High Flow Oxygen Therapy at Two Initial Flow Settings versus Conventional Oxygen Therapy in Cardiac Surgery Patients with Postextubation Hypoxemia: A Single-Center, Unblinded, Randomized, Controlled Trial.

In cardiac surgery patients with pre-extubation PaO2/inspired oxygen fraction (FiO2) < 200 mmHg, the possible benefits and optimal level of high-flow nasal cannula (HFNC) support are still unclear; therefore, we compared HFNC support with an initial gas flow of 60 or 40 L/min and conventional oxygen therapy. Ninety nine patients were randomly allocated (respective ratio: 1:1:1) to I = intervention group 1 (HFNC initial flow = 60 L/min, FiO2 = 0.6), intervention group 2 (HFNC initial flow = 40 L/min, FiO2 = 0.6), or control group (Venturi mask, FiO2 = 0.6). The primary outcome was occurrence of treatment failure. The baseline characteristics were similar. The hazard for treatment failure was lower in intervention group 1 vs. control (hazard ratio (HR): 0.11, 95% CI: 0.03-0.34) and intervention group 2 vs. control (HR: 0.30, 95% CI: 0.12-0.77). During follow-up, the probability of peripheral oxygen saturation (SpO2) > 92% and respiratory rate within 12-20 breaths/min was 2.4-3.9 times higher in intervention group 1 vs. the other 2 groups. There was no difference in PaO2/FiO2, patient comfort, intensive care unit or hospital stay, or clinical course complications or adverse events. In hypoxemic cardiac surgery patients, postextubation HFNC with an initial gas flow of 60 or 40 L/min resulted in less frequent treatment failure vs. conventional therapy. The results in terms of SpO2/respiratory rate targets favored an initial HFNC flow of 60 L/min.

Club cells form lung adenocarcinomas and maintain the alveoli of adult mice.

Lung cancer and chronic lung diseases impose major disease burdens worldwide and are caused by inhaled noxious agents including tobacco smoke. The cellular origins of environmental-induced lung tumors and of the dysfunctional airway and alveolar epithelial turnover observed with chronic lung diseases are unknown. To address this, we combined mouse models of genetic labeling and ablation of airway (club) and alveolar cells with exposure to environmental noxious and carcinogenic agents. Club cells are shown to survive KRAS mutations and to form lung tumors after tobacco carcinogen exposure. Increasing numbers of club cells are found in the alveoli with aging and after lung injury, but go undetected since they express alveolar proteins. Ablation of club cells prevents chemical lung tumors and causes alveolar destruction in adult mice. Hence club cells are important in alveolar maintenance and carcinogenesis and may be a therapeutic target against premalignancy and chronic lung disease.

Inhibition of HMGCoA reductase by simvastatin protects mice from injurious mechanical ventilation.

