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.

International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma

“…Chronic airway obstruction may result in airway closure or uneven ventilation of small airways, which associates with severe exacerbations [121]. Severe asthmatics were found to exhibit air trapping (reduced FVC in relation to FEV1/FVC) when compared with non-severe asthmatics at matched levels of airflow limitation measured by FEV1/FVC ratio [122].…”

Small airways in asthma

“…FEF 25-75% is often mentioned as a good indicator of small airway obstruction. However, its value is largely affected by the obstruction in the large airways; it lacks specificity due to its inconsistency during multiple measurements, and as such is less reliable (19).…”

The irreversible component of persistent asthma

“…However, several important observations have been made including the fact that more severe air-trapping has been shown to be associated with severe asthma. (23)(24)(25) This demonstrates that important physiologic mechanisms that do not necessarily relate to FEV 1 may also relate to an irreversible component of airflow obstruction. Whether or not onset of asthma during childhood or adulthood results in more severe asthma is not clear because of conflicting data (26;27) Importantly, although enrollment in studies of severe asthma tends to be defined more by medication use, and morbidity, (23;28) low lung function (FEV 1 ) and less bronchodilator reversibility are strongly associated with severity.…”