Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized Trial of GM-CSF in Patients With ALI/ARDS
Brief Summary: This study will test the hypothesis that administration of granulocyte-macrophage colony stimulating factor (GM-CSF) to patients with acute lung injury/acute respiratory distress syndrome (ALI/ARDS) will improve the clinical course and outcome by shortening the duration of mechanical ventilation for these patients.


Options:
A: Inclusion Criteria:

Acute onset of illness with:

* PaO2/FiO2 ratio of less than 300 (ALI) or PaO2/FiO2 ratio of less than 200 (ARDS)
* Bilateral infiltrates consistent with pulmonary edema on frontal chest radiograph (infiltrates may be patchy, diffuse, homogeneous, or asymmetric)
* Requirement for positive pressure ventilation via an endotracheal tube
* No clinical evidence of left atrial hypertension (pulmonary arterial wedge pressure measure up to 18 mm Hg)
* First three criteria must occur together within a 24-hour interval

Exclusion criteria:

* Greater than 7 days elapsed following institution of mechanical ventilation
* Pregnancy
* Chronic respiratory failure as defined by any of the following: 1) FEV1 less than 20 ml/kg of PBW; or 2) FEV1/FVC less than 50%
* Chronic hypercapnia or hypoxemia
* Hospitalization within the past 6 months for acute respiratory failure
* Chronic home use of oxygen or mechanical ventilation
* Left ventricular failure as defined by New York Heart Association (NYHA) class IV status
* Neutropenia (absolute neutrophil count less than 1000 cells/mm3)
* History of hematological malignancy or bone marrow transplant
* Entry into other intervention clinical trials
* Decision of the patient or attending physician to forego aggressive care
* Expected survival rate of less than 6 months (based solely on pre-existing medical problems \[i.e., poorly controlled neoplasm or other end-stage disease\])
* AIDS or known history of HIV infection
* Prednisone (or equivalent) therapy greater than or equal to 20 mg/day for a period of not less than 2 months with treatment continuing within 3 weeks prior to screening
* Cytotoxic therapy within 3 weeks of screening
* Morbid obesity defined as greater than 1 kg/c, body weight
* At risk for increased intracranial pressure that may result from permissive hypercapnia or in whom permissive hypercapnia may be otherwise contraindicated
* Neuromuscular disease that would potentially impact ability to wean from mechanical ventilation
* Receiving extracorporeal membrane oxygenation when meeting screening criteria
B: Inclusion Criteria:

* age ≥ 18
* intubated and mechanically ventilated male and female patients of the Intensive Care Units of the Department of Anesthesia, General Intensive Care and Pain Control
* meets the criteria of ALI (as defined by the American-European Consensus Conference on ALI/ ARDS):
* Onset of ALI within 48 hours
* Bilateral infiltrates seen on frontal chest radiograph
* PCWP ≤ 18 mm Hg or no clinical evidence of left atrial hypertension
* paO2/ FiO2 ratio ≤ 300 mm Hg
* EVLW in PiCCO® at screening ≥ 8 ml/PBW
* Meeting criteria for extensive hemodynamic monitoring according to investigators discretion
* ICU Patients being mechanically ventilated and are stable in this condition for at least 8 hours
* Negative pregnancy test and adequate contraception in female patients of childbearing potential
* Informed consent:
* For patients that are temporarily unable to consent (e.g. comatose patients) a subsequent informed consent has to be provided.

Exclusion Criteria:

* History of clinically relevant allergies or idiosyncrasies to AP301 or any other inactive ingredient(s) of the investigational product
* Brainstem death at screening
* Current evidence of septic shock as defined by the Surviving Sepsis Campaign (Presence of acute organ dysfunction secondary to infection plus hypotension with systolic blood pressure \< 90 mm Hg or mean arterial pressure (MAP) \< 70 mm Hg for not less than one hour which cannot be reversed with fluid resuscitation)
* Neutrophil count \<0.3 x 109 L
* Patients under immunosuppression: high dose steroids (\> 80 mg Prednisolone /d; \> 300 mg hydrocortisone / d), cancer treatment (chemotherapy or biological) or therapy with other immunosuppressive agents for organ transplantation within 2 weeks
* BMI \< 18.5 or \> 35
* Cardiogenic pulmonary edema diagnosed by echocardiography or pulmonary artery catheter
* Pregnancy / lactation or intention to fall pregnant during the time course of the study
* Women of childbearing potential as well as men of procreative capacity who are not using adequate contraception
* Participation in other interventional drug trials
C: Men and women, 13 years of age or older, with ARDS or risk factors for ARDS. Patients will be considered at risk if they are critically ill and have trauma, sepsis, shock, pneumonia, inhalation injury, drug overdose, pancreatitis, hypertransfusion.
D: Inclusion Criteria:

