Observational StudyThe APS Phenotyping Study

Inclusion Criteria:

To be eligible for enrollment, a patient must meet all the following inclusion criteria at the time of the first study-specified biospecimen collection (Time 0):

1. Age ≥ 18 years old
2. Admitted (or planned to be admitted) to an intensive care unit (ICU) or other in-patient hospital location where IV vasopressors or advanced respiratory support (invasive mechanical ventilation, non-invasive ventilation, or high flow nasal cannula) are routinely provided (referred to as an "eligible unit.")
3. Acute cardiovascular or pulmonary organ dysfunction defined by meeting at least one of the two criteria below:

• New receipt of invasive mechanical ventilation, non-invasive ventilation, high flow nasal cannula, or supplemental oxygen at a flow rate of ≥ 6 lpm for acute hypoxemia.

a. Patients who use chronic oxygen therapy are eligible to participate if they are receiving at least 6 lpm higher than their baseline oxygen requirement (e.g., a patient on 3 lpm O2 at baseline is eligible if they require ≥9 lpm for hypoxemia) or are started on advanced respiratory support (invasive mechanical ventilation, non- invasive ventilation, or high flow nasal cannula).

• Receipt of intravenous infusion of a vasopressor medication for at least one hour.

4. Acute cardiovascular or pulmonary organ dysfunction (inclusion criterion #3) is attributed to an acute inflammatory condition, including but not limited to any of the following:

• Any infection including pneumonia.
• Aspiration pneumonitis.
• Pancreatitis.
• Auto-inflammatory condition such as:

1. Hemophagocytic lymphohistiocytosis.
2. Suspected acute rheumatologic or auto-immune disease with pulmonary or cardiovascular manifestations.
3. Suspected cryptogenic organizing pneumonia presenting acutely.
4. Suspected diffuse alveolar hemorrhage.
5. Suspected acute anaphylaxis.
6. Suspected acute pulmonary drug toxicity.

Exclusion Criteria:

To be eligible for enrollment, a patient must not meet any of the following exclusion criteria at the time of the first study-specified biospecimen collection (Time 0):

1. Patient/legally authorized representative (LAR) declines participation.
2. Acute cardiovascular or pulmonary organ dysfunction (inclusion criterion #3) has been present for > 48 hours.
3. Patient has been in an eligible unit (inclusion criterion #2) for more than 120 hours (five days).
4. Patient is no longer expected to meet the acute cardiovascular or pulmonary organ dysfunction inclusion criterion (inclusion criterion #3) 24 hours after enrollment.
5. Patient desires comfort measures only.
6. Patient is a prisoner.
7. Patient had out-of-hospital cardiac arrest leading to this hospitalization.
8. Residence immediately before this hospitalization in a long-term acute care facility.
9. Presence of tracheostomy for respiratory failure.
10. Home invasive mechanical ventilation or non-invasive ventilation (except patients with non-invasive ventilation prescribed as a treatment for a sleep disorder may participate).
11. Suspected cause of the patient's acute cardiovascular and/or pulmonary dysfunction (inclusion criterion #3) is an alternative condition (not ARDS, pneumonia, or sepsis), including but not limited to the list below:

• Drug overdose (without aspiration, lung injury, pneumonia, or infection).
• Trauma (without aspiration, pneumonia, or infection).
• Chronic lung disease without suspected infection, aspiration, or inflammation.
• Asthma, chronic obstructive pulmonary disease (COPD), sarcoidosis, interstitial lung disease, neuromuscular respiratory failure.
• Status epilepticus.
• Acute pulmonary embolism.
• Acute decompensated heart failure.
• Diabetic ketoacidosis.
• Acute stroke or intracranial hemorrhage.
• Acute bleeding (GI bleeding, post-procedural bleeding, hemolysis).
• Cytokine release syndrome due to chemotherapy.

12. Inability or unwillingness to complete study-specified blood draws, for example, due to local policies about hemoglobin thresholds for research blood draws.