Received oral or intravenous (IV) antibiotics within 2 weeks prior to cycle 1, day 1; patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible

Received oral or intravenous (IV) antibiotics within 2 weeks prior to randomization; patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible

Severe pulmonary, cardiac or other systemic disease, specifically:

Severe, active co-morbidity, defined as follows:\r\n* Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months\r\n* Transmural myocardial infarction within the last 6 months\r\n* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration\r\n* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration\r\n* Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects or severe liver dysfunction\r\n* Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol; protocol-specific requirements may also exclude immuno-compromised patients

Received oral or intravenous (IV) antibiotics within 2 weeks prior to cycle 1, day 1; patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible

Severe and/or active co-morbidity defined as follows:\r\n* History of inflammatory bowel disease\r\n* History of active hepatitis B or C; blood tests are not required to determine if the patient has had hepatitis B or C, unless the patient reports a history of hepatitis\r\n* Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months\r\n* Transmural myocardial infarction within the last 6 months\r\n* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of step 1 registration\r\n* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization within 15 days of step 1 registration or precluding study therapy at the time of step 1 registration\r\n* Uncontrolled severe illness or medical condition (including uncontrolled diabetes), which in the judgment of the treating physician would make the administration of chemotherapy inadvisable

Received oral or intravenous (IV) antibiotics within 14 days prior to randomization; patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible

Severe, active co-morbidity, defined as follows:\r\n* Major medical or psychiatric illness, which in the investigator’s opinion would interfere with the completion of therapy and follow up or with full understanding of the risks and potential complications of the therapy\r\n* Unstable angina and/or uncontrolled congestive heart failure\r\n* Myocardial infarction within the last 6 months\r\n* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration; note that patients switched from IV antibiotics and currently on oral antibiotics whose infection is assessed to be adequately treated or controlled are eligible\r\n* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days prior to registration\r\n* Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol

Severe, active co-morbidity, defined as follows:\r\n* Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months\r\n* Transmural myocardial infarction within the last 6 months\r\n* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration\r\n* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration\r\n* Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, coagulation parameters are not required for entry into this protocol\r\n* Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol\r\n* Pre-existing >= grade 2 neuropathy\r\n* Prior organ transplant

Severe, active co-morbidity, defined as follows:\r\n* Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months\r\n* Transmural myocardial infarction within the last 6 months\r\n* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of study entry\r\n* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of study entry \r\n* Coagulation defects; note, however, that coagulation parameters are not required for entry into this protocol

Severe, active co-morbidity defined as follows:\r\n* Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months\r\n* Transmural myocardial infarction within the last 6 months\r\n* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration\r\n* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration

Patients must not have an active infection requiring oral or IV antibiotics within 14 days prior to registration; patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible

Severe, active co-morbidity, defined as follows:\r\n* Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months\r\n* Transmural myocardial infarction within the last 6 months\r\n* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of study entry\r\n* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of study entry\r\n* Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; hepatic or biliary disease that is acute or currently active or that requires antiviral therapy (with the exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases, or stable chronic liver disease per investigator assessment)\r\n* History of left ventricular ejection fraction (LVEF) below institutional normal unless repeated and within institutional normal range within 90 days of study entry

Concomitant diseases/conditions: Angina, myocardial infarction, congestive heart failure or clinically significant valvular heart disease, arrhythmia, immunodeficiency (including known HIV seropositive), ongoing or treatment-requiring chronic liver disease, active infection, oxygen requirement within two weeks prior to randomization, diffuse interstitial lung disease (ILD) or pulmonary fibrosis, second invasive malignancy treated with chemotherapy and/or radiotherapy, invasive fungal infections requiring systemic treatment within 12 weeks of randomization.

Subjecting has any condition, including compromised pulmonary function, that would preclude the use of lomustine.

Restrictive or obstructive pulmonary disease

Patients with any pulmonary infiltrate including those suspected to be of infectious origin; in particular, patients with resolution of clinical symptoms of pulmonary infection but with residual pulmonary infiltrates on chest x-ray are not eligible until pulmonary infiltrates have completely resolved

The FHCRC PI of the study must approve of enrollment of all patients with pulmonary nodules

History of clinically severe lung disease, asthma, or chronic obstructive pulmonary disease (COPD) requiring emergency management and/or hospitalization in the last year

Severe, active co-morbidity, defined as follows:\r\n* Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months\r\n* Transmural myocardial infarction within the last 6 months\r\n* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration\r\n* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration\r\n* Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, coagulation parameters are not required for entry into this protocol\r\n* Pre-existing >= grade 2 neuropathy\r\n* Prior organ transplant\r\n* Systemic lupus\r\n* Psoriatic arthritis

Participants with significant symptomatic deterioration of lung function; if clinically indicated, pulmonary function tests including measures of predicted lung volumes, carbon monoxide diffusing capability test (DLco), oxygen (O2) saturation at rest on room air should be considered to exclude restrictive pulmonary disease, pneumonitis or pulmonary infiltrates

Received oral or intravenous (IV) antibiotics within 2 weeks prior to cycle 1, day 1; patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible

Subject has a history of interstitial lung disease, history of slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies; any lung disease that may interfere with the detection or management of suspected drug-related pulmonary toxicity

Current symptomatic pulmonary embolism

Prior or concurrent pulmonary embolism

Participants with unilateral pleural effusion (other than non-small cell lung cancer [NSCLC] indication) should fulfill the following criteria for pulmonary and cardiac functions: Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification 0 ? 1 level and New York Heart Association (NYHA) classification class 1

Pulmonary disease (e.g. COPD, asthma, etc) that is not controlled (moderate to severe symptoms) with current medication

Cardiac or pulmonary disorders within 6 months of enrollment.

Patients with any unstable medical issue (including cardiac issues as above, active treatment for symptomatic pulmonary embolism, cerebrovascular accident [CVA], renal or hepatic insufficiency, active infection/sepsis requiring intravenous [IV] antibiotics)

Cardiac or pulmonary conditions that preclude aggressive cytoreductive surgery

Major organ system dysfunction including (but not limited to): New York Heart Association class III or IV, pulmonary disease requiring the use of inhaled steroids or bronchodilators, renal, hepatic, gastrointestinal, neurologic, or psychiatric dysfunction which would impair patient’s ability to participate in the trial

Subjects in whom the required program of PO and IV fluid hydration is contraindicated, e.g., due to pre-existing pulmonary, cardiac, or renal impairment

Pts in whom the required program of oral and intravenous fluid hydration is contraindicated, e.g. due to pre-existing pulmonary, cardiac, or renal impairment

Severe, active co-morbidity, defined as follows:\r\n* Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months\r\n* Transmural myocardial infarction within the last 6 months\r\n* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration\r\n* Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol

Severe, active co-morbidity, defined as follows:\r\n* Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months\r\n* Transmural myocardial infarction within the last 6 months\r\n* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration\r\n* Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol

Patients with pulmonary, cardiac, hepatic or renal impairment that would limit their ability to receive cytoreductive therapy and compromise their survival; this should include patients with any of the following:\r\n* Severe pulmonary dysfunction associated with a carbon monoxide diffusing capacity (DLCO) (corrected for hemoglobin) < 60%, or requires supplemental oxygen\r\n* Uncontrolled malignant arrhythmias, or clinical evidence of congestive heart failure (New York class III-IV) or ejection fraction < 50%\r\n* Renal disease with estimated glomerular filtration rate (GFR) by creatinine clearance or iothalamate clearance < 50 ml/min/1.73 m^2 body surface area\r\n* Serum glutamate pyruvate transaminase (SGPT)/aspartate aminotransferase (AST) > 3 times normal or direct bilirubin greater than 2.5 mg/dL on two repeated tests

The subject has radiographic evidence of cavitating pulmonary lesion(s)

Patients must not have serious medical risk factors involving any of the major organ systems, or serious psychiatric disorders, which could compromise the subject's safety or the study data integrity; these include, but are not limited to: history of interstitial lung disease, slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies

Pulmonary disease requiring chronic medical therapy, unrelated to underlying cancer

Received oral or intravenous (IV) antibiotics within 2 weeks prior to cycle 1, day 1; patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible

New or progressive pulmonary infiltrates on screening chest x-ray or chest CT scan that has not been cleared by Pulmonary. Infiltrates attributed to infection must be stable/improving (with associated clinical improvement) after 1 week of appropriate therapy (4 weeks for presumed or documented fungal infections)

Extrahepatic spread; for the dose escalation, regional lymphadenopathy and subcentimeter pulmonary nodules are allowed.

Participants who have undergone a pneumonectomy due to known potential for pulmonary toxicities and heightened risk for complications

Subjects with a history of interstitial lung disease (e.g., sarcoidosis) that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity; subjects with chronic obstructive pulmonary disease (COPD) whose disease is controlled at study entry are allowed

No clinical indications such as evidence of dyspnea at rest, or exercise intolerance due to pulmonary insufficiency

Pulmonary embolism within 30 days prior to study entry

Severe, active co-morbidity, defined as follows:\r\n* Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months;\r\n* Transmural myocardial infarction within the last 6 months;\r\n* Chronic obstructive pulmonary disease exacerbation or other respiratory illness other than the diagnosed lung cancer requiring hospitalization or precluding study therapy within 30 days before registration;\r\n* Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol

History of interstitial lung disease, history of slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies.

Individuals with any of the following conditions are excluded from this study:\r\n* Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months\r\n* Transmural myocardial infarction within the last 6 months\r\n* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration\r\n* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration\r\n* History of hepatic insufficiency resulting in clinical jaundice and/or coagulation defects within the last 12 months

Pulmonary embolism

Severe chronic obstructive pulmonary disease (COPD) defined as disease requiring an inpatient stay for respiratory deterioration within the past 3 months

Active pulmonary disease requiring medication to include multiple inhalers (>2 inhalers and one containing steroids)

The patient has uncontrolled, clinically significant pulmonary disease (e.g., chronic obstructive pulmonary disease, pulmonary hypertension) that, in the Investigator's opinion, would put the patient at significant risk for pulmonary complications during the study.

Pulmonary: no requirement for supplemental oxygen and no evidence of moderate-severe chronic obstructive pulmonary disease (COPD) by pulmonary function tests (PFTs)

ARM 2 - A: Pulmonary: patients with a requirement for supplemental oxygen or evidence of moderate-severe COPD by PFTs are permitted to enroll

History or current diagnosis of Pulmonary Alveolar Proteinosis or Hypoxemia

Interstitial lung disease, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, or pulmonary hypersensitivity pneumonitis

Uncontrolled medical conditions including diabetes, heart failure, chronic obstructive pulmonary disease (COPD), ulcerative colitis, or Crohn’s disease

Other cardiac or pulmonary disease that, at the investigator’s discretion, can impair treatment safety

Participants with unilateral pleural effusion will be eligible for inclusion if they fulfill the Global Initiative for Obstructive Lung Disease classification of 0-1 level for pulmonary function and New York Heart Association (NYHA) classification class 1 for cardiac function

Received oral or intravenous (IV) antibiotics within 2 weeks prior to Cycle 1, Day 1. Participants receiving prophylactic antibiotics (for prevention of a urinary tract infection chronic obstructive pulmonary disease) are eligible

Have evidence suggesting pulmonary fibrosis or interstitial pneumonia.

Pulmonary failure (requiring mechanical ventilation) not due to active LCH.

Isolated liver sclerosis or pulmonary fibrosis, without active LCH.

Forced expiratory volume in 1 second (FEV1) > 65% of prediction for those patients with extensive pulmonary metastases or chronic pulmonary disease history

Forced vital capacity (FVC) > 65% of prediction for those patients with extensive pulmonary metastases or chronic pulmonary disease history

Other serious illnesses or medical conditions including but not limited to:\r\n* Unstable cardiac disease despite treatment, myocardial infarction within 6 months prior to study entry\r\n* History of significant neurologic or psychiatric disorders including dementia or seizures \r\n* Active clinically significant uncontrolled infection \r\n* Active peptic ulcer disease defined as unhealed or clinically active \r\n* Active drug addiction including alcohol, cocaine or intravenous drug use defined as occurring within the 6 months preceding diagnosis \r\n* Chronic obstructive pulmonary disease, defined as being associated with a hospitalization for pneumonia or respiratory decompensation within 12 months of diagnosis; this does not include obstruction from tumor \r\n* Autoimmune disease requiring therapy, prior organ transplant, or known human immunodeficiency virus (HIV) infection\r\n* Interstitial lung disease\r\n* Hepatitis C by history \r\n* Concurrent treatment with any other anticancer therapy\r\n* Participation in an investigational therapeutic drug trial within 30 days of study entry

PFT (pulmonary function test) with a FEV1 > 0.75 liters/second within 16 weeks prior to study registration.

