Comprehensive Physiology Wiley Online Library

Gas Exchange in the Respiratory Distress Syndromes

Full Article on Wiley Online Library



Abstract

This article describes the gas exchange abnormalities occurring in the acute respiratory distress syndrome seen in adults and children and in the respiratory distress syndrome that occurs in neonates. Evidence is presented indicating that the major gas exchange abnormality accounting for the hypoxemia in both conditions is shunt, and that approximately 50% of patients also have lungs regions in which low ventilation‐to‐perfusion ratios contribute to the venous admixture. The various mechanisms by which hypercarbia may develop and by which positive end‐expiratory pressure improves gas exchange are reviewed, as are the effects of vascular tone and airway narrowing. The mechanisms by which surfactant abnormalities occur in the two conditions are described, as are the histological findings that have been associated with shunt and low ventilation‐to‐perfusion. © 2012 American Physiological Society. Compr Physiol 2:1585‐1617, 2012.

Comprehensive Physiology offers downloadable PowerPoint presentations of figures for non-profit, educational use, provided the content is not modified and full credit is given to the author and publication.

Download a PowerPoint presentation of all images


Figure 1. Figure 1.

Distributions of shunt, VA/Q and dead space in patients with acute respiratory distress syndrome not receiving positive end‐expiratory pressure (from Dantzker et al. 12).

Figure 2. Figure 2.

Effect of oleic acid on end‐expiratory lung volume and tidal oscillations (data recorded supine and prone, and marker beads located in dorsal lung regions) (from Martynowicz, 56).

Figure 3. Figure 3.

Effect of positive end‐expiratory pressure on end‐expiratory lung volume and ventilatory oscillations after oleic acid. (Modified from Martynowicz et al. 56).

Figure 4. Figure 4.

Regional distribution of lung density quantified by CT scan in normal subjects and patients with acute respiratory distress syndrome (Modified from Pelosi et al. 276).

Figure 5. Figure 5.

Lobar end‐expiratory lung volumes and functional residual capacities in normal subjects and patients with acute respiratory distress syndrome. (Modified from Puybasset et al. (68).

Figure 6. Figure 6.

The electron microscopic image of alveolar surface film of the guinea pig lung. (Modified from Schurch et al. 125).

Figure 7. Figure 7.

(A) Pressure‐volume curves with air and saline for a normal rat lung, and (B) the surface pressure to surface area relationship for an extract of this rat lung measured on a surface balance. (Modified from Clements et al. 125).

Figure 8. Figure 8.

Pressure‐volume curves of human lungs. Volume is expressed as ml/g tissue for a normal infant, a stillborn, and infants who died of RDS. (Modified from Gribetz et al. 133).

Figure 9. Figure 9.

Schematic illustration of the effect of surface tension at the meniscus of fluid filling progressively smaller airways ending in a fluid‐filled and collapsed alveolus (A‐C). The pressure needed to open the alveolus may exceed the pressure that will stress the more primoral airway (D). (Modified from Amato et al. 138).

Figure 10. Figure 10.

Stresses on cells lining a collapsed compliant airway (A) or a fluid occluded airway (B) as a fluid meniscus passes over the cells. (Modified from Bilek et al. 142).

Figure 11. Figure 11.

Tantalum bronchograms of a normal rat lung at end expiration or end inspiration using a high tidal volume of 2.5 ml/kg with no positive end‐expiratory pressure (PEEP) (ZEEP) or 10 cmH2O PEEP. The marker Do indicates bronchus diameter at end expiration with Zeep, and the airway diameter increased with tidal volume and PEEP (from Sinclair et al. 143).

Figure 12. Figure 12.

Conditional expression of SP‐B regulated by doxacillin in transgenic mice. Adult mice have normal SP‐B levels in surfactant (A), normal minimal surface tensions (Min ST) (B), low protein in BALF (C), low inflammatory cells in BALF (D), and low IL‐1 protein in lung tissue. (E) Withdrawal of Dox results in a progressive fall in SP‐B, an increase in Min ST, and increases in indicators of lung injury, which revert to normal when Dox is reintroduced (from Ikegami et al. 149). * P < 0.05 vs. C

Figure 13. Figure 13.

Withdrawal of doxacillin (Dox0 resulted in a fall in oxygen saturation (A), a loss of vascular protrusions into alveoli (B), and increased trapping of microspheres in the microvasculature of the lungs (C) of transgenic mice. In frame D, the shape of a vesicle in SP‐B sufficient mouse (D and A) flattens with a decreased diameter with (D and B) SP‐B deficiency (from Ikegami, M, Weaver, TE, Grant, SN, Whitsett, A. Am J Respir Cell Mol Biol 41: 433‐439, 2009)

.

Figure 14. Figure 14.

Light micrographs of normal rabbit lungs fixed at 40% (A), 80% (B), and 100% (C) of total lung capacity on the inflation limb of the pressure‐volume curve (from Bachofen et al. 150).

Figure 15. Figure 15.

Alveolar appearances of the lungs of preterm sheep that were not ventilated fetal lungs) frame A of upper and frame A of lower panel. Lungs of lambs ventilated for 24 h without surfactant treatment, frame B in upper and lower panels show overinflation of alveolar ducts. In contrast, the lung of a lamb that was surfactant treated and ventilated for 24 h is more uniformly inflated (from Pinkerton, KE, Lewis JF, Rider ED, Peake J, Chen W, Madl AK, Luu RH, Ikegami M, Jobe AH. J. Appl. Physiol 77: 1953‐1960, 1994).

Figure 16. Figure 16.

Changes in PaO2 and minimum surface tensions of airway samples from preterm ventilated lambs following treatment with surfactant (from Ikegami M, Jobe A, Glatz T. J Appl Physiol 51: L306‐L312, 1981).

Figure 17. Figure 17.

Infants with RDS on high frequency oscillation had mean airway pressures increased until the lungs opened (defined as adequate oxygenation on an FIO2 <0.25), lined bar, and then mean airway pressures were decreased until oxygenation deteriorated (closed). Optimal pressure was the pressure sufficient to maintain oxygenation during continued ventilation. Pressures for the recruitment maneuver were lower after surfactant treatment (Modified from de Jaegere, 20).

Figure 18. Figure 18.

RDS with respiratory failure is associated with high minimum surface tensions. Airway samples taken at intubation of infants with RDS and progressive respiratory failure have high minimum surface tensions in contrast to samples from infants without RDS, left frame. However, surfactant with low surface tensions can be isolated from those airway samples. The supernatant fluid contains proteins that inhibit surfactant function, right frame, and the proteins in airway samples are more potent inhibitors than proteins from infants without RDS (Modified from Ikegami M, Jacobs H, Jobe AH. J Pediatr 102: 443‐447, 1982).

Figure 19. Figure 19.

Posterior view of dog lung after inhaling blue vapor for 2 h 50 min after 3 h and 45 min supine under Nembutal anesthesia (Modified from Drinker and Harenbergh 204).

Figure 20. Figure 20.

Effect of spontaneous and mechanical ventilation on respiratory system compliance (Modified from Mead and Collier 268).

Figure 21. Figure 21.

Dorsal‐caudal atelectasis in supine dogs ventilated for 3 h without periodic hyperinflations. With successive inflations re‐expansion occurred (Modified from Mead and Collier 268).



Figure 1.

Distributions of shunt, VA/Q and dead space in patients with acute respiratory distress syndrome not receiving positive end‐expiratory pressure (from Dantzker et al. 12).



Figure 2.

Effect of oleic acid on end‐expiratory lung volume and tidal oscillations (data recorded supine and prone, and marker beads located in dorsal lung regions) (from Martynowicz, 56).



Figure 3.

Effect of positive end‐expiratory pressure on end‐expiratory lung volume and ventilatory oscillations after oleic acid. (Modified from Martynowicz et al. 56).



Figure 4.

Regional distribution of lung density quantified by CT scan in normal subjects and patients with acute respiratory distress syndrome (Modified from Pelosi et al. 276).



Figure 5.

Lobar end‐expiratory lung volumes and functional residual capacities in normal subjects and patients with acute respiratory distress syndrome. (Modified from Puybasset et al. (68).



Figure 6.

The electron microscopic image of alveolar surface film of the guinea pig lung. (Modified from Schurch et al. 125).



Figure 7.

(A) Pressure‐volume curves with air and saline for a normal rat lung, and (B) the surface pressure to surface area relationship for an extract of this rat lung measured on a surface balance. (Modified from Clements et al. 125).



Figure 8.

Pressure‐volume curves of human lungs. Volume is expressed as ml/g tissue for a normal infant, a stillborn, and infants who died of RDS. (Modified from Gribetz et al. 133).



Figure 9.

Schematic illustration of the effect of surface tension at the meniscus of fluid filling progressively smaller airways ending in a fluid‐filled and collapsed alveolus (A‐C). The pressure needed to open the alveolus may exceed the pressure that will stress the more primoral airway (D). (Modified from Amato et al. 138).



Figure 10.

Stresses on cells lining a collapsed compliant airway (A) or a fluid occluded airway (B) as a fluid meniscus passes over the cells. (Modified from Bilek et al. 142).



Figure 11.

Tantalum bronchograms of a normal rat lung at end expiration or end inspiration using a high tidal volume of 2.5 ml/kg with no positive end‐expiratory pressure (PEEP) (ZEEP) or 10 cmH2O PEEP. The marker Do indicates bronchus diameter at end expiration with Zeep, and the airway diameter increased with tidal volume and PEEP (from Sinclair et al. 143).



Figure 12.

Conditional expression of SP‐B regulated by doxacillin in transgenic mice. Adult mice have normal SP‐B levels in surfactant (A), normal minimal surface tensions (Min ST) (B), low protein in BALF (C), low inflammatory cells in BALF (D), and low IL‐1 protein in lung tissue. (E) Withdrawal of Dox results in a progressive fall in SP‐B, an increase in Min ST, and increases in indicators of lung injury, which revert to normal when Dox is reintroduced (from Ikegami et al. 149). * P < 0.05 vs. C



Figure 13.

Withdrawal of doxacillin (Dox0 resulted in a fall in oxygen saturation (A), a loss of vascular protrusions into alveoli (B), and increased trapping of microspheres in the microvasculature of the lungs (C) of transgenic mice. In frame D, the shape of a vesicle in SP‐B sufficient mouse (D and A) flattens with a decreased diameter with (D and B) SP‐B deficiency (from Ikegami, M, Weaver, TE, Grant, SN, Whitsett, A. Am J Respir Cell Mol Biol 41: 433‐439, 2009)

.



Figure 14.

Light micrographs of normal rabbit lungs fixed at 40% (A), 80% (B), and 100% (C) of total lung capacity on the inflation limb of the pressure‐volume curve (from Bachofen et al. 150).



Figure 15.

Alveolar appearances of the lungs of preterm sheep that were not ventilated fetal lungs) frame A of upper and frame A of lower panel. Lungs of lambs ventilated for 24 h without surfactant treatment, frame B in upper and lower panels show overinflation of alveolar ducts. In contrast, the lung of a lamb that was surfactant treated and ventilated for 24 h is more uniformly inflated (from Pinkerton, KE, Lewis JF, Rider ED, Peake J, Chen W, Madl AK, Luu RH, Ikegami M, Jobe AH. J. Appl. Physiol 77: 1953‐1960, 1994).



Figure 16.

Changes in PaO2 and minimum surface tensions of airway samples from preterm ventilated lambs following treatment with surfactant (from Ikegami M, Jobe A, Glatz T. J Appl Physiol 51: L306‐L312, 1981).



Figure 17.

Infants with RDS on high frequency oscillation had mean airway pressures increased until the lungs opened (defined as adequate oxygenation on an FIO2 <0.25), lined bar, and then mean airway pressures were decreased until oxygenation deteriorated (closed). Optimal pressure was the pressure sufficient to maintain oxygenation during continued ventilation. Pressures for the recruitment maneuver were lower after surfactant treatment (Modified from de Jaegere, 20).



Figure 18.

RDS with respiratory failure is associated with high minimum surface tensions. Airway samples taken at intubation of infants with RDS and progressive respiratory failure have high minimum surface tensions in contrast to samples from infants without RDS, left frame. However, surfactant with low surface tensions can be isolated from those airway samples. The supernatant fluid contains proteins that inhibit surfactant function, right frame, and the proteins in airway samples are more potent inhibitors than proteins from infants without RDS (Modified from Ikegami M, Jacobs H, Jobe AH. J Pediatr 102: 443‐447, 1982).



Figure 19.

Posterior view of dog lung after inhaling blue vapor for 2 h 50 min after 3 h and 45 min supine under Nembutal anesthesia (Modified from Drinker and Harenbergh 204).



Figure 20.

Effect of spontaneous and mechanical ventilation on respiratory system compliance (Modified from Mead and Collier 268).



Figure 21.

Dorsal‐caudal atelectasis in supine dogs ventilated for 3 h without periodic hyperinflations. With successive inflations re‐expansion occurred (Modified from Mead and Collier 268).

