Breath Analysis Technique to Diagnose Pulmonary Embolism

PE is the second leading cause of sudden, unexpected death in the United States. In 90% of
the cases, it is caused by deep vein thrombosis: a blood clot forms in a vein, travels
through the bloodstream, and lodges in the lungs. PE symptoms vary, and can include cough,
shortness of breath, chest pain, rapid breathing, or increased heart rate. Some medical
procedures and diseases activate inflammation and blood coagulation, thereby making
individuals more vulnerable to PE. Surgery, kidney dialysis, cancer, connective tissue
diseases, infectious diseases, and being over 70 years old put individuals at increased risk
for developing PEs. A common screening test for PE is the D-dimer blood test, which measures
the level of a specific protein that is released following a PE. This test, however, has
proven to be an unreliable diagnostic tool for individuals who are at high risk for PE. A
more reliable diagnostic tool is needed. The Carboximeter is a new device that measures the
ratio of CO2/O2 pressure in an individual's expired breath. By monitoring these components,
researchers may be able to accurately diagnose PEs in high risk individuals. The purpose of
this study is to evaluate the effectiveness of the Carboximeter at diagnosing PE in
individuals at risk for developing PEs.

This study will be conducted in two phases. In Phase I, CO2/O2 ratio and D-dimer levels will
be measured prior to and following orthopedic or cancer-related surgery in 100 individuals at
risk for developing PEs. In Phase II, the same measurements will be carried out on 350 high
risk individuals who are experiencing PE symptoms. These individuals will also undergo
computed tomography (CT) angiography and venography, in which blood flow will be visualized
using x-rays. A follow-up evaluation will occur 30 days later. If any participant from Phase
I or II experiences a PE or a medical condition that affects their lungs, such as asthma or
chronic obstructive pulmonary disease (COPD), researchers may schedule a follow-up evaluation
to obtain repeat measurements.

Phase I Inclusion Criteria:

- Experienced or is scheduled for at least one of the following:

1. Hip or knee replacement surgery

2. Hip or acetabular fracture surgery

3. Pelvic fracture

4. Decompression for spinal stenosis surgery

5. Scoliosis corrective surgery

6. Craniotomy surgery for brain tumor

7. Surgery for any of the following cancers: bladder, colon (including caecum and
rectum), kidney, ovary, pancreas, or uterus

Phase I Exclusion Criteria:

- Currently undergoing treatment for PE or has received treatment for PE in the 4 weeks
prior to study entry

- Hospitalized for fewer than 2 days

- Anatomic abnormality that would prevent use of a mouthpiece

- Living situation that makes follow-up difficult (e.g., homeless, incarcerated)

Phase II Inclusion Criteria:

- Clinical suspicion of PE with signs or symptom suggestive of PE within 24 hours of
presentation and at least one risk factor for PE, as defined under the criteria as
outlined in this protocol

- CTA of pulmonary arteries ordered by clinical care providers

- 18 years or older or an emancipated 17 year old

- Written informed consent

Phase II Exclusion Criteria:

- Hemodynamic instability, including patients with a systolic blood pressure less than
90 mm Hg

- Severe respiratory distress or the inability to breathe room air without the sensation
of severe dyspnea

- Pulse oximetry reading that declines more than 10% when exogenous oxygen is
discontinued with accompanying worsening or new dyspnea

- Intubated

- Cannot breathe through the mouth owing to anatomic, physical or mental limitation

- No fixed address, no telephone number, are from out of town or have other reason to
suspect difficulty with follow-up

- Incarceration

- Known active tuberculosis

- Prior PE or DVT with history of medical noncompliance with oral anticoagulation
therapy based upon a history of unplanned subtherapeutic INR measurements (less than
1.5)

- Active PE within previous 6 months and currently under treatment with anticoagulation

- Pregnant

- Disallowed medications: treatment with any fibrinolytic agent within 48 hours prior to
enrollment