If they have New York Heart Association (NYHA) class 3 or 4: myocardial infarction, acute coronary syndrome, diabetes mellitus with ketoacidosis or chronic obstructive pulmonary disease (COPD) requiring hospitalization in the preceding 6 months; or any other intercurrent medical condition that contraindicates treatment with sEphB4HSA or places the patient at undue risk for treatment related complications

Forced expiratory volume in 1 second (FEV1) >= 2.0 liters or >= 75% of predicted for height and age; (pulmonary function tests (PFTs) are required for patients over 50 or with significant pulmonary or smoking history defined as > 20 pack years or history of chronic obstructive pulmonary disease [COPD]/emphysema)

Pulmonary disease which, in the opinion of the investigator, may impair the patient's respiratory tolerance to moderate pulmonary fluid overload (e.g., interstitial lung disease, severe chronic obstructive pulmonary disease)

Adequate pulmonary function defined as no evidence of dyspnea at rest

Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results or that could increase risk to the patient, including renal disease that would preclude chemotherapy administration or pulmonary disease (including obstructive pulmonary disease and history of bronchospasm).

New York Heart Association class 3 or 4 heart failure; myocardial infarction, acute coronary syndrome, diabetes mellitus with ketoacidosis, or chronic obstructive pulmonary disease (COPD) requiring hospitalization in the preceding 6 months; or any other intercurrent medical condition that contraindicates treatment with sEPHB4-HSA or places the patient at undue risk for treatment related complications

No evidence of acute pulmonary infiltrates on chest radiograph

Significant pulmonary disease or condition

Subjects with serious intercurrent chronic or acute illness, such as cardiac or pulmonary disease, hepatic disease, or other illness considered by the Investigator as high risk for investigational drug treatment

Uncontrolled chronic obstructive pulmonary disease or previous known pulmonary fibrosis

Chronic medical illness including diabetes with the use of insulin, hemoglobin A1c > 7 (study physician discretion), heart disease diagnosed by angiogram, chronic obstructive pulmonary disease (COPD) diagnosed by pulmonary function testing and requiring an oxygen supply

Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results or that could increase risk to the patient, including renal disease that would preclude chemotherapy administration or pulmonary disease (including obstructive pulmonary disease and history of bronchospasm)

History of clinically significant chronic obstructive pulmonary disease (COPD), asthma, or other chronic lung disease.

Known chronic obstructive pulmonary disease (COPD) (defined as a forced expiratory volume in 1 second [FEV1] < 50% of predicted normal), persistent asthma, or a history of poorly controlled asthma within the last 2 years (controlled intermittent asthma or controlled mild persistent asthma is allowed)

Therapeutic oral or intravenous (IV) antibiotics within 2 weeks prior to first day of study treatment:\r\n* Patients receiving prophylactic antibiotics (eg, to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible

Subjects with a history of serious intercurrent chronic or acute illness, such as cardiac or pulmonary disease, hepatic disease, or other illness considered by the investigator as high risk for investigational drug treatment

Severe pulmonary hypertension (PHT) (on echo or right side cardiac catheterization);

Known severe chronic obstructive pulmonary disease or asthma

Significant pulmonary disease, including pulmonary hypertension or interstitial pneumonitis

The patient has idiopathic pulmonary fibrosis (IPF) as documented in their medical history.

GENERAL: Received oral or intravenous (IV) antibiotics within 2 weeks prior to cycle 1, day 1.\r\n* Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible.

Known moderate to severe chronic obstructive pulmonary disease, interstitial lung disease, or pulmonary fibrosis

Any significant medical condition, including any suggested by screening laboratory findings that, in the opinion of the investigator or sponsor, may place the subject at undue risk from the study, including but not necessarily limited to uncontrolled hypertension and/or diabetes, clinically significant pulmonary disease (e.g., chronic obstructive pulmonary disease requiring hospitalization within 3 months) or neurological disorder (e.g., seizure disorder active within 3 months).

Received oral or intravenous (IV) antibiotics within 2 weeks prior to cycle 1, day 1; patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible

Pulmonary disease (e.g. COPD, asthma, etc) that is not controlled (moderate to severe symptoms) with current medication

Symptomatic pulmonary embolism within 6 months prior to study entry

Severe, active co-morbidity defined as follows\r\n* Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months\r\n* Transmural myocardial infarction within the last 6 months\r\n* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration\r\n* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days of registration\r\n* Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects\r\n* Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers for Disease Control (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol

Received oral or IV antibiotics within 2 weeks prior to start of study treatment.\r\n* Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible.

History of pulmonary edema or decompensated congestive heart failure with in six (6) week of enrollment.

Known moderate to severe chronic obstructive pulmonary disease (COPD), interstitial lung disease, and pulmonary fibrosis

Other severe acute or chronic medical conditions including colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis, severe Chronic obstructive pulmonary disease (COPD) requiring > 3 hospitalization in the past year

Significant pulmonary disease or condition

Severe, active co-morbidity, defined as follows:\r\n* Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months\r\n* Transmural myocardial infarction within the last 6 months\r\n* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration\r\n* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration\r\n* Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol; (patients on Coumadin or other blood thinning agents are eligible for this study)\r\n* Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol; the need to exclude patients with AIDS from this protocol is necessary

Severe pulmonary disease (despite above oxygen saturation and DLCO) including severe and uncontrolled asthma (per 2007 National Heart, Lung, and Blood Institute [NHLBI] Guidelines for the Diagnosis and Treatment of Asthma Expert Panel Report 3), chronic obstructive pulmonary disease, and/or pulmonary hypertension (PH); a diagnosis of PH will be made by finding of mean pulmonary artery pressure (mPAP) < 25 mm Hg on right heart catherization; in patients unable and/or unwilling to undergo cardiac catheterization, patients will be excluded with the following constellation of findings based upon presumptive diagnosis of PH (positive predictive value [PPV] of 62%): TRJ velocity > 2.5 m/sec AND either N-terminal pro-brain natriuretic peptide (NT-pro-BNP) >= 160 pg/ml OR 6-minute walk distance < 333 m

Intestinal obstruction, uncontrolled gastrointestinal hemorrhage, pulmonary fibrosis, renal failure, liver failure, or cerebrovascular disorder

Severe, active comorbidity, including any of the following:\r\n* Unstable angina and/or congestive heart failure requiring hospitalization\r\n* Transmural myocardial infarction within the last 6 months\r\n* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of study initiation\r\n* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy\r\n* Known hepatic insufficiency resulting in clinical jaundice and/or coagulation defects\r\n* Known autoimmune disorder, such as human immunodeficiency virus (HIV)\r\n* Major medical illnesses or psychiatric impairments that, in the investigator's opinion, will prevent administration or completion of protocol therapy\r\n* Active connective tissue disorders, such as lupus or scleroderma that, in the opinion of the treating physician, may put the patient at high risk for radiation toxicity

Received therapeutic oral or IV antibiotics within 2 weeks prior to first day of study treatment:\r\nPatients receiving prophylactic antibiotics (eg, to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible

Patients who have major medical problems such as severe cardiac, pulmonary (COPD requiring constant oxygen), or non-healing ulceration.

Severe, active co-morbidity defined as follows:\r\n* Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months\r\n* Transmural myocardial infarction within the last 6 months\r\n* Acute bacterial or fungal infection intravenous antibiotics at the time of registration\r\n* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days of registration\r\n* Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol\r\n* Acquired immune deficiency syndrome (AIDS); note, however, that HIV testing is not required for entry into this protocol; protocol-specific requirements may also exclude immune-compromised patients

New or progressive pulmonary infiltrates on screening chest X-ray or chest CT scan unless cleared for study by pulmonary; infiltrates attributed to infection must be stable/improving (with associated clinical improvement) after 1 week of appropriate therapy (4 weeks for presumed or documented fungal infections)

The subject has radiographic evidence of cavitating pulmonary lesion(s)

Treatment with therapeutic oral or IV antibiotics within 14 days prior to initiation of study treatment; patients receiving prophylactic antibiotics (e.g. for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible

Received oral or IV antibiotics within 2 weeks prior to study treatment; but patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible

The subject has radiographic evidence of cavitating pulmonary lesion(s)

Patients with severe emphysema, pulmonary vasculitis, or a history of pulmonary emboli

Received oral or IV antibiotics within 2 weeks prior to cycle 1, day 1 a) Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible

Received therapeutic oral or IV antibiotics within 1 week prior to cycle 1 day 1\r\n* Subjects receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or to prevent chronic obstructive pulmonary disease exacerbation) are eligible

Significant chronic obstructive pulmonary disease (COPD) or other chronic pulmonary restrictive disease with pulmonary function test (PFT)’s indicating an forced expiratory volume in 1 second (FEV1) less than 50% or a carbon monoxide diffusing capability test (DLCO) less than 40% predicted for age\r\n* Note: Patients who have shortness of breath with minimal exertion or who are at risk for pulmonary disease will undergo pulmonary function testing and will not be eligible if their FEV1 is < 50% of expected

Severe pulmonary hypertension (PHT) (on echo or right side cardiac catheterization)

Severe, active co-morbidity, defined as follows:\r\n* Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months.\r\n* Transmural myocardial infarction within the last 6 months.\r\n* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration.\r\n* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days before registration.\r\n* Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and\r\n* Acquired immune deficiency syndrome (AIDS) based upon current U.S. Centers for Disease Control and Prevention (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol. Protocol-specific requirements may also exclude immuno-compromised patients.\r\n* History of treatment with potent immunosuppressive drugs for such conditions as post organ transplant, severe rheumatoid arthritis, etc. within the past 6 months.

Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage

New or progressive pulmonary infiltrates on screening chest X-ray or chest computed tomography (CT) scan unless cleared for study by Pulmonary; infiltrates attributed to infection must be stable/improving (with associated clinical improvement) after 1 week of appropriate therapy (4 weeks for presumed or documented fungal infections)

New or progressive pulmonary infiltrates concerning for new or uncontrolled infectious process

New or progressive pulmonary infiltrates on screening chest X-ray or chest computed tomography (CT) scan unless cleared for study by pulmonary; infiltrates attributed to infection must be stable/improving (with associated clinical improvement) after 1 week of appropriate therapy (4 weeks for presumed or documented fungal infections)

Patients with active systemic, pulmonary, or pericardial infection

Received oral or IV antibiotics =< 2 weeks prior to cycle 1, day 1\r\n* Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible

Received oral or IV antibiotics within 2 weeks prior to cycle 1, day 1\r\n* Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible

New or progressive pulmonary infiltrates on screening chest x-ray or chest computed tomography (CT) scan unless cleared for study by pulmonary; infiltrates attributed to infection must be stable/improving (with associated clinical improvement) after 1 week of appropriate therapy (4 weeks for presumed or documented fungal infections)

Uncontrolled, clinically significant pulmonary disease (for example, chronic obstructive pulmonary disease, pulmonary hypertension, idiopathic pulmonary fibrosis) that in the opinion of the investigator would put the participant at significant risk for pulmonary complications during the study

The subject has experienced any of the following:\r\n* Clinically-significant gastrointestinal bleeding within 6 months before the first dose of study treatment\r\n* Hemoptysis of >= 0.5 teaspoon (2.5 mL) of red blood within 3 months before the first dose of study treatment\r\n* Any other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment\r\n* The subject has radiographic evidence of cavitating pulmonary lesion(s); chest x-ray will not be required as part of this trial, unless cavitating pulmonary lesion is clinically suspected

Significant pulmonary artery hypertension (PAH) defined as:\r\n* Peak systolic pulmonary artery pressure > 50 mmHg by resting echocardiogram will require right heart catheterization; if pulmonary artery pressure (PAP) is not evaluable on echocardiogram due to lack of a Tricuspid regurgitant jet, then normal anatomy and function as evidenced by normal right atrium and ventricle size, shape and wall thickness and septum shape must be documented to rule-out PAH; otherwise, right heart catheterization is indicated; prior history of PAH but controlled with medications will not exclude patients from the protocol; PAH is considered controlled with medications if peak systolic pulmonary artery pressure is < 45 mmHg or mean pulmonary artery pressure by right heart catheterization is < 30 mmHg at rest\r\n* Mean pulmonary artery pressure by right heart catheterization exceeding 30 mmHg at rest; if mean PAP is elevated and pulmonary vascular resistance and transpulmonary gradient are normal then the patient is eligible for the protocol\r\n* New York Heart Association (NYHA)/World Health Organization Class III or IV

The subject has radiographic evidence of cavitating pulmonary lesion(s)

Pulmonary embolism.