References
 1. Bernard GR, Artigas A, Brigham KL, Carlet J, Falke K, Hudson L, Lamy M, Legall JR, Morris A, Spragg R. The American‐European consensus conference on ARDS. Definitions, mechanisms, relevant outcomes and clinical trial coordination. Am J Respir Crit Care Med 149(3): 818‐824, 1994.
 2. Avery MA. The Lung and Its Disorders in the Newborn Infant. Philadelphia: Saunders WB, 1964, p. 109‐143.
 3. Pison U, Bock JC, Pietschmann S, Veit S, Slama K. The adult respiratory distress syndrome: Pathophysiological concepts related to the pulmonary surfactant system. In: Robertson B, Taeusch HW, editors. Surfactant Therapy for Lung Disease. New York: Marcel Dekker, Inc., 1995. p. 169‐197.
 4. Jobe AH. Why surfactant works for respiratory distress syndrome. Neo Rev 7: e95‐e105, 2006.
 5. Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 342: 1301‐1308, 2000.
 6. Jobe AH, Ikegami M. Mechanisms initiating lung injury in the preterm. Early Hum Dev 53: 81‐94, 1998.
 7. Lines A, Hooper SB, Harding R. Lung liquid production rates and volumes do not decrease before labor in healthy fetal sheep. J Appl Physiol 82: 927‐932, 1997.
 8. Gowda MS, Klocke RA. Variability of indices of hypoxemia in adult respiratory distress syndrome. Crit Care Med 25: 41‐45, 1997.
 9. Briscoe WA, Cree EM, Filler J, Houssay HEJ, Cournand A. Lung volume, alveolar ventilation and perfusion interrelationship in chronic pulmonary emphysema. J Appl Physiol 15: 785‐795, 1960.
 10. Wagner PD, Laravuso RB, Uhl RR, West JB. Continuous distributions of ventilation‐perfusion ratios in normal subjects breathing air and 100% O2. J Clin Invest 54: 54‐68, 1974.
 11. Lamy M, Fallat RJ, Koeniger E, Dietrich HP, Ratliff JL, Eberhart RC, Tucker HJ, Hill JD. Pathologic features and mechanisms of hypoxemia in adult respiratory distress syndrome. Am Rev Respir Dis 114(2): 267‐284, 1976.
 12. Dantzker DR, Brook CJ, Dehart P, Lynch DP, Weg JG. Ventilation‐perfusion distributions in the adult respiratory distress syndrome. Am Rev Respir Dis 120: 1039‐1052, 1979.
 13. Kiiski R, Takala J, Kari A, Milic‐Emili J. Effect of tidal volume on gas exchange and oxygen transport in the adult respiratory distress syndrome. Am Rev Respir Dis 146(5): 1131‐1135, 1992.
 14. Blanch L, Fernandez R, Valles J, Sole J, Roussos C, Artigas A. Effect of two tidal volumes on oxygenation and respiratory system mechanics during the early stage of adult respiratory distress syndrome. J Crit Care 9(3): 151‐158, 1994.
 15. Ralph DD, Robertson HT, Weaver LJ, Hlastala MP, Carrico CJ, Hudson LD. Distribution of ventilation and perfusion during positive end‐expiratory pressure in the adult respiratory distress syndrome. Am Rev Respir Dis 131(1): 54‐60, 1985.
 16. Strang LB, McLeish MH. Ventilation failure and right‐to‐left shunt in newborn infants with respiratory distress. Pediatrics 28: 17‐27, 1961.
 17. Thibeault DW, Poblete E, Auld PA. Alveolar‐arterial oxygen difference in premature infants breathing 100 per cent oxygen. J Pediatrics. 71(6): 814‐824, 1967.
 18. Corbet AJ, Ross JA, Beaudry PH, Stern L. Ventilation‐perfusion relationships as assessed by a‐ADN2 in hyaline membrane disease. J Appl Physiol 36(1): 74‐81, 1974.
 19. Smith HL, Jones JG. Non‐invasive assessment of shunt and ventilation/perfusion ratio in neonates with pulmonary failure. Arch Dis Child Fetal Neonatal Ed 85: F127‐F132, 2001.
 20. de Jaegere A, van Veenendaal MB, Michiels A, van Kaam AH. Lung recruitment using oxygenation during open lung high‐frequency ventilation in preterm Infants. Am J Respir Crit Care Med 174: 639‐664, 2006.
 21. Riley RL, Permutt S, Said S, Godfrey M, Cheng TO, Howell JBL, Shepard RH. Effect of posture on pulmonary dead space in man. J Appl Physiol 14(3): 339‐343, 1959.
 22. Suter PM, Fairley B, Isenberg MD. Optimum end‐expiratory airway pressure in patients with acute pulmonary failure. N Engl J Med 292(6): 284‐289, 1975.
 23. Beydon L, Uttman L, Rawal R, Jonson B. Effects of positive end‐expiratory pressure on dead space and its partitions in acute lung injury. Intensive Care Med 28: 1239‐1245, 2002.
 24. Nuckton TJ, Alonso JA, Kallet RH, Daniel BM, Pittet J‐F, Eisner MD, Matthay MA. Pulmonary dead‐space fraction as a risk factor for death in the acute respiratory distress syndrome. N Engl J Med 346(17): 1281‐1286, 2002.
 25. Cepkova M, Kapur V, Ren X, Quinn T, Zhua H, Foster E, Liu KD, Matthay MA. Pulmonary dead space fraction and pulmonary artery systolic pressure as early predictors of clinical outcome in acute lung injury. Chest 132: 836‐842, 2007.
 26. Severinghaus JW, Stupfel M. Alveolar dead space as an index of distribution of blood flow in pulmonary capillaries. J Appl Physiol 10(3): 335‐348, 1957.
 27. Dueck R, Wagner PD, West JB. Effects of positive end‐expiratory pressure on gas exchange in dogs with normal and edematous lungs. Anesthesiology 47: 359‐366, 1977.
 28. Coffey RL, Robertson HT, Albert RK. Mechanisms of physiological dead space response to PEEP after oleic acid lung injury. J Appl Physiol 55: 1550‐1557, 1983.
 29. Matamis D, Lemaire F, Harf A, Teisseire B, Brun‐Buisson C. Redistribution of pulmonary blood flow induced by positive end‐expiratory pressure and dopamine infusion in acute respiratory failure. Am Rev Respir Dis 129: 39‐44, 1984.
 30. Rouby J‐J, Puybasset L, Cluzel P, Richecoeur J, Lu Q, Grenier P; and the CT Scan ARDS Study Group. Regional distribution of gas and tissue in acute respiratory distress syndrome. II. Physiological correlations and definition of an ARDS severity score. Intensive Care Med 26: 1046‐1056, 2000.
 31. Ashbaugh DG, Bigelow DB, Petty TL, Levine BE. Acute respiratory distress in adults. Lancet 2: 319‐323, 1967.
 32. Gregory GA, Kitterman JA, Phibbs RH, Tooley WH, Hamilton WK. Treatment of the idiopathic respiratory‐distress syndrome with continuous positive airway pressure. N Engl J Med 284: 1333‐1340, 1971.
 33. Murdock AI, Linsao L, Reid MM, Sutton MD, Tilak KS, Ulan OA, Swyer PR. Mechanical ventilation in the respiratory distress syndrome: A controlled trial. Arch Dis Child. 45(243): 624‐633, 1970.
 34. Rhodes PG, Hall RT. Continuous positive airway pressure delivered by face mask in infants with the idiopathic respiratory distress syndrome: A controlled study. Pediatrics 52: 1‐5, 1973.
 35. Ahlstrom H, Jonson B, Svenningsen NW. Continuous positive airways pressure treatment by a face mask chamber in idiopathic respiratory distress syndrome. Arch Dis Child 51(1): 13‐21, 1976.
 36. Dunn PM, Thearle MJ, Parsons AC, Watts JL. Use of the ‘Gregory box’ (CPAP) in treatment of RDS of the newborn: Preliminary report. Arch Dis Child 47: 674‐675, 1972.
 37. Dunn PM, Respiratory distress syndrome. Continuous positive airway pressure (CPAP) using the Gregory box. Proc R Soc Med 67(4): 245‐247, 1974.
 38. Lynch JP, Mhyre JG, Dantzker DR. Influence of cardiac output on intrapulmonary shunt. J Appl Physiol: Resp Environ Exercise Physiol 46(2): 315‐321, 1979.
 39. Domino KB, Wetstein L, Glasser SA, Lindgren L, Marshall C, Harken A, Marshall BE. Influence of mixed venous oxygen tension (Pvo2) on blood flow to atelectatic lung. Anesthesiology 59(5): 428‐434, 1983.
 40. Smith G, Cheney FW, Winter PM. The effect of change in cardiac output on intrapulmonary shunting. Br J Anaesthesiol 46: 337‐342, 1974.
 41. Sandoval J, Long GR, Skoog C, Wood LD, Oppenheimer L. Independent influence of blood flow rate and mixed venous PO2 on shunt fraction. J Appl Physiol 55(4): 1128‐1133, 1983.
 42. Rossaint R, Hahn SM, Pappert D, Falke KJ, Radermacher P. Influence of mixed venous PO2 and inspired O2 fraction on intrapulmonary shunt in patients with severe ARDS. J Appl Physiol 78(4): 1532‐1536, 1995.
 43. Caldini P, Leith JD, Brennan MJ. Effect of continuous positive‐pressure ventilation (CPPV) on edema formation in dog lung. J Appl Physiol 39: 672‐679, 1975.
 44. Lamm WJE, Kirk, KR, Hanson WL, Wagner WW, Jr, Albert RK. Flow through zone 1 lungs utilizes alveolar corner vessels. J Appl Physiol 70(4): 1518‐1523, 1991.
 45. Pare PD, Warriner B, Baile EM, Hogg JC. Redistribution of pulmonary extravascular water with positive end‐expiratory pressure in canine pulmonary edema. Am Rev Respir Dis 127(5): 590‐593, 1983.
 46. Malo J, Ali J, Wood LD. How does positive end‐expiratory pressure reduce intrapulmonary shunt in canine pulmonary edema. J Appl Physiol 57(4): 1002‐1010, 1984.
 47. McIntyre RW, Laws AK, Ramachandran PR. Positive expiratory pressure plateau: Improved gas exchange during mechanical ventilation. Can Anaesth Soc J 16(6): 477‐486, 1969.
 48. Mutoh T, Lamm WJE, Hildebrandt J, Albert RK. Abdominal distension alters regional pleural pressures and chest wall mechanics in pigs in vivo. J Appl Physiol 70: 2611‐2618, 1991.
 49. Mutoh T, Guest RJ, Lamm WJE, Albert RK. Prone position alters the effect of volume overload on regional pleural pressures and improves hypoxemia in pigs in‐vivo. Am Rev Respir Dis 146: 300‐306, 1992.
 50. Kumar A, Falke KJ, Geffin B, Aldredge CF, Laver MB, Lowenstein E, Pontoppidan H. Continuous positive‐pressure ventilation in acute respiratory failure. N Engl J Med. 283(26): 1430‐1436, 1970.
 51. Falke KJ, Pontoppidan H, Kumar A, Leith DE, Geffin B, Laver MB. Ventilation with end‐expiratory pressure in acute lung disease. J Clin Invest 51: 2315‐2323, 1972.
 52. Slutsky AS, Scharf SM, Brown R, Ingram RH Jr. The effect of oleic acid‐induced pulmonary edema on pulmonary and chest wall mechanics in dogs. Am Rev Respir Dis 121: 91‐96, 1980.
 53. Cook CD, Mead J, Schreiner GL, Frank NR, Craig JM. Pulmonary mechanics during induced pulmonary edema in anesthetized dogs. J Appl Physiol 14(2): 177‐186, 1959.
 54. Gray BA, McCaffree DR, Sivak ED, McCurdy HT. Effect of pulmonary vascular engorgement on respiratory mechanics in the dog. J Appl Physiol Respirat Environ Exercise Physiol 45(1): 119‐127, 1978.
 55. Wilson TA, Anafi RC, Hybmayr RD. Mechanics of edematous lungs. J Appl Physiol 90: 2088‐2093, 2001.
 56. Martynowicz MA, Minor TA, Walters BJ, Hubmayr RD. Regional expansion of oleic acid‐injured lungs. Am J Respir Crit Care Med 160: 250‐258, 1999.
 57. Martynowicz MA, Walters BJ, Hubmayr RD. Mechanisms of recruitment in oleic acid‐injured lungs. J Appl Physiol 90: 1744‐1753, 2001.
 58. Mertens M, Tabuchi A, Meissner S, Krueger A, Schirrmann K, Kertzscher U, Pries AR, Slutsky AS, Koch E, Kuebler WM. Alveolar dynamics in acute lung injury: Heterogeneous distension rather than cyclic opening and collapse. Crit Care Med 37(9): 2604‐2611, 2009.
 59. Schiller HJ, McCann UG Jr, Carney DE, Gatto LA, Steinberg JM, Nieman GF. Altered alveolar mechanics in the acutely injured lung. Crit Care Med 29(5): 1049‐1055, 2001.
 60. McCann UG Jr, Schiller HJ, Carney DE, Gatto LA, Steinberg JM, Nieman GF. Visual validation of the mechanical stabilizing effects of positive end‐expiratory pressure at the alveolar level. J Surg Res 99(2): 335‐342, 2001.
 61. Halter JM, Steinberg JM, Schiller HJ, DaSilva M, Gatto LA, Landas S, Nieman GF. Positive end‐expiratory pressure after a recruitment maneuver prevents both alveolar collapse and recruitment/derecruitment. Am J Respir Crit Care Med 167(12): 1620‐1626, 2003.
 62. DiRocco JD, Pavone LA, Carney DE, Lutz CJ, Gatto LA, Landas SK, Nieman GF. Dynamic alveolar mechanics in four models of lung injury. Intensive Care Med 32(1): 140‐148, 2006.
 63. Gattinoni L, Mascheroni D, Torresin A, Marcolin R, Fumagalli R, Vesconi S, Rossi GP, Rossi F, Baglioni S, Bassi F, Nastri G, Pesenti A. Morphological response to positive end expiratory pressure in acute respiratory failure. Computerized tomography study. Intensive Care Med 2: 137‐142, 1986.
 64. Maunder RJ, Shuman WP, McHugh JW, Marglin SI, Butler J. Preservation of normal lung regions in the adult respiratory distress syndrome. Analysis by computed tomography. J Am Med Assoc 255(18): 2463‐2465, 1986.
 65. Pelosi P, D'Andrea L, Vitale G, Pesenti A, Gattinoni L. Vertical gradient of regional lung inflation in adult respiratory distress syndrome. Am J Respir Crit Care Med 149(1): 8‐13, 1994.
 66. Malbouisson LM, Muller JC, Constantin JM, Lu Q, Puybasset L, Rouby, JJ. Computed tomography assessment of positive end‐expiratory pressure‐induced alveolar recruitment in patients with acute respiratory distress syndrome. Am J Respir Crit Care Med 163: 1444‐1450, 2001.
 67. Gattinoni L, Pesenti A, Bombino M, Baglioni S, Rivolta M, Rossi F, Rossi G, Fumagalli R, Marcolin R, Mascheroni D, Torresin A. Relationships between lung computed tomography density, gas exchange and PEEP in acute respiratory failure. Anesthesiology 69: 824‐832, 1988.
 68. Puybasset L, Cluzel P, Chao N, Slutsky AS, Coriat P, Rouby J‐J; and the CT Scan ARDS Study Group. A computed tomography scan assessment of regional lung volume in acute lung injury. Am J Respir Crit Care Med 158: 1644‐1655, 1988.
 69. Puybasset L, Cluzel P, Gusman P, Grenier P, Preteau F, Rouby JJ. Regional distribution of gas and tissue in acute respiratory distress syndrome—part 1: Consequences on lung morphology. Intensive Care Med 26: 857‐863, 2000.
 70. Albert RK, Hubmayr RD. The prone position eliminates compression of the lungs by the heart. Am J Respir Crit Care Med 161: 1660‐1665, 2000.
 71. Malbouisson LM, Busch CJ, Puybasset L, Lu Q, Cluzel P, Rougy J‐J; CT Scan ARDS Study Group. Role of the heart in the loss of aeration characterizing lower lobes in acute respiratory distress syndrome. Am J Respir Crit Care Med 161: 2005‐2012, 2000.
 72. Washko GR, O'Donnell CR, Loring SH. Volume‐related and volume‐independent effects of posture on esophageal and transpulmonary pressures in health subjects. J Appl Physiol 100: 753‐758, 2006.
 73. Gattinoni L, Pelosi P, Crotti S, Valenza F. Effects of positive end‐expiratory pressure on regional distribution of tidal volume and recruitment in adult respiratory distress syndrome. Am J Respir Crit Care Med 151: 1807‐1814, 1995.
 74. Vieira Sr, Puybasset L, Lu Q, Richecoeuer J, Cluzel P, Coriat P, Rouby JJ. A scanographic assessment of pulmonary morphology in acute lung injury. Significance of the lower inflection point detected on the lung pressure‐volume curve. Am J Respir Crit Care Med 159: 1612‐1623, 1999.
 75. Gainnier M, Michelet P, Thirion X, Arnal J‐M, Sainty J‐M, Papazian L. Prone position and positive end‐expiratory pressure in acute respiratory distress syndrome. Crit Care Med 31: 2719‐2726, 2003.
 76. Pelosi P, Goldner M, McKibben A, Adams A, Eccher G, Caironi P, Losappio S, Gattinoni L, Marini JJ. Recruitment and derecruitment during acute respiratory failure. An experimental study. Am J Respir Crit Care Med 164: 122‐130, 2001.
 77. Crotti S, Mascheroni D, Caironi P, Pelosi P, Ronzoni G, Mondino M, Marini J, Gattinoni L. Recruitment and derecruitment during acute respiratory failure. Am J Respir Crit Care Med 164: 131‐140, 2001.
 78. Albaiceta CM, Taboada F, Parra D, Luyando LH, Calvo J, Menendez R, Otero J. Tomographic study of the inflection points of the pressure volume cure in acute lung injury. Am J Respir Crit Care Med 170: 1066‐1072, 2004.
 79. Gattinoni L, Caironi P, Cressoni M, Chiumello D, Ranieri VM, Quintel M, Russo S, Patroniti N, Cornejo R, Bugedo G. Lung recruitment in patients with the acute respiratory distress syndrome. N Engl J Med 354(7): 1775‐1786, 2006.
 80. Gattinoni L, Pelosi P, Suter PM, Pedoto A, Vercesi P, Lissoni A. Acute respiratory distress syndrome caused by pulmonary and extrapulmonary disease. Different syndromes? Am J Respir Crit Care Med 158: 3‐11, 1998.
 81. Gattinoni L, Caironi P, Cressoni M, Chiumello D, Ranieri VM, Quintel M, Russo S, POatroniti N, Cornejo R, Bugedo G. Lung recruitment in patients with the acute respiratory distress syndrome. N Engl J Med 354: 1775‐1786, 2006.
 82. Terragni PP, Rosboch G, Tealdi A, Corno E, Menaldo E, Davini O, Gandini G, Herrmann P, Mascia L, Quintel M, Slutsky AS, Gattinoni L, Ranieri VM. Tidal hyperinflation during low tidal volume ventilation in acute respiratory distress syndrome. Am J Respir Crit Care Med 175(2): 160‐166, 2007.
 83. Zapol WM, Snider MT. Pulmonary hypertension in severe acute respiratory failure. N Engl J Med 296(9): 476‐480, 1977.
 84. Snow RL, Davies P, Pontoppidan H, Zapol WM, Reid L. Pulmonary vascular remodeling in adult respiratory distress syndrome. Am Rev Respir Dis 126: 87‐92, 1982.
 85. Tomashefski JF Jr, Davies P, Boggis C, Greene R, Zapol WM, Reid LM. The pulmonary vascular lesions of the adult respiratory distress syndrome. Am J Pathol 112: 112‐126, 1983.
 86. Weigelt JA, Gewertz BL, Aurbakken CM, Snyder WH. Pharmacologic alterations in pulmonary artery pressure in the adult respiratory distress syndrome. J Surg Res 32: 243‐248, 1982.
 87. Holcroft JW, Vassar MJ, Weber CJ. Prostaglandin E1 and survival in patients with the adult respiratory distress syndrome. Ann Surg 203: 371‐378, 1986.
 88. Melot C, Naeije R, Mols P, Hallemans R, Lejune P, Jaspar N. Pulmonary vascular tone improves pulmonary gas exchange in the adult respiratory distress syndrome. Am Rev Respir Dis 136: 1232‐1236, 1987.
 89. Radermacher P, Huet Y, Pluskwa F, Herigault R, Mal H, Teisseire B, Lemaire F. Comparison of ketanserin and sodium nitroprusside in patients with severe ARDS. Anesthesiology 68: 152‐157, 1988.
 90. Melot C, Lejeune P, Leeman M, Moraine J‐J, Naeije R. Prostaglandin E1 in the adult respiratory distress syndrome. Am Rev Respir Dis 139: 106‐110, 1989.
 91. Radermacher P, Santak B, Becker H, Falke K. Prostaglandin E1 and nitroglycerin reduce pulmonary capillary pressure but worsen ventilation‐perfusion distributions in patients with adult respiratory distress syndrome. Anesthesiology 70: 601‐606, 1989.
 92. Radermacher P, Santak B, Wust HJ, Tarnow J, Falke KJ. Prostacyclin for the treatment of pulmonary hypertension in the adult respiratory distress syndrome: Effects on pulmonary capillary pressure and ventilation‐perfusion distributions. Anesthesiology 72: 238, 1990.
 93. Rossaint R, Falke KJ, Lopez F, Slama K, Pison U, Zapol WM. Inhlaed nitric oxide for the adult respiratory distress syndrome. N Engl J Med 328(6): 399‐405, 1993.
 94. Rossaint R, Gerlach H, Schmidt‐Ruhnke H, Pappert D, Lewandowski K, Steudel W, Falke K. Efficacy of inhaled nitric oxide in patients with severe ARDS. Chest 107: 1107‐1115, 1995.
 95. Walmarth D, Schneider T, Schermuly R, Olschewski H, Grimminger F, Seeger W. Direct comparison of inhaled nitric oxide and aerosolized prostacyclin in acute respiratory distress syndrome. Am J Respir Crit Care Med 153(3): 991‐996, 1996.
 96. Zwissler B, Kemming G, Habler O, Kleen M, Merkel M, Haller M, Briegel J, Welte M, Peter K. Inhaled prostacyclin (PGI2) versus inhaled nitric oxide in adult respiratory distress syndrome. Am J Respir Crit Care Med 154(6): 1671‐1677, 1996.
 97. Putensen C, Hormann C, Kleinsasser A, Putensen‐Himmer G. Cardiopulmonary effects of aerosolized prostaglandin E1 and nitric oxide inhalation in aptients with acute respiratory distress syndrome. Am J Respir Crit Care Med 157: 1743‐1747, 1998.
 98. Troncy E, Collet J‐P, Shapiro S, Guimond J‐G, Blair L, Ducruet T, Francoeur M, Charbonneau M, Blaise G. Inhaled nitric oxide in acute respiratory distress syndrome. A pilot randomized controlled study. Am J Respir Crit Care Med 157: 1483‐8, 1998.
 99. Dellinger RP, Zimmer JL, Taylor RW, Straube RC, Hauser DL, Criner GJ, Davis K Jr, Hyers TM, Papadakos P. Effects of inhaled nitric oxide in patients with acute respiratory distress syndrome. Results of a randomized phase II trial. Crit Care Med 26(1): 15‐23, 1998.
 100. Lundin S, Mang H, Smithies M, Stenqvist O, Frostell C; for the European Study Group of Inhaled Nitric Oxide. Inhalation of nitric oxide in acute lung injury: Results of a European multicentre study. Intensive Care Med 25: 911‐919, 1999.
 101. Gerlach H, Keh D, Semmerow A, Busch T, Lewandowski K, Pappert DM, Rossaint R, Falke KJ. Dose‐response characteristics during long‐term inhalation of nitric oxide in patients with severe acute respiratory distress syndrome. A prospective, randomized, controlled study. Am J Respir Crit Care Med 167: 1008‐1015, 2003.
 102. Taylor RW, Zimmerman JL, Dellinger RP, Straube RC, Criner GJ, Davis K, Kelly KM, Smith TC, Small RJ; Inhaled nitric oxide in ARDS Study Group. Low‐dose inhaled nitric oxide in patients with acute lung injury. A randomized controlled trial. J Am Med Assoc 291(13): 1603‐1609, 2004.
 103. Abman SH, Kinsella JP, Schaffer MS, Wilkening RB. Inhaled nitric oxide in the management of premature newborn with severe respiratory distress and pulmonary hypertension. Pediatrics 92: 606‐609, 1993
 104. Peliowski A, Finer NN, Etches PC, Tierney AJ, Ryan CA. Inhaled nitric oxide for premature infants after prolonged rupture of the membranes. J Pediatr 126: 450‐453, 1995.
 105. Subhedar NV, Shaw NJ. Changes in oxygenation and pulmonary haemodynamics in preterm infants treated with inhaled nitric oxide. Arch Dis Child Fetal Neonatal Ed 77: F191‐F197, 1997.
 106. Kinsella JP, Walsh WF, Bose CL. Inhaled nitric oxide in premature neonates with severe hypoxaemic respiratory failure: A randomized controlled trial. Lancet 354: 1061‐1065, 1999.
 107. van Meurs KP, Wright LL, Ehrenkranz RA, Lemons JA, Ball MB, Poole WK, Perritt R, Higgins RD, Oh W, Hudak ML, Laptook AR, Shankaran S, Finer NN, Carlo WA, Kennedy KA, Fridriksson JH, Steinhorn RH, Sokol GM, Konduri GG, Aschner JL, Stoll BJ, D'Angio CT, Stevenson DK; for the Preemie Inhaled Nitric Oxide Study. Inhaled nitric oxide for premature infants with severe respiratory failure. N Engl J Med 353: 13‐22, 2005.
 108. Polglase GR, Hooper SB, Gill AW, Allison BJ, McLean CJ, Nitsos I, Pillow JJ, Kluckow M. Cardiovascular and pulmonary consequences of airway recruitment in preterm lambs. J Appl Physiol 2009; 106: 1347‐1355.
 109. Berry D, Jobe A, Jacobs H, Ikegami M. Distribution of pulmonary blood flow in relation to atelectasis in premature ventilated lambs. Am Rev Respir Dis 1985; 132: 500‐503.
 110. Askie LM, Ballard RA, Cutter G, Dani C, Elbourne D, Field D, Hascoet JM, Hibbs AM, Kinsella JP, Mercier JC, Rich W, Schreiber MD, Srisuparp P, Subhedar NV, Van Meurs KP, Voysey M, Barrington K, Ehrenkranz RA, Finer N; Mappino Collaboration MA. Inhaled nitric oxide in preterm infants: A systematic review and individual patient data meta‐analysis. BMC Pediatr 10: 15, 2010.
 111. Thebaud B, Abman SH. Bronchopulmonary dysplasia: Where have all the vessels gone? Roles of angiogenic growth factors in chronic lung disease. Am J Respir Crit Care Med 175: 978‐985, 2007.
 112. Reyes A, Roxa J, Rodriguez‐Rosin R, Torres A, Ussetti P, Wagner PD. Effects of almitrine on ventilation‐perfusion distribution in adult respiratory distress syndrome. Am Rev Respir Dis 137(5): 1062‐1067, 1998.
