CONSENT TO ACT AS A PARTICIPANT IN A RESEARCH STUDY
TITLE: Severe Asthma Research Program: Inflammation, Myofibroblasts and Loss of Elastic Recoil in Severe Asthma (with Ancillary CT Sub-study, MOP Version 7, Pittsburgh genetic sample)
PRINCIPAL INVESTIGATOR: Sally E. Wenzel, M.D.
Professor of Medicine, Pulmonary, Allergy and Critical Care Medicine (PACCM)
NW 628 Montefiore
3459 Fifth Ave
Pittsburgh, PA 15213
412-802-6859
CO-INVESTIGATORS:
Andrej Petrov, M.D. Phillip Lamberty, MD Amy Lee, MD
PACCM PACCM PACCM
Danielle M. Goetz, MD Jay Kolls, MD Shean Aujla, MD
Children’s Hospital Children’s Hospital Children’s Hospital
J. Ken Leader, PhD Diane Strollo, MD David Stukus, MD
Dept. of Radiology Dept. of Radiology Children’s Hospital
Merritt Fajt, MD Fernando Holguin, MD
Children’s Hospital PACCM
STUDY COORDINATOR: Erin K. Aiken 412-692-4747
PACCM
SOURCE OF SUPPORT: National Institutes of Health
SEVERE ASTHMA CONSENT
This consent form may contain words that you do not understand. Please ask the study doctor or the study staff to explain any words or information that you do not clearly understand.
Why is this research being done?
You are being invited to take part in a research study that will extensively evaluate severe asthma, which may lead to the development of severe disease. We will also study some of the genes that control allergies, as well as the production of mucus and inflammation in asthma airways.
In addition, you are being asked to allow us to share samples and information with 3 other sites (Cleveland Clinics, University of Wisconsin and Wake Forest University). These data and samples will be shared with these other sites to better characterize
severe asthma and to allow the other sites to use your samples for their research. In all cases, however, your samples will not be identifiable to the other investigators in any way; they will be de-identified (without any identifiable information such as name, initials, birth date, social security number).
You are being asked to participate in these studies because you are a severe asthmatic subject. It is hoped that the information obtained from this study may help determine why you do not respond in the usual way to regular asthma medications.
If you participate in this study, then it is likely you have been asked to participate in corresponding studies of severe asthma. If you decide to participate in these studies, please be aware that we will ask you to undergo each procedure only one time. All procedures that we will ask you undergo are outlined in this consent.
Who is being asked to take part in this research study?
Subjects with asthma of varying severity and subjects without asthma will be asked to participate in this study. Participation will be for approximately 1 month, however, this time may vary depending on scheduling conflicts. People invited to participate in this study must be between 18-65 years of age and, if female, cannot be pregnant. The study is being performed on approximately of 250 individuals over 5 years at UPMC.
What procedures will be performed for research purposes?
As you are a severe asthmatic in whom some of these procedures are done to clinically evaluate your disease, two of the procedures will be done for BOTH clinical AND research purposes. Those tests are specifically identified below. In those cases either additional research evaluation or additional samples will be taken as part of that test that will be used for research only. You will only be reimbursed for the research portion of these studies. If you decide to take part in this research study, you will undergo the following procedures:
Screening Procedures
Procedures to determine if you are eligible to take part in a research study are called “screening procedures”. For this research study, the screening procedures include:
1. We may wish to do a medical record review. We are asking your permission to review your UPMC Medical Records Chart to obtain the results of clinical procedures that you have undergone.
2. For women who could possibly be pregnant, a urine pregnancy test will be performed at visit 1. A small sample (about 1 teaspoonful) of blood will be taken from a vein in your arm for a pregnancy test at visit 6. Pregnant women, or women who are currently breast-feeding an infant, will not be allowed to take part in this study.
3. Simple breathing test that measures the amount of air you have in your lungs and how well you can move that air by forcefully blowing 3 or more times into a mouthpiece that is attached to a computer.
4. One of the investigators will do a physical examination.
There will only be one screening evaluation. It will take up to 2 hrs.
Experimental Procedures
If you qualify to take part in this research study, you will undergo the experimental procedures listed below.
1. Questionnaires
A series of questionnaires will ask you a wide range of questions including, but not limited to, information about your asthma, medication history, smoking history, socioeconomic status, healthcare, emergency room visits, immunotherapy, family history, environmental living conditions, your quality of life and your emotional well being.
2. Allergy Skin Tests
One drop of 14 common allergens (for example: house dust mite, grass pollen, mold) will be put on the underside of your forearm or on your back. Your skin will be lightly pricked with a needle. Fifteen minutes later a study coordinator will look for redness and or swelling (like a mosquito bite) where the tests were done.
3. Spirometry (Simple Breathing Tests)
Spirometry tests are breathing tests that measure the amount of air you have in your lungs and how well you can move that air by forcefully blowing into a spirometer.
4. Urine collection
You will be asked to provide a urine sample for measurements of oxidants and tobacco smoke exposure in the urine. Women of childbearing potential will also have a urine pregnancy test performed 2 times during the course of the study (at screening and prior to the methacholine challenge testing).
5. Blood draw
A total of approximately 1-2 Tablespoons of blood will be removed by putting a needle into your vein. This is the standard method used to obtain blood samples. The samples will be used for genetic studies (see next section), and for analysis of factors believed to be important in asthma. We will also check your immunoglobulin E levels (antibodies found in higher amounts in people with allergies/asthma), cortisol levels(a chemical in your blood that may increase during physical stress or changes in the body such as inflammation), inflammatory markers and oxidants, clotting factors, and blood counts. In addition, you may later be asked to provide extra blood (150 ml or about 10 Tablespoons) to isolate cells called eosinophils, which are potentially involved in asthma. Serum pregnancy test will also be performed prior to the bronchoscopy. .