* 1. Systemic inflammatory response syndrome (SIRS) defined as meeting at least criteria (a) or (b)for a systemic inflammatory response:

  1. White blood cell count \>12,000 or \<4,000 or \>10% band forms
  2. Body temperature \>38 degrees Celsius (C) (any route) or \<36 degrees C (accepting core temperatures only; indwelling catheter, esophageal, rectal)
  3. Heart rate (\> 90 beats/min) or receiving medications that slow heart rate or paced rhythm 2. Suspected or proven infection: Sites of infection include thorax, urinary tract, abdomen, skin, sinuses, central venous catheters, and bacterial meningitis (Appendix A).

     3. ALI as defined by acute onset of:

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  1. PaO2 / FiO2 ≤ 300 (intubated). If altitude \> 1000m, then PaO2 / FiO2 ≤ 300 x (PB/760), and
  2. Bilateral infiltrates consistent with pulmonary edema on frontal chest radiograph, and
  3. Requirement for positive pressure ventilation via an endotracheal tube, and
  4. No clinical evidence of left atrial hypertension, or if measured, a Pulmonary Arterial Wedge Pressure (PAOP) less than or equal to 18 mm Hg. If a patient has a PAOP \> 18 mmHg, then the other criteria must persist for more than 12 hours after the PAOP has declined to ≤ 18 mmHg, and still be within the 48-hour enrollment window.

"Acute onset" is defined as follows: the duration of the hypoxemia criterion (#1) and the chest radiograph criterion (#2) must be ≤ 28 days at the time of randomization. Opacities considered "consistent with pulmonary edema" include any patchy or diffuse opacities not fully explained by mass, atelectasis, or effusion or opacities known to be chronic (\> 28 days). The findings of vascular redistribution, indistinct vessels, and indistinct cardiac borders are not considered "consistent with pulmonary edema".

All ALI criteria (3a-d above) must occur within the same 24 hour period. The onset of ALI is when the last ALI criterion is met. Patients must be enrolled within 48 hours of ALI onset and no more than 7 days from the initiation of mechanical ventilation. SIRS criteria must occur within the 72 hours before or the 24 hours after ALI onset. Information for determining when these time window criteria were met may come from either the Network hospital or a referring hospital reports.

Exclusion Criteria:

1. No consent/inability to obtain consent
2. Age less than 18 years
3. More than 7 days since initiation of mechanical ventilation
4. More than 48 hours since meeting ALI inclusion criteria
5. Patient, surrogate, or physician not committed to full support ).
6. Unable to receive or unlikely to absorb enteral study drug
7. Rosuvastatin specific exclusions

   * Receiving a statin medication within 48 hours of randomization
   * Allergy or intolerance to statins
   * Physician insistence for the use or avoidance of statins during the current hospitalization
   * Creatine Kinase (CK) , alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 5 times the upper limit of normal
   * Diagnosis of hypothyroidism and not on thyroid replacement therapy
   * Pregnancy or breast feeding
   * Receiving niacin, fenofibrate or cyclosporine, gemfibrozil, atazanavir, lopinavir, ritonavir, daptomycin
8. Severe chronic liver disease
9. Moribund patient not expected to survive 24 hours
10. Chronic respiratory failure defined as PaCO2 \> 60 mm Hg in the outpatient setting
11. Home mechanical ventilation (noninvasive ventilation or via tracheotomy) except for CPAP/BIPAP (Continuous Positive Airway Pressure/BiLevel Positive Airway Pressure) used solely for sleep-disordered breathing
12. Diffuse alveolar hemorrhage from vasculitis
13. Burns \> 40% total body surface
14. Interstitial lung disease of severity sufficient to require continuous home oxygen therapy
15. Unwillingness or inability to utilize the ARDS network 6 ml/kg Predicted Body Weight (PBW) ventilation protocol
16. Cardiac disease classified as NYHA (New York Heart Association) class IV
17. Myocardial infarction within past 6 months
18. Intraparenchymal Central Nervous System (CNS) bleed within a month of randomization.
19. Temperature \>40.3 C in the 6 hours before randomization

Answer: A