 113. Prost JF, Desche P, Jardin F, Margairaz A. Comparison of the effects of intravenous almitrine and positive end‐expiratory pressure on pulmonary gas exchange in adult respiratory distress syndrome. Eur Respir J 4(6): 683‐687, 1991.
 114. Gallart L, Lu Q, Puybasset L, Umamaheswara Rao GS, Coriat P, Rouby J‐J; and the NO Almitrine Study Group. Intravenous almitrine combined with inhaled nitric oxide for acute respiratory distress syndrome. Am J Respir Crit Care Med 158: 1770‐1777, 1998.
 115. Papazian L, Roch A, Bregeon F, Thirion XZ, Gaillat F, Sauz P, Fulachier V, Jammes Y, Auffray J‐P. Inhaled nitric oxide and vasoconstrictors in acute respiratory distress syndrome. Am J Respir Crit Care Med 160: 473‐479, 1999.
 116. Broseghini C, Brandolese R, Poggi R, Polese G, Manzin E, Milic‐Emili J, Rossi A. Respiratory mechanics during the first day of mechanical ventilation in patients with pulmonary edema and chronic airway obstruction. Am Rev Respir Dis 138: 355‐361, 1988.
 117. Wright PE, Bernard GR. The role of airflow resistance inpatients with the adult respiratory distress syndrome. Am Rev Respir Dis 139: 1169‐1174, 1989.
 118. Hjalmarson O, Sandberg K. Abnormal lung function in healthy preterm infants. Am J Respir Crit Care Med 165: 83‐87, 2002.
 119. Robertson D. Pathology and pathophysiology of neonatal surfactant deficiency. In: Robertson B, Van Golde L, Batenburg JJ, editors. Pulmonary Surfactant. Amsterdam: Elseiver Science Publishers, 1984, p. 383‐418.
 120. Baraldi E, Filippone M. Chronic lung disease after premature birth. N Engl J Med 357: 1946‐1955, 2007.
 121. von Neergaard K. Nueu auffasungen uber einen grundbegriff der atemmechanik. Z Gesamte Exp Med 66: 373‐394, 1929.
 122. Pattle RE. Properties, function and origin of the alveolar lining layer. Nature 175: 1125‐1126, 1955.
 123. Clements JA. Dependence of pressure‐volume characteristics of lungs on intrinsic surface‐active material. Am J Physiol 187: 592, 1956.
 124. Brown ES, Johnson RP, Clements JA. Pulmonary surface tension. J Appl Physiol 14(5): 717‐720, 1959.
 125. Schurch S, Green FHY, Bachofen H. Formation and structure of surface films: Captive bubble surfactometry. Biochimica et Biophysica Acta 1408: 180‐202, 1998.
 126. Whitsett JA, Weaver TE. Hydrophobic surfactant proteins in lung function and disease. N Engl J Med 347: 2141‐2148, 2002.
 127. Wright JR. Immunoregulatory functions of surfactant proteins. Nat Rev Immunol 5: 58‐68, 2005.
 128. Clements JA, Hustead RF, Johnson RP, Gribetz I. Pulmonary surface tension and alveolar stability. J Appl Physiol 16(3): 444‐450, 1961.
 129. Marcy TW, Merrill WW, Rankin JA, Reynolds HY. Limitations of using urea to quantify epithelial lining fluid recovered by bronchoalveolar lavage. Am Rev Respir Dis 135: 1276‐1280, 1987.
 130. Rebello CM, Jobe AH, Eisele JW, Ikegami M. Alveolar and tissue surfactant pool sizes in humans. Am J Respir Crit Care Med 154: 625‐628, 1996.
 131. Ochs M, Nyengaard JR, Jung A, Knudsen L, Voigt M, Wahlers T, Richter J, Gundersen HJ. The number of alveoli in the human lung. Am J Respir Crit Care Med 169: 120‐124, 2004.
 132. Bjorklund LL, Ingimarsson J, Curstedt T, John J, Robertson B, Werner O, Vilstrup CT. Manual ventilation with a few large breaths at birth compromises the therapeutic effect of subsequent surfactant replacement in immature lambs. Pediatr Res 42: 348‐355, 1997.
 133. Gribetz I, Frank NR, Avery ME. Static volume‐pressure relations of excised lungs of infants with hyaline membrane disease, newborn and stillborn infants. J Clin Invest 38: 2168‐2175, 1959.
 134. Elkady T, Jobe AH. Corticosteroids and surfactant increase lung volumes and decrease rupture pressures of preterm rabbit lungs. J Appl Physiol 63: 1616‐1621, 1987.
 135. Faridy EE. Air opening pressure in fetal lungs. Respir Physiol 68: 293‐300, 1987.
 136. Kamlin CO, O'Donnell CP, Davis PG, Morley CJ. Oxygen saturation in healthy infants immediately after birth. J Pediatr 148: 585‐558, 2006.
 137. Hooper SB, Kitchen MJ, Wallace MJ, Yagi N, Uesugi K, Morgan MJ, Hall C, Siu KK, Williams IM, Siew M, Irvine SC, Pavlov K, Lewis RA. Imaging lung aeration and lung liquid clearance at birth. Faseb J 21: 3329‐3337, 2007.
 138. Amato, MBP, Marini, JJ. In: Marini JJ, Slutsky AS, editors. Barotrauma, Volutrauma and the ventilation of acute lung injury. 1st Ed. Physiological Basis of Ventilatory Support. New York: Marcel Dekker, Inc., 1187‐1245, 1998.
 139. Rider ED, Ikegami M, Whitsett JA, Hull W, Absolom D, Jobe AH. Treatment responses to surfactants containing natural surfactant proteins in preterm rabbits. Am Rev Respir Dis 147: 669‐676, 1993.
 140. Enhorning G, Robertson B. Lung expansion in the premature rabbit fetus after tracheal deposition of surfactant. Pediatrics 50: 58‐66, 1972.
 141. Gaver DP, Samsel RW, Solway J. Effects of surface tension and viscosity on airway reopening. J Appl Physiol 69: 74‐85, 1990.
 142. Bilek AM, Dee CY, Gaver DP III. Mechanisms of surface‐tension‐induced epithelial cell damage in a model of pulmonary airway reopening. J Appl Physiol 94: 770‐783, 2003.
 143. Sinclair SE, Molthen RC, Haworth ST, Dawson CA, Waters CM. Airway strain during mechanical ventilation in an intact animal model. Am J Respir Crit Care Med 176: 786‐794, 2007.
 144. Hillman NH, Moss TJ, Kallapur SG, Bachurski C, Pillow JJ, Polglase GR, Nitsos I, Kramer BW, Jobe AH. Brief, large tidal volume ventilation initiates lung injury and a systemic response in fetal sheep. Am J Respir Crit Care Med 176(6): 575‐581, 2007.
 145. Wada K, Jobe AH, Ikegami M. Tidal volume effects on surfactant treatment responses with the initiation of ventilation in preterm lambs. J Appl Physiol 83: 1054‐1061, 1997.
 146. Nilsson R, Grossmann G, Robertson B. Lung surfactant and the pathogenesis of neonatal bronchiolar lesions induced by artificial ventilation. Ped Res 1978; 12: 249‐255.
 147. Taskar V, John J, Evander E, Robertson B, Jonson B. Surfactant dysfunction makes lungs vulnerable to repetitive collapse and reexpansion. Am J Respir Crit Care Med 155: 313‐320, 1997.
 148. Clark JC, Wert SE, Bachurski CJ, Stahlman MT, Stripp BR, Weaver TE, Whitsett JA. Targeted disruption of the surfactant protein B gene disrupts surfactant homeostasis, causing respiratory failure in newborn mice. Proc Natl Acad Sci U S A 92: 7794‐7798, 1995.
 149. Ikegami J, Whitsett JA, Martis PC, Weaver TE. Reversibility of lung inflammation caused by SP‐B deficiency. Am J Physiol Cell Mol Physiol 289: L962‐L970, 2005.
 150. Bachofen H, Schurch, S, Urbinelli M, Weibel ER. Relations among alveolar surface tension, surface area, volume, and recoil pressure. J Appl Physiol 62: 1878‐1887, 1987.
 151. Pinkerton KE, Lewis JF, Rider ED, Peake J, Chen W, Madl AK, Luu RH, Ikegami M, Jobe A, Glatz T. Surface activity following natural surfactant treatment in premature lambs. J Appl Physiol. 51(2): 306‐312, 1981.
 152. Harrison VC, Heese Hde V, Klein M. The significance of grunting in hyaline membrane disease. Pediatrics 41: 549‐559, 1968.
 153. Ammari A, Suri MS, Milisavljevic V, Sahni R, Bateman DA, Sanocka U, Ruzal‐Shapiro C, Wung JT, Polin RA. Variables associated with the early failure of nasal CPAP in very low birth weight infants. J Peds 147: 341‐347, 2005.
 154. Jobe AH. Surfactant‐edema interactions. In: Weir EK, Reeves JT, editors. The Pathogenesis and Treatment of Pulmonary Edema. Armonk, NY: Futura Publishing Company, Inc., 1998. p. 113‐131.
 155. Holm BA, Enhorning G, Notter RH. A biophysical mechanism by which plasma proteins inhibit lung surfactant activity. Chem Phys Lipids 49: 49‐55, 1988.
 156. Ikegami M, Jobe A, Berry D. A protein that inhibits surfactant in respiratory distress syndrome. Biol Neonate 50: 121‐129, 1986.
 157. Keough KMW, Parsons CS, Tweeddale MG. Interactions between plasma proteins and pulmonary surfactant: Pulsating bubble studies. Can J Physiol Pharmacol 38: 663‐666, 1989.
 158. Gunther A, Siebert C, Schmidt R, Ziegler S, Grimminger F, Yabut M, Temmesfeld B, Walmrath D, Morr H, Seeger W. Surfactant alterations in severe pneumonia acute respiratory distress syndrome, and cardiogenic lung edema. Am J Respir Crit Care Med 1996; 153: 176‐184.
 159. Tierney DF, Johnson RP. Altered surface tension of lung extracts and lung mechanics. J Appl Physiol 20: 1253‐1260, 1965.
 160. Taylor FB, Abrams ME. Effect of surface active lipoprotein on clotting and fibrinolysis, and of fibrinogen on surface tension of surface active lipoprotein. Am J Med 40: 346‐350, 1966.
 161. Balis JU, Shelley SA, McCue MJ, Rappaport ES. Mechanisms of damage to the lung surfactant system, ultrastructure and quantitation of normal and in vitro inactivated lung surfactant. Exper Mol Pathol 14: 243‐262, 1971.
 162. Markart P, Ruppert C, Grimminger F, Seeger W, Gunther A. Fibrinolysis‐inhibitory capacity of clot‐embedded surfactant is enhanced by SP‐B and SP‐C. Am J Physiol Lung Cell Mol Physiol 284: L69‐L76, 2003.
 163. Cockshutt AM, Weitz J, Possmayer F. Pulmonary surfactant‐associated protein‐A enhances the surface activity of lipid extract surfactant and reverses inhibition by blood proteins in vitro. Biochem 29: 8424‐8429, 1990.
 164. Cockshutt AM, Possmayer F. Lysophosphatidylcholine sensitizes lipid extracts of pulmonary surfactant to inhibition by serum proteins. Biochem Biophys Acta 1086: 63‐71, 1991.
 165. Holm BA, Keicher L, Liu MY, Sokolowski J, Enhorning G. Inhibition of pulmonary surfactant function by phospholipases. J Appl Physiol 71: 317‐321, 1991.
 166. Haddad IY, Zhu S, Ischiropoulos H, Matalon S. Nitration of surfactant protein A results in decreased ability to aggregate lipids. Am J Physiol 270: L261‐L288, 1996.
 167. Gilliard N, Heldt GP, Loredo J, Gasser H, Redl H, Merritt TA, Spragg, RG. Exposure of the hydrophobic components of porcine lung surfactant to oxidant stress alters surface tension properties. J Clin Invest 93: 2608‐2615, 1994.
 168. Rodriguez‐Capote K, Manzanares D, Haines T, Possmayer F. Reactive oxygen species inactivation of surfactant involves structural and functional alterations to surfactant proteins SP‐B and SP‐C. Biophys J 90: 2808‐2821, 2006.
 169. Lewis JF, Jobe AH. Surfactant and the adult respiratory distress syndrome. Am Rev Respir Dis 147: 218‐233, 1993.
 170. Lewis JF, Ikegami M, Jobe AH. Altered surfactant function and metabolism in rabbits with acute lung injury. J Appl Physiol 69(6): 2303‐2310, 1990.
 171. Maruscak AA, Vockeroth DW, Girardi B, Sheikh T, Possmayer F, Lewis JF, Veldhuizen RA. Alterations to surfactant precede physiological deterioration during high tidal volume ventilation. Am J Physiol Lung Cell Mol Physiol 294: L974‐L983, 2008.
 172. Gross NJ, Veldhuizen R, Possmayer F, Dhand R. Surfactant convertase action is not essential for surfactant film formation. Am J Physiol 273: L907‐L912, 1997.
 173. Gross NJ, Schultz RM. Requirements for extracellular metabolism of pulmonary surfactant ‐ tentative identification of serine protease. Am J Physiol 262: L446‐L453, 1992.
 174. Von Wichert P, Kohl FV. Decreased dipalmitoyllecithin content found in lung specimens from patients with so‐called shock lung. Intensive Care Med 1: 27‐30, 1977.
 175. Petty TL, Reiss OK, Paul GW, Silvers GW, Elkins NC. Characteristics of pulmonary surfactant in adult respiratory distress syndrome associated with trauma and shock. Am Rev Respir Dis 115: 531‐536, 1977.
