Lung Disease and Its Affect on the Work of White Blood Cells in the Lungs

Study Overview
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Brief Summary
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The purpose of this study is to look at how Alpha-1-antitrypsin (AAT) deficiency and Cystic Fibrosis (CF) affect white blood cells in the lungs, called macrophages, and their ability to work.

Detailed Description
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AAT deficiency is a genetic disorder that affects around 100,000 people in the USA, including 1-3% of all people diagnosed with chronic obstructive pulmonary disease (COPD). In AAT deficient people diagnosed with COPD, it was originally believed the cause of the disease was due to a lack of supply of alpha-1 antitrypsin. However, early information gathered in our laboratory suggests another cause of the development of COPD and the progressing of the disease may be due to a malfunction in macrophages. CF is also a genetic disorder which affects 1/300 births among the Caucasian population. One of the main symptoms of CF is inflammation of the lung tissue. Lung macrophages play a major role in lung inflammation as well as in helping to resolve the inflammation. Inflammation is an important defense of the body. It is the body's response to infection causing germs and things that may cause irritation, as well as, a way for the body to repair damaged tissue. We suggest that the effects of AAT deficiency and CF decreases the inflammation response in the lungs and also restricts the ability of macrophages to correct that inflammation once it occurs.

Official Title
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The Role of Conformational Diseases on Macrophage Function

Conditions
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Alpha-1 Antitrypsin Deficiency, AAT Deficiency, AATD, Cystic Fibrosis (CF)

Intervention / Treatment
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* Procedure: History and physical exam.
* Procedure: Blood draw.
* Procedure: Pulmonary function testing.
* Drug: Albuterol inhaler.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent Male or female 18 years of age or older Negative pregnancy test for women of childbearing potential Hemoglobin >12.5 g/dl measured on the day of participation Negative urine nicotine test Exclusion Criteria: Pregnancy or breastfeeding Weight < 50 kg History of anemia requiring blood transfusions, erythropoietin supplementation, or iron supplementation within the past 36 months Known hemoglobin <12.5 g/dl within the past 90 days Systolic blood pressure > 180 mmHg and/or diastolic blood pressure >100 mmHg Poor venous access Large volume blood donation (>200 ml or 7 ounces) within the previous 56 days (e.g. blood donation for the purposes of blood banking) Clinically significant cardiac, hemostatic or neurological impairment or any other significant medical condition that, in the opinion of the investigator would affect subject safety (e.g., recent myocardial infarction, history of prolonged bleeding time, cerebral vascular accident, advanced cancer or uncontrolled medical condition) Psychiatric or cognitive disturbance or illness that would affect subject safety Current smoker

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| AAT Deficiency<br>Those diagnosed with Alpha-1 Antitrypsin (AAT) Deficiency. At every study visit, a history and physical exam (H&P), blood draw, and pulmonary function testing (PFTs) with the use of an albuterol inhaler will be done. | Procedure: History and physical exam.<br>* At every study visit, participant's will be asked about their medical history and will have a physical exam.<br>* Other names: H&P;Procedure: Blood draw.<br>* At each study visit, participants will have an intravenous catheter (IV) placed in one of their veins and blood will be drawn from the IV for study testing.<br>* Other names: Phlebotomy;Procedure: Pulmonary function testing.<br>* At every study visit, participants will have their lung function assessed. This is done by blowing forcefully at least 3 times into a tube. Testing will be done two times; before and after the use of an Albuterol inhaler.<br>* Other names: PFTs;Drug: Albuterol inhaler.<br>* At every study visit, participating subjects will take 2 puffs of an Albuterol inhaler after the first set of PFTs, but before the second set of PFTs. There will be at least a 30 minute period after the use of the Albuterol inhaler and the second set of PFTs.<br>* Other names: ProAir;|
| Cystic Fibrosis<br>Those diagnosed with Cystic Fibrosis (CF) with mutation Delta F508. At every study visit, a history and physical exam (H&P), blood draw, and pulmonary function testing (PFTs) with the use of an albuterol inhaler will be done. | Procedure: History and physical exam.<br>* At every study visit, participant's will be asked about their medical history and will have a physical exam.<br>* Other names: H&P;Procedure: Blood draw.<br>* At each study visit, participants will have an intravenous catheter (IV) placed in one of their veins and blood will be drawn from the IV for study testing.<br>* Other names: Phlebotomy;Procedure: Pulmonary function testing.<br>* At every study visit, participants will have their lung function assessed. This is done by blowing forcefully at least 3 times into a tube. Testing will be done two times; before and after the use of an Albuterol inhaler.<br>* Other names: PFTs;Drug: Albuterol inhaler.<br>* At every study visit, participating subjects will take 2 puffs of an Albuterol inhaler after the first set of PFTs, but before the second set of PFTs. There will be at least a 30 minute period after the use of the Albuterol inhaler and the second set of PFTs.<br>* Other names: ProAir;|
| Without Lung Disease Diagnosis<br>Those without the diagnosis of AAT Deficiency or CF. At every study visit, a history and physical exam (H&P), blood draw, and pulmonary function testing (PFTs) with the use of an albuterol inhaler will be done. | Procedure: History and physical exam.<br>* At every study visit, participant's will be asked about their medical history and will have a physical exam.<br>* Other names: H&P;Procedure: Blood draw.<br>* At each study visit, participants will have an intravenous catheter (IV) placed in one of their veins and blood will be drawn from the IV for study testing.<br>* Other names: Phlebotomy;Procedure: Pulmonary function testing.<br>* At every study visit, participants will have their lung function assessed. This is done by blowing forcefully at least 3 times into a tube. Testing will be done two times; before and after the use of an Albuterol inhaler.<br>* Other names: PFTs;Drug: Albuterol inhaler.<br>* At every study visit, participating subjects will take 2 puffs of an Albuterol inhaler after the first set of PFTs, but before the second set of PFTs. There will be at least a 30 minute period after the use of the Albuterol inhaler and the second set of PFTs.<br>* Other names: ProAir;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of macrophage function. | From every study participant, we will collect blood from a vein through the placement of an intravenous catheter (IV). We will complete various experiments that will allow us to see how well each participant's macrophage cells are working. | On average, within 30 days from the time the blood is collected. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of the amount of alpha-1 antitrypsin in the blood. | From every study participant, we will collect blood from a vein through an IV. | On average, within 30 days from the time the blood was collected. | 
| Comparison of the amount of an inflammatory marker in the blood, called C-reactive protein. | From every study participant, we will collect blood from a vein through and IV. | On average, within 30 days from the time the blood is collected. | 
| Evaluation of lung function. | Lung function testing will be done on every study participant. This is is done by forcefully blowing into a tube on at least 3 separate occasions. Albuterol, an inhaled medication used to expand lung airways, will be given after lung function testing and then the testing will be repeated after 30 minutes. | On average, within 30 days from the time the testing is completed. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Macrophage, Alpha-1 Antitrypsin Deficiency, Cystic Fibrosis