BACKGROUND: Mortality from severe acute respiratory distress syndrome exceeds 40% and there is no available pharmacologic treatment. Mechanical ventilation contributes to lung dysfunction and mortality by causing ventilator-induced lung injury. We explored the utility of simvastatin in a mouse model of severe ventilator-induced lung injury. METHODS: Male C57BL6 mice (n = 7/group) were pretreated with simvastatin or saline and received protective (8 mL/kg) or injurious (25 mL/kg) ventilation for four hours. Three doses of simvastatin (20 mg/kg) or saline were injected intraperitoneally on days -2, -1 and 0 of the experiment. Lung mechanics, (respiratory system elastance, tissue damping and airway resistance), were evaluated by forced oscillation technique, while respiratory system compliance was measured with quasi-static pressure-volume curves. A pathologist blinded to treatment allocation scored hematoxylin-eosin-stained lung sections for the presence of lung injury. Pulmonary endothelial dysfunction was ascertained by bronchoalveolar lavage protein content and lung tissue expression of endothelial junctional protein Vascular Endothelial cadherin by immunoblotting. To assess the inflammatory response in the lung, we determined bronchoalveolar lavage fluid total cell content and neutrophil fraction by microscopy and staining in addition to Matrix-Metalloprotease-9 by ELISA. For the systemic response, we obtained plasma levels of Tumor Necrosis Factor-α, Interleukin-6 and Matrix-Metalloprotease-9 by ELISA. Statistical hypothesis testing was undertaken using one-way analysis of variance and Tukey's post hoc tests. RESULTS: Ventilation with high tidal volume (HVt) resulted in significantly increased lung elastance by 3-fold and decreased lung compliance by 45% compared to low tidal volume (LVt) but simvastatin abrogated lung mechanical alterations of HVt. Histologic lung injury score increased four-fold by HVt but not in simvastatin-pretreated mice. Lavage pleocytosis and neutrophilia were induced by HVt but were significantly attenuated by simvastatin. Microvascular protein permeability increase 20-fold by injurious ventilation but only 4-fold with simvastatin. There was a 3-fold increase in plasma Tumor Necrosis Factor-α, a 7-fold increase in plasma Interleukin-6 and a 20-fold increase in lavage fluid Matrix-Metalloprotease-9 by HVt but simvastatin reduced these levels to control. Lung tissue vascular endothelial cadherin expression was significantly reduced by injurious ventilation but remained preserved by simvastatin. CONCLUSION: High-dose simvastatin prevents experimental hyperinflation lung injury by angioprotective and anti-inflammatory effects.

The effect of high-frequency oscillatory ventilation combined with tracheal gas insufflation on extravascular lung water in patients with acute respiratory distress syndrome: a randomized, crossover, physiologic study.

PURPOSE: High-frequency oscillation combined with tracheal gas insufflation (HFO-TGI) improves oxygenation in patients with acute respiratory distress syndrome (ARDS). There are limited physiologic data regarding the effects of HFO-TGI on hemodynamics and pulmonary edema during ARDS. The aim of this study was to investigate the effect of HFO-TGI on extravascular lung water (EVLW). MATERIALS AND METHODS: We conducted a prospective, randomized, crossover study. Consecutive eligible patients with ARDS received sessions of conventional mechanical ventilation with recruitment maneuvers (RMs), followed by HFO-TGI with RMs, or vice versa. Each ventilatory technique was administered for 8 hours. The order of administration was randomly assigned. Arterial/central venous blood gas analysis and measurement of hemodynamic parameters and EVLW were performed at baseline and after each 8-hour period using the single-indicator thermodilution technique. RESULTS: Twelve patients received 32 sessions. Pao2/fraction of inspired oxygen and respiratory system compliance were higher (P<.001 for both), whereas extravascular lung water index to predicted body weight and oxygenation index were lower (P=.021 and .029, respectively) in HFO-TGI compared with conventional mechanical ventilation. There was a significant correlation between Pao2/fraction of inspired oxygen improvement and extravascular lung water index drop during HFO-TGI (Rs=-0.452, P=.009). CONCLUSIONS: High-frequency oscillation combined with tracheal gas insufflation improves gas exchange and lung mechanics in ARDS and potentially attenuates EVLW accumulation.

High-frequency oscillation and tracheal gas insufflation in patients with severe acute respiratory distress syndrome and traumatic brain injury: an interventional physiological study.