Inadequate pulmonary function

Presence of cavitation of central pulmonary lesion

Received oral or IV antibiotics within 2 weeks prior to cycle 1, day 1\r\n* Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible

Known moderate to severe chronic obstructive pulmonary disease (COPD), interstitial lung disease, and pulmonary fibrosis

Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days of registration;

Evidence of significant cardiovascular disease including history of recent (< 6 months prior) myocardial infarction, congestive heart failure, primary cardiac arrhythmias (not due to electrolyte disorder or drug toxicity, for example) beyond occasional premature ventricular contractions (PVC's), angina, positive low-level stress test, or cerebrovascular accident; all patients should have baseline pulmonary function tests; adequate pulmonary function should be documented (forced expiratory volume-one second [FEV1] > 2 liters or >= 75% of predicted for height and age) prior to initiating therapy

Patients with pre-existing uncontrolled pulmonary disease will be excluded; uncontrolled refers to patients having had at least one hospitalization due to pulmonary disease (for example, asthma, chronic obstructive pulmonary disease) within the 6 months prior to enrollment in the study; patients with previous history of pneumonitis will be excluded

Other serious illnesses or medical conditions including but not limited to:\r\n* Unstable cardiac disease despite treatment, myocardial infarction within 6 months prior to study entry\r\n* History of significant neurologic or psychiatric disorders including dementia or seizures\r\n* Active clinically significant uncontrolled infection\r\n* Active peptic ulcer disease defined as unhealed or clinically active\r\n* Hypercalcemia\r\n* Active drug addiction including alcohol, cocaine or intravenous drug use defined as occurring within the 6 months preceding diagnosis\r\n* Chronic obstructive pulmonary disease, defined as being associated with a hospitalization for pneumonia or respiratory decompensation within 12 months of diagnosis; this does not include obstruction from tumor\r\n* Autoimmune disease requiring therapy, prior organ transplant, or human immunodeficiency virus (HIV) infection\r\n* Interstitial lung disease\r\n* Hepatitis C by history, and confirmed by serology

No history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease, or requirement for supplemental oxygen

Active systemic infections (for e.g.: requiring anti-infective treatment), coagulation disorders or other active major medical illnesses of the cardiovascular, respiratory or immune system, as evidenced by a positive stress thallium or comparable test, myocardial infarction, cardiac arrhythmias, severe obstructive or restrictive pulmonary disease; patients with abnormal pulmonary function tests but stable obstructive or restrictive pulmonary disease may be eligible

Pulmonary conditions such as sarcoidosis, silicosis, idiopathic pulmonary fibrosis, or hypersensitivity pneumonitis are excluded

Anuria, dehydration, severe pulmonary congestion or pulmonary edema or fixed low cardiac input

Pulmonary conditions, which in the principal investigator's (PI’s) opinion would increase the risk of immunotherapy-related pulmonary toxicity, for example, interstitial lung diseases, such as idiopathic pulmonary fibrosis, and hypersensitivity pneumonitis, silicosis or sarcoidosis

Treated with appropriate maximal medical therapy for pulmonary toxicity

New or progressive pulmonary infiltrates; progressive pulmonary infiltrate is defined as an increase of 20% or greater from prior radiologic exam; radiologic assessment methods may be computed tomography (CT) or posterioranterior (PA)/lateral (L) x-ray imaging; infiltrates attributed to infection must be stable or improving after 1 week of appropriate therapy, or 4 weeks for presumed or proven fungal infections to be eligible

Pulmonary conditions - any of the following:\r\n* Respiratory condition that required any oxygen supplementation =< 6 months prior to registration\r\n* Prior or current pneumonitis\r\n* Clinically significant pulmonary hypertension =< 12 months prior to registration\r\n* Lung infection requiring treatment =< 3 months prior to registration\r\n* Pulmonary embolism requiring treatment =< 6 months prior to registration\r\n* Pleural effusion requiring drainage =< 12 months prior to registration

history of mediastinal or pulmonary irradiation

use of systemic steroids or immunosuppressive medication Pulmonary hypertension will not be an exclusion criterion as patients with pulmonary hypertension were shown to have higher bursting pressures following PA sealing in previous studies.

Known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease; requirement for supplemental oxygen

Has New York Heart Association (NYHA) class 3 or 4, myocardial infarction, acute coronary syndrome, diabetes mellitus with ketoacidosis or chronic obstructive pulmonary disease (COPD) requiring hospitalization in the preceding 6 months; or any other intercurrent medical condition that contraindicates treatment with sEphB4HSA or pembrolizumab (MK-3475) or places the patient at undue risk for treatment related complications

EXCLUSION CRITERIA FOR PATIENTS WITH NSCLC OR TNBC (COHORT B): Patients with clinically significant pulmonary dysfunction, as determined by medical history and physical exam should undergo pulmonary function testing; those with an FEV1 of =< 65% or DLCO (corrected) < 40% will be excluded

EXCLUSION CRITERIA FOR TNBC: Patients with clinically significant pulmonary dysfunction, as determined by medical history and physical exam should undergo pulmonary function testing; those with an FEV1 of =< 65% or DLCO (corrected) < 40% will be excluded

Active systemic, pulmonary, or pericardial infection

pulmonary conditions e.g. unstable or uncompensated respiratory disease

Significant extrahepatic disease\r\n* Symptomatic extrahepatic disease (including primary tumor, if unresected)\r\n* Greater than 10 pulmonary nodules (each =< 20 mm in diameter) or combined diameter of all pulmonary nodules > 15 cm\r\n* Peritoneal carcinomatosis

No prior history of idiopathic pulmonary fibrosis

Patient has severe pulmonary, cardiac, or other systemic disease, specifically:

Current signs or symptoms of severe progressive or uncontrolled hepatic, hematologic, gastrointestinal, endocrine, pulmonary or cardiac disease other than directly related to RCC

The subject has radiographic evidence of cavitating pulmonary lesion(s)

Active pulmonary disease requiring medication to include multiple inhalers (>2 inhalers and one containing steroids)

Known history of uncontrolled sleep apnea syndrome or other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease or a requirement for supplemental oxygen

Any serious and/or unstable pre-existing medical disorder (aside from malignancy exception above), psychiatric disorder, or other conditions that could interfere with subject’s safety, obtaining informed consent or compliance to the study procedures, in the opinion of the investigator; this could include severe, active co-morbidities such as:\r\n* Uncontrolled cardiac disease (hypertension, unstable angina, myocardial infarction within last 6 months, uncontrolled congestive heart failure, cardiomyopathy with decreased ejection fraction)\r\n* Acute bacterial or fungal infection requiring intravenous antibiotics at time of registration\r\n* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days of registration\r\n* Hepatic insufficiency resulting in jaundice and/or coagulation defects

Adequate pulmonary and cardiac function: no clinical evidence of cardiopulmonary disease, which, in the opinion of the investigator, precludes enrollment

ARM A COHORT 1: Patients must not have a history of slowly progressive dyspnea and unproductive cough, or of conditions such as sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis, or multiple allergies

No cardiomegaly or bilateral pulmonary infiltrates on chest radiograph; patients may have pulmonary metastatic lesions

ELIGIBILITY CRITERIA- LYMPHODEPLETION/INFUSION OF tvs-CTL: No cardiomegaly or bilateral pulmonary infiltrates on chest radiograph; patients may have pulmonary metastatic lesions

Subjects with a history of pulmonary embolism are excluded

Pulmonary embolism

History of interstitial lung disease, idiopathic pulmonary fibrosis, silicosis, sarcoidosis or connective tissue disorders (including rheumatoid arthritis and systemic lupus erythematosus)

Patients with chronic kidney disease who are on chronic renal replacement therapy are allowed; other tests, such as pulmonary function tests, cardiac echocardiogram or stress test, will be performed if clinically indicated

History of interstitial lung disease, history of slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis or pulmonary hypersensitivity pneumonitis

Pulmonary conditions such as sarcoidosis, silicosis, idiopathic pulmonary fibrosis, or hypersensitivity pneumonitis

Presence of leukemic or infectious pulmonary parenchymal disease

No overt cardiac, gastrointestinal, pulmonary or psychiatric disease

Has a history of blood clots, pulmonary embolism, or DVT unless controlled by anticoagulant treatment

Patients diagnosed with severe, active co-morbidity, defined as follows are not eligible:\r\n* Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months\r\n* Transmural myocardial infarction within the last 6 months\r\n* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration\r\n* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days before registration\r\n* Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol\r\n* Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol; the need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive; protocol-specific requirements may also exclude immuno-compromised patients\r\n* Patients with history of inflammatory colitis (including Crohn’s disease and ulcerative colitis), active lupus, scleroderma or active collagen vascular disease are not eligible

Patients with renal, hepatic, pulmonary, or cardiac disease that exclude delivery of standard chemotherapy

Serious medical illness or severe debilitating pulmonary disease that would potentially increase the patients’ risk for toxicity

Severe or debilitating pulmonary disease (dyspnea at rest, significant shortness of breath, chronic obstructive pulmonary disease [COPD])

Radiographic evidence of cavitating pulmonary lesion(s)

known pneumonitis or pulmonary fibrosis with clinically significant impairment of pulmonary function

History of active connective tissue disease (scleroderma) or idiopathic pulmonary fibrosis

Any serious and/or unstable pre-existing medical disorder (aside from malignancy exception above), psychiatric disorder, or other conditions that could interfere with subject’s safety, obtaining informed consent or compliance to the study procedures, in the opinion of the investigator; this could include severe, active co-morbidities such as:\r\n* Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months\r\n* Transmural myocardial infarction within the last 6 months\r\n* Acquired immune deficiency syndrome (AIDS) based upon the current Centers for Disease Control and Prevention (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol\r\n* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days of registration\r\n* Hepatic insufficiency resulting in jaundice and/or coagulation defects

Cardiac or pulmonary conditions that preclude aggressive cytoreductive surgery

Known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness such as severe chronic obstructive pulmonary disease requiring supplemental oxygen

Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration

Clinically no evidence of pulmonary disease

The subject has radiographic evidence of cavitating pulmonary lesion(s)

Evidence of pulmonary insufficiency

Other cardiac or pulmonary disease that, at the investigators discretion, can impair treatment safety

The subject has radiographic evidence of cavitating pulmonary lesion(s)

Pulmonary disease: severe chronic obstructive lung disease, or symptomatic restrictive lung disease

Patient with a history of interstitial lung disease, history of slowly progressive dyspnea, sarcoidosis, silicosis, idiopathic pulmonary fibrosis or pulmonary hypersensitivity pneumonitis

Severe acute co-morbidity, defined as follows:\r\n* Unstable angina and/or congestive heart failure requiring hospitalization in the last 3 months\r\n* Transmural myocardial infarction within the last 6 months\r\n* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration\r\n* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration \r\n* Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol; protocol-specific requirements may also exclude immunocompromised patients

Active and severe medical co-morbidity defined as follows: unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months, transmural myocardial infarction within the last 6 months, acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration, chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration, hepatic insufficiency resulting in clinical jaundice, active inflammatory bowel disease (Crohn’s disease or ulcerative colitis), diagnosed connective tissue disorder, or congenital coagulation defects (patients on medical therapy with Coumadin or other blood thinning agents are eligible for participation)

Concomitant disease or malformation severely affecting the cardiovascular, pulmonary, liver or renal function

Serious medical conditions (congestive heart failure [CHF], angina, diabetes mellitus type 1, chronic obstructive pulmonary disease [COPD], bleeding diathesis)

Patients must have no overt cardiac, gastrointestinal, pulmonary or psychiatric disease

Chronic pulmonary aspergillosis, pulmonary sarcoidosis, aspergilloma, or allergic bronchopulmonary aspergillosis (ABPA).

Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage

Symptomatic pulmonary KS

Refractory congestive heart failure unresponsive to medical treatment; active infection resistant to all antibiotics; or non-AML-associated pulmonary disease requiring >2 liters per minute (LPM) oxygen, or any other condition that puts the subject at an imminent risk of death.

Severe, active co-morbidity, defined as follows:\r\n* Unstable angina and/or congestive heart failure requiring hospitalization within the past 6 months\r\n* Transmural myocardial infarction within the last 6 months\r\n* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration\r\n* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration\r\n* Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects\r\n* Uncontrolled diabetes, defined as diabetes mellitus, which in the opinion of any of the patient’s physicians requires an immediate change in management; a patient may be considered eligible for the study if the physician managing the patient’s diabetes considers that the appropriate changes in management have resulted in adequate control\r\n* Uncompensated heart disease or uncontrolled high blood pressure, which in the opinion of any of patient’s physicians, requires immediate change in management; a patient may be considered eligible for the study if the physician managing the patient’s heart disease or blood pressure considers that the appropriate changes in management have resulted in adequate control\r\n* Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; patients with AIDS will be ineligible for this protocol; patients with clinical suspicion of AIDS and who are unwilling to have an HIV test are not eligible for this trial\r\n* Uncontrolled infection\r\n* Other immunocompromised status (e.g., organ transplant or chronic glucocorticoid use, or any other immunocompromised status that in the opinion of the investigator would preclude the patient from receiving protocol therapy)

No overt renal, hepatic, cardiac or pulmonary disease

Active systemic, pulmonary, or pericardial infection

Clinical evidence of pulmonary insufficiency

Patients with radiographic changes including pulmonary disease, including but not limited to: pulmonary nodules, infiltrates, pleural effusion are excluded unless cleared by pulmonary biopsy showing no evidence for pulmonary infection

No overt cardiac, gastrointestinal, pulmonary or psychiatric disease

Severe liver dysfunction or pulmonary insufficiency

Severe liver dysfunction or pulmonary insufficiency

Pulmonary hypertension moderate to severe by echocardiographic standards

Significant pulmonary disease or condition

Patients with active systemic, pulmonary, or pericardial infection

Criteria 7 Known chronic obstructive pulmonary disease (COPD) with a FEV1 < 50% of predicted normal

History of pulmonary disease or abnormal pulmonary function studies

DLCO ? 40% predicted with no symptomatic pulmonary disease. If DLCO is ?35% and < 40% and the patient is asymptomatic, a pulmonary consult is required

Pulmonary metastases

Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels and/or hemoptysis in excess of 2.5 mL (or one half teaspoon) =< 8 weeks of registration

Patients in whom IV fluid hydration is contraindicated (e.g. due to pre-existing pulmonary, cardiac, or renal impairment) will NOT be eligible for participation

Chronic Obstructive Pulmonary Disease, defined as being associated with a hospitalization for pneumonia or respiratory decompensation within 12 months of diagnosis; this does not include obstruction from tumor

Patients who have received oral or IV antibiotics within 2 weeks before initiation of study treatment; patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible

If they have New York Heart Association (NYHA) class 3 or 4; myocardial infarction, acute coronary syndrome, diabetes mellitus with ketoacidosis or chronic obstructive pulmonary disease (COPD) requiring hospitalization in the preceding 6 months; or any other intercurrent medical condition that contraindicates treatment with sEphB4-HSA or places the patient at undue risk for treatment related complications

Severe chronic obstructive pulmonary disease (COPD) with hypoxemia

Received oral or IV antibiotics within 2 weeks prior to cycle 1, day 1 (Patients receiving prophylactic antibiotics [e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease] are eligible.)

History of chronic obstructive pulmonary disease (COPD) or other chronic pulmonary disease requiring systemic steroid therapy, oxygen, or hospitalization

Known moderate to severe chronic obstructive pulmonary disease (COPD), interstitial lung disease, and pulmonary fibrosis

The subject has radiographic evidence of cavitating pulmonary lesion(s)

Severe chronic obstructive pulmonary disease (COPD) requiring > 3 hospitalizations in the past year

Received oral or IV antibiotics within 2 weeks prior to week 1, day 1\r\n* Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible

New or progressive pulmonary infiltrates on screening chest x-ray or chest computed tomography (CT) scan unless cleared for study by pulmonary. Infiltrates attributed to infection must be stable/improving (with associated clinical improvement) after 1 week of appropriate therapy (4 weeks for presumed or documented fungal infections).

Pulmonary conditions such as sarcoidosis, silicosis, idiopathic pulmonary fibrosis, or hypersensitivity pneumonitis

Received oral or IV antibiotics within 2 weeks prior to cycle 1, day 1\r\n* Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible

Pulmonary hemorrhage or hemoptysis > 2.5 ml blood within 6 weeks unless cause has been addressed and is medically resolved.

Refractory congestive heart failure unresponsive to medical treatment, active infection resistant to all antibiotics, or advanced non-MDS associated pulmonary disease requiring >2 liters per minute oxygen.

Patients with concurrent local and pulmonary recurrence at the time of enrollment; note: patients who had local recurrence previously that has been treated and now present with an isolated pulmonary recurrence and meet the surgical resection criteria stated above will be eligible

Idiopathic pulmonary fibrosis or other severe interstitial lung disease that requires oxygen therapy or is thought to require oxygen therapy within 1 year prior to step 1 registration

Received oral or intravenous (IV) antibiotics within 2 weeks prior to cycle 1, day 1; patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible

Severe, active co-morbidity defined as follows:\r\n* Unstable angina and/or congestive heart failure requiring hospitalization within 6 months prior to registration\r\n* Transmural myocardial infarction within 6 months prior to registration\r\n* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration; Note: if the infection resolves and the patient is on oral (p.o.) and still within, the required registration timeframe, then the patient is eligible\r\n* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration\r\n* Idiopathic pulmonary fibrosis or other severe interstitial lung disease that requires oxygen therapy or is thought to require oxygen therapy within 1 year prior to registration\r\n* History of (non-infectious) pneumonitis that required steroids or current pneumonitis\r\n* Acquired immune deficiency syndrome (AIDS) based upon current Center for Disease Control and Prevention (CDC) definition; note: human immunodeficiency virus (HIV) testing is not required for entry into this protocol; the need to exclude patients with AIDS from this protocol is necessary because the cisplatin and IMRT involved in this protocol may be significantly immunosuppressive; patients with known HIV, CD4 counts >= 250/uL, and undetectable viral loads who are stable on an antiretroviral regimen may be included\r\n* A diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of the MK-3475 (pembrolizumab)\r\n* Known history of active TB (Bacillus tuberculosis)\r\n* Known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis c virus [HCV] ribonucleic acid [RNA] [qualitative] is detected); Note: patients who have been curatively treated for hepatitis C and have no detectable viral load are eligible\r\n* Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs); replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment

Severe, active co-morbidity, defined as follows:\r\n* Unstable angina and/or congestive heart failure requiring hospitalization within 6 months prior to registration\r\n* Transmural myocardial infarction within 6 months prior to registration\r\n* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration\r\n* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration\r\n* Idiopathic pulmonary fibrosis or other severe interstitial lung disease that requires oxygen therapy or is thought to require oxygen therapy within 1 year prior to registration\r\n* Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for coagulation parameters are not required for entry into this protocol\r\n* Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease and Control and Prevention (CDC) definition; note: human immunodeficiency virus (HIV) testing is not required for entry into this protocol; protocol-specific requirements may also exclude immuno-compromised patients

Uncontrolled, clinically significant pulmonary disease (e.g., chronic obstructive pulmonary disease [COPD], pulmonary hypertension) that in the opinion of the investigator would put the patient at significant risk for pulmonary complications during the study

Evidence of current serious uncontrolled concomitant cardiovascular nervous system, pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine (include uncontrolled diabetes mellitus) or gastrointestinal disease

Known history of pulmonary fibrosis

The subject has cavitating pulmonary lesion(s) or a pulmonary lesion abutting or encasing a major blood vessel

Pulmonary nodules > 10 mm\r\n* Pulmonary nodules > 10 mm that have been stable for > 6 months and are not clearly metastatic disease per the treating investigator are permitted

History of pulmonary disease such as emphysema or chronic obstructive pulmonary disease (COPD) (forced expiratory volume in one second [FEV1] < 60% of predicted for height and age); pulmonary function tests (PFTs) are required in patients with prolonged smoking history or symptoms of respiratory dysfunction

History of pulmonary disease such as emphysema or chronic obstructive pulmonary disease (COPD), (forced expiratory volume [FEV] > 60% of predicted for height and age required in patients with prolonged smoking history or symptoms of respiratory dysfunction)

No history of severe chronic obstructive pulmonary disease (COPD) or emphysema or interstitial lung disease currently on home supplemental oxygen; patients with NSCLC with stable COPD or emphysema not requiring supplemental oxygen are eligible

Severe, active co-morbidity, defined as follows:\r\n* Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months;\r\n* Transmural myocardial infarction within the last 6 months;\r\n* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration;\r\n* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration;\r\n* Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol\r\n* Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol; protocol-specific requirements may also exclude immuno-compromised patients

Received oral or IV antibiotics within 2 weeks prior to cycle 1, day 1\r\n* Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible

Significant pulmonary disease, including pulmonary hypertension or interstitial pneumonitis

Severe, active co-morbidity defined as follows:\r\n* Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months\r\n* Transmural myocardial infarction within the last 6 months\r\n* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration\r\n* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days of registration\r\n* Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol other than those requested\r\n* Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that HIV testing is not required for entry into this protocol; protocol-specific requirements may also exclude immuno-compromised patients

Pulmonary embolism

Severe chronic obstructive pulmonary disease requiring oxygen supplementation

History of pulmonary disease such as emphysema or chronic obstructive pulmonary disease (COPD), (forced expiratory volume of the lung in 1 second [FEV1] > 60% of predicted for height and age); pulmonary function tests (PFTs) are required in patients with prolonged smoking history or signs, symptoms, or history of respiratory dysfunction)

Patients who require chronic oxygen therapy for chronic obstructive pulmonary disease or pleural effusions (malignant or benign)

History of pulmonary disease such as emphysema or chronic obstructive pulmonary disease (COPD), (forced expiratory volume in one second [FEV1] > 60% of predicted for height and age); pulmonary function tests (PFTs) are required in patients with prolonged smoking history or symptoms of respiratory dysfunction

Severe, active co-morbidity, defined as follows:\r\n* Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months\r\n* Transmural myocardial infarction within the last 6 months\r\n* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration\r\n* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days before registration \r\n* Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol\r\n* Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol; protocol-specific requirements may also exclude immuno-compromised patients

Ejection fraction (EF) < 40% or myocardial infarction (MI) within the past 3 months; known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease; requirement for supplemental oxygen; or any conditions that could result in excessive toxicity associated with the benzodiazepine-like effects of MLN8237

Pulmonary function tests (PFT)s > 50% of predicted

No prior radiographic evidence of cavitating pulmonary lesion(s)

Severe, active co-morbidity, defined as follows:\r\n* Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months\r\n* Transmural myocardial infarction within the last 6 months\r\n* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration\r\n* Other major medical illness that requires hospitalization or precludes study therapy at the time of registration\r\n* Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory test coagulation parameters are not required for entry into this protocol\r\n* Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control (CDC) definition; not, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol; protocol-specific requirements may also exclude immunocompromised patients

Clinically significant and uncontrolled major medical condition(s) that places the\n             subject at an unacceptably high risk for toxicities. These include, but are not\n             limited to: active infections, symptomatic pulmonary disease, inadequate pulmonary\n             function, seizure disorder, psychiatric illness.

