The full content of Annals is available to subscribers

Subscribe/Learn More  >
Articles |

Anti-Neutrophil-Elastase Defenses of the Lower Respiratory Tract in α1-Antitrypsin Deficiency Directly Augmented with an Aerosol of α1-Antitrypsin

Richard C. Hubbard, MD; Mark L. Brantly, MD; Stephanie E. Sellers, BS; Marc E. Mitchell, MD; and Ronald G. Crystal, MD
[+] Article, Author, and Disclosure Information

Requests for Reprints: Richard C. Hubbard, MD, Building 10, Room 6D03, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.

Current Author Addresses: Drs. Hubbard, Brantly, Sellers, and Crystal: National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.

Dr. Mitchell: Department of General Surgery, University of Mississippi Medical Center, 2500 North State Street, Jackson, MI 39216.

Ann Intern Med. 1989;111(3):206-212. doi:10.7326/0003-4819-111-3-206
Text Size: A A A

Study Objective: To determine if aerosolization of purified human plasma α1-antitrypsin is an effective means for increasing lower respiratory anti-neutrophil-elastase defenses in α1-antitrypsin deficiency.

Design: Nonrandomized, before-and-after trial with a 7-day treatment period. Companion studies in animals to determine lung epithelial permeability to α1-antitrypsin.

Patients: Twelve patients with homozygous Z-type α1-antitrypsin deficiency and mild to moderate emphysema.

Interventions: Aerosol administration of human plasma α1-antitrypsin, 100 mg every 12 hours for 7 days. Single, 100-mg aerosol dose to anesthetized sheep with indwelling thoracic lymph duct catheters for direct assessment of lung permeability.

Measurements and Main Results: Treatment resulted in increased α1-antitrypsin levels in the lung epithelial lining fluid (0.28 ±0.07 µM before therapy to 5.86 ±1.03 µM after therapy) and increased anti-neutrophil-elastase capacity (0.78 ±0.38 ΩM before therapy to 4.16 ±0.95 µM after therapy). Aerosolized α1-antitrypsin diffused across the respiratory epithelium and entered lung interstitial lymph (in sheep) and reached the systemic circulation (in sheep and humans). No side effects were noted.

Conclusion: Short-term aerosol administration of human plasma α1-antitrypsin to patients with α1-antitrypsin deficiency is safe and feasible, resulting in a return to normal of anti-neutrophil-elastase defenses in the lower respiratory tract. The aerosol approach, therefore, merits serious longterm evaluation as an alternative to other parenteral forms of administering therapeutic proteins.





Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).


Submit a Comment/Letter
Submit a Comment/Letter

Summary for Patients

Clinical Slide Sets

Terms of Use

The In the Clinic® slide sets are owned and copyrighted by the American College of Physicians (ACP). All text, graphics, trademarks, and other intellectual property incorporated into the slide sets remain the sole and exclusive property of the ACP. The slide sets may be used only by the person who downloads or purchases them and only for the purpose of presenting them during not-for-profit educational activities. Users may incorporate the entire slide set or selected individual slides into their own teaching presentations but may not alter the content of the slides in any way or remove the ACP copyright notice. Users may make print copies for use as hand-outs for the audience the user is personally addressing but may not otherwise reproduce or distribute the slides by any means or media, including but not limited to sending them as e-mail attachments, posting them on Internet or Intranet sites, publishing them in meeting proceedings, or making them available for sale or distribution in any unauthorized form, without the express written permission of the ACP. Unauthorized use of the In the Clinic slide sets will constitute copyright infringement.


Buy Now for $42.00

to gain full access to the content and tools.

Want to Subscribe?

Learn more about subscription options

Topic Collections
Forgot your password?
Enter your username and email address. We'll send you a reminder to the email address on record.