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: 3.06). 03/2008; 104(2):394-403. DOI: 10.1152/japplphysiol.00329.2007
Source: PubMed


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, Sep 30, 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 · 3.09 Impact Factor
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    • "Similarly, Perez and colleagues have demonstrated the presence of small airways impairment (defined primarily by body plethysmography measures of lung hyperinflation such as functional residual capacity (FRC), residual volume (RV) and the ratio of RV/total lung capacity) in nearly 40% of clinically stable moderate-to-severe asthmatics treated with ICS/LABA who had a normal FEV1, supporting the observation that conventional physiological measurements are unable to sensitively evaluate this airway region.45 The forced vital capacity (FVC) is gaining support as an indirect marker of air trapping, where in the severe asthma research programme, the FVC as a percentage of predicted was shown to be highly inversely correlated to the ratio of residual volume to total lung capacity (RV/TLC) as a percentage of predicted46 Indeed, Papi and colleagues have shown that improvements in FVC may reflect reduction in air trapping and small airways obstruction.47 The authors investigated the effects of 3 months of treatment with small particle (~1.5 microns) combination ICS/LABA aerosols (beclomethasone dipropionate [BDP] with formoterol [Form], 400/24 µg daily) delivered via an hydrofluoroalkane (HFA)-solution pressurised metered dose inhaler (pMDI) and compared this to large particle (~2.7 microns) combination ICS/LABA aerosols (fluticasone propionate (FP) with salmeterol (Salm), 500/100 µg daily) administered as an HFA-suspension pMDI, and observed a significant improvement in FVC with the small particle aerosols. "
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    ABSTRACT: The small airways have been neglected for many years, but interest in the topic has been rekindled with recent advances in measurement techniques to assess this region and also the ability to deliver therapeutics to the distal airways. Current levels of disease control in asthmatic patients remain poor and there are several contributory factors including; poor treatment compliance, heterogeneity of asthma phenotypes and associated comorbidities. However, the proposition that we may not be targeting all the inflammation that is present throughout the whole respiratory tree may also be an important factor. Indeed decades ago, pathologists and physiologists clearly identified the importance of small airways dysfunction in asthmatic patients. With improved inhaler technology to deliver drug to target the whole respiratory tree and more sensitive measures to assess the distal airways, we should certainly give greater consideration to treating the small airway region when seeing our asthmatic patients in clinic. The aim of this review is to address the relevance of small airways dysfunction in the daily clinical management of patients with asthma. In particular the role of small particle aerosols in the management of patients with asthma will be explored.
    Allergy, asthma & immunology research 09/2014; 6(5):376-88. DOI:10.4168/aair.2014.6.5.376 · 2.43 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 · 3.09 Impact Factor
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