. (electrical impedance tomography) outside the submitted work. R. M. K. is a consultant for Medtronic and Orange Med, has received research grants from both Medtronic and Orange Medical, and has provided webinars for Nihon Kohden. L. B. receives technologies and devices from iNO Therapeutics LLC, Praxair, Inc., and Masimo Corp. and receives grants from “Fast Grants for COVID-19 research” at Mercatus Center of George Mason University and from iNO Therapeutics LLC. None declared (G. F., R. R. D., J. F., D. A. I., F. M., A. S., A. B., A. K. F., C. V. A., P. A.).

Additional information: The e-Appendix, e-Figure, and e-Tables can be found in the Supplemental Materials section of the online article.

Footnotes

FUNDING/SUPPORT: This study was supported by the Reginald Jenney Endowment Chair at Harvard Medical School (L. B.), by the Dr. Berra Sundry Funds at Massachusetts General Hospital, and by laboratory funds of the Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care and Pain Medicine at Massachusetts General Hospital. P. A. is supported by the National Institutes of Health [Mentored Patient-Oriented Research Award 1K23HL146887-01]. L. B. is supported by the National Heart, Lung and Blood Institute [Grant K23 HL128882].

Supplementary Data

e-Online Data
mmc1.pdf (1.7MB, pdf)

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