Lung function in adults with stable but severe asthma: Air trapping and incomplete reversal of obstruction with bronchodilation

Univ. of Wisconsin, 777 Highland Ave., Madison, WI 53705, USA.
Journal of Applied Physiology (Impact Factor: 3.43). 03/2008; 104(2):394-403. DOI: 10.1152/japplphysiol.00329.2007
Source: PubMed

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.

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Available from: William J Calhoun, Aug 09, 2015
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    • "It is recognized that the majority of asthmatics may be controlled by regular treatment with ICS/LABA. However there remains a small proportion of patients who do not respond to this treatment [1] [2]. Severe asthma accounts for a major part of financial burden to health care system posed by asthma [3]. "
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    ABSTRACT: The Belgian severe asthma registry is a web-based registry encompassing demographic, clinical, functional and inflammatory data of severe asthmatics (SA), aiming at improving awareness, knowledge on its natural history and subphenotypes, and offering tools to optimize care of this asthma population. The cross-sectional analyses of this registry included 350 SA as defined by the ATS (2000) from 9 Belgian centres, with at least one year follow up. Mean age was 55 ± 14 yrs. SA were more frequently female (57%) and atopic (70%). Late-onset asthma (≥40 yr) was observed in 31% of SA. Current smokers represented 12% while 31% were ex-smokers. In addition to high doses ICS + LABA, 65% of patients were receiving LTRA, 27% anti-IgE and 24% maintenance oral corticosteroids (8 mg (Interquartile range-IQR:4-8) methylprednisolone). Despite impaired airflow (median FEV1:67%; IQR: 52-81) only 65% had a post-bronchodilator FEV1/FVC ratio <70%. The median blood eosinophil count was 240/mm³. The median FENO was 26 ppb (IQR: 15-43) and 22% of SA had FENO ≥ 50 ppb. Induced sputum was successful in 86 patients. Eosinophilic asthma (sputum Eos ≥ 3%) was the predominant phenotype (55%) while neutrophilic (sputum Neu ≥ 76%) and paucigranulocytic asthma accounted for 22% and 17% respectively. Comorbidities included rhinitis and chronic rhinosinusitis (49%), nasal polyposis (19%), oesophageal reflux (36%), overweight and obesity (47%) and depression (19%). In addition, 8% had aspirin-induced asthma and 3% ABPA. Asthma was not well-controlled in 83% according to ACT < 20 and 77% with ACQ > 1.5. In this cohort of patients with severe asthma, the majority displayed indices of persistent airflow limitation and eosinophilic inflammation despite high-dose corticosteroids, suggesting potential for eosinophil-targeted biotherapies. Copyright © 2014 Elsevier Ltd. All rights reserved.
    Respiratory Medicine 12/2014; 108(12):1723-32. DOI:10.1016/j.rmed.2014.10.007 · 2.92 Impact Factor
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    • "However, its use in clinical practice is hampered by physiological variability and measurement inconsistency issues [3] [28] [29]. In addition, FEF 25e75% can be interpreted only when FVC stands within normal value limits; what is more, this parameter appears of limited reliability to assess distal airway function according to the findings from the Severe Asthma Research Program of the National Heart Lung and Blood Institute, which showed a lack of correlation between FEF 25e75% and indices of air trapping [3]. Similarly, FEF 50% was unable to predict hyperinflation in asthmatic children with mainly normal lung function [30]. "
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    ABSTRACT: Asthma is a disease characterized by inflammation which affects both proximal and distal airways. We evaluated the prevalence of small airway obstruction (SAO) in a group of clinically stable asthmatics with both normal forced expiratory volume in the first second (FEV1) and normal FEV1/forced vital capacity (FVC) and treated with an association of inhaled corticosteroids (ICSs) and long acting β2-agonists (LABAs). Clinical evaluation included the measurement of dyspnea, asthma control test and drug compliance. The prevalence of SAO was estimated by spirometry and plethysmography and defined by the presence of one or more of the following criteria: functional residual capacity (FRC) > 120% predicted (pred), residual volume (RV) > pred + 1.64 residual standard deviation (RSD), RV/total lung capacity (TLC) > pred + 1.64 RSD, forced expiratory flow (FEF)25-75% < pred - 1.64 RSD, FEF50% < pred - 1.64 RSD, slow vital capacity (SVC) - FVC > 10%. Among the 441 patients who were included, 222 had normal FEV1 and FEV1/FVC. At least one criteria of SAO was found in 115 (52%) mainly lung hyperinflation (39% based on high FRC, RV or RV/TLC) and more rarely distal airflow limitation (15% based on FEF25-75% or FEF50%) or expiratory trapping (10% based on increased SVC - FVC). In the patients with only SAO (no PAO), there was no relationship between SAO, asthma history and the scores of dyspnea, asthma control or drug compliance. These results suggest that in asthmatics with normal FEV1 and FEV1/FVC, treated with ICSs and LABAs, SAO is found in more than half of the patients indicating that the routinely used lung function tests can underestimate dysfunctions occurring in the small airways.
    Respiratory medicine 08/2013; 107(11). DOI:10.1016/j.rmed.2013.08.009 · 2.92 Impact Factor
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    • "Another was whether our selected patients group belonged to peculiar or ordinary phenotype of adult asthma. Interestingly recent analysis of the Severe Asthma Research Program (SARP) revealed that severe asthma was peculiar to be characterized by abnormal lung function that is responsive to bronchodilators [13] and prominent air trapping (detected as increased RV/TLC ratio) over the entire range of airflow obstruction severity and that nonsevere asthmatic patients did not exhibit significant air trapping even at the more severe stages of airflow limitation expressed as FEV 1 /FVC ratio [14]. Mead developed the slope ratio (SR), defined as tangent slope (d ˙ V /dV) divided by the chord ˙ V /(FVC-V), as an index of the curvilinearity of the MEFV curve [15]. "
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    ABSTRACT: Background. In patients with bronchial asthma, spirometry could identify the airflow limitation of small airways by evaluating the concave shape of the maximal expiratory flow-volume (MEFV) curve. As the concave shape of the MEFV curve is not well documented, we reevaluated the importance of this curve in adult asthmatic patients. Methods. We evaluated spirometric parameters, the MEFV curve, and its concave shape (scoop between the peak and endpoint of expiration) in 27 nonsmoking asthmatic patients with physician-confirmed wheeze and positive bronchial reversibility after a short-acting β2-agonist inhalation. We also calculated angle β and shape factors (SF(25%) and SF(50%)) to quantitate the curvilinearity of the MEFV curve. Results. The MEFV curve was concave in all patients. Along with improvements in standard spirometric parameters, curvilinear parameters, angle β, SF(25%), and SF(50%) were significantly improved after bronchodilator inhalation. There were significant correlations between improvements in angle β, and FEF(50%), and FEF(25-75%), and between improvements in SF(25%), and SF(50%), and FEF(75%). Conclusions. The bronchodilator greatly affected the concave shape of the MEFV curve, correlating with spirometric parameters of small airway obstructions (FEF(50%), FEF(75%), and FEF(25-75%)). Thus, the concave shape of the MEFV curve is an important indicator of airflow limitation in adult asthmatic patients.
    11/2012; 2012:797495. DOI:10.1155/2012/797495
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