Transforming Growth Factor-ß1 in predicting early lung fibroproliferation in patients with acute respiratory distress syndrome.

BACKGROUND: Fibroproliferative repair phase of the acute respiratory distress syndrome (ARDS) is followed by a restitutio ad integrum of lung parenchyma or by an irreversible lung fibrosis and patients' death. Transforming Growth Factor-ß1 (TGF-ß1) is involved in collagen production and lung repair. We investigated whether alveolar TGF-ß1 was associated with the presence of fibroproliferation and the outcome of ARDS patients. METHODS: Sixty-two patients were included the first day of moderate-to-severe ARDS. Bronchoalveolar lavage fluid (BALF) was collected at day 3 (and day 7 when the patients were still receiving invasive mechanical ventilation) from the onset of ARDS. Survival was evaluated at day 60. TGF-ß1 was measured by immunoassay. The patients were classified as having lung fibroproliferation when the alveolar N-terminal peptide for type III procollagen (NT-PCP-III) measured on day 3 was > 9 µg/L as recently reported. The main objective of this study was to compare the alveolar levels of total TGF-ß1 according to the presence or not a lung fibroproliferation at day 3. RESULTS: Forty-three patients (30.6%) presented a fibroproliferation at day 3. BALF levels of total TGF-ß1 were not statistically different at day 3 (and at day 7) according to the presence or not lung fibroproliferation. Mortality at day 60 was higher in the group of patients with fibroproliferation as compared with patients with no fibroproliferation (68.4% vs. 18.6% respectively; p < 0.001). Total TGF-ß1 measured on BALF at day 3 was not associated with the outcome. Multiple logistic regression showed that the presence of lung fibroproliferation was associated with death. In contrast, TGF-ß1 was not independently associated with death. CONCLUSIONS: Pulmonary levels of TGF-ß1 during the first week of ARDS were not associated nor with the presence of fibroproliferation neither with death. TGF-ß1 should not be used as a biomarker to direct anti-fibrotic therapies.

Closed loop ventilation mode in Intensive Care Unit: a randomized controlled clinical trial comparing the numbers of manual ventilator setting changes.

BACKGROUND: There is an equipoise regarding closed-loop ventilation modes and the ability to reduce workload for providers. On one hand some settings are managed by the ventilator but on another hand the automatic mode introduces new settings for the user. METHODS: This randomized controlled trial compared the number of manual ventilator setting changes between a full closed loop ventilation and oxygenation mode (INTELLiVENT-ASV®) and conventional ventilation modes (volume assist control and pressure support) in Intensive Care Unit (ICU) patients. The secondary endpoints were to compare the number of arterial blood gas analysis, the sedation dose and the user acceptance. Sixty subjects with an expected duration of mechanical ventilation of at least 48 hours were randomized to be ventilated using INTELLiVENT-ASV® or conventional modes with a protocolized weaning. All manual ventilator setting changes were recorded continuously from inclusion to successful extubation or death. Arterial blood gases were performed upon decision of the clinician in charge. User acceptance score was assessed for nurses and physicians once daily using a Likert Scale. RESULTS: The number of manual ventilator setting changes per 24 h-period per subject was lower in INTELLiVENT-ASV® as compared to conventional ventilation group (5 [4-7] versus 10 [7-17]) manuals settings per subject per day [P<0.001]). The number of arterial blood gas analysis and the sedation doses were not significantly different between the groups. Nurses and physicians reported that INTELLiVENT-ASV® was significantly easier to use as compared to conventional ventilation (P<0.001 for nurses and P<0.01 for physicians). CONCLUSIONS: For mechanically ventilated ICU patients, INTELLiVENT-ASV® significantly reduces the number of manual ventilator setting changes with the same number of arterial blood gas analysis and sedation dose, and is easier to use for the caregivers as compared to conventional ventilation modes.

Role of open-lung biopsy in acute respiratory distress syndrome.

PURPOSE OF REVIEW: When classic examinations such as bronchoalveolar lavage are not contributory in the etiologic diagnosis of unresolving acute respiratory distress syndrome, surgical lung biopsy would appear to be useful to determine the specific cause, particularly infection or postaggressive fibrosis, which could benefit from an adapted treatment. RECENT FINDINGS: Postaggressive pulmonary fibrosis is a possible evolution for unresolving acute respiratory distress syndrome and its association with a poor prognosis has been demonstrated. The administration of corticoids would make it possible to improve certain ventilatory parameters as well as the prognosis in the fibroproliferation stage. No clinical or usual microbiological criterion can confirm both the existence of fibrosis and nosocomial pneumonia. Biological markers for fibrosis such as procollagen III are not validated to confirm the appearance of a postaggressive fibrosis. A recent study has shown that surgical lung biopsy performed in patients with unresolving acute respiratory distress syndrome led to a therapeutic modification in 78% of the cases and made it possible to avoid empiric corticotherapy in nearly 50% of the cases considering the absence of fibrosis. SUMMARY: Surgical lung biopsy could be proposed for patients with unresolving acute respiratory distress syndrome after 7-10 days of evolution despite well-conducted initial treatment when the etiology of acute respiratory distress syndrome has not been confirmed or when the appearance of postaggressive fibrosis is suspected.