 176. Petty TL, Silvers GW, Paul GW, Stanford RE. Abnormalities in lung elastic properties and surfactant function in adult respiratory distress syndrome. Chest 75(5): 571‐574, 1979.
 177. Hallman M, Spragg R, Harrell JH, Moser KM. Evidence of lung surfactant abnormality in respiratory failure. J Clin Invest 70: 673‐83, 1982.
 178. Pison U, Seeger W, Buchhorn R, Joka T, Brand M, Obertacke U, Neuhof H, Schmit‐Neuerburg KP. Surfactant abnormalities in patients with respiratory failure after multiple trauma. Am Rev Respir Dis 140(4): 1033‐1039, 1989.
 179. Gregory TJ, Longmore WJ, Moxley MA, Whitsett JA, Reed CR, Fowler AA III, Hudson LD, Maunder RJ, Crim C, Hyers TM. Surfactant chemical composition and biophysical activity in acute respiratory distress syndrome. J Clin Invest 88: 1976‐1981, 1991.
 180. Veldhuizen RQW, McCaig LA, Akino T, Lewis JF. Pulmonary surfactant subfractions in patients with the acute respiratory distress syndrome. Am J Respir Crit Care Med l152: 1867‐18671, 1995.
 181. Raymondos K, Leuwer M, Haslam PL, Vangerow B, Ensink M, Tschorn H, Schurmann W, Husstedt H, Rueckoldt H, Piepenbrock S. Compositional, structural, and functional alterations in pulmonary surfactant in surgical patients after the early onset of systemic inflammatory response syndrome or sepsis. Crit Care Med 27(1): 82‐88, 1999.
 182. Greene KE, Wright JR, Steinberg KP, Ruzinski JT, Caldwell E, Wong WB, Hull W, Whitsett JA, Akino T, Kuroki Y, Nagae H, Hudson LD, Martin TR. Serial changes in surfactant‐associated proteins in lung and serum before and after onset of ARDS. Am J Respir Crit Care Med 160: 1843‐1850, 1999.
 183. Baker CS, Evans TW, Randle BJ, Haslam PL. Damage to surfactant‐specific protein in acute respiratory distress syndrome. Lancet 353(9160): 1232‐1237, 1999.
 184. Schmidt R, Markart P, Ruppert C, Wygrecka M, Kuchenbuch T, Walmrath D, Seeger W, Guenther A. Time‐dependent changes in pulmonary surfactant function and composition in acuter respiratory distress syndrome due to pneumonia or aspiration. Respir Res 8: 55, 2007.
 185. Tsangaris I, Lekka ME, Kisiouli E, Constantopoulos S, Nakos G. Bronchoalveolar lavage alterations during prolonged ventilation of patients without acute lung injury. Eur Respir J 21: 495‐501, 2003.
 186. Spragg RG, Gilliard N, Richman P, Spragg RG, Gilliard N, Richman P, Smith RM, Hite RD, Pappert D, Robertson B, Curstedt T, Strayer D. Acute effects of a single dose of porcine surfactant on patients with the adult respiratory distress syndrome. Chest 105: 195‐202, 1994.
 187. Weg JG, Balk RA, Tharratt RS, Jenkinson SG, Shah JB, Zaccardelli D, Horton J, Pattishall E; for the Exosurf ARDS Sepsis Study Group. Safety and potential efficacy of an aerosolized surfactant in human sepsis‐induced adult respiratory distress syndrome. J Am Med Assoc 272(18): 1433‐1438, 1994.
 188. Anzueto A, Jubran A, Ohar JA, Piquette CA, Rennard SI, Colice G, Pattishall EN, Barrett J, Engle M, Perret KA, Rubin BK. Effects of aerosolized surfactant in patients with stable chronic bronchitis: A prospective randomized controlled trial. J Am Med Assoc 278(17): 1426‐1431, 1997.
 189. Walmrath D, Grimminger F, Pappert D, Knothe C, Obertacke U, Benzing A, Günther A, Schmehl T, Leuchte H, Seeger W. Bronchoscopic surfactant administration in patients with severe adult respiratory distress syndrome and sepsis. Am J Respir Crit Care Med 154: 57‐62, 1996.
 190. Wiswell TE, Smith RM, Katz LB, Mastroianni L, Wong DY, Willms D, Heard S, Wilson M, Hite RD, Anzueto A, Revak SD, Chochrane CG. Bronchopulmonary segmental lavage with surfaxin (KL4‐surfactant) for acute respiratory distress syndrome. Am J Respir Crit Care Med 160: 1188‐1195, 1999.
 191. Spragg RG, Lewis JF, Wurst W, Häfner D, Baughman RP, Wewers MD, Marsh JJ. Treatment of acute respiratory distress syndrome with recombinant surfactant protein C surfactant. Am J Respir Crit Care Med 167: 1562‐1566, 2003.
 192. Gregory TJ, Steinberg KP, Spragg R, Gadek JE, Hyers TM, Longmore WJ, Moxley MA, Cai GZ, Hite RD, Smith RM, Hudson LD, Crim C, Newton P, Mitchell BR, Gold AJ. Bovine surfactant therapy for patients with acute respiratory distress syndrome. Am J Respir Crit Care Med 155(4): 1309‐1315, 1997.
 193. Spragg RG, Lewis JF, Walmrath HJ‐D, Johannigman J, Bellingan G, Laterre P‐F, Witte MC, Richards GA, Rippin G, Rathgeb F, Hafner D, Taut FJH, Seeger W. Effects of recombinant surfactant protein C‐based surfactant on the acute respiratory distress syndrome. N Engl J Med 351: 884‐892, 2004.
 194. Kesecioglu J, Beale R, Stewart TE, Findlay GP, Rouby J‐J, Holzapfel L, Bruins P, Steenken EJ, Jeppesen OK, Lachmann B. Exogenous natural surfactant for treatment of acute lung injury and the acute respiratory distress syndrome. Am J Respir Crit Care Med 180: 989‐994, 2009.
 195. Willson DF, Thomas JN, Markovitz BP, Bauman LA, DiCarlo JV, Pon S, Jacobs BR, Jefferson LS, Conaway MR, Eagan EA; for the Pediatric Acute Lung Injury and Sepsis Investigators. Effect of exogenous surfactant (calfactant) in pediatric acute lung injury. A randomized controlled trial. J Am Med Assoc 293: 470‐476, 2005.
 196. Mulrooney N, Champion Z, Moss TJ, Nitsos I, Ikegami M, Jobe AH. Surfactant and physiological responses of preterm Lambs to continuous positive airway pressure. Am J Respir Crit Care Med 171: 1‐6, 2005.
 197. Ikegami M, Jacobs H, Jobe AH. Surfactant function in the respiratory distress syndrome. J Pediatr 102: 443‐447, 1983.
 198. Hallman M, Merritt TA, Jarvenpaa A, Boynton B, Mannino F, Bluck L, Moore T, Edwards D. Exogenous human surfactant for treatment of severe respiratory distress syndrome: A randomized prospective clinical trial. J Peds 196: 963‐969, 1985.
 199. Enhorning G, Shennan A, Possmayer F, Dunn M, Chen CP, Milligan J. Prevention of neonatal respiratory distress syndrome by tracheal instillation of surfactant: A randomized clinical trial. Pediatrics 76: 145‐153, 1985.
 200. Been JV, Rours IG, Kornelisse RF, Jonkers F, Krieger RR, Zimmermann LJ. Chorioamnionitis alters the response to surfactant in preterm infants. J Pediatr 156: 10‐15.e11, 2010.
 201. Bryan AC. Comments of a devil's advocate. Am Rev Respir Dis 110(Suppl): 143‐144, 1994.
 202. Dock W. The evil sequelae of complete bed rest. J Am Med Assoc 125: 1083‐1085, 1994.
 203. Drinker CK. Pulmonary Edema and Inflammation. An Analysis of Processes Involved in the Formation and Removal of Pulmonary Transudates and Exudates. Harvard University Press, Cambridge, 1945. p. 3‐106.
 204. Drinker CK, Harenbergh MA. The effects of the supine position upon the ventilation of the lungs of dogs. Surgery 24: 113‐118, 1947.
 205. Moore RH. The volume of blood flow per minute through the lungs following collapse of one lung by bronchial occlusion. Arch Surg 22: 225‐257, 1931.
 206. Wu N, Miller WF, Luhn NR. Studies of breathing in anesthesia. Anesthesiology 17(5): 696‐707, 1956.
 207. Butler J, Smith BH. Pressure‐volume relationships of the chest in the completely relaxed anaesthetized patient. Clin Sci 16: 125‐145, 1957.
 208. Brismar B, Hedenstierna G, Lundquist H, Strandberg A, Svensson L, Tokics L. Pulmonary densities during anesthesia with muscular relazation—a proposal of atelectasis. Anesthesiology 62(4): 422‐428, 1985.
 209. Strandberg A, Tokics L, Brismar B, Lundquist H, Hedenstierna G. Atelectasis during anaesthesia and in the postoperative period. Acta Anaesthesiol Scand 39(2): 154‐158, 1986.
 210. Strandberg A, Hedenstierna G, Tokics L, Lundquist H, Brismar B. Densities in dependent lung regions during anaesthesia: Atelectasis or fluid accumulation? Acta Anaesthesiol Scand 10(3): 256‐259, 1986.
 211. Strandberg A, Tokics L, Brismar B, Lundquist H, Hedenstierna G. Constitutional factors promoting development of atelectasis during anaesthesia. Acta Anaesthesiol Scand 31(1): 21‐24, 1987.
 212. Tokics L, Strandberg A, Brismar B, Lundquist H, Hedenstierna G. Computerized tomography of the chest and gas exchange measurements during ketamine anaesthesia. Acta Anaesthesiol Scand 31(8): 84‐92, 1987.
 213. Klingstedt C, Hedenstierna G, Lundquist H, Strandberg A, Tlkics L, Brismar B. The influence of body position and differential ventilation on lung dimensions and atelectasis formation in anaesthetized man. Acta Anaesthesiol Scand 34(4): 315‐322, 1990.
 214. Hachenberg T, Lundquist H, Tokics L, Brismar B, Hedenstierna G. 1993. Analysis of lung density by computed tomography before and during general anaesthesia. Acta Anaesthesiol Scand 37(6): 549‐555, 1993.
 215. Hedenstierna G, Tokics L, Lundquist H, Andersson T, Strandberg A, Brismar B. Phrenic nerve stimulation during halothane anesthesia. Effects on atelectasis. Anesthesiology 80: 751‐760, 1994.
 216. Lundquist H, Hedenstierna G, Strandberg A, Tokics L, Brismar B. CT‐assessment of dependent lung densities in man during general anaesthesia. Acta Radiol 36(6): 626‐632, 1995.
 217. Rothen HU, Sporre B, Engberg G, Wegenius G, Reber A, Hedenstierna G. Prevention of atelectasis during general anaesthesia. Lancet 345(8962): 1387‐1391, 1995.
 218. Rothen HU, Sporre B, Engberg G, Wegenious G, Hogman M, Hedenstierna G. Influence of gas composition on recurrence of atelectasis alter reexpansión maneuver during general anesthesia. Anesthesiology 82(4): 832‐842, 1995.
 219. Rothen HU, Sporre B, Engberg G, Wegenious G, Reber A, Hedenstierna G. Atelectasis and pulmonary shunting during induction of general anaesthesia—can they be avoided? Acta Anaesthesiol Scand 40(5): 524‐529, 1996.
 220. Reber A, Engberg G, Sporre B, Kviele L, Rothen H‐U, Wegenius, G, Nylung U, Hedenstierna G. Volumetric analysis of aeration in the lungs during general anaesthsia. Br J Anaesth 76: 760‐766, 1996.
 221. Neumann P, Rothen HU, Berglund JE, Valtysson J, Magnusson A, Hedenstierna G. Positive end‐expiratory pressure prevents atelectasis during general anaesthesia even in the presence of a high inspired oxygen concentration. Acta Anaesthesiol Scand 43(3): 295‐301, 1999.
 222. Tokics L, Hedenstierna G, Strandberg A, Brismar B, Lundquist H. Lung collapse and gas exchange during general anesthesia: Effects of spontaneous breathing, muscle paralysis, and positive end‐expiratory pressure. Anesthesiology 66: 157‐167, 1987.
 223. Tokics L, Hedenstierna G, Svensson L, Brismar B, Cederlund T, Lundquist H, Strandberg A. V/Q distribution and correlation to atelectasis in anesthetized paralyzed humans. J Appl Physiol 81(4): 1822‐1833, 1996.
 224. Woo SW, Berlin D, Hedley‐Whyte J. Surfactant function and anesthetic agents. J Appl Physiol 26(5): 571‐577, 1969.
 225. Stanley TH, Zikria BA, Sullivan SF. The surface tension of tracheobronchial secretions during general anesthesia. Anesthesiology 37(4): 445‐449, 1972.
 226. Katz JA, Sellin SE, Ozanne GM, Fairley BH. Pulmonary, chest wall and lung‐thorax elastances in acute respiratory failure. Chest 80: 304‐311, 1981.
 227. Milic‐Emili J, Henderson AM, Dolovich MB, Trop D, Kaneko K. Regional distribution of inspired gas in the lung. J Appl Physiol 21(3): 749‐759, 1966.
 228. Glazier JB, Hughes JMB, Maloney JE, West JE. Vertical gradient of alveolar size in lung of dogs frozen intact. J Appl Physiol 23(5): 694‐705, 1967.
 229. Hoppin FG Jr, Green ID, Mead J. Distribution of pleural surface pressure in dogs. J Appl Physiol 27: 863‐873, 1969.