INTRODUCTION: In acute respiratory distress syndrome (ARDS), combined high-frequency oscillation (HFO) and tracheal gas insufflation (TGI) improves gas exchange compared with conventional mechanical ventilation (CMV). We evaluated the effect of HFO-TGI on PaO2/fractional inspired O2 (FiO2) and PaCO2, systemic hemodynamics, intracranial pressure (ICP), and cerebral perfusion pressure (CPP) in patients with traumatic brain injury (TBI) and concurrent severe ARDS. METHODS: We studied 13 TBI/ARDS patients requiring anesthesia, hyperosmolar therapy, and ventilation with moderate-to-high CMV-tidal volumes for ICP control. Patients had PaO2/FiO2 <100 mm Hg at end-expiratory pressure ≥10 cm H2O. Patients received consecutive, daily, 12-hour rescue sessions of HFO-TGI interspersed with 12-hour periods of CMV. HFO-TGI was discontinued when the post-HFO-TGI PaO2/FiO2 exceeded 100 mm Hg for >12 hours. Arterial/central-venous blood gases, hemodynamics, and ICP were recorded before, during (every 4 hours), and after HFO-TGI, and were analyzed by using repeated measures analysis of variance. Respiratory mechanics were assessed before and after HFO-TGI. RESULTS: Each patient received three to four HFO-TGI sessions (total sessions, n = 43). Pre-HFO-TGI PaO2/FiO2 (mean ± standard deviation (SD): 83.2 ± 15.5 mm Hg) increased on average by approximately 130% to163% during HFO-TGI (P < 0.01) and remained improved by approximately 73% after HFO-TGI (P < 0.01). Pre-HFO-TGI CMV plateau pressure (30.4 ± 4.5 cm H2O) and respiratory compliance (37.8 ± 9.2 ml/cm H2O), respectively, improved on average by approximately 7.5% and 20% after HFO-TGI (P < 0.01 for both). During HFO-TGI, systemic hemodynamics remained unchanged. Transient improvements were observed after 4 hours of HFO-TGI versus pre-HFO-TGI CMV in PaCO2 (37.7 ± 9.9 versus 41.2 ± 10.8 mm Hg; P < 0.01), ICP (17.2 ± 5.4 versus 19.7 ± 5.9 mm Hg; P < 0.05), and CPP (77.2 ± 14.6 versus 71.9 ± 14.8 mm Hg; P < 0.05). CONCLUSIONS: In TBI/ARDS patients, HFO-TGI may improve oxygenation and respiratory mechanics, without adversely affecting PaCO2, hemodynamics, or ICP. These findings support the use of HFO-TGI as a rescue ventilatory strategy in patients with severe TBI and imminent oxygenation failure due to severe ARDS.

Opposing effects of bortezomib-induced nuclear factor-κB inhibition on chemical lung carcinogenesis.

Since recent evidence indicates a requirement for epithelial nuclear factor (NF)-κB signaling in lung tumorigenesis, we investigated the impact of the NF-κB inhibitor bortezomib on lung tumor promotion and growth. We used an experimental model in which wild-type mice or mice expressing an NF-κB reporter received intraperitoneal urethane (1 g/kg) followed by twice weekly bortezomib (1 mg/kg) during distinct periods of tumor initiation/progression. Mice were serially assessed for lung NF-κB activation, inflammation and carcinogenesis. Short-term proteasome inhibition with bortezomib did not impact tumor formation but retarded the growth of established lung tumors in mice via effects on cell proliferation. In contrast, long-term treatment with bortezomib resulted in significantly increased lung tumor number and size. This tumor-promoting effect of prolonged bortezomib treatment was associated with perpetuation of urethane-induced inflammation and chronic upregulation of interleukin-1ß and proinflammatory C-X-C motif chemokine ligands (CXCL) 1 and 2 in the lungs. In addition to airway epithelium, bortezomib inhibited NF-κB in pulmonary macrophages in vivo, presenting a possible mechanism of tumor amplification. In this regard, RAW264.7 macrophages exposed to bortezomib showed increased expression of interleukin-1ß, CXCL1 and CXCL2. In conclusion, although short-term bortezomib may exert some beneficial effects, prolonged NF-κB inhibition accelerates chemical lung carcinogenesis by perpetuating carcinogen-induced inflammation. Inhibition of NF-κB in pulmonary macrophages appears to play an important role in this adverse process.

Scanographic comparison of high frequency oscillation with versus without tracheal gas insufflation in acute respiratory distress syndrome.

