Aspergillus sensitization is associated with airflow limitation and bronchiectasis in severe asthma

Allergy ◽  
2011 ◽  
Vol 66 (5) ◽  
pp. 679-685 ◽  
Author(s):  
D. Menzies ◽  
L. Holmes ◽  
G. McCumesky ◽  
C. Prys-Picard ◽  
R. Niven
Keyword(s):  
Severe Asthma ◽  
Airflow Limitation

scholarly journals Systems Approaches to Treatment Response to Imatinib in Severe Asthma: A Pilot Study

2021 ◽  
Vol 11 (4) ◽  
pp. 240
Author(s):  
Seung Han Baek ◽  
Dinah Foer ◽  
Katherine N. Cahill ◽  
Elliot Israel ◽  
Enrico Maiorino ◽  
...  
Keyword(s):  
Gene Expression ◽  
Clinical Trial ◽  
Systems Biology ◽  
Pilot Study ◽  
Severe Asthma ◽  
Treated Patient ◽  
Expression Patterns ◽  
Airflow Limitation ◽  
Response To Treatment ◽  
Imatinib Treatment

There is an acute need for advances in pharmacologic therapies and a better understanding of novel drug targets for severe asthma. Imatinib, a tyrosine kinase inhibitor, has been shown to improve forced expiratory volume in 1 s (FEV1) in a clinical trial of patients with severe asthma. In a pilot study, we applied systems biology approaches to epithelium gene expression from these clinical trial patients treated with imatinib to better understand lung function response with imatinib treatment. Bronchial brushings from ten imatinib-treated patient samples and 14 placebo-treated patient samples were analyzed. We used personalized perturbation profiles (PEEPs) to characterize gene expression patterns at the individual patient level. We found that strong responders—patients with greater than 20% increase in FEV1—uniquely shared multiple downregulated mitochondrial-related pathways. In comparison, weak responders (5–10% FEV1 increase), and non-responders to imatinib shared none of these pathways. The use of PEEP highlights its potential for application as a systems biology tool to develop individual-level approaches to predicting disease phenotypes and response to treatment in populations needing innovative therapies. These results support a role for mitochondrial pathways in airflow limitation in severe asthma and as potential therapeutic targets in larger clinical trials.

scholarly journals Pharmacological Rationale for Targeting IL-17 in Asthma

2021 ◽  
Vol 2 ◽  
Author(s):  
Siti Farah Rahmawati ◽  
Maurice te Velde ◽  
Huib A. M. Kerstjens ◽  
Alexander S. S. Dömling ◽  
Matthew Robert Groves ◽  
...  
Keyword(s):  
Severe Asthma ◽  
Inhaled Corticosteroids ◽  
Current Knowledge ◽  
Experimental Models ◽  
Airflow Limitation ◽  
Interleukin 17 ◽  
Asthma Phenotype ◽  
T Helper 2 ◽  
Bronchial Biopsies

Asthma is a respiratory disease that currently affects around 300 million people worldwide and is defined by coughing, shortness of breath, wheezing, mucus overproduction, chest tightness, and expiratory airflow limitation. Increased levels of interleukin 17 (IL-17) have been observed in sputum, nasal and bronchial biopsies, and serum of patients with asthma compared to healthy controls. Patients with higher levels of IL-17 have a more severe asthma phenotype. Biologics are available for T helper 2 (Th2)-high asthmatics, but the Th17-high subpopulation has a relatively low response to these treatments, rendering it a rather severe asthma phenotype to treat. Several experimental models suggest that targeting the IL-17 pathway may be beneficial in asthma. Moreover, as increased activation of the Th17/IL-17 axis is correlated with reduced inhaled corticosteroids (ICS) sensitivity, targeting the IL-17 pathway might reverse ICS unresponsiveness. In this review, we present and discuss the current knowledge on the role of IL-17 in asthma and its interaction with the Th2 pathway, focusing on the rationale for therapeutic targeting of the IL-17 pathway.