 230. Gehr P, Weibel ER. Morphometric estimation of regional differences in the dog lung. J Appl Physiol 37(5): 648‐653, 1974.
 231. Froese AB, Bryan AC. Effects of anesthesia and paralysis on diaphragmatic mechanics in man. Anesthesiology 41: 242‐254, 1974.
 232. Hoffman EA. Effect of body orientation on regional lung expansion: A computed tomographic approach. J Appl Physiol 59: 468‐480, 1985.
 233. Hoffman EA, Ritman EL. Effect of body orientation on regional lung expansion in dog and sloth. J Appl Physiol 59(2): 481‐491, 1985.
 234. Lamm WJE, Graham MM, Albert RK. Mechanism by which the prone position improves oxygenation in acute lung injury. Am J Resp Crit Care Med 1994; 150: 184‐193.
 235. Pappert D, Rossaint R, Slama K, Gruning T, Falke KJ. Influence of positioning on ventilation–perfusion relationships in severe adult respiratory distress syndrome. Chest 106: 1511‐1516, 1994.
 236. Liu S, Margulies SS, Wilson TA. Deformation of the dog lung in the chest wall. J Appl Physiol 68(5): 1979‐1987, 1990.
 237. Krayer S, Rehder K, Vettermann J, Didier EP, Ritman EL. Position and motion of the human diaphragm during anesthesia‐paralysis. Anesthesiology 70: 891‐898, 1989.
 238. Hubmayr RD, Walters JB, Chevalier PA, Rodarte JR, Olson LE. Topographical distribution of regional lung volume in anesthetized dogs. J Appl Physiol: Respir Environ Exercise Physiol 54(4): 1048‐1056, 1983.
 239. Douglas WW, Rehder K, Beynen FM, Sessler AD, Marsh HM. Improved oxygenation in patients with acute respiratory failure: The prone position. Am Rev Respir Dis 115: 559‐566, 1977.
 240. Piehl MA, Brown RS. Use of extreme position changes in acute respiratory failure. Crit Care Med 4: 13‐15, 1976.
 241. Bar‐Yishay E, Hyatt RE, Rodarte JR. Effect of heart weight on distribution of lung surface pressures in vertical dogs. J Appl Physiol 61(2): 712‐718, 1986.
 242. Albert RK, Leasa D, Sanderson M, Robertson HT, Hlastala MP. The prone position improves oxygenation and reduces shunt in oleic acid‐induced acute lung injury. Am Rev Respir Dis 135: 628‐633, 1987.
 243. Wiener CM, Kirk W, Albert RK. The prone position reverses the gravitational distribution of perfusion in dog lungs with oleic acid‐induced injury. J Appl Physiol 68: 1386‐1392, 1990.
 244. Cakar N, Van Der Kloot T, Youngblood A, Adams A, Nahum A. Oxygenation response to a recruitment maneuver during supine and prone positions in oleic acid‐induced lung injury model. Am J Respir Crit Care Med 161: 1949‐1956, 2000.
 245. Chatte G, Sab J‐B, Dobois J‐M, Sirodot M, Gaussorgues P, Robert D. Prone position in mechanically ventilated patients with severe acute respiratory failure. Am J Respir Crit Care Med 155: 473‐478, 1997.
 246. Mure M, Domino KB, Lindahl SGE, Hlastala MP, Altemeier WA, Glenny RW. Regional ventilation‐perfusion distribution is more uniform in the prone position. J Appl Physiol 88: 1076‐1083, 2000.
 247. Gattinoni L, Tognoni G, Pesenti A, Taccone P, Mascheroni D, Labarta V, Malacrida R, DiGiulio P, Fumagalli R, Pelosi P. Effect of prone positioning on the survival of patients with acute respiratory failure. N Engl J Med 345: 568‐573, 2001.
 248. Guerin C, Badet M, Rosselli S, Heyer L, Sab JM, Langevin B, Philit F, Fournier G, Robert D. Effects of prone position on alveolar recruitment and oxygenation in acute lung injury. Intensive Care Med 25(11): 1222‐1230, 1999.
 249. Guerin C, Gaillard S, Lemasson S, Ayzac L, Girard R, Beuret P, Palmier B, Le QV, Sirodot M, Rosselli S, Cadiergue V, Sainty J‐M, Barbe P, Combourieu E, Debatty D, Rouffiineau J, Ezingeard E, Millet O, Guelon D, Rodriguez L, Martin O, Renault A, Sibille J‐P, Kaidomar M. Effects of systematic prone positioning in hypoxemic acute respiratory failure. A randomized controlled trial. J Am Med Assoc 292: 2379‐2387, 2004.
 250. Fernandez R, Trenchs X, Klamburg J, Castedo J, Serrano JM, Besso G, Tirapu JP, Santos A, Mas A, Parraga M, Jubert P, Frutos F, Anon JM, Garcia M, Rodriguez F, Yebenes JC, Lobez MJ. Prone positioning in acute respiratory distress syndrome: A multicenter randomized clinical trial. Intensive Care Med 34: 1487‐1491, 2008.
 251. Mancebo J, Fernandez R, Blanch L, Rialp G, Gordo F, Ferrer M, Rodriguez F, Garro P, Ricart P, Valiverdu I, Gich I, Castano J, Saura P, Dominguez G, Bonet A, Albert RK. A multicenter trial of prolonged prone ventilation in severe acute respiratory distress syndrome. Am J Respir Crit Care Med 173: 1233‐1239, 2006.
 252. Reutershan J, Schmitt A, Dietz K, Unertl K, Fretschner R. Alveolar recruitment during prone position: Time matters. Clin Sci 110(6): 655‐663, 2006.
 253. Richter T, Bellani G, Harris RS, Melo MFV, Winkler T, Venegas JG, Musch G. Effect of prone position on regional shunt, aeration, and perfusion in experimental acute lung injury. Am J Respir Crit Care Med 172: 480‐487, 2005.
 254. Papazian L, Gainnier M, Marin V, Donati S, Arnal JM, Demory D, Roch A, Forel JM, Bongrand P, Bregeon F, Sainty JM. Comparison of prone positioning and high‐frequency oscillatory ventilation in patients with acute respiratory distress syndrome. Crit Care Med. 33(10): 2162‐2171, 2005.
 255. Pelosi P, Bottino N, Chiumello D, Caironi P, Panigada M, Gamberoni C, Colombo G, Bigatello LM, Gattinoni L. Sigh in supine and prone position during acute respiratory distress syndrome. Am J Respir Crit Care Med 167: 521‐527, 2003.
 256. Curley MAQ, Hibberd PL, Fineman LD, Wypij D, Shih M‐C, Thompson JE, Grant MJC, Barr FE, Cvijanovich NZ, Sorce L, Luckett PM, Matthay MA, Arnold JH. Effect of prone positioning on clinical outcomes in children with acute lung injury: A randomized controlled trial. J Am Med Assoc 294(4): 229‐237, 2005.
 257. Gattinoni L, Pelosi P, Vitale G, Pesenti A, D'Andrea L, Mascheroni D. Body position changes redistribute lung computed‐tomographic density in patients with acute respiratory failure. Anesthesiology 74: 15‐23, 1991.
 258. Cortese DA, Rodarte JR, Rehder K, Hyatt RE. Effect of posture on the single‐breath oxygen test in normal subjects. J Appl Physiol 41(4): 474‐479, 1976.
 259. Clarke SW, Jones JG, Glaister DH. Change in pulmonary ventilation in different postures. Clin Sci 37: 357‐369, 1969.
 260. Beck KC, Vettermann J, Rehder K. Gas exchange in dogs in the prone and supine positions. J Appl Physiol 72(6): 2292‐2297, 1992.
 261. Taccone P, Pesenti A, Latini R, Polli F, Vagginelli F, Mietto C, Caspani L, Raimondi F, Bordone G, Iapichino G, Mancebo J, Guerin C, Ayzac L, Blanch L, Fumagalli R, Tognoni G, Gattinoni L. Prone‐Supine II Study Group. Prone positioning in patients with moderate and severe acute respiratory distress syndrome: A randomized controlled trial. J Am Med Assoc 302(18): 1977‐1984, 2009.
 262. Oczenski W, Hormann C, Keller C, Lorenzi N, Kepka A, Schwarz S, Fitzgerald RD. Recruitment maneuvers during prone positioning in patients with acute respiratory distress syndrome. Crit Care Med 33(1): 54‐61, 2005.
 263. Valenza F, Guglielmi M, N\Maffioletti M, Tedesco C, Maccagni P, Fossali T, Aletti G, Porro GA, Irace M, Carlesso E, Carboni N, Lazzerini M, Gattinoni L. Prone position delays the progression of ventilator‐induced lung injury in rates: Does lung strain distribution play a role? Crit Care Med 33(2): 361‐367, 2005.
 264. Viellard‐Baron A, Rabiller A, Chergui K, Peyrouset O, Page B, Beauchet A, Jardin F. Prone position improves mechanics and alveolar ventilation in acute respiratory distress syndrome. Intensive Care Med 31: 220‐226, 2005.
 265. Voggenreiter G, Aufmkolk M, Stiletto RJ, Baacke MG, Waydhas C, Ose C, Bock E, Gotzen L, Obertacke U, Nast‐Kolb D. Prone positioning improves oxygenation in post‐traumatic lung injury—a prospective randomized trial. J Trauma 59: 333‐343, 2005.
 266. Walther SM, Johansson MJ, Flatebo T, Nicolaysen A, Nicolaysen G. Marked differences between prone and supine sheep in effect of PEEP on perfusion distribution in zone II lung. J Appl Physiol 99: P909‐P914, 2005.
 267. Bernstein L. The elastic pressure‐volume curves of the lungs and thorax of the living rabbit. J Physiol 138: 473‐487, 1957.
 268. Mead J, Collier C. Relation of volume history of lungs to respiratory mechanics in anesthetized dogs. J Appl Physiol 14(5): 669‐678, 1959.
 269. Ferris BG, Pollard DS. Effect of deep and quite breathing on pulmonary compliance in man. J Clin Invest 39: 143‐149, 1959.
 270. Caro CG, Butler J, DuBois AB. Some effects of restriction of chest cage expansion on pulmonary function in man: An experimental study. J Clin Invest 39: 573‐583, 1960.
 271. Bendixen HH, Hedley‐Whyte J, Laver MB. Impaired oxygenation in surgical patients during general anesthesia with controlled ventilation. A concept of atelectasis. N Engl J Med 269: 991‐996, 1963.
 272. Bendixen HH, Smith GM, Mead J. Pattern of ventilation in young adults. J Appl Physiol 19(2): 195‐198, 1964.
 273. Housley E, Lauzada N, Becklake MR. To sigh or not to sigh. Am Rev Respir Dis 101: 611‐614, 1979.
 274. Davis K, Branson RD, Campbell RS, Porembka DT, Johnson DJ. The addition of sighs during pressure support ventilation. Is there a benefit? Chest 104: 867‐870, 1993.
 275. Levine M, Gilbert R, Auchincloss JH Jr. A comparison of the effects of sighs, large tidal volumes and positive end‐expiratory pressure in assisted ventilation. Scand J Respir Dis 53: 101‐108, 1972.
 276. Pelosi P, Cadringher P, Bottino N, Panigada M, Carrieri F, Riva E. Sigh in acute respiratory distress syndrome. Am J Respir Crit Care Med 159: 872‐880, 1999.
 277. Patroniti N, Foti G, Cortinovis B, Maggioni E, Bigatello LM, Cereda M, Pesenti A. Sigh improves gas exchange and lung volume in patients with acute respiratory distress syndrome undergoing pressure support ventilation. Anesthesiology 96: 788‐794, 2002.
 278. Bailey TC, Maruscak AA, Martin EL, Forbes AR, Petersen A, McCaig LA, Yao L‐J, Lewis JF, Veldhuizen RAW. The effects of long‐term conventional mechanical ventilation on the lungs of adult rats. Crit Care Med 36: 2381‐2387, 2008.
 279. Amato MB, Barbas CSV, Medeiros DM, Magaldi RB, Schettino G de PP, Lorenzi‐Filho G, Kairalla RA, Deheinzelin D, Munoz C, Oliveira R, Takagaki TY, Carvalho CRR. Effect of a protective‐ventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med 338: 347‐354, 1998.
 280. Van Der Kloot TE, Blanch L, Youngblood AM, Weiner C, Adams A, Marini JJ, Shapiro RS, Nahum A. Recruitment maneuvers in thress experimental models of acute lung injury: Effect on lung volume and gas exchange. Am J Respir Crit Care Med 161: 1485‐1494, 1999.
 281. Foti G, Cereda M, Sparacino ME, DeMarchi L, Villa F, Pesenti A. Effects of periodic lung recruitment naneuvers on gas exchange and respiratory mechanics in mechanically ventilated acute respiratory distress syndrome (ARDS) patients. Intensive Care Med 26(5): 501‐507, 2000.
 282. Lim CM, Koh Y, Park W, Chin JY, Shim TS, Lee SD, Kim WS, Kim DS, Kim WD. Mechanistic scheme and effect of “extended sigh” as a recruitment maneuver in patients with acute respiratory distress syndrome: A preliminary study. Crit Care Med 29(6): 1255‐1260, 2001.
 283. Brower RG, Morris A, MacIntyre N, Matthay MN, Hayden D, Thompson T, Clemmer T, Lanken PN, Schoenfeld D. ARDS Clinical Trials Network. Effects of recruitment maneuvers in patients with acute lung injury and acute respiratory distress syndrome ventilated with high positive end‐expiratory pressure. Crit Care Med 31(11): 2592‐2597, 2003.