Severe, active co-morbidity, defined as follows:\r\n* Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months\r\n* Transmural myocardial infarction within the last 6 months\r\n* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration\r\n* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration \r\n* Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol\r\n* Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol

Severe, active co-morbidity, defined as follows:            \r\n* Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months\r\n* Transmural myocardial infarction within the last 6 months\r\n* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration\r\n* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days before registration\r\n* Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol\r\n* Known pre-existing immunodeficiency as seen in organ transplant recipient

History of documented pulmonary embolus within 6 months of enrollment

No overt renal, hepatic, cardiac or pulmonary disease

Patients with any non-malignant intercurrent illness (e.g. cardiovascular, pulmonary, central nervous system disease) which is either poorly controlled with currently available treatment, or which is of such severity that the investigators deem it unwise to enter the patient on protocol

Patients with an abnormal chest X-ray and/or any pulmonary infiltrate including those suspected to be of infectious origin; in particular, patients with resolution of clinical symptoms of pulmonary infection but with residual pulmonary infiltrates on chest x-ray are not eligible until pulmonary infiltrates have completely resolved

Severe, active co-morbidity, including any of the following:\r\n* Current uncontrolled cardiac disease; i.e., uncontrolled hypertension, unstable angina, myocardial infarction (within the past 6 months), uncontrolled congestive heart failure, and cardiomyopathy with decreased ejection fraction (< 50%)\r\n* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration\r\n* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 4 weeks of registration\r\n* Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for coagulation parameters are not required for entry into this protocol\r\n* Patients with acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition or patients known to be human immunodeficiency virus (HIV) positive; note, however, that HIV testing is not required for entry into this protocol

History or other evidence of chronic pulmonary disease associated with functional limitation

History or other evidence of chronic pulmonary disease associated with functional limitation

Patients with any unstable medical issue (including cardiac issues as above, active treatment for pulmonary embolism, cerebrovascular accident [CVA], renal or hepatic insufficiency, active infection/sepsis requiring IV antibiotics)

History of pulmonary fibrosis/inflammation, including active tuberculosis

Any significant medical condition, including any suggested by screening laboratory findings that, in the opinion of the investigator or sponsor, may place the subject at undue risk from the study, including but not necessarily limited to uncontrolled hypertension and/or diabetes, clinically significant pulmonary disease (e.g., chronic obstructive pulmonary disease requiring hospitalization within 6 months) or neurological disorder (e.g., seizure disorder active within 6 months)

Previous history of pulmonary embolism or pulmonary embolism found on screening exam.

Participant has known chronic obstructive pulmonary disease (COPD) (defined as a forced expiratory volume in 1 second [FEV1] <50% of predicted normal), persistent asthma, or a history of asthma within the last 2 years (controlled intermittent asthma or controlled mild persistent asthma is allowed)

Subject has a history of interstitial lung disease, history of slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies. Any lung disease that may interfere with the detection or management of suspected drug-related pulmonary toxicity.

ENTRY CRITERIA:\n\n        DISEASE CHARACTERISTICS:\n\n          -  Histologic confirmation of non-muscle invasive bladder cancer of the transitional cell\n             carcinoma high-grade subtype.\n\n               -  Patients are eligible if the diagnostic biopsy was done within 3 months of\n                  treatment start and a cystoscopy demonstrating no resectable disease was done\n                  within 6 weeks of treatment start. Patients with high-grade Ta and/or T1 disease\n                  should have complete resection before study treatment.\n\n               -  Upper tract imaging within 6 months prior to study entry must not be suspicious\n                  for upper tract malignancy.\n\n          -  No history of or evidence of muscle-invasive, locally advanced, metastatic and/or\n             extravesical bladder cancer or presence of any other cancer.\n\n        PRIOR/CONCURRENT THERAPY:\n\n          -  No prior BCG treatment or known hypersensitivity to BCG. Patients who have received\n             more than a single-dose post-operative treatment of mitomycin-C or gemcitabine are\n             excluded.\n\n          -  No concurrent use of other investigational agents.\n\n        PATIENT CHARACTERISTICS:\n\n        Performance Status • ECOG 0, 1, or 2. Bone Marrow Reserve\n\n          -  Absolute neutrophil count (AGC/ANC) ? 1,000/uL\n\n          -  Platelets ? 100,000/uL\n\n          -  Hemoglobin ? 8g/dL Renal Function\n\n          -  Glomerular Filtration Rate (GFR) > 40mL/min or serum creatinine ? 1.5 x ULN Hepatic\n             Function\n\n          -  Total bilirubin ? 2.0 X ULN\n\n          -  AST, ALT, ALP ? 3.0 X ULN Cardiovascular\n\n          -  No symptomatic congestive heart failure Class III or IV.\n\n          -  No severe/unstable angina pectoris < 6 months.\n\n          -  No myocardial infarction < 6 months. Pulmonary\n\n          -  Adequate pulmonary function without any clinical sign of severe pulmonary dysfunction.\n\n        Other\n\n          -  Currently eligible for intravesical BCG therapy.\n\n          -  Negative serum pregnancy test if female and of childbearing potential.\n\n          -  No women who are pregnant or nursing.\n\n          -  Subjects, both females and males, with reproductive potential must agree to use\n             effective contraceptive measures for the duration of the study.\n\n          -  No known positive HIV status.\n\n          -  No history or evidence of uncontrollable CNS disease.\n\n          -  No psychiatric illness/social situation that would limit compliance with study\n             requirements.\n\n          -  No other illness that in the opinion of the investigator would exclude the patient\n             from participating in this study.\n\n          -  Must provide signed informed consent and HIPPA authorization and agree to comply with\n             all protocol-specified procedures and follow-up evaluations.\n\n          -  No active systemic infection requiring parenteral antibiotic therapy.\n\n          -  No ongoing chronic systemic steroid therapy required.\n\n          -  No concurrent febrile illness, active urinary tract infection, active tuberculosis, a\n             history of hypotension or anaphylactic reactions.

The patient has uncontrolled, clinically significant pulmonary disease (e.g., COPD, pulmonary hypertension) that in the opinion of the investigator would put the patient at significant risk for pulmonary complications during the study.

Radiographic evidence of cavitating pulmonary lesion(s)

Restrictive or obstructive pulmonary disease that would limit study compliance or place the patient at unacceptable risk for participation in the study

Presentation of pulmonary insufficiency or clinically evident chronic obstructive pulmonary disease

Pulmonary LCNEC;

Severe, active co-morbidity, defined as follows per time points indicated below (or per time points indicated below prior to the first day of chemotherapy for patients having started chemotherapy prior to first step registration): \r\n* Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months\r\n* Transmural myocardial infarction within the 3 months of study registration\r\n* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration\r\n* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration

Stable cardiovascular, pulmonary health status

Patients who have a known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness (such as severe chronic obstructive pulmonary disease or requirement for supplemental oxygen) are not eligible

Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage

Known chronic obstructive pulmonary disease, persistent asthma, or a history of asthma within 2 years

Chronic Obstructive Pulmonary Disease (COPD) exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration. COPD requiring chronic oral steroid therapy

Normal clinical assessment of pulmonary function

Active pulmonary infection not responsive to conventional antibiotics

Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 calendar days prior to registration

Evidence of pulmonary insufficiency or clinically evident chronic obstructive pulmonary disease

The FHCRC principal investigator (PI) of the study must approve enrollment of all patients with pulmonary nodules

Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment; patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study

Received therapeutic oral or IV antibiotics within 2 weeks prior to cycle 1, day 1; patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible

Pulmonary embolism.

Pulmonary embolism within 12 months before screening

Impaired pulmonary function

Active and ongoing steroid use, except for non-systemically absorbed treatments (such as inhaled or topical steroid therapy for asthma, chronic obstructive pulmonary disease [COPD], allergic rhinitis)

Known chronic obstructive pulmonary disease (COPD) OR moderate or severe persistent asthma within the past 2 years

Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration

Known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease; patients who use continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BIPAP) at night and have controlled sleep apnea syndrome are allowed

Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage

Inflammatory lung disease including moderate and severe asthma and chronic obstructive pulmonary disease (COPD) requiring chronic medical therapy.

Patient must not have any of the following severe, active co-morbidity, defined as follows:\r\n* Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months\r\n* Transmural myocardial infarction within the last 6 months\r\n* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration\r\n* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days before registration\r\n* Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol\r\n* Acquired immune deficiency syndrome (AIDS) or human immunodeficiency virus (HIV) positive based upon current Centers for Disease and Control and Prevention (CDC) definition; note, however, that HIV testing is not required for entry into this protocol; the need to exclude patients with AIDS or HIV from this protocol is necessary\r\n* Gastrointestinal/malabsorption disorder at the discretion of the principal investigator\r\n* Inflammatory bowel disease\r\n* Celiac disease\r\n* Chronic pancreatitis\r\n* Chronic diarrhea or vomiting\r\n* Active eating disorder

Severe, active co-morbidity, defined as follows:\r\n* Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months\r\n* Transmural myocardial infarction within the last 6 months\r\n* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration\r\n* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days before registration\r\n* Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol\r\n* Acquired immune deficiency syndrome (AIDS) or HIV positive based upon current CDC definition; note, however, that HIV testing is not required for entry into this protocol; the need to exclude patients with AIDS or HIV from this protocol is necessary

Known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease; requirement for supplemental oxygen, or any conditions that could result in excessive toxicity associated with the benzodiazepine-like effects of MLN8237

Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration

Other concurrent serious diseases that may interfere with planned treatment including severe pulmonary conditions/illness

Severe, active co-morbidity, defined as follows:\r\n* Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months\r\n* Transmural myocardial infarction within the last 6 months\r\n* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration\r\n* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration\r\n* Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol\r\n* Acquired immune deficiency syndrome (AIDS) based upon the current Centers for Disease Control and Prevention (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol; protocol-specific requirements may also exclude immuno-compromised patients

Severe, active co-morbidity, defined as follows:\r\n* Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months\r\n* Transmural myocardial infarction within the last 6 months\r\n* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration\r\n* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days before registration\r\n* Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol\r\n* Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol; patients who are HIV seropositive but do not meet criteria for diagnosis of AIDS are eligible for study participation

Participant has pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring active treatment, including the use of oxygen.

Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days before registration

Therapeutic oral or IV antibiotics within 2 weeks prior to cycle 1, day 1\r\n* Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or to prevent chronic obstructive pulmonary disease exacerbation) are eligible

Uncontrolled, clinically significant pulmonary disease (e.g., chronic obstructive pulmonary disease, pulmonary hypertension) that in the opinion of the Investigator would put the patient at significant risk for pulmonary complications during the study.

No active systemic, pulmonary, or pericardial infection

Subjects with serious intercurrent chronic or acute illness, such as cardiac or pulmonary disease, hepatic disease, or other illness considered by the Investigator as high risk for investigational drug treatment

Known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) <50% of predicted normal or known moderate or severe persistent asthma within the past 2 years, or uncontrolled asthma of any classification

Received oral or intravenous (IV) antibiotics within 2 weeks prior to cycle 1, day 1; patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible

Presence of interstitial lung disease, pulmonary fibrosis, or pulmonary hypersensitivity reaction

Receipt of glucocorticoids (with the exception of inhaled glucocorticoid steroids for the use of allergic rhinitis or pulmonary disease) within 2 weeks of registration

Severe, active co-morbidity, defined as follows:\r\n* Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months\r\n* Transmural myocardial infarction within the last 6 months\r\n* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration\r\n* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days before registration\r\n* Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol\r\n* Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol; protocol-specific requirements may also exclude immuno-compromised patients\r\n* History of treatment with potent immunosuppressive drugs for such conditions as post organ transplant, severe rheumatoid arthritis, etc. within the past 6 months

Patients with known moderate/severe pleural effusions that are unrelated to malignancy or established diagnosis of pulmonary arterial hypertension

Severe, active comorbidity, including any of the following:\r\n* Unstable angina and/or congestive heart failure requiring hospitalization\r\n* Transmural myocardial infarction within the last 6 months\r\n* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of study initiation\r\n* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy\r\n* Known hepatic insufficiency resulting in clinical jaundice and/or coagulation defects\r\n* Known human immunodeficiency virus (HIV) and hepatitis C positive status\r\n* Major medical illnesses or psychiatric impairments that, in the investigator's opinion, will prevent administration or completion of protocol therapy\r\n* Active connective tissue disorders, such as lupus or scleroderma that, in the opinion of the treating physician, may put the patient at high risk for radiation toxicity

Severe, active co-morbidity, defined as follows:\r\n* Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months\r\n* Transmural myocardial infarction within the last 6 months\r\n* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration\r\n* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days before registration\r\n* Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol\r\n* Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol; protocol-specific requirements may also exclude immuno-compromised patients\r\n* Patients with history of inflammatory colitis (including Crohn’s disease and ulcerative colitis) are not eligible

