Acute respiratory distress syndrome (ARDS) is a serious disease with high mortality. In patients who survive ARDS, respiratory, neurological and motor sequelae are frequent, negatively impacting on the patient's quality of life, and engendering substantial healthcare costs (rehabilitation, long-term care, delayed return to work). There may also be repercussions on the patient's family and entourage. The severity of ARDS and the burden it represents have underpinned intensive research to identify treatment strategies that could improve mortality. However, it is important to ensure that any improvement in mortality does not come at the price of an excess of sequelae and disability in survivors.

The oxygenation strategy used to treat ARDS may have an impact on mortality in these patients. The CLOSE study, in which our group participated, recently demonstrated the feasibility of two oxygenation strategies in intensive care unit (ICU) patients with ARDS. We have also initiated the LOCO-2 study (NCT02713451), whose aim is to show a reduction in mortality in ARDS using a "conservative" oxygenation strategy (PaO2 maintained between 55 and 70 mmHg) as compared to a classical "liberal" oxygenation strategy (PaO2 between 90 and 105 mmHg).

The LTO-BLOXY study is a substudy of the on-going LOCO-2 study

The LTO-BLOXY study will compare respiratory, cognitive and exercise function outcomes in patients who underwent one of the two oxygenation strategies in the context of the on-going LOCO-2 study:

• Experimental group: oxygenation will be maintained at a level between 55 and 70 mmHg of PaO2 as measured by blood gas test ("conservative" oxygenation). Between blood gas measures, oxygenation will be optimized to achieve an SpO2 between 88% and 92%.
• Control group: oxygenation will be maintained at a level between 90 and 105 mmHg of PaO2 as measured by blood gas test ("liberal" oxygenation). Between blood gas measures, oxygenation will be optimized to achieve an SpO2 >96%.

The primary objective is to demonstrate a lower level of impairment of respiratory function at 6 months in survivors of acute respiratory distress syndrome (ARDS) after a "conservative" oxygenation strategy, as compared to a "liberal" oxygenation strategy.

Secondary objectives are numerous and will explore different areas such as evalution of disability, respiratory function, exercise function, cognitive function and quality of life.

Participation in the LTO-BLOXY study will be proposed to all patients included in LOCO-2 at discharge from the ICU. A total of 259 patients from the overall total of 850 expected inclusions in LOCO-2, will participate in the LTO-BLOXY study. These patients will be followed up to 1 year after their initial inclusion in LOCO-2, with a view to evaluate respiratory function, exercise function and cognitive function, as well as QoL.

The calendar of their study participation is as follows:

• Inclusion in LOCO-2 study and randomization LOCO-2
• Inclusion in LTO-BLOXY study at discharge from the ICU
• 3 month visit ± 2 weeks (3 months after inclusion in LOCO-2 study)
• 6 month visit ± 2 weeks (6 months after inclusion in LOCO-2 study)
• 12 month visit ± 2 weeks (12 months after inclusion in LOCO-2 study)

At each follow-up visit, the patient will attend a consultation in the Department of Physiology - Functional Explorations, where the study questionnaires will be given to the patient for completion. The neuropsychologist will perform the cognitive tests, the respiratory function and exercise tests will also be performed at the same visit.

Inclusion Criteria:

• ARDS defined as a PF ratio <300
• Patients under ventilation for <12 hours
• Stabilization period of 3 hours with standardization of ventilation parameters

Inclusion criterion specific for neurological evaluation:

- Patient aged between 20 and 89 years

Exclusion Criteria:

• Chronic respiratory failure or on home ventilation (excluding obstructive sleep apnoea)
• Cardiac arrest
• Moribund patients (death likely within 48 hours as assessed by the ICU physician)
• Gaseous embolism
• CO poisoning
• Pregnant women
• Indication for hyperbaric oxygen treatment
• Persistent pneumothorax
• Gaseous gangrene
• DNR or limited care order

Exclusion criteria specific for neurological evaluation:

• History of neurological disorders: cranial trauma, stroke, cerebral tumor, epilepsy, neuro-degenerative disease.
• Psychiatric disorders: bipolar disorder, psychosis, addiction, schizophrenia.
• Lack of autonomy due to previously documented cognitive and/or psychomotor impairment.
• Hearing and/or sight impairment that prevent the patient from performing the study tests

Patients presenting exclusion criteria for the neurological evaluation can nonetheless be included in the study for the evaluation of respiratory function.