 284. Johannigman JA, Miller SL, Davis RB, Davis K Jr, Campbell RS, Branson RD. Influence of low tidal volumes on gas exchange in acute respiratory distress syndrome and the role of recruitment maneuvers. J Trauma 54(2): 320‐325, 2003.
 285. Lim CM, Jung H, Koh Y, Lee JS, Shim TS, Lee SD, Kim WS, Kim DS, Kim WD. Effect of alveolar recruitment maneuver in early acute respiratory distress syndrome according to antiderecruitment strategy, etiological category of diffuse lung injury, and body position of the patient. Crit Care Med 31(2): 411‐418, 2003.
 286. Oczenski W, Hormann C, Keller C, Lorenzl N, Kepka A, Schwarz S, Fitgerald RD. Recruitment maneuvers after a positive end‐expiratory pressure trial do not induce sustained effects in early adult respiratory distress syndrome. Anesthesiology 101(3): 620‐625, 2004.
 287. Allen GB, Suratt BT, Rinaldi L, Petty JM, Bates JHT. Choosing the frequency of deep inflation in mice: Balancing recruitment against ventilator‐induced lung injury. Am J Physiol Lung Cell Mol Physiol 291: L710‐L717, 2006.
 288. Fan E, Wilcox ME, Brower RG, Stewart TE, Mehta S, Lapinsky SE, Meade MO, Ferguson ND. Recruitment maneuvers for acute lung injury: A systematic review. Am J Respir Crit Care Med 78(11): 1156‐1163, 2008.
 289. Grasso S, Mascia L, Del Turco M, Malacarne P, Giunta F, Brouchard L, Slutsky AS, Ranieri VM. Effects of recruiting maneuvers in patients with acute respiratory distress syndrome ventilated with protective ventilatory strategy. Anesthesiol 96: 795‐802, 2002.
 290. Mutch WAC, Harms S, Graham MR, Kowalski SE, Girling LG, Lefevre GR. Biologically variable or naturally noisy mechanical ventilation recruits atelectactatic lung. Am J Respir Crit Care Med 162: 319‐23, 1996.
 291. Biker A, Graham MR, Walley KR, McManus BM, Girling LG, Walker E, Lefevre GR, Mutch WA. Improved arterial oxygenation with biologically variable or fractal ventilation using low tidal volumes in a porcine model of acute respiratory distress syndrome. Am J Respir Crit Care Med 165(4): 456‐462, 2002.
 292. Lefevre GR, Kowalski SE, Girling LG, Thiessen DB, Mutch WA. Improved arterial oxygenation after oleic acid lung injury in the pig using a computer‐controlled mechanical ventilator. Am J Respir Crit Care Med 154(5): 1567‐1572, 1996.
 293. Suki B, Alencar AM, Sugeer MK, Lutchen KR, Collins JJ, Andrade JS Jr, Ingenito EP, Zapperi S, Stanley HE. Life‐support system benefits from noise. Nature 393: 127‐128, 1998.
 294. Mutch WA, Eschun GM, Kowalski SE, Graham MR, Girling LG, Lefevre GR. Biologically variable ventilation prevents deterioration of gas exchange during prolonged anaesthesia. Br J Anaesth 84(2): 197‐203, 2000.
 295. Arnold SP, Mora R, Lutchen KR, Ingenito EP, Suki B. Variable tidal volume ventilation improves lung mechanics and gas exchange in a rodent model of acute lung injury. Am J Respir Crit Care Med 165(3): 366‐371, 2002.
 296. Boker Q, Graham MR, Walley KR, McManus BM, Girling LG, Walker E, Lefevre GR, Mutch WA. Improved arterial oxygenation with biologically variable or fractal ventilation using low tidal volumes in a procine model of acute respiratory distress syndrome. Am J Respir Crit Care Med 165(4): 456‐462, 2002.
 297. Bellardine CL, Hoffman AM, Tsai L, Ingenito EP, Arold SP, Lutchen KR, Suki B. Comparison of variable and conventional ventilation in a sheep saline lavage lung injury model. Crit Care Med 34(2): 439‐445, 2006.
 298. Greenfield LJ, Ebgert PA, Benson DW. Effect of positive pressure ventilation on surface tension properties of lung extracts. Anesthesiol 25: 312‐316, 1964.
 299. Faridy EE, Permutt S, Riley RL. Effect of ventilation on surface forces in excised dogs’ lungs. J Appl Physiol 21(5): 1453‐1462, 1966.
 300. McClenahan JB, Urtnowski A. Effect of ventilation on surfactant, and its turnover rate. J Appl Physiol 23: 215‐20, 1967.
 301. Shannon DC, Kazemi H, Merrill EW, Smith KA, Wong PS‐L. Restoration of volume‐pressure curves with a lecithin fog. J Appl Physiol 28(4): 470‐473, 1969.
 302. Forrest JB. The effect of hyperventilation on pulmonary surface activity. Brit J Anaesth 44: 313‐320, 1972.
 303. Wyszogrodski I, Kyei‐Aboagye K, Taeusch HW Jr, Avery ME. Surfactant inactivation by hyperventilation: Conservation by end‐expiratory pressure. J Appl Physiol 38(3): 461‐466, 1975.
 304. Verbrugge SJC, Bohm SH, Gommers D, Zimmerman LJI, Lachman B. Surfactant impairment after mechanical ventilation with large alveolar surface area changes and effects of positive end‐expiratory pressure. Br J Anaesth 80: 360‐364, 1998.
 305. Faridy EE. Effect of ventilation on movement of surfactant in airways. Respir Physiol 27: 323‐334, 1976.
 306. Oyarzun MJ, Clements JA. Ventilatory and cholinergic control of pulmonary surfactant in the rabbit. J Appl Physiol: Respir Environ Exercise Physiol 43: 39‐45, 1977.
 307. Klass D. Dibutyryl cGMP and hyperventilation promote rat lung phospholipid release. J Appl Physiol 47: 285‐289, 1979.
 308. Nicholas TE, Barr HA. Control of release of surfactant phospholipids in the isolated perfused rat lung. J Appl Physiol 51(1) :90‐98, 1981.
 309. Hildebran JN, Goerke J, Clements JA. Surfactant release in excised rat lung is stimulated by air inflation. J Appl Physiol: Respir Environ Exercise Physiol 51(4): 905‐910, 1981.
 310. Massaro GD, Massaro D. Morphologic evidence that large inflations of the lung stimulate secretion of surfactant. Am Rev Respir Dis 127: 235‐236, 1983.
 311. Oyarzun MJ, Iturriaga R, Donoso P, Dussaubat N, Santos M, Schiappacasse ME, Lathrop ME, CLarrain C, Zapata P. Factors affecting distribution of alveolar surfactant during resting ventilation. Am J Physiol 261(2 Pt 1): L210‐L17, 1991.
 312. Martinez F, Lewis J, Copland I, Engelberts D, Kavanagh BP, Post M, Schurch S, Belik J. Mechanical ventilation effect on surfactant content, function and lung compliance in the newborn rat. Ped Res 56: 19‐25, 2004.
 313. Clements JA, Tierney DF, Trahan HJ. Influence of kinetic behavior of surface films on pulmonary elasticity. Physiologist 6: 159, 1963.
 314. Gross NJ, Narine KR. Surfactant subtypes of mice: Metabolic relationships and conversion in vitro. J Appl Physiol 67(1): 414‐421, 1989.
 315. Veldhuizen RAW, Marcou J, Yao L, McCaig L, Ito Y, Lewis JF. Alveolar surfactant aggregate conversion in ventilated normal and injured rabbits. Am J Physiol270: L152‐L158, 1996.
 316. Ito Y, Veldhuizen RAW, Yao L‐J, McCaig LA, Bartlett AJ, Lewis JF. Ventilation strategies affect surfactant aggregate conversion in acute lung injury. Am J Respir Crit Care Med 155: 493‐499, 1997.
 317. Veldhuizen RA, Tremblay LN, Govindarajan A, van Rozendaal BA, Haagsman HP, Slutsky AS. Pulmonary surfactant is altered during mechanical ventilation of isolated rat lung. Crit Care Med 28(7): 2545‐2551, 2000.
 318. Veldhuizen RAW, Slutsky AS, Joseph M, McCaig L. Effects of mechanical ventilation of isolated mouse lungs on surfactant and inflammatory cytokines. Eur Respir J 17: 488‐494, 2001.
 319. Webb HH, Tierney DF. Experimental pulmonary edema due to intermittent positive pressure ventilation with high inflation pressures. Protection by positive end‐expiratory pressure. Am Rev Respir Dis 110: 556‐565, 1974.
 320. Staub NC, Nagano H, Pearce ML. Pulmonary edema in dogs, especially the sequence of fluid accumulation in lungs. J Appl Physiol 22: 227‐240, 1967.
 321. Bhattacharya J, Gropper MA, Staub NC. Interstitial fluid pressure gradient measured by micropuncture in excised dog lung. J Appl Physiol 56: 271‐277, 1984.
 322. Howell JBL, Permutt S, Proctor DF, Riley RL. Effect of inflation of the lung on different parts of pulmonary vascular bed. J Appl Physiol 16: 71‐76, 1961.
 323. Whayne T, Severinghaus J. Experimental hypoxic pulmonary edema in the rat. J Appl Physiol 25: 729‐732, 1968.
 324. Mead J, Takishima T, Leith D. Stress distribution in lungs: A model of pulmonary elasticity. J Appl Physiol 28: 596‐608, 1970.
 325. Rosenzweig DY, Hughes JMB, Glazier JB. Effects of transpulmonary and vascular pressures on pulmonary blood volume in isolated lungs. J Appl Physiol 28: 553‐560, 1970.
 326. Iliff LD. Extra‐alveolar vessels and oedema development in excised dog lungs. J Physiol. 207(2): 85P‐86P, 1970.
 327. Smith HC, Gould VF, Cheney FW, Butler J. Pathogenesis of hemodynamic pulmonary edema in excised dog lungs. J Appl Physiol 37: 904‐911, 1974.
 328. Demling RH, Staub NC, Edmunds LH. Effect of end‐expiratory airway pressure on accumulation of extravascular lung water. J Appl Physiol 38: 672‐679, 1975.
 329. Thornton D, Ponhold H, Butler J, Morgan T, Cheney FW. Effects of pattern of ventilation on pulmonary metabolism and mechanics. Anesthesiology 42(1): 4‐10, 1975.
 330. Bø G, Hauge A, Nicolaysen G. Alveolar pressure and lung volume as determinants of net transvascular fluid filtration. J Appl Physiol 42: 476‐482, 1977.
 331. Mitzner W, Robotham JL. Distribution of interstitial compliance and filtration coefficient in canine lung. Lymphology 12: 140‐148, 1979.
 332. Albert RK, Lakshminarayan S, Kirk W, Butler J. Lung inflation can cause pulmonary edema in zone I of in‐situ dog lungs. J Appl Physiol: Respir Environ Exercise Physiol 49: 815‐819, 1980.
 333. Albert RK, Lakshminarayan S, Charan NB, Kirk W, Butler J. Extra‐alveolar vessel contribution to hydrostatic pulmonary edema in in‐situ dog lungs. J Appl Physiol: Respir Environ Exercise Physiol 54: 1010‐1017, 1983.
 334. Albert RK, Kirk W, Pitts C, Butler J. Extra‐alveolar vessel fluid filtration coefficients in excised and in‐situ canine lobes. J Appl Physiol 59: 1555‐1559, 1985.
 335. Lamm WJE, Albert RK. Continuity of arterial and venous extra‐alveolar interstitium in excised rabbit lungs. J Appl Physiol 63: 634‐638, 1987.
 336. Dreyfuss D, Basset G, Soler P, Saumon G. Intermittent positive‐pressure hyperventilation with high inflation pressures produces pulmonary microvascular injury in rats. Am Rev Respir Dis 132: 880‐884, 1985.
 337. Dreyfuss D, Soler P, Basset G, Saumon G. High inflation pressure pulmonary edema. Respective effects of high airway pressure, high tidal volume and positive end‐expiratory pressure. Am Rev Respir Dis 137: 1159‐1164, 1988.
 338. Bowton DL, Kong DL. High tidal volume ventilation produces increased lung water in oleic acid‐injured rabbit lungs. Crit Care Med 17: 908‐911, 1989.
 339. Hernandez LA, Peevy KJ, Moise AA, Parker JC. Chest wall restriction limits high airway pressure‐induced lung injury in young rabbits. J Appl Physiol 66: 2364‐2368, 1989.
 340. Corbridge TC, Wood LDH, Crawford GP, Chudoba MJ, Yanos J, Sznajder JI. Adverse effects of large tidal volume and low PEEP on canine acid aspiration. Am Rev Respir Dis 142: 311‐315, 1990.
 341. Dreyfuss D, Soler P, Saumon G. Mechanical ventilation‐induced pulmonary edema. Interaction with previous lung alterations. Am J Respir Crit Care Med 151: 1568‐1575, 1995.
 342. Frank JA, Gutierrex JA, Jones KD, Allen L, Dobbs L, Matthay MA. Low tidal volume reduced epithelial and endothelial injury in acid‐injured rat lungs. Am J Respir Crit Care Med 165: 242‐249, 2002.
 343. Kwano T, Mori S, Cybulsky M, Burger R, Ballin A, Cutz E, Bryan AX. Effect of granulocyte depletion in a ventilated surfactant‐depleted lung. J Appl Physiol 62: 27‐33, 1987.