6. Genetic studies. A portion of your blood will be used to evaluate genes that may be related to the development of asthmatic inflammation. No other genes will be studied. The samples will be collected and coded in such a way that only the primary investigators will be able to link your genes to you, the individual. These coded samples will be sent to Wake Forest University and one sample will be kept here at the University of Pittsburgh for analysis. These specimens may be stored up to 30 years to research scientific questions related to asthma inflammation and the wound repair process.
7. Sputum Induction
A sputum induction will be performed for determination of inflammatory cells (called eosinophils, neutrophils, lymphocytes and macrophages) and related biochemical markers (substances involved in the inflammatory process that make asthma worse) in the sputum. Prior to the induced sputum procedure (and if your breathing test is good enough), you will be given 4 puffs of an inhaled bronchodilator (albuterol) to open the airways. For this procedure you will be asked to inhale aerosolized saline (salt-water) solution (3%) for up to 12 minutes through a mouthpiece. Every 4 minutes you will be asked to spit your saliva into a cup. This will help keep your sputum from being contaminated with saliva. Then you will be asked to take 2 additional breaths of the salt solution and cough into a collection cup. During the procedure, lung function (peak flows) will also be monitored every 4 minutes to be sure your asthma has not worsened. If you experience wheezing or shortness of breath, you will be given a bronchodilator (albuterol). Prior to leaving the hospital, lung functions will be performed to ensure your breathing has returned to baseline.
8. Maximum Post Bronchodilator Value of Lung Function
You will do spirometry and then take 2 puffs of albuterol, an inhaler medicine to relax the airways. 15 minutes later you will do spirometry again and take another 2 puffs of albuterol. 15 minutes later you will do spirometry again and take another 2 puffs of albuterol. 15 minutes later you will repeat spirometry. If there is little or no difference between the last 2 sets of spirometry values, the test will stop. If comparison of the last 2 sets of spirometry values shows a continued improvement in your breathing, you will take 2 more puffs of albuterol, and spirometry will be repeated one last time. For this test you will receive no more than 8 puffs of albuterol.
9. Methacholine Challenge Test.
A methacholine challenge is a common test often used to diagnose asthma. Methacholine is a chemical that causes the airways to narrow. The challenge test consists of inhaling increasing doses (0.000, 0.078, 0.156, 0.3125, 0.625, 1.25, 2.50, 5.00 10, then 25 milligrams/milliliters) of methacholine through a nebulizer to assess how quickly your airways narrow. Your airways will tighten slightly as the test proceeds. As you have asthma, we are doing the test to see how quickly your airways narrow. We will start with very small doses, gradually increasing the dose of methacholine. Spirometry (breathing tests) will be performed 3 minutes after each dose to look for changes in your lung function. The procedure will be terminated if you demonstrate a significant change in your pulmonary function test or you reach the highest concentration of methacholine. Prior to this test, a urine pregnancy test will be performed on women of childbearing potential. The test should take 30-60 minutes. You will receive albuterol (an inhaler medicine that relaxes the airways) after the test is done to reverse any asthma symptoms.
10. Complete pulmonary function tests (PFTs) with pressure volume curve
PFTs are breathing tests that measure the amount of air you have in your lungs during quiet breathing and how well you can move that air by forcefully blowing the air out. These studies will be done in a "body plethysmograph", a standard piece of equipment that looks like a telephone booth. You will sit inside the booth for these tests, but will be able to communicate with the person performing the test through a microphone and speaker. The tests will be done without any breathing medicines (baseline), and after you inhale a bronchodilator (albuterol). The bronchodilator will be inhaled as 2 to 4 puffs of albuterol or in a nebulizer. This test should take about 1 1/2 to 2 hours.
11. Exhaled Nitric Oxide
We will also ask you to perform exhaled nitric oxide testing to measure concentrations of a gas called nitric oxide (NO, for short) present in the breath of every person. The levels of NO in the breath may rise or fall in certain diseases, like asthma. If you agree to take part in this study you will be asked to inhale deeply and then exhale very slowly into a mouthpiece for between 10-15 seconds. This test may last for 10 to 15 minutes.
12. Multi-detector CT Scan
Multi-detector (a form of a “spiral” CT scan) CT scans are a type of x-ray to look in more detail at your lung structure. You will need to lie flat and still for about 15 minutes while the scan is performed. It will be performed twice, at two levels of inspiration and expiration. You will be asked to inhale 2 puffs of albuterol, a medication that opens up (bronchodilates) airways in asthmatics 15-30 minutes prior to the test.
Your CT Scan image will be generated and transferred to Dr. Eric Hoffman's Physiologic Imaging Center at the University of Iowa for detailed computer analysis. Your image will be sent without any identifiers (no name, birth date, social security number) but with a special number specific to the study. Only the study team can link your CT Scan to you.
CT scans are routinely done to improve your clinical care. However, we will also do additional tests as part of these procedures for research purposes. If you have already had a CT scan, it will be done for only research purposes.
CT Ancillary Study:
In addition to the computer analysis performed at the Imaging Center at the University of Iowa, some subjects will be eligible for additional imaging studies. For eligible subjects the CT analysis will include the creation of a 3 dimensional image of your airways. This image will be used to pinpoint the locations to collect biopsies from when the bronchoscopy is performed. This will help the researchers compare the results of the CT airway measurements with the results of the biopsy measurements.
CT Reliability study: