The Journal of Allergy and Clinical Immunology
Volume 118, Issue 5 , Pages 1075-1081, November 2006

Small airways response to naturalistic cat allergen exposure in subjects with asthma

  • Michelle R. Zeidler, MD, MS

      Affiliations

    • From the Divisions of Pulmonary, Critical Care Medicine and Hospitalists
  • ,
  • Jonathan G. Goldin, MD, PhD

      Affiliations

    • Thoracic Radiology, David Geffen School of Medicine
  • ,
  • Eric C. Kleerup, MD

      Affiliations

    • From the Divisions of Pulmonary, Critical Care Medicine and Hospitalists
  • ,
  • Hyun J. Kim, MS

      Affiliations

    • Thoracic Radiology, David Geffen School of Medicine
  • ,
  • Dao A. Truong, BS

      Affiliations

    • Thoracic Radiology, David Geffen School of Medicine
  • ,
  • David W. Gjertson, PhD

      Affiliations

    • Thoracic Radiology, David Geffen School of Medicine
  • ,
  • Nola J. Kennedy, PhD

      Affiliations

    • School of Public Health, University of California, Los Angeles
  • ,
  • Kenneth B. Newman, MD

      Affiliations

    • Forest Laboratories, New York
  • ,
  • Donald P. Tashkin, MD

      Affiliations

    • From the Divisions of Pulmonary, Critical Care Medicine and Hospitalists
  • ,
  • Jeffrey M. Silverman, MD

      Affiliations

    • Keck School of Medicine at the University of Southern California and Landmark Imaging
  • ,
  • Jonathan Corren, MD

      Affiliations

    • Division of Clinical Immunology and Allergy, David Geffen School of Medicine and Allergy Research Foundation
    • Corresponding Author InformationReprint requests: Jonathan Corren, MD, Allergy Research Foundation, 11620 Wilshire Blvd, Suite 200, Los Angeles, CA 90025.

Received 24 April 2006; received in revised form 21 June 2006; accepted 22 June 2006. published online 12 September 2006.

Los Angeles, Calif, and New York, NY

Background

It is currently unclear whether the small airways (diameter <2 μm) contribute significantly to late asthmatic reactions to inhaled allergen.

Objectives

We sought to determine whether naturalistic exposure to cat allergen induced late responses in the small airways as measured by pulmonary function testing and high-resolution computed tomography (HRCT) of the chest performed at end-expiration.

Methods

In a group of 10 subjects with cat-induced asthma, physiologic studies (spirometry and lung volumes, including closing volume) and HRCT were performed before and 6 and 23 hours after a cat room challenge that caused a 20% or greater acute fall in FEV1.

Results

There was no significant decline in FEV1 at 6 or 23 hours after cat exposure. Forced expiratory flow at 25% to 75% of forced vital capacity was significantly decreased at 6 hours after the challenge and returned to normal by 23 hours. HRCT image analysis as well as closing volume demonstrated increased air trapping from baseline at both 6 and 23 hours after the challenge. In addition, image analysis demonstrated a significant increase in small airways hyperresponsiveness to methacholine at 23 hours after the challenge. No significant mean changes were noted in lung volumes at either 6 or 23 hours or in PC20 FEV1 at 23 hours postchallenge.

Conclusion

These findings demonstrate that naturalistic exposure to cat allergen results in significant small airways obstruction and hyperresponsiveness persisting for at least 23 hours, at which time these changes cannot be detected by conventional physiologic measures.

Clinical implications

Physiologically silent distal lung inflammation persists after an antigenic challenge.

Key words: Asthma, bronchial hyperreactivity, Fel d 1 protein, image analysis, computer-assisted, tomography, x-ray computed

Abbreviations used: BDP-CFC, Beclomethasone–dipropionate chlorofluorocarbon, BDP-HFA, Beclomethasone dipropionate hydrofluoroalkane, CRC, Cat room challenge, CV, Closing volume, CV/VC%, Closing volume as a percent of the vital capacity, FEF25-75, Forced expiratory flow at 25% to 75% of forced vital capacity, FRC, Functional residual capacity, FVC, Forced vital capacity, HRCT, High-resolution computed tomography, HU, Hounsfield unit, LAC, Lung attenuation curve, MCT, Methacholine challenge test, RV, Residual volume, TLC, Total lung capacity

 

 Supported by Forest Pharmaceuticals.Disclosure of potential conflict of interest: E. C. Kleerup has received grant support from Forest; K. B. Newman is employed by Forest Labs; D. P. Tashkin has consultant arrangements with IVAX Pharmaceuticals, has received grant support from Merck and IVAX Pharmaceuticals, and is on the speakers bureau for IVAX Pharmaceuticals; J. Corren has received grant support from SPRI, AstraZeneca, Sepracor, GlaxoSmithKline, and Sky Pharma and is on the speakers bureau for SPRI and Sepracor. The rest of the authors have declared they have no conflict of interest.

PII: S0091-6749(06)01577-6

doi:10.1016/j.jaci.2006.06.042

The Journal of Allergy and Clinical Immunology
Volume 118, Issue 5 , Pages 1075-1081, November 2006