 344. Imal Y, Kawano T, Miyasaka K, Takata M, Imai T, Okuyama K. Inflammatory chemical mediators during conventional ventilation and during high frequency oscillatory ventilation. Am J Respir Crit Care Med 150: 1550‐1554, 1994.
 345. Tremblay L, Valenza F, Ribeiro SP, Li J, Slutsky AS. Injurious ventilatory strategies increase cytokines and c‐fos mRNA expression in an isolated rat lung model. J Clin Invest 99: 944‐952, 1997.
 346. Von Bethmann, AN, Brasch F, Nusing R, Vogt K, Volk HD, Muller K‐M, Wendel A, Uhlig S. Hyperventilation induces release of cytokines from perfused mouse lung. Am J Respir Crit Care Med 157: 263‐272, 1998.
 347. Chiumello D, Pristine G, Slutsky AS. Mechanical ventilation affects local and systemic cytokines in an animal model of acute respiratory distress syndrome. Am J Respir Crit Care Med 160: 109‐116, 1999.
 348. Ranieri VM, Suter PM, Tortorella, C, De Tullio R, Dayer JM, Brienza A, Bruno F, Slutsky AS. Effect of mechanical ventilation on inflammatory mediators in patients with acute respiratory distress syndrome. A randomized controlled trial. J Am Med Assoc 282: 54‐61, 1999.
 349. Ricard JD, Dreyfuss D, Saumon G. Production of inflammatory cytokines in ventilator‐induced lung injury: A reappraisal. Am J Respir Crit Care Med 163: 1176‐1180, 2001.
 350. Wilson MR, Choudhury S, Takata M. Pulmonary inflammation induced by high‐stretch ventilation is mediated by tumor necrosis factor signaling in mice. Am J Physiol Cell Mol Physiol 288: L599‐L607, 2005.
 351. Kolobow T, Moretti MP, Fumagalli R, Mascheroni D, Prato P, Chen V, Joris M. Severe impairment in lung function induced by high peak airway pressure during mechanical ventilation. Am Rev Respir Dis 135: 312‐315, 1987.
 352. Carlton DP, Cummings JJ, Scheerer RG, Poulain FR, Bland RD. Lung overexpansion increases pulmonary microvascular protein permeability in young lambs. J Appl Physiol 69: 577‐583, 1990.
 353. Tsuno K, Prato P, Kolobow T. Acute lung injury from mechanical ventilation at moderately high airway pressures. J Appl Physiol 69(3): 956‐961, 1990.
 354. Dreyfuss D, Saumon G. Role of tidal volume, FRC, and end‐inspiratory volume in the development of pulmonary edema following mechanical ventilation. Am Rev Respir Dis. 148(5): 1194‐1203, 1993.
 355. Egan EA, Nelson RM, Oliver RE. Lung inflation and alveolar permeability to non‐electrolytes in the adult sheep in vivo. J Physiol 260: 409‐424, 1976.
 356. Kim K‐J, Crandall ED. Effects of lung inflation on alveolar epithelial solute and water transport properties. J Appl Physiol 52(6): 1498‐1505, 1982.
 357. Egan EA. Lung inflation, lung solute permeability and alveolar edema. J Appl Physiol 53: 121‐125, 1982.
 358. Parker JC, Townsley MI, Rippe B, Tayler AE, Thigpen J. Increased microvascular permeability in dog lungs due to high airway pressure. J Appl Physiol 57: 1809‐1816, 1984.
 359. Fu Z, Costello ML, Tsukimoto K, Prediletto R, Elliott AR, Mathier‐Costello O, West JB. High lung volume increases stress failure in pulmonary capillaries. J Appl Physiol 73(1): 123‐133, 1992.
 360. Dreyfuss D, Soler P, Saumon G. Spontaneous resolution of pulmonary edema caused by short periods of cyclic overinflation. J Appl Physiol 72(6): 2081‐2089, 1992.
 361. McCulloch PR, Forkert PG, Froese AB. Lung volume maintenance prevents lung injury during high frequency oscillatory ventilation in surfactant‐deficient rabbits. Am Rev Respir Dis 137: 1185‐1192, 1988.
 362. Fort P, Farmer C, Westerman J, Johannigman J, Beninati W, Dolan S, Derdak S. High‐frequency oxcillatory ventilation for adults respiratory distress syndrome—a pilot study. Crit Care Med 25(6): 937‐947, 1997.
 363. Mehta S, Lapinsky SE, Hallett DC, Merker D, Groll RJ, Cooper AB, MacDonald RJ, Stewart TE. Prospective trial of high‐frequency oscillation in adults with acute respiratory distress syndrome. Crit Care Med 29(7): 1360‐1369, 2001.
 364. Derdak S, Mehta S, Stewart TE, Smith T, Rogers M, Buchman TG, Carlin B, Lowson S, Granton J, and the Multicenter Oscillatory Ventilation for Acute Respiratory Distress Syndrome Trial (MOAT) Study Investigators. High‐frequency oscillatory ventilation for acute respiratory distress syndrome in adults. A randomized, controlled trial. Am J Respir Crit Care Med 166: 801‐808, 2002.
 365. Bollen CW, van Well GTH, Sherry T, Reale RJ, Shah S, Findlay G, Monchi M, Chiche J‐D, Weiler N, Uiterwaal CSPM, van Vaught AJ. High frequency oscillataory ventilation compared with conventional mechanical ventilation in adult respiratory distress syndrome: A randomized controlled trial. Crit Care 9: R430‐R439, 2005.
 366. Ennema JJ, Reijngoud D‐J, Egberts, IJ, Mook PH, Wildevuur ChRH. High‐frequency oscillation affects surfactant phospholipid metabolism in rabbits. Respir Physiol 58: 29‐39, 1984.
 367. Muscedere JG, Mullen JB, Gan K, Slutsky AS. Tidal ventilation at low airway pressures can augment lung injury. Am J Respir Crit Care Med 149(5): 1327‐1334, 1994.
 368. Gattinoni L, Pesenti A, Avalli L, Rossi F, Bombino M. Pressure‐volume curve of total respiratory system in acute respiratory failure: CT scan study. Am Rev Respir Dis 136: 730‐736, 1987.
 369. Hickling KG, Henderson SJ, Jackson R. Low mortality associated with low volume pressure limited ventilation with permissive hypercapnia in severe adult respiratory distress syndrome. Intensive Care Med 16(6): 372‐377, 1990.
 370. Hickling KG, Walsh J, Henderson S, Jackson R. Low mortality rate in adult respiratory distress syndrome using low‐volume, pressure‐limited ventilation with permissive hypercapnia: A prospective study. Crit Care Med 22(10): 1568‐1567, 1994.
 371. Brouchard L, Roudot‐Thoraval F, Roupie E, Delclaux C, Chastre J, Fernandez‐Mondejar E, Clementi E, Mancebo J, Factor P, Matamis D, Ranieri M, Blanch L, Rodi G, Mentec H, Dreyfuss D, Ferrer M, Brun‐Buisson C, Tobin M, Lemaire F. Tidal volume reduction for prevention of ventilator‐induced lung injury in acute respiratory distress syndrome. The Multicenter Trial Group on Tidal Volume reduction in ARDS. Am J Respir Crit Care Med 158(6): 1831‐1838, 1998.
 372. Brower RG, Shanholtz CB, Fessler HE, Shade DM, White P Jr, Wiener CM, Teeter JG, Doodo JM, Almog Y, Piantadosi S. Prospective randomized controlled trial comparing traditional versus reduced tidal volume ventilation in acute respiratory distress syndrome patients. Crit Care Med 27: 1492‐1498, 1999.
 373. Brower RG, Laniken PN, MacIntyre N, Matthay MA, Morris A, Ancukiewicz M, Schoenfeld D, Thompson BT; ARDS Clinical Trials Network. Higher versus lower positive end‐expiratory pressures in patients with the acute respiratory distress syndrome. N Engl J Med 351(4): 327‐336, 2004.
 374. National Heart Lung and Blood Institute ARDS Clinical Trials Network. Higher versus lower positive end‐expiratory pressures in patients with the acute respiratory distress syndrome. N Engl J Med 351: 327‐36, 2004.
 375. Meade MO, Cook DJ, Guyatt GH, Slutsky AS, Arabi YM, Cooper DJ, Davies AR, Hand LE, Zhou Q, Thabane L, Austin P, Lapinsky S, Baxter A, Russell J, Skrobik Y, Ronco JJ, Stewart TE; for the Lung Open Ventilation Study Investigators. Ventilation strategy using low tidal volumes, recruitment maneuvers, and high positive end‐expiratory pressure for acute lung injury and acute respiratory distress syndrome. J Am Med Assoc 299(6): 637‐645, 2008.
 376. Amato MB, Barbas CS, Medeiros DM, Magaldi RB, Schettino GP, Lorenzi‐Filho G, Kairalla RA, Deheinzelin D, Munoz C, Oliveira R, Takagaki TY, Carvalho CR. Effect of a protective‐ventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med. 338(6): 347‐354, 1998.
 377. Stewart TE, Meade MO, Cook DJ, Granton JT, Hodder RV, Lapinsky SE, Mazer CD, McLean RF, Rogovein TS, Schouten BD, Todd TR, Slutsky AS. Evaluation of a ventilation strategy to prevent barotraumas in patients at high risk for acute respiratory distress syndrome. N Engl J Med 338: 355‐361, 1998.
 378. Mercat A, Richard J‐CM, Vielle B, Jaber S, Osman D, Diehl J‐L, Lefrant J‐Y, Prat G, Richecoeur J, Nieszkowska A, Gervais C, Baudot J, Bouadma L, Brouchard L; for the Expiratory Pressure Study Group. Positive end‐expiratory pressure stetting in adults with acute lung injury and acute respiratory distress syndrome. J Am Med Assoc 299(6): 646‐655, 2008.
 379. Tobin MJ. Culmination of era in research on the acute respiratory distress syndrome. N Engl J Med 42: 1360‐1361, 2000.
 380. Weigelt JA, Mitchell RA, Snyder WH. Early positive end‐expiratory pressure in the adult respiratory distress syndrome. Arch Surg 114: 497‐501, 1979.
 381. Pepe PE, Hudson LD, Carrico CJ. Early application of positive end‐expiratory pressure in patients at risk for the adult respiratory distress syndrome. N Engl J Med 311(5): 281‐286, 1984.
 382. Richard J‐C, Maggiore SM, Jonson B, Mancebo J, Lemaire F, Brochard L. Influence of tidal volume of alveolar recruitment. Respective role of PEEP and a recruitment maneuver. Am J Respir Crit Care Med 163: 1609‐1613, 2001.
 383. Pelosi P, Cereda P, Foti G, Giacomini M, Pesenti A. Alterations of lung and chest wall mechanics in patients with acute lung injury: Effects of positive end‐expiratory pressure. Am J Respir Crit Care Med 152: 531‐537, 1995.
 384. Ranieri VM, Brienza N, Santostasi S, Puntillo F, Mascia L, Vitale N, Guiuliani R, Memeo V, Bruno F, Fiore T, Brienza A, Slutsky AS. Impairment of lung and chest wall mechanics in patients with acute respiratory distress syndrome. Am J Respir Crit Care Med 58: 1082‐1091, 1997.
 385. Talmor D, Sarge T, O'Donnell CR, Ritz R, Malhotra A, Lisbon A, Loring SH. Esophageal and transpulmonary pressures in acute respiratory failure. Crit Care Med 34(5): 1389‐1394, 2006.
 386. Talmor D, Sarge T, Malhotra A, O'Donnell CR, Ritz R, Lisbon A, Novack V, Loring SH. Mechanical ventilation guided by esophageal pressure in acute lung injury. N Engl J Med 359: 2095‐2104, 2008.
 387. Eichacker PQ, Gerstenberger EP, Banks SM, Cui Z, Natanson C. Meta‐analysis of acute lung injury and acute respiratory distress syndrome trials testing low tidal volumes. Am J Respir Crit Care Med 166: 1510‐1514, 2002.
 388. Hager DN, Krishnan JA, Hayden DL, Brower RG; for the ARDS Clinical Trials Network. Tidal volume reduction in patients with acute lung injury when plateau pressures are not high. Am J Respir Crit Care Med 172: 1241‐1245, 2005.
 389. Grasso S, Stripoli T, Sacchi M, Trerotoli P, Staffieri F, Franchini D, De Monte V, Valentini V, Publiese P, Crovace A, Driessen B, Fiore T. Inhomogeneity of lung parenchyma during the open lung strategy: A computed tomography scan study. Am J Respir Crit Care Med 180(5): 415‐423, 2009.
 390. Marshall RP, Bellingan G, Webb Z, Puddicombe A, Goldsack N, McAnulty RJ, Laurent GJ. Fibroproliferation occurs early in the acute respiratory distress syndrome and impacts on outcome. Am J Respir Crit Care Med 162: 1783‐1788, 2000.
 391. Nash G, Blennerhassett JB, Pontoppidan H. Pulmonary lesions associated with oxygen therapy and artificial ventilation. New Engl J Med 276(7): 368‐374, 1967.
 392. Musch G, Bellani G, Melo MFV, Harris RS, Winkler T, Schroeder T, Venegas JG. Relation between shunt, aeration, and perfusion in experimental acute lung injury. Am J Respir Crit Care Med 177: 292‐300, 2008.

Contact Editor

Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite

Richard K. Albert, Alan Jobe. Gas Exchange in the Respiratory Distress Syndromes. Compr Physiol 2012, 2: 1585-1617. doi: 10.1002/cphy.c090019