PURPOSE: In acute respiratory distress syndrome (ARDS), combined high frequency oscillation (HFO) and tracheal gas insufflation (TGI) improves oxygenation versus standard HFO, likely through TGI-induced lung recruitment. Experimental data suggest that steady flows such as TGI favor the filling of the lower (i.e., subcarinal) lung. We used whole-lung computerized tomography (CT) to determine whether HFO-TGI versus HFO improves the recruitment of the lower lung, and especially of its dependent region, where loss of aeration is maximized in ARDS. METHODS: We enrolled 15 patients who had ARDS for 96 h or less, and pulmonary infiltrates in at least three chest X-ray quadrants. Patients were subjected to whole-lung CT after lung-protective conventional mechanical ventilation (CMV) and after 45 min of HFO and 45 min of HFO-TGI. HFO/HFO-TGI were employed in random order. CT scans were obtained at a continuous positive airways pressure equal to the mean tracheal pressure (P (tr)) of CMV. During HFO/HFO-TGI, mean airway pressure was titrated to the CMV P (tr) level. Gas exchange and intra-arterial pressure/heart rate were determined for each ventilatory technique. RESULTS: Regarding total lung parenchyma, HFO-TGI versus HFO and CMV resulted in a lower percentage of nonaerated lung tissue (mean ± SD, 51.4 ± 5.1% vs. 60.0 ± 2.5%, and 62.1 ± 9.0%, respectively; P≤0.04); this was due to HFO-TGI-induced recruitment of nonaerated tissue in the dependent and nondependent lower lung. HFO-TGI increased normally aerated tissue versus CMV (P=0.04) and poorly aerated tissue versus HFO and CMV (P≤0.04), and improved oxygenation versus HFO and CMV (P≤0.04). CONCLUSIONS: HFO-TGI improves oxygenation versus HFO and CMV through the recruitment of previously nonaerated lower lung units.

Neutralization of tumor necrosis factor bioactivity ameliorates urethane-induced pulmonary oncogenesis in mice.

Tumor necrosis factor (TNF) has been implicated in inflammation-associated tumor progression. Although multiple reports identified a role for TNF signaling in established cancers, few studies have assessed the impact of TNF blockade on early tumor formation promotion. We aimed at exploring the effects of TNF neutralization in a preclinical mouse model of lung carcinogenesis. For this, Balb/c mice (n = 42) received four weekly intraperitoneal urethane injections (1 g/kg) and twice-weekly intraperitoneal soluble TNF receptor (etanercept; 10 mg/kg) administered during tumor initiation/promotion, tumor progression, or continuously (months 1, 6, and 1-8 after urethane start, respectively). Lung oncogenesis was assessed after 8 months. In separate short-term studies, Balb/c mice (n = 21) received a single control or urethane injection followed by twice-weekly intraperitoneal control or sTNFR:Fc injections. Lung inflammation was assessed after 1 week. We found that sTNFR:Fc treatment during tumor initiation/promotion resulted in a significant reduction of tumor number but not dimensions. However, sTNFR:Fc administered during tumor progression did not impact tumor multiplicity but significantly decreased tumor diameter. Continued sTNFR:Fc administration was effective in halting both respiratory tumor formation and progression in response to urethane. This favorable impact was associated with impaired cellular proliferation and new vessel formation in lung tumors. In addition, TNF neutralization altered the lung inflammatory response to urethane, evidenced by reductions in TNF and macrophage and increases in interferon γ and interleukin 10 content of the air spaces. sTNFR:Fc treatment of RAW264.7 macrophages downregulated TNF and enhanced interferon γ and interleukin 10 expression. In conclusion, TNF neutralization is effective against urethane-induced lung oncogenesis in mice and could present a lung chemoprevention strategy worth testing clinically.

Allergic inflammation does not impact chemical-induced carcinogenesis in the lungs of mice.