Known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease; requirement for supplemental oxygen; or any conditions that could result in excessive toxicity associated with the benzodiazepine-like effects of MLN8237

Significant pulmonary disease, including pulmonary hypertension or interstitial pneumonitis

Severe, active comorbidity, defined as follows:\r\n* Unstable angina and/or congestive heart failure requiring hospitalization within the last 12 months\r\n* Transmural myocardial infarction within the last 6 months\r\n* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration\r\n* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days prior to registration\r\n* Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects\r\n* Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol\r\n* Evidence of uncontrolled seizures, central nervous system disorders, or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent, or interfering with compliance of treatment protocol or follow up\r\n* Known, existing uncontrolled coagulopathy; subjects on therapeutic anticoagulation may be enrolled provided that they have been clinically stable on anti-coagulation for at least 2 weeks\r\n* Major surgery within 28 days of study enrollment (other than diverting colostomy)\r\n* Crohn’s disease or ulcerative colitis requiring hospitalization, surgery or immunosuppressive medications

History of other pulmonary disease such as emphysema or chronic obstructive pulmonary disease (COPD), (forced expiratory volume in 1 second [FEV1] < 60% of predicted for height and age); pulmonary function tests (PFTs) are required in patients with prolonged smoking history or symptoms of respiratory dysfunction

Severe or debilitating pulmonary disease (dyspnea at rest, significant shortness of breath, chronic obstructive pulmonary disease [COPD])

Known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease; requirement for supplemental oxygen

Participant has known chronic obstructive pulmonary disease (COPD) (defined as a forced expiratory volume in 1 second [FEV1] <50% of predicted normal), known moderate or severe persistent asthma within the last 2 years or currently has uncontrolled asthma of any classification (controlled intermittent asthma or controlled mild persistent asthma is allowed)

Severe, active comorbidity, defined as follows:\r\n* Unstable angina, history of myocardial infarction and/or congestive heart failure requiring hospitalization within the last 6 months\r\n* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration\r\n* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration\r\n* Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol\r\n* Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol; protocol-specific requirements may also exclude immuno-compromised patients

Anuria, dehydration, severe pulmonary congestion or pulmonary edema or fixed low cardiac input since all are conditions for which osmotic diuresis are contraindicated and ascorbic acid has high osmolarity

Patients with pulmonary disease limiting daily function or requiring oxygen supplementation

The presence of co-existing medical conditions that would limit compliance with study medications, including, but not limited to active infection, active or untreated cardiac or pulmonary disease, or malignancy

Pulmonary disease including or greater than grade 2 dyspnea or laryngeal edema, grade 3 pulmonary edema or pulmonary hypertension according to CTCAE 4.03

The subject has radiographic evidence of cavitating pulmonary lesion(s)

Patient has up to 6 local pulmonary metastases targetable by cryoablation.

Patient has evidence of active systemic, pulmonary, or pericardial infection.

Subjects with a history of interstitial lung disease or lung disease that has required intubation in the past (i.e. such as asthma or chronic obstructive pulmonary disease [COPD]); patients requiring continuous supplemental oxygen are excluded

Severe, active co-morbidity defined as follows:\r\n* Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months\r\n* Transmural myocardial infarction within the last 6 months\r\n* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration\r\n* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days of registration\r\n* Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects

Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels

Known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease; requirement for supplemental oxygen

Known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease; requirement for supplemental oxygen

Any history of symptomatic pulmonary compromise, such as chronic obstructive pulmonary disease

No known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage; patients with lesions infiltrating major pulmonary vessels (contiguous tumor and vessels) are excluded; however, the presence of a tumor that is touching, but not infiltrating (abutting) the vessels is acceptable (computed tomography [CT] with contrast is strongly recommended to evaluate such lesions); patients with large protruding endobronchial lesions in the main or lobar bronchi are excluded; however, endobronchial lesions in the segmented bronchi are allowed

Pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring the use of oxygen

Concurrent major medical conditions, such as uncontrolled hypertension, diabetes mellitus, ischemic heart disease, chronic obstructive pulmonary disease, autoimmune disease, adrenal insufficiency, or prior allogeneic organ transplant requiring chronic immunosuppressive therapy, including systemic glucocorticoid treatment or replacement therapy

Subjects in whom the required program of PO and IV fluid hydration is contraindicated, eg, due to pre-existing pulmonary, cardiac, or renal impairment

Participants must have baseline echocardiogram and pulmonary function tests within 3 months prior to study entry

Severe, active co-morbidity, defined as follows:\r\n* Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months prior to registration\r\n* Transmural myocardial infarction within the last 6 months prior to registration\r\n* History of stroke or transient ischemic attack within 6 months prior to registration\r\n* Significant vascular disease (e.g., aortic aneurysm, history of aortic dissection) or clinically significant peripheral vascular disease\r\n* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration\r\n* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration\r\n* Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function other than screening panel and coagulation parameters are not required for entry into this protocol\r\n* Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol; the need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive; protocol specific requirements may also exclude immuno-compromised patients

Pulmonary embolism on active therapy

Patient must not have any known endobronchial lesions and/or lesions infiltrating major pulmonary vessels

Other serious illnesses or medical conditions including but not limited to:\r\n* Unstable cardiac disease despite treatment, myocardial infarction within 6 months prior to study entry\r\n* History of significant neurologic or psychiatric disorders including dementia or seizures\r\n* Active clinically significant uncontrolled infection\r\n* Active peptic ulcer disease defined as unhealed or clinically active\r\n* Hypercalcemia \r\n* Active drug addiction including alcohol, cocaine or intravenous drug use defined as occurring within the 6 months preceding diagnosis\r\n* Chronic obstructive pulmonary disease, defined as being associated with a hospitalization for pneumonia or respiratory decompensating within 12 months of diagnosis; this does not include obstruction from tumor\r\n* Autoimmune disease requiring therapy, prior organ transplant, or human immunodeficiency virus (HIV) infection \r\n* Interstitial lung disease\r\n* Hepatitis C by history

Patient must not have a known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease

Patients with severe pulmonary hypertension \r\n* Tricuspid jet velocity > 2.5 m/sec

Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels

Symptomatic pulmonary disease currently requiring regular medication including but not restricted to bronchodilators

Prior to day 1 of brentuximab vedotin, please verify the patient does not meet the criteria below:\r\n* Symptomatic pulmonary disease currently requiring regular medication including but not restricted to bronchodilators

Severe hyperactive airway disease (chronic obstructive pulmonary disease, asthma)

Known history of uncontrolled sleep apnea syndrome and other conditions according to enrolling investigator that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease; requirement for supplemental oxygen therapy; or requirement of recurrent thoracentesis to manage pleural effusions

The subject has a pulmonary lesion abutting or encasing a major blood vessel

Patients must not have serious intercurrent medical illness. Serious, active co-morbidity, defined as follows: a) Unstable angina and/or congestive heart failure requiring hospitalization within the last 12 months. b) Transmural myocardial infarction within the last 6 months. c) Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration. d) Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration. e) Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol.

Evidence of an active pulmonary, gastrointestinal, genitourinary, or other serious infection at time of enrollment

Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels

The FHCRC PI of the study must approve of enrollment of all patients with pulmonary nodules

Patients with severe, active co-morbidity, defined as follows:\r\n* Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months\r\n* Transmural myocardial infarction within the last 6 months\r\n* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration\r\n* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days before registration\r\n* Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol\r\n* Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol; protocol-specific requirements may also exclude immuno-compromised patients

Received oral or intravenous (IV) antibiotics within 2 weeks prior to cycle 1, day 1; patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible

Received oral or IV antibiotics within 2 weeks prior to cycle 1, day 1 for treatment of active infection (patients receiving prophylactic antibiotics [e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease] are eligible)

Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible

Moderate or severe pulmonary hypertension defined as pulmonary artery systolic pressure (PASP) > 50mm Hg; for those patients where PASP is indeterminate, moderate to severe symptoms of pulmonary hypertension (World Health Organization functional assessment class III or IV) will be used to determine exclusion criteria

Patients with compromised pulmonary disease.

Receipt of glucocorticoids (with the exception of inhaled glucocorticoid steroids for the use of allergic rhinitis or pulmonary disease) within 2 months prior to registration

Patients must have at least one of the following for inclusion into protocol:\r\n* Lupus nephritis, defined as renal biopsy (biopsy within 6 months of transplant decision) showing glomerulonephritis, with active diffuse proliferative lesion (World Health Organization [WHO] stage IV or Vd, with biopsy classified by WHO criteria)\r\n* Refractory and severe seizures or encephalopathy attributed to SLE\r\n* Severe pulmonary involvement with recurrent pulmonary hemorrhage; and/or refractory pulmonary infiltrate not attributed to infection; and/or interstitial lung disease- defined by presence of alveolitis or pneumonitis on high-resolution computed tomography (CT) scan or documentation of DLCO < 80% at least twice\r\n* Transfusion-dependent cytopenias that are unresponsive to standard treatment\r\n* Catastrophic antiphospholipid syndrome, which is defined as an antiphospholipid titer greater than 5 standard deviations above the mean and two or more antiphospholipid related manifestations, including either cytopenias or vascular thrombosis that failed to respond to anticoagulant therapy\r\n* Vasculitis and/or immune complex deposition causing end-organ signs or symptoms, e.g. cerebritis, cardiac failure, or renal failure, refractory to standard treatment

History of interstitial lung disease, or slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies.

Participant has known chronic obstructive pulmonary disease (COPD) with a Forced Expiratory Volume in 1 second (FEV1) less than (<) 50% predicted normal. Note that FEV1 testing is required for participants suspected of having COPD and participants must be excluded if FEV1 <50% b) Participant has known moderate or severe persistent asthma within 2 years (see Attachment 4: NHLBI table of asthma severity), or currently has uncontrolled asthma of any classification. (Note that participants who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed in the study)

Known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease; requirement for supplemental oxygen

Patients with idiopathic pulmonary fibrosis

Pulmonary:

Previous history of pulmonary embolism or pulmonary embolism found on screening exam.

Subjects with a history of interstitial lung disease, history of slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies.

Participants for whom front-line cytotoxic therapy is indicated (i.e., symptomatic visceral or pulmonary KS or symptomatic KS impairing functional status); all participants must have a chest X-ray to rule out pulmonary KS within 28 days of study enrollment

Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels

Severe chronic obstructive or other pulmonary disease with hypoxemia

History of symptomatic pulmonary dysfunction

Evidence of chronic obstructive pulmonary disease

Severe, active co-morbidity, defined as follows:\r\n* Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months\r\n* Transmural myocardial infarction within the last 6 months\r\n* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration\r\n* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration; hepatic insufficiency resulting in clinical jaundice and/or coagulation defects\r\n* Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol; protocol-specific requirements may also exclude immuno-compromised patients

Ineligible for curative pulmonary metastasectomy

Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage.

Severe, active co-morbidity, defined as follows:\r\n* Unstable angina, and/or congestive heart failure requiring hospitalization within the last 6 months\r\n* Transmural myocardial infarction within the last 6 months\r\n* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration\r\n* Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects\r\n* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization, or precluding study therapy at the time of registration\r\n* Uncontrolled, clinically significant cardiac arrhythmias\r\n* Radiologic or clinical evidence of hydrocephalus, or history of previously treated hydrocephalus

The subject has radiographic evidence of cavitating pulmonary lesion(s)

Participants with diabetes mellitus with ketoacidosis or chronic obstructive pulmonary disease (COPD) requiring hospitalization in the preceding 6 months, or any other intercurrent medical condition that contraindicates treatment with sEphB4-HSA or places the participant at undue risk for treatment related complications

Received IV antibiotics within 2 weeks prior to cycle 1, day 1; patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible

Grade 3 or greater edema (eg, peripheral, pulmonary)

Severe or debilitating pulmonary disease (dyspnea at rest, significant shortness of breath, chronic obstructive pulmonary disease [COPD])

Patients must have adequate cardiac and pulmonary function and otherwise be expected to tolerate general anesthesia

a short duration (< 5 days) of systemic corticosteroids e.g., of chronic obstructive pulmonary disease, or as an antiemetic corresponding at maximum to the anti-inflammatory potency of 4 mg dexamethasone for treatment;

Clinically significant pulmonary symptoms and signs, any active pulmonary or respiratory infection at enrollment, pulmonary infiltrates on screening CT scan of the chest that are associated with symptoms (including dyspnea), resting or exercise arterial oxygen saturation (SpO2) less than (<) 90 percent (%), requirement for supplementary oxygen at rest or exercise (either continuously or intermittently), moderate (40%-60% predicted) or severe (<40% predicted) decreased diffusing capacity for carbon monoxide (DLCO) or mild (>60% </= lower limit of normal [LLN]% predicted) decrease with clinically significant symptoms

Subject has cavitating pulmonary lesion(s) or a pulmonary lesion or tumor abutting or encasing a major blood vessel

Asthma or chronic obstructive pulmonary disease (COPD) requiring daily medication.

