title: Lung function in adults with stable but severe asthma: air trapping and incomplete reversal of obstruction with bronchodilation.
abstract: Five to ten percent of asthma cases are poorly controlled chronically and refractory to treatment, and these severe cases account for disproportionate asthma-associated morbidity, mortality, and health care utilization. While persons with severe asthma tend to have more airway obstruction, it is not known whether they represent the severe tail of a unimodal asthma population, or a severe asthma phenotype. We hypothesized that severe asthma has a characteristic physiology of airway obstruction, and we evaluated spirometry, lung volumes, and reversibility during a stable interval in 287 severe and 382 nonsevere asthma subjects from the National Heart, Lung, and Blood Institute Severe Asthma Research Program. We partitioned airway obstruction into components of air trapping [indicated by forced vital capacity (FVC)] and airflow limitation [indicated by forced expiratory volume in 1 s (FEV(1))/FVC]. Severe asthma had prominent air trapping, evident as reduced FVC over the entire range of FEV(1)/FVC. This pattern was confirmed with measures of residual lung volume/total lung capacity (TLC) in a subgroup. In contrast, nonsevere asthma did not exhibit prominent air trapping, even at FEV(1)/FVC <75% predicted. Air trapping also was associated with increases in TLC and functional reserve capacity. After maximal bronchodilation, FEV(1) reversed similarly from baseline in severe and nonsevere asthma, but the severe asthma classification was an independent predictor of residual reduction in FEV(1) after maximal bronchodilation. An increase in FVC accounted for most of the reversal of FEV(1) when baseline FEV(1) was <60% predicted. We conclude that air trapping is a characteristic feature of the severe asthma population, suggesting that there is a pathological process associated with severe asthma that makes airways more vulnerable to this component.
authors.affiliation: Univ. of Wisconsin, 777 Highland Ave., Madison, WI 53705, USA. rlsorkne@wisc.edu
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Sorkness
authors.forename: Eugene R
authors.initials: ER
authors.lastname: Bleecker
authors.forename: William W
authors.initials: WW
authors.lastname: Busse
authors.forename: William J
authors.initials: WJ
authors.lastname: Calhoun
authors.forename: Mario
authors.initials: M
authors.lastname: Castro
authors.forename: Kian Fan
authors.initials: KF
authors.lastname: Chung
authors.forename: Douglas
authors.initials: D
authors.lastname: Curran-Everett
authors.forename: Serpil C
authors.initials: SC
authors.lastname: Erzurum
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Gaston
authors.forename: Elliot
authors.initials: E
authors.lastname: Israel
authors.forename: Nizar N
authors.initials: NN
authors.lastname: Jarjour
authors.forename: Wendy C
authors.initials: WC
authors.lastname: Moore
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Peters
authors.forename: W Gerald
authors.initials: WG
authors.lastname: Teague
authors.forename: Sally E
authors.initials: SE
authors.lastname: Wenzel
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000403:Airway Resistance / Q000187:drug effects*; D000420:Albuterol / Q000494:pharmacology / Q000627:therapeutic use*; D001249:Asthma / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects*; D016085:Bronchoconstrictor Agents; D001993:Bronchodilator Agents / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008131:London; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D008176:Lung Volume Measurements; D008297:Male; D016210:Methacholine Chloride; D008875:Middle Aged; D010641:Phenotype; D012720:Severity of Illness Index; D013147:Spirometry; D014481:United States; D014797:Vital Capacity
chemical_list: D000305:Adrenal Cortex Hormones; D016085:Bronchoconstrictor Agents; D001993:Bronchodilator Agents; D016210:Methacholine Chloride; D000420:Albuterol