Letter to Editor

Conceptual errors underlie much of today’s interpretation of mechanical ventilation and the rationale of Lung-Protective Strategies (LPS). In LPS Tidal Volume (TV) must be minimized, even when ventilation remains far below vital capacity. This view treats “stretch” as intrinsically injurious. Yet the mechanical consequences of any given volume change depend critically on the pressure environment in which that volume change occurs.

During spontaneous breathing or Negative Pressure Ventilation (NPV), inspiration is driven by a fall in Pleural Pressure (P_pl). The lung is drawn away from the chest wall and expands under external physiological “pulling” forces. During Positive Pressure Ventilation (PPV) in a closed thorax, the same volume is achieved by raising airway pressure (P_aw). This inevitably raises P_pl and intrathoracic Pressure (P_th, the mean of P_pl and P_aw), so the lung changes volume while being pressed against the chest wall and while tissue is compressed by surrounding pressures (P_th) (Fig.1).

Clinical practice implicitly acknowledges this distinction. During PPV we restrict TV to “protect” the lung, yet after extubation we encourage deep spontaneous breaths to counteract atelectasis. Apparently we realize that PPV promotes collapse whereas strong negative P_pl reverses it, but we still accept the claim that PPV and NPV are physiologically equivalent with respect to ventilator-induced lung injury (VILI).

Two influential concepts have fueled this misconception.

First, Dreyfuss’ volutrauma [1]. In his seminal rat experiments, summarized under the provocative title “barotrauma = volutrauma”, lung injury occurred when animals were ventilated above their vital capacity. Dreyfuss’ experiments also showed that injury could be avoided when lung expansion was prevented by external pressure. Thus, injury was not caused by volume per se, but by the pressure conditions that allowed excessive expansion to occur: barotrauma after all. Nevertheless, the volutrauma concept became the conceptual foundation for limiting TV in clinical ventilation and for the central premise of LPS: that smaller TVs are inherently safer, while the role of P_pl and P_th was largely neglected.

Second, Loring’s widely cited assertion that PPV and NPV are equivalent because both can generate the same volume by the same transpulmonary pressure [2,3]. This argument traces back to Comroe’s observations in the era of open-thorax surgery, when lungs were passively inflated without an intact chest wall [4]. While appropriate in that setting, it does not describe ventilation in a closed thorax. NPV generates transpulmonary pressure by lowering P_pl. PPV can generate the same transpulmonary gradient only by elevating P_aw and unavoidably, elevating P_pl and P_th. Equal transpulmonary pressure therefore does not imply equivalence of P_pl behavior, lung-chest wall interaction or compressive loading of lung tissue.

Additional confusion stems from experimental studies that purported to compare PPV and NPV in excised animal lungs [5]. By removing the thoracic cage they eliminate the pleural space, the very structure that creates the physiological distinction between PPV and NPV in-vivo. Without a chest wall, the lung behaves approximately as a single compliant structure; PPV and NPV will then, by definition, produce similar transpulmonary pressures for a given volume. Such preparations therefore cannot test the mechanics of ventilation in the intact chest and their findings cannot support a clinical claim of equivalence between PPV and NPV.

A simple thought experiment illustrates the point. Consider a relaxed supine subject at functional residual capacity with P_pl ≈ −5 mbar. Place a weight on the abdomen: lung volume falls and P_pl rises. The original volume can be restored either by raising P_aw (PPV) or by lowering the surrounding pressure around thorax and abdomen (NPV). The first strategy further elevates P_pl; the second removes the load from the diaphragm and restores both volume and the original, negative P_pl. Identical volumes are achieved under fundamentally different P_pl conditions.

In ARDS this is not subtle: P_pl may become markedly positive while PEEP is also positive, shifting the P_th milieu from sub-atmospheric to strongly super-atmospheric. The lung must then change volume while being compressed and pressed against the chest wall.

Klassen, et al., provided direct experimental support for this distinction using porcine lungs with a small visceral pleural leak: for the same TV, PPV required substantially higher driving pressure than NPV, while air leakage from the peripheral lung was several-fold greater during NPV, indicating more effective ventilation of the subpleural regions [6]. These results were confirmed by Eckert in similar experiments investigating staple-line position during lung resection surgery [7].

Taken together, the prevailing equivalence claim rests on a category error: it either generalizes volutrauma beyond its mechanistic context or “compares” PPV and NPV in models where the pleural space has been removed. Because NPV is the only form of mechanical assistance that preserves the physiological mechanism of inspiration (a fall in P_pl with atmospheric P_aw), it deserves renewed consideration in modern respiratory care.

Figure 1: Lung parenchyma sandwiched between P_aw and P_pl, illustrating that lung tissue stress depends on the surrounding pressure environment, not on volume alone.

Keywords: Mechanical Ventilation; Pleural Pressure; Intra-Thoracic Pressure; Lung Protective Strategies; VILI

Conflict of Interest

Apart from their university/hospital affiliations, both authors (JvE and JPM) are members of the Exovent Developing Group, which is a UK registered charity (no. 1189967:10 Queen St Pl, London EC4R 1BE, UK.) https://exovent.org None of the authors is receiving any honoraria from this charity. On behalf of all authors, the corresponding author states that there is no conflict of interest. JPM reports payments or honoraria from Medec international outside the submitted work. JPM is a member of a Belgium registered charity ESPCOP vzw (no. 1030137921: Beukenpark 19 9930 Lievegem, BE). https://espcop.eu and co-founder of MT4L. https://mt4l.com, a company developing not related airway products.

Funding Statement

This research did not receive any specific grant from funding agencies in the public, commercial or non-profit sectors.

Acknowledgement

Support from AI has been sought for copyediting of the manuscript.

Data Availability Statement

Not applicable.

Ethical Statement                                                

The project did not meet the definition of human subject research under the purview of the IRB according to federal regulations and therefore was exempt.

Informed Consent Statement

Not applicable.

Authors’ Contributions

All authors have contributed equally to this work and have reviewed and approved the final manuscript for publication.

References

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2. Loring SH, Banzett RB. Whole-body “negative-pressure” ventilation: Is it really different? Am J Respir Crit Care Med. 2008;178(5):542.
3. Butler JP, Banzett RB, Loring SH. Julius Comroe is right: Positive and negative pressure ventilation are the same. Am J Respir Crit Care Med. 2023;208:208-9.
4. Comroe JH Jr. Inflation-1904 model. Am Rev Respir Dis. 1975;112:713-6.
5. Sattari S, Mariano CA, Kuschner WG, Taheri H, Bates JHT, Eskandari M. Positive and negative-pressure ventilation characterized by local and global pulmonary mechanics. Am J Respir Crit Care Med. 2023;207:577-86.
6. Klassen C, Eckert CE, Wong J, Guyette JP, Harris JL, Thompson S, et al. Ex-vivo modeling of perioperative air leaks in porcine lungs. IEEE Trans Biomed Eng. 2018;65:2827-36.
7. Eckert CE, Harris JL, Wong JB, Thompson S, Kassis ES, Tsuboi M, et al. Preclinical quantification of air leaks in a physiologic lung model: Effects of ventilation modality and staple design. Med Devices (Auckl). 2018;11:433-42.