BACKGROUND: Although the relationship between allergic inflammation and lung carcinogenesis is not clearly defined, several reports suggest an increased incidence of lung cancer in patients with asthma. We aimed at determining the functional impact of allergic inflammation on chemical carcinogenesis in the lungs of mice. METHODS: Balb/c mice received single-dose urethane (1 g/kg at day 0) and two-stage ovalbumin during tumor initiation (sensitization: days -14 and 0; challenge: daily at days 6-12), tumor progression (sensitization: days 70 and 84; challenge: daily at days 90-96), or chronically (sensitization: days -14 and 0; challenge: daily at days 6-12 and thrice weekly thereafter). In addition, interleukin (IL)-5 deficient and wild-type C57BL/6 mice received ten weekly urethane injections. All mice were sacrificed after four months. Primary end-points were number, size, and histology of lung tumors. Secondary end-points were inflammatory cells and mediators in the airspace compartment. RESULTS: Ovalbumin provoked acute allergic inflammation and chronic remodeling of murine airways, evident by airspace eosinophilia, IL-5 up-regulation, and airspace enlargement. Urethane resulted in formation of atypical alveolar hyperplasias, adenomas, and adenocarcinomas in mouse lungs. Ovalbumin-induced allergic inflammation during tumor initiation, progression, or continuously did not impact the number, size, or histologic distribution of urethane-induced pulmonary neoplastic lesions. In addition, genetic deficiency in IL-5 had no effect on urethane-induced lung tumorigenesis. CONCLUSIONS: Allergic inflammation does not impact chemical-induced carcinogenesis of the airways. These findings suggest that not all types of airway inflammation influence lung carcinogenesis and cast doubt on the idea of a mechanistic link between asthma and lung cancer.

Comparison of high-frequency oscillation and tracheal gas insufflation versus standard high-frequency oscillation at two levels of tracheal pressure.

PURPOSE: In acute respiratory distress syndrome (ARDS), combined high-frequency oscillation (HFO) and tracheal gas insufflation (TGI) may improve oxygenation through a TGI-induced increase in mean tracheal pressure (P(tr)). We compared standard HFO and HFO-TGI matched for P(tr), in order to determine whether TGI affects gas exchange independently from P (tr). METHODS: We conducted a prospective, randomized, crossover, physiological study in a 37-bed intensive care unit. Twenty-two patients with early acute lung injury (ALI) or ARDS were enrolled. On day 1, patients were ventilated with HFO, without (60 min) and combined with TGI (60 min) in random order. HFO/HFO-TGI sessions were repeated in inverse order within 7 h. HFO/HFO-TGI mean airway pressure (P(aw)) was titrated to a P(tr) that was either equal to (low P(aw)) or 3 cmH(2)O higher than (high P(aw)) the P(tr) of the preceding conventional mechanical ventilation. On day 2, the protocol was repeated at the alternative P(tr) level relative to day 1. RESULTS: Gas exchange and hemodynamics were determined before, during, and after HFO/HFO-TGI sessions. HFO-TGI-high P(aw) versus HFO-high P(aw) resulted in significantly higher PaO(2)/inspired O(2) fraction (FiO(2)) [mean +/- standard error of the mean (SEM): 281.6 +/- 15.1 versus 199.0 +/- 15.0 mmHg; mean increase: 42%; P < 0.001]. HFO-TGI-low P(aw), versus HFO-low P(aw), resulted in significantly higher PaO(2)/FiO(2) (222.8 +/- 14.6 versus 141.3 +/- 8.7 mmHg; mean increase: 58%; P < 0.001). PaCO(2) was significantly lower during HFO-TGI-high P(aw) versus HFO-high P(aw) (45.3 +/- 1.6 versus 53.7 +/- 1.9 mmHg; mean decrease: 16%; P = 0.037). CONCLUSIONS: At the same P(tr) level, HFO-TGI results in superior gas exchange compared with HFO.

Acute effects of combined high-frequency oscillation and tracheal gas insufflation in severe acute respiratory distress syndrome.

