Characterization of the Pathobiology of Early Lung Destruction in Alpha 1-Antitrypsin Deficient Individuals

NCT00001462 | Completed

• 2 other identifiers: 95011695-H-0116
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Alpha 1-antitrypsin-deficient individuals develop severe destructive lung disease much earlier and their lung function declines faster than the general population of individuals with chronic obstructive lung disease. This study is designed to better understand the pathogenesis of lung destruction in alpha 1-antitrypsin deficient individuals and to characterize the pathobiology of early lung destruction. To accomplish this we intend to use bronchoalveolar lavage to determine and quantify the factors that initiate and sustain lung inflammation in alpha 1-antitrypsin deficient individuals with lung function above a force expiratory volume in one second (FEV1) of greater than 50% of predicted.

Conditions

Emphysema; Lung Diseases, Obstructive; Alpha 1-Antitrypsin Deficiency

Keywords

Alpha 1-Antitrypsin Deficiency; Emphysema; Genetic Diseases; Inflammation; Nitric Oxide; Protease

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

Any alpha 1 antitrypsin-deficient individuals. 18-65 years old. FEV1 greater than 1 equal to 50 percent of predicted (forced expiratory volume). Study participation is required for one year. A total of four bronchoscopies will be performed over a year period. Methacholine challenge test will be performed at the beginning and end of the study to assess the degree of reactive airways disease. Pneumococcal and annual influenza vaccine will be given. No prolastin within one year prior to start of the study. No oral systemic corticosteroids within 30 days prior to start of study. No allergy to topical or local anesthetic (i.e., lidocaine). No pregnancy. No HIV positive patients. No Hepatitis B/C virus positive patients. No patients with any condition associated with immunodeficiency. No patients with presence of significant cardiac diseases. No patients with presence of uncorrected blood-clotting disorders. No patients with any oxygen at home on a regular basis. No adverse reactions to methacholine.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (1)

National Heart, Lung and Blood Institute (NHLBI)

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Buist AS. Alpha 1-antitrypsin deficiency in lung and liver disease. Hosp Pract (Off Ed). 1989 May 15;24(5):51-9. doi: 10.1080/21548331.1989.11703712. No abstract available.

  PMID: 2497126 BACKGROUND

• Crystal RG. Alpha 1-antitrypsin deficiency, emphysema, and liver disease. Genetic basis and strategies for therapy. J Clin Invest. 1990 May;85(5):1343-52. doi: 10.1172/JCI114578. No abstract available.

  PMID: 2185272 BACKGROUND

• Gadek JE, Pacht ER. The protease-antiprotease balance within the human lung: implications for the pathogenesis of emphysema. Lung. 1990;168 Suppl:552-64. doi: 10.1007/BF02718178.

  PMID: 2117164 BACKGROUND

• Paris AE, Vragovic O, Sonalkar S, Finneseth M, Borgatta L. Mifepristone and misoprostol compared to osmotic dilators for cervical preparation prior to surgical abortion at 15-18 weeks' gestation: a randomised controlled non-inferiority trial. BMJ Sex Reprod Health. 2019 Nov 21:bmjsrh-2019-200367. doi: 10.1136/bmjsrh-2019-200367. Online ahead of print.

  PMID: 31754065 DERIVED

MeSH Terms

Conditions

Emphysema; Lung Diseases, Obstructive; alpha 1-Antitrypsin Deficiency; Genetic Diseases, Inborn; Inflammation

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lung Diseases; Respiratory Tract Diseases; Liver Diseases; Digestive System Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Subcutaneous Emphysema

Study Design

• Study Type: observational
• Sponsor Type: NIH

Study Record Dates

• First Submitted: November 3, 1999
• First Posted: December 10, 2002
• Study Start: May 1, 1995
• Study Completion: April 1, 2000
• Last Updated: March 4, 2008

Record last verified: 1999-08

Locations

US (1)