History of interstitial lung disease, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, or pulmonary hypersensitivity pneumonitis

Pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring the use of oxygen

Inflammatory lung disease including moderate and severe asthma and chronic obstructive pulmonary disease (COPD) requiring chronic medical therapy.

Major concomitant medical illness inclusive of severe chronic obstructive pulmonary disease, multiple sclerosis, symptomatic coronary artery disease, heart failure, recent major cerebrovascular accident, brittle diabetes, renal dialysis, end stage liver disease, labile hypertension, or any autoimmune disorder

Any history or signs of pulmonary lymphangitic spread;

Previous pulmonary embolism within 12 months before study entry

History of interstitial lung disease, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, or pulmonary hypersensitivity pneumonitis.

History of other pulmonary disease such as emphysema or chronic obstructive pulmonary disease, (forced expiratory volume in one second [FEV1] < 60% of predicted for height and age); pulmonary function tests (PFTs) are required in patients with prolonged smoking history or symptoms of respiratory dysfunction

Severe central nervous system, pulmonary, or renal disease not related to the participant's cancer.

History of uncontrolled sleep apnea syndrome or other condition that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease.

Known moderate to severe chronic obstructive pulmonary disease (COPD), interstitial lung disease, pulmonary fibrosis, and pulmonary arterial hypotension.

Known pulmonary hypertension of any severity.

Chronic steroid or immunosuppressive therapy (except for low dose corticosteroids for chronic obstructive pulmonary disease [COPD] or topical steroids, which are allowed)

Previous pulmonary embolism within 12 months prior to study entry

The subject has radiographic evidence of cavitating pulmonary lesion(s)

Prior history of pulmonary fibrosis.

Significant pulmonary compromise

Known moderate to severe chronic obstructive pulmonary disease, interstitial lung disease, and pulmonary fibrosis

Known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease; requirement for supplemental oxygen

Clinical Pulmonary Infection Score (CPIS) of at least 6

Known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease; requirement for supplemental oxygen.

History of symptomatic pulmonary disease or non-malignant pulmonary disease requiring treatment.

Patients in whom the required program of oral and IV fluid hydration is contraindicated, e.g. due to severe pre-existing pulmonary, cardiac, or renal impairment

No history of pulmonary disease such as emphysema or chronic obstructive pulmonary disease (COPD), (forced expiratory volume in one second [FEV1] > 2L or >= 50% of predicted for height and age); pulmonary function tests (PFTs) are required in patients with significant pulmonary or smoking history

Patients in whom the required program of oral and IV fluid hydration is contraindicated, e.g. due to pre-existing pulmonary, cardiac, or renal impairment

The patient has uncontrolled, clinically significant pulmonary disease (e.g., chronic obstructive pulmonary disease, pulmonary hypertension) that in the opinion of the Investigator would put the patient at significant risk for pulmonary complications during the study.

Pulmonary: new onset hypoxia

The subject has radiographic evidence of cavitating pulmonary lesion(s)

The subject has radiographic evidence of cavitating pulmonary lesion(s)

Known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease; requirement for supplemental oxygen; or any conditions that could result in excessive toxicity associated with the benzodiazepine-like effects of MLN8237

Echocardiographic evidence of pulmonary hypertension.

Patients with active pulmonary or pericardial infection

Recipient must have adequate pulmonary function defined as NO severe or symptomatic restrictive or obstructive lung disease, and formal pulmonary function testing showing an FEV1 >50% (predicted) and a DLCO >40% (predicted), corrected for hemoglobin.

Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage.

Patient has a history of significant cardiovascular, neurological, endocrine, gastrointestinal, respiratory, or inflammatory illness including recent myocardial infarction (within 6 months)or stroke; hypertension requiring >2 medications for adequate control; diabetes mellitus with >2 episodes of ketoacidosis in the preceding 12 months; or chronic obstructive pulmonary disease (COPD) requiring >2 hospitalizations in the preceding 12 months.

e. Unstable pulmonary disease requiring hospitalization or emergency room visit within the last 3 months.

Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 4 weeks of registration

Active systemic, pulmonary, or pericardial infection

Clinical diagnosis of congestive heart failure and/or pulmonary capillary wedge pressure >15 mmHg, or uncorrected congenital heart disease.

No symptomatic cardiac or pulmonary disease and a performance status equal to or =< 2

Known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease; requirement for supplemental oxygen

Received therapeutic oral or intravenous (IV) antibiotics within 2 weeks prior to first day of study treatment; patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible

Patients with specific contraindications to the use of anti-EGFR therapy such as pulmonary fibrosis, interstitial pneumonia history

Severe, active co-morbidity defined as follows:\r\n* Unstable angina or congestive heart failure requiring hospitalization within 6 months prior to enrollment\r\n* Transmural myocardial infarction within the last 6 months prior to registration; evidence of recent myocardial infarction or ischemia by the findings of S-T elevations of >= 2 mm using the analysis of an electrocardiogram (EKG) performed within 28 days prior to registration (Note: EKG to be performed only if clinical suspicion of cardiac issue)\r\n* New York Heart Association grade II or greater congestive heart failure requiring hospitalization within 12 months prior to registration\r\n* Serious and inadequately controlled arrhythmia at step 2 registration\r\n* Serious or non-healing wound, ulcer or bone fracture or history of abdominal fistula, intra-abdominal abscess requiring major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to registration, with the exception of the craniotomy for surgical resection\r\n* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration\r\n* Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for coagulation parameters are not required for entry into this protocol\r\n* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration\r\n* Human immunodeficiency virus (HIV) positive with CD4 count < 200 cells/microliter; acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that HIV testing is not required for entry into this protocol\r\n* Any other severe immunocompromised condition\r\n* Active connective tissue disorders, such as lupus or scleroderma, that in the opinion of the treating physician may put the patient at high risk for radiation toxicity\r\n* End-stage renal disease (i.e., on dialysis or dialysis has been recommended)\r\n* Any other major medical illnesses or psychiatric treatments that in the investigator’s opinion will prevent administration or completion of protocol therapy

Chronic obstructive pulmonary disease (COPD) exacerbation at the time of study enrollment.

Severe chronic obstructive pulmonary disease (COPD) by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) staging system

Must not have any of the following absolute contraindications to cardiopulmonary exercise testing and/or aerobic training as determined by the attending oncologist:\r\n* Absolute contraindications\r\n** Acute myocardial infarction (within 3-5 days of any planned study procedures)\r\n** Unstable angina\r\n** Uncontrolled arrhythmia causing symptoms or hemodynamic compromise\r\n** Recurrent syncope\r\n** Active endocarditis\r\n** Acute myocarditis or pericarditis\r\n** Symptomatic severe aortic stenosis\r\n** Uncontrolled heart failure\r\n** Acute (within 3 months) pulmonary embolus or pulmonary infarction\r\n** Thrombosis of lower extremities\r\n** Suspected dissecting aneurysm\r\n** Uncontrolled asthma\r\n** Pulmonary edema\r\n** Room air desaturation at rest =< 85%\r\n** Respiratory failure\r\n** Acute non-cardiopulmonary disorders that may affect exercise performance or be aggravated by exercise (i.e. infection, renal failure, thyrotoxicosis)\r\n** Mental impairment leading to inability to cooperate

Pulmonary embolism (PE) within the last 6 months prior to registration

Chronic lung disease or Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration.

Uncontrolled cardiac or pulmonary disease

Subjects on supplemental oxygen or history of chronic obstructive pulmonary disease (COPD)

Active or uncontrolled pulmonary disease

History of functionally limiting chronic or acute cardiac, pulmonary, or neuromuscular disease

Patients with severe chronic obstructive pulmonary disease (COPD) defined as a forced expiratory volume in one second (FEV1) < 50%

Patients with acute chronic obstructive disease exacerbation as the primary etiology for respiratory failure

Acute pulmonary embolus or pulmonary infarction in the last week

Fatigue brought on by conditions other than cancer such as (the indicated tests are required only if that mechanism of fatigue is suspected):\r\n* Uncontrolled hypothyroidism (thyroid-stimulating hormone [TSH] > 10 IU)\r\n* Hypercalcemia (calcium > 11 mg/dL) calcium (Ca)=SerumCA + 0.8* (Normal/Albumin –PatientAlbumin)\r\n* Decompensated congestive heart failure\r\n* Chronic obstructive pulmonary disease requiring oxygen replacement

Any of the following contraindications to cardiopulmonary exercise testing:\r\n* Acute myocardial infarction within 3-5 days of any planned study procedures\r\n* Unstable angina\r\n* Uncontrolled arrhythmia causing symptoms or hemodynamic compromise\r\n* Recurrent syncope\r\n* Active endocarditis\r\n* Acute myocarditis or pericarditis\r\n* Symptomatic severe aortic stenosis\r\n* Uncontrolled heart failure\r\n* Acute pulmonary embolus or pulmonary infarction within 3 months of any planned study procedures\r\n* Thrombosis of lower extremities\r\n* Suspected dissecting aneurysm\r\n* Uncontrolled asthma\r\n* Pulmonary edema\r\n* Respiratory failure\r\n* Acute non-cardiopulmonary disorders that may affect exercise performance or be aggravated by exercise (i.e., infection, renal failure, thyrotoxicosis)

Any of the following absolute contraindications to cardiopulmonary exercise testing:\r\n* Acute myocardial infarction within 3–5 days of any planned study procedures\r\n* Unstable angina\r\n* Uncontrolled arrhythmia causing symptoms or hemodynamic compromise\r\n* Recurrent syncope\r\n* Active endocarditis\r\n* Acute myocarditis or pericarditis\r\n* Symptomatic severe aortic stenosis\r\n* Uncontrolled heart failure\r\n* Acute pulmonary embolus or pulmonary infarction within 3 months of any planned study procedures\r\n* Thrombosis of lower extremities\r\n* Suspected dissecting aneurysm\r\n* Uncontrolled asthma\r\n* Pulmonary edema\r\n* Respiratory failure\r\n* Acute non-cardiopulmonary disorders that may affect exercise performance or be aggravated by exercise (i.e., infection, renal failure, thyrotoxicosis)

Diagnosis of acute pulmonary embolism within past 2 weeks

Severe chronic obstructive pulmonary disease (COPD) requiring oxygen dependence, as this is a contraindication of EMST

Severe comorbidities (atrial fibrillation, pulmonary hypertension, etc...)

Pulmonary conditions such as chronic obstructive pulmonary disease, emphysema, interstitial lung disease, use of supplemental oxygen

Active or symptomatic cardiopulmonary disease (myocardial infarction < 1 month, heart failure >= New York Heart Association [NYHA] II, atrial fibrillation with poor rate control, high grade atrioventricular [AV] block, obstructive valvular disease, chronic obstructive pulmonary disease [COPD])

Absolute contraindications by pulmonary function testing

Other causes of cachexia such as: liver disease (aspartate aminotransferase [AST] or alanine aminotransferase [ALT] > 3 x normal levels); renal failure (creatinine > 1.5 mg/dL), untreated thyroid disease, class III-IV congestive heart failure (CHF), acquired immune deficiency syndrome (AIDS), other cancer diagnosed within the past 5 years other than non-melanoma skin cancer, severe chronic obstructive pulmonary disease (COPD) requiring use of home oxygen (O2)

History or current clinical evidence of moderate -to-severe obstructive pulmonary disease or reactive airway diseases (i.e.: asthma) requiring therapy

History of severe chronic obstructive pulmonary disease (COPD) and resting oxygen saturation (SpO2) < 90%

Chronic obstructive pulmonary disease (COPD)

Documented pulmonary disease with DLCO ?65% or FEV1 ?65%, provided that patients do not require more than 2 L of oxygen per minute or,

Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity; NOTE: subjects must have baseline oxygen/saturation level requirements as above

Pulmonary hemorrhage or hemoptysis > 2.5 mL blood within six weeks unless cause has been addressed and is medically resolved

Severe, active co-morbidity, defined as follows:\r\n* Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months\r\n* Transmural myocardial infarction within the last 6 months\r\n* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration\r\n* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration\r\n* Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, coagulation parameters are not required for entry into this protocol\r\n* Pre-existing >= grade 2 neuropathy\r\n* Prior organ transplant

Any of the following contraindications to cardiopulmonary exercise testing\r\n* Acute myocardial infarction within 3–5 days of any planned study procedures;\r\n* Unstable angina;\r\n* Uncontrolled arrhythmia causing symptoms or hemodynamic compromise;\r\n* Recurrent syncope;\r\n* Active endocarditis;\r\n* Acute myocarditis or pericarditis;\r\n* Symptomatic severe aortic stenosis;\r\n* Uncontrolled heart failure;\r\n* Acute pulmonary embolus or pulmonary infarction within 3 months of any planned study procedures;\r\n* Thrombosis of lower extremities;\r\n* Suspected dissecting aneurysm;\r\n* Uncontrolled asthma;\r\n* Pulmonary edema;\r\n* Room air desaturation at rest =< 85%;\r\n* Respiratory failure;\r\n* Acute non-cardiopulmonary disorders that may affect exercise performance or be aggravated by exercise (i.e., infection, renal failure, thyrotoxicosis); or\r\n* Mental impairment leading to inability to cooperate

Diagnosis of acute pulmonary embolism within past 2 weeks

Any of the following absolute contraindications to cardiopulmonary exercise testing:\r\n* Acute myocardial infarction within 3-5 days of any planned study procedures\r\n* Unstable angina\r\n* Uncontrolled arrhythmia causing symptoms or hemodynamic compromise\r\n* Recurrent syncope\r\n* Active endocarditis\r\n* Acute myocarditis or pericarditis\r\n* Symptomatic severe aortic stenosis\r\n* Uncontrolled heart failure\r\n* Acute pulmonary embolus or pulmonary infarction within 3 months of any planned study procedures\r\n* Thrombosis of lower extremities\r\n* Suspected dissecting aneurysm\r\n* Uncontrolled asthma\r\n* Pulmonary edema\r\n* Room air desaturation at rest =< 85%\r\n* Respiratory failure\r\n* Acute non-cardiopulmonary disorders that may affect exercise performance or be aggravated by exercise (i.e., infection, renal failure, thyrotoxicosis)\r\n* Mental impairment leading to inability to cooperate

Chronic obstructive pulmonary disease (COPD) exacerbation at the time of study enrollment

Severe, active co-morbidity, defined as follows:\r\n* Unstable angina, and/or congestive heart failure requiring hospitalization within the last 6 months\r\n* Transmural myocardial infarction within the last 6 months\r\n* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration\r\n* Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects\r\n* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization, or precluding study therapy at the time of registration\r\n* Uncontrolled, clinically significant cardiac arrhythmias\r\n* Radiologic or clinical evidence of hydrocephalus, or history of previously treated hydrocephalus

Diagnosed with chronic obstructive pulmonary disease (COPD) oxygen dependent

Patients must be able to ambulate a minimum of 100 feet prior to enrollment in pulmonary rehab

Patients must be willing and able to travel to the pulmonary rehabilitation site at the Morehouse Medical Plaza

Patients with pulmonary edema, congestive heart failure or pulmonary embolus

Severe cardiovascular, pulmonary or other systemic conditions that prevent participation in the study

Diabetes mellitus (insulin, oral, or both), chronic obstructive pulmonary disease, emphysema, reactive airway disease; chronic renal disease; multiple sclerosis; seizure disorder; murmurs; hepatitis; human immunodeficiency virus/acquired immunodeficiency syndrome; congestive heart failure; coronary artery disease; aortic aneurysm; history of coronary artery bypass graft; heart valve issues (prolapse, regurgitation, etc.); tachycardia; bradycardia; history of myocardial infarction

History or current clinical evidence of moderate-to-severe obstructive pulmonary disease or reactive airway diseases (i.e. asthma) requiring therapy

CONTROL (HEALTHY) GROUP: Severe pulmonary hypertension

Active pulmonary disease requiring medication to include multiple inhalers (>3 inhalers including one containing steroids)

Conditions that could cause swelling (e.g., pregnancy, congestive heart failure, chronic/acute renal disease, cor pulmonale, nephrotic syndrome, nephrosis, liver failure or cirrhosis, pulmonary edema, and thrombophlebitis, or deep vein thrombosis in arms

Chronic Obstructive Pulmonary Disease (COPD) exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days before registration

Any of the following absolute contraindications to cardiopulmonary exercise testing and/or aerobic training:\r\n* Acute myocardial Infarction (within 3-5 days of any planned study procedures);\r\n* Unstable angina;\r\n* Uncontrolled arrhythmia causing symptoms or hemodynamic compromise;\r\n* Recurrent syncope;\r\n* Active endocarditis;\r\n* Acute myocarditis or pericarditis;\r\n* Symptomatic severe aortic stenosis;\r\n* Uncontrolled heart failure;\r\n* Acute pulmonary embolus or pulmonary infarction within 3 months of any planned study procedures;\r\n* Thrombosis of lower extremities;\r\n* Suspected dissecting aneurysm;\r\n* Uncontrolled asthma;\r\n* Pulmonary edema;\r\n* Respiratory failure;\r\n* Acute non-cardiopulmonary disorders that may affect exercise performance or be aggravated by exercise (i.e. infection, renal failure, thyrotoxicosis)

Has a serious cardiopulmonary medical condition (including cardiovascular disease, congestive heart failure [CHF], chronic obstructive pulmonary disease [COPD], restrictive lung disease, interstitial lung disease, asthma, acute or chronic bronchitis, cystic fibrosis, pneumonia, tuberculosis, pneumoconiosis, pulmonary hypertension, pulmonary embolism, pleural effusion, pneumothorax, obesity hyperventilation syndrome, neuromuscular lung disease)

Corrected DLCO > 40% by pulmonary function test

Participant has ever experienced one or more hepatic decompensation events or a history of decompensated liver disease as listed below:\r\n* Clinical ascites\r\n* Variceal bleeding documented by endoscopy\r\n* Spontaneous bacterial peritonitis documented by positive culture\r\n* Hepatic encephalopathy\r\n* Hepatorenal syndrome (type 1 or 2)\r\n* Porto-pulmonary hypertension\r\n* Hepato-pulmonary hypertension\r\n* Any liver-related event which led to a hospitalization or a grade 4 event

Known history of chronic pulmonary disease

Physician-diagnosed chronic obstructive pulmonary disease (COPD)

Severe obstructive lung disease (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage III or IV, FEV1 < 30% predicted)

Active pulmonary disease requiring medication to include multiple inhalers

acute pulmonary embolism or pulmonary infarction,

unstable pulmonary or cardiovascular conditions.

Severe acute co-morbidity, defined as follows:\r\n* Unstable angina and/or congestive heart failure requiring hospitalization in the last 3 months\r\n* Transmural myocardial infarction within the last 6 months\r\n* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration\r\n* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration \r\n* Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol; protocol-specific requirements may also exclude immunocompromised patients

Patients with pulmonary hypertension or unstable cardiopulmonary conditions

Pulmonary disease precluding monitored anesthesia care or general anesthesia

Patients with pulmonary hypertension or unstable cardiopulmonary conditions

Patients with severe emphysema, pulmonary vasculitis, or a history of pulmonary emboli

Patients with contraindication/s for general anesthesia (e.g., severe and active coronary artery disease, chronic obstructive pulmonary disease [COPD] with forced expiratory volume in 1 second [FEV1] < 1 liter, uncontrolled hypertension, increased intracranial pressure, history of intolerance to general anesthesia)

Patients with evidence of moderate or severe pulmonary hypertension on echocardiogram

Patients with stage II chronic obstructive pulmonary disease (COPD) or worse, per Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification

Suspected pulmonary hypertension: additional testing required, such as echocardiogram

Moderate-to-severe pulmonary fibrosis

Critically ill or medically unstable and whose critical course during the observation period would be unpredictable (e.g., chronic obstructive pulmonary disease [COPD] requiring oxygen)

Right to left shunt, severe pulmonary hypertension (pulmonary artery pressure > 90 mmHg), or adult respiratory distress syndrome

PATIENT: Patients with severe emphysema, pulmonary vasculitis, pulmonary hypertension or a history of pulmonary emboli

Critically ill or medically unstable and whose critical course during the observation period would be unpredictable (e.g., chronic obstructive pulmonary disease [COPD])

Right to left shunt, severe pulmonary hypertension (pulmonary artery pressure > 90 mmHg), or adult respiratory distress syndrome

Patients must have suspicious or known to be malignant solitary pulmonary nodule at least 1 cm in size

Patients with more than 5 sites of extrahepatic disease (including nodes and pulmonary nodules)

Patient must not have known endobronchial lesions and/or lesions infiltrating major pulmonary vessels

Patients with severe emphysema, pulmonary vasculitis, pulmonary hypertension, respiratory distress syndrome, or a history of pulmonary embolism.

Patients with uncontrollable emphysema, pulmonary vasculitis, pulmonary hypertension or a history of pulmonary emboli

Severe emphysema, pulmonary emboli, or other conditions that cause pulmonary hypertension due to compromised pulmonary-arterial vasculature

Patients who have a known cardiac shunt or pulmonary hypertension

Severe or uncontrolled/unstable cardiac, pulmonary, hepatic or renal disease, including MI or CVA within 3 months prior to treatment.

Patients with severe emphysema, pulmonary vasculitis, or a history of pulmonary emboli

Ongoing acute or chronic pulmonary bronchospastic disease, including a history of chronic obstructive pulmonary disease or asthma, with an exacerbation within the past year

Pre-existing respiratory conditions:\r\n* Severe chronic obstructive pulmonary disease (including chronic bronchitis and/or emphysema)\r\n* Other respiratory or lung conditions, which would place the participant at risk\r\n* Presence of any other significant cardiac or pulmonary symptoms, such as moderate or severe dyspnea on exertion, orthopnea, or paroxysmal nocturnal dyspnea

Patients must have pulmonary function as defined below:\r\n* Abnormal pulmonary function test within 3 months of study entry\r\n* Prior radiation to the lungs\r\n* Prior surgical resection of lung tissue (i.e. wedge resection, lobectomy, or pneumonectomy)\r\n* Clinical diagnosis of chronic obstructive pulmonary disease (COPD) or emphysema\r\n* Ongoing oxygen use

Patients with active systemic, pulmonary, or pericardial infection

Patients with severe emphysema, pulmonary vasculitis, or a history of pulmonary emboli

Presence of significant medical illness: autoimmune/inflammatory diseases, cardiopulmonary disorders (i.e., angina, congestive heart failure, severe chronic obstructive pulmonary disease [COPD]), uncontrolled endocrine disorders (i.e., hypothyroidism, diabetes), vestibular neuritis, Meniere's syndrome, benign paroxysmal positional vertigo, or known or previously diagnosed structural disorder of the peripheral vestibular system

Immune system disorders, pulmonary diseases (e.g., asthma within the prior 5 years, acute bronchitis within 1 year, chronic obstructive pulmonary disease [COPD], chronic bronchitis, and restrictive lung disease), clinically diagnosed kidney or liver diseases, or any other medical disorders that will increase the risk from bronchoscopy, affect biomarker data, or increase risk of an adverse effect from e-cig use; all subjects are screened by a pulmonologist obtaining a medical history and a physical examination (heart, lungs and oral cavity) to ensure no increased risk from bronchoscopy or e-cig use

Participants with type 2 diabetes, documented stomach ulcers and pulmonary embolism

With significant heart or pulmonary disease.

recent history (past 3 months) of Chronic Obstructive Pulmonary Disease (COPD), cancer (any non-dermatologic), or uncontrolled diabetes mellitus

pre-existing clinically significant dysfunction of the heart or Chronic Obstructive Pulmonary Disease (COPD)

Life-threatening metastatic visceral disease (defined as extensive hepatic involvement or symptomatic pulmonary lymphangitic spread).