The irreversible component of persistent asthma

Received 29 August 2009; received in revised form 28 September 2009; accepted 29 September 2009.

Irreversible airflow obstruction or limitation occurs in some patients with asthma, can develop early in life, and becomes more common as asthma becomes more severe. Efforts to understand irreversible airflow obstruction or limitation have been hampered by the lack of a standardized definition of the phenotype and by the lack of appropriate research models. Unfortunately, it appears that currently available asthma treatments do not prevent this important asthma complication. Herein, the evidence of an irreversible component of asthma, its underlying pathology, and the limitations of current asthma treatments are reviewed.

Key words: Asthma, airway remodeling, irreversible airway obstruction, irreversible airflow limitation

Abbreviations used: BHR, Bronchial hyperresponsiveness, COPD, Chronic obstructive pulmonary disease, FVC, Forced vital capacity, RBM, Reticular basement membrane

Center for Human Genomics and the Department of Internal Medicine, Section on Pulmonary, Critical Care, Allergy and Immunologic Diseases, Wake Forest University School of Medicine, Winston-Salem, NC

Reprint requests: Rodolfo M. Pascual, MD, Wake Forest University School of Medicine, Center for Human Genomics, Medical Center Blvd, Winston-Salem, NC 27157.

(Supported by an educational grant from Merck & Co., Inc.)

Series editors: Joshua A. Boyce, MD, Fred Finkelman, MD, William T. Shearer, MD, PhD, and Donata Vercelli, MD

Supported in part by grants U10HL074225 and 1R21AI076699 to S.P.P. and 1K12HL 089992 to R.M.P.

Terms in boldface and italics are defined in the glossary on page 884.

PII: S0091-6749(09)01466-3

doi:10.1016/j.jaci.2009.09.047

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