OBJECTIVE: In acute respiratory distress syndrome (ARDS), high-frequency oscillation (HFO) improves oxygenation relative to conventional mechanical ventilation (CMV). Alveolar ventilation is improved by adding tracheal gas insufflation (TGI) to CMV. We hypothesized that combined HFO and TGI (HFO-TGI) might result in improved gas exchange relative to both standard HFO and CMV according to the ARDS Network protocol. DESIGN: Prospective, randomized, crossover study. SETTING: A 30-bed university intensive care unit. PATIENTS: A total of 14 patients with early (<72 hrs in duration), severe (PaO2/FiO2 of <150 mm Hg and prerecruitment oxygenation index of 22.8 +/- 1.9 [mean +/- SEM]), primary ARDS. INTERVENTIONS: Patients were ventilated with HFO without (60 mins) and combined with TGI (6.1 +/- 0.1 L/min, 60 mins) in random order. HFO sessions were repeated in inverse order within 24 hrs. HFO sessions were preceded and followed by ARDS Network CMV. Four recruitment maneuvers were performed during the study period. During HFO sessions, mean airway pressure was set at 1 cm H2O above the point of maximal curvature of the respiratory system expiratory pressure-volume curve. MEASUREMENTS AND MAIN RESULTS: Gas exchange and hemodynamics were determined before, during, and after HFO sessions. HFO-TGI improved PaO2/FiO2 relative to HFO and CMV (174.5 +/- 10.4 vs. 136.0 +/- 10.0 and 105.0 +/- 3.7 mm Hg, respectively, p < .05 for both) and oxygenation index relative to HFO (17.1 +/- 1.3 vs. 22.3 +/- 1.7, respectively p < .05). PaO2/FiO2 returned to baseline within 3 hrs after HFO. During HFO-TGI, shunt fraction and mixed venous oxygen saturation improved relative to CMV (0.36 +/- 0.01 vs. 0.45 +/- 0.01 and 77.8% +/- 1.2% vs. 71.8% +/- 1.3%, respectively, p < .05 for both). PaCO2 and hemodynamics were unaffected by HFO sessions. Respiratory mechanics remained unchanged throughout the study period. CONCLUSIONS: In early onset, primary, severe ARDS, short-term HFO-TGI improves oxygenation relative to standard HFO and ARDS Network CMV.

An evaluation of McCoy balloon laryngoscopy in patients with moderate-to-major endotracheal intubation difficulty.

UNLABELLED: We hypothesized that combined McCoy-balloon laryngoscopy may facilitate airway management relative to McCoy or balloon laryngoscopy. In 10 anesthetized/paralyzed patients with prior intubation difficulty scale scores of >5, McCoy-balloon laryngoscopy versus conventional/balloon/McCoy laryngoscopies resulted in greater laryngeal aperture exposure (2.3 +/- 0.6 versus 0.6 +/- 0.2/1.4 +/- 0.4/1.5 +/- 0.6 cm2, respectively), lower intubation difficulty scale score (0.00 (0.00-0.00) versus 6.00 (6.00-8.25)/1.50(0.00-4.00)/2.00(0.75-5.00), respectively, median [interquartile range]), and 9%-74% shorter time to intubation confirmation (P < 0.05-0.001 for all). Balloon and McCoy laryngoscopies improved laryngoscopic/intubating conditions relative to conventional laryngoscopy. In patients with moderate-to-major conventional airway management difficulty, McCoy-balloon laryngoscopy further improves laryngoscopic/intubating conditions. IMPLICATIONS: This study shows that, in patients with moderate-to-major conventional airway management difficulty, combined McCoy-balloon laryngoscopy results in improved laryngoscopic/intubating conditions when compared with the conventional, McCoy, and balloon laryngoscopic techniques. McCoy-balloon laryngoscopy combines the merits of McCoy and balloon laryngoscopy and can be recommended for patients with moderate-to-major intubation difficulty.

Sepsis severity is the major determinant of circulating thrombopoietin levels in septic patients.

OBJECTIVE: To measure serum thrombopoietin levels and to investigate their relationship with platelet counts and other potential determinants in septic patients. DESIGN: Prospective study comparing septic patients and healthy volunteers. SETTING: General intensive care units in two tertiary university hospitals. PATIENTS: A total of 152 consecutive septic patients (69 with sepsis, 24 with severe sepsis, and 59 with septic shock). Twenty-two healthy volunteers served as control subjects. Sepsis severity was determined by grading septic patients in those having sepsis, severe sepsis, and septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: After blood sampling, platelet counts, and serum thrombopoietin, interleukin-6 and C-reactive protein levels were measured. Platelets did not decrease in patients with sepsis, but they significantly decreased in patients with severe sepsis and septic shock (p <.01 vs. controls and sepsis). In contrast, thrombopoietin levels (median [range]) increased in patients with sepsis (159 [34-1272] pg/mL) compared with controls (57 [33-333] pg/mL, p <.001), exhibiting further significant increase in patients with severe sepsis and septic shock (461 [73-1550] and 522 [45-2313] pg/mL, respectively, p <.001 vs. sepsis). In multiple regression analysis, thrombopoietin levels were independently related only to sepsis severity (higher in patients with increased sepsis severity, p <.001) and platelet counts (higher in patients with lower platelet counts, p =.004). Sepsis severity accounted for most of the variance explained by the model. Thrombopoietin was significantly related to interleukin-6 (r =.26) and C-reactive protein (r =.37, p <.001 for both). In serial measurements, interleukin-6 peak values constantly preceded those of thrombopoietin, whereas peaks in thrombopoietin levels coincided with clinical episodes of septic shock. CONCLUSIONS: Sepsis severity is the major determinant of elevated thrombopoietin levels in septic patients, whereas platelet count is a secondary determinant. Thrombopoietin represents a potential marker of sepsis severity.

Prone position improves lung mechanical behavior and enhances gas exchange efficiency in mechanically ventilated chronic obstructive pulmonary disease patients.

UNLABELLED: Pronation might favorably affect respiratory system (rs) mechanics and function in volume-controlled, mode-ventilated chronic obstructive pulmonary disease (COPD) patients. We studied 10 COPD patients, initially positioned supine (baseline supine [supine(BAS)]) and then randomly and consecutively changed to protocol supine (supine(PROT)), semirecumbent, and prone positions. Rs mechanics and inspiratory work (W(I)) were assessed at baseline (0.6 L) (all postures) and sigh (1.2 L) (supine(BAS) excluded) tidal volume (V(T)) with rapid airway occlusion during constant-flow inflation. Hemodynamics and gas exchange were assessed in all postures. There were no complications. Prone positioning resulted in (a) increased dynamic-static chest wall (cw) elastance (at both V(Ts)) and improved oxygenation versus supine(BAS), supine(PROT), and semirecumbent, (b) decreased additional lung (L) resistance-elastance versus supine(PROT) and semirecumbent at sigh V(T), (c) decreased L-static elastance (at both V(Ts)) and improved CO(2) elimination versus supine(BAS) and supine(PROT), and (d) improved oxygenation versus all other postures. Semirecumbent positioning increased mainly additional cw-resistance versus supine(BAS) and supine(PROT) at baseline. V(T) W(I)-sub-component changes were consistent with changes in rs, cw, and L mechanical properties. Total rs-W(I) and hemodynamics were unaffected by posture change. After pronation, five patients were repositioned supine (supine(POSTPRO)). In supine(POSTPRO), static rs-L elastance were lower, and oxygenation was still improved versus supine(BAS). Pronation of mechanically ventilated COPD patients exhibits applicability and effectiveness and improves oxygenation and sigh-L mechanics versus semirecumbent ("gold standard") positioning. IMPLICATIONS: By assessing respiratory mechanics, inspiratory work, hemodynamics, and gas exchange, we showed that prone positioning of mechanically ventilated chronic obstructed pulmonary disease patients improves oxygenation and lung mechanics during sigh versus semirecumbent positioning. Furthermore, certain pronation-related benefits versus preprone-supine positioning (reduced lung elastance and improved oxygenation) are maintained in the postprone supine position.