scholarly journals Transcriptomic gene signatures associated with persistent airflow limitation in patients with severe asthma

2017 ◽  
Vol 50 (3) ◽  
pp. 1602298 ◽  
Author(s):  
Pieter-Paul Hekking ◽  
Matthew J. Loza ◽  
Stelios Pavlidis ◽  
Bertrand De Meulder ◽  
Diane Lefaudeux ◽  
...  
Keyword(s):  
Severe Asthma ◽  
Airflow Limitation ◽  
Gene Signatures

scholarly journals Distinct Phenotypes of Smokers with Fixed Airflow Limitation Identified by Cluster Analysis of Severe Asthma

2018 ◽  
Vol 15 (1) ◽  
pp. 33-41 ◽  
Author(s):  
Satoshi Konno ◽  
Natsuko Taniguchi ◽  
Hironi Makita ◽  
Yuji Nakamaru ◽  
Kaoruko Shimizu ◽  
...  
Keyword(s):  
Cluster Analysis ◽  
Severe Asthma ◽  
Airflow Limitation

Effect of MgSO4 on FEV1 in stable severe asthma patients with chronic airflow limitation

2009 ◽  
Vol 22 (4) ◽  
pp. 256-261 ◽  
Author(s):  
Alinda MG Zandsteeg ◽  
Petra Hirmann ◽  
Henk R Pasma ◽  
Jan-Peter Yska ◽  
Anneke ten Brinke
Keyword(s):  
Severe Asthma ◽  
Airflow Limitation ◽  
Asthma Patients

scholarly journals Sex dependence of airflow limitation and air trapping in children with severe asthma

2011 ◽  
Vol 127 (4) ◽  
pp. 1073-1074 ◽  
Author(s):  
Ronald L. Sorkness ◽  
W. Gerald Teague ◽  
Madhuri Penugonda ◽  
Anne M. Fitzpatrick
Keyword(s):  
Severe Asthma ◽  
Airflow Limitation ◽  
Air Trapping

scholarly journals Problematic, severe asthma in children: a new concept and how to manage it

2010 ◽  
Vol 17 (1-2) ◽  
pp. 51-64
Author(s):  
Andrew BUSH
Keyword(s):  
Severe Asthma ◽  
Inhaled Corticosteroids ◽  
Treatment Plan ◽  
Airflow Limitation ◽  
Steroid Resistance ◽  
Single Intramuscular Injection ◽  
Children With Asthma ◽  
Oral Corticosteroids ◽  
The Stability ◽  
Future Work

Most children with asthma respond to low doses of inhaled corticosteroids, but a few remain symptomatic despite being prescribed the routine usual asthma medications. The first steps are to ensure that the diagnosis is correct and that the inhaled medications are being given regularly with an appropriately used device. If the children continue to be symptomatic, with any or all of chronic symptoms, acute exacerbations, the need for regular oral corticosteroids, or persistent airflow limitation, then they are considered to have problematic, severe asthma. The next step is to perform a detailed evaluation, including a nurse-lead home visit, to determine whether the child has difficult to treat asthma which improves if the basics are got right, or severe, therapy-resistant asthma; the latter group would be candidates for cytokine-specific therapies. If severe, therapy-resistant asthma is the likely issue, then a detailed invasive investigation is performed, including bronchoscopy, bronchoalveolar lavage and endobronchial biopsy, and trial of adherence with a single intramuscular injection of depot triamcinolone. After detailed phenotyping, an individualised treatment plan is determined. Future work will determine the roles of proximal and distal inflammation, as well as the relative importance of intramural (mucosal) and intraluminal infection. The stability of paediatric asthma phenotypes over time is more variable than those of adults, and the implications of a change of phenotype are yet to be determined. Keywords: steroid resistance, allergen exposure, passive smoking, omalizumab, prednisolone, steroid-sparing agent, phenotype, nitric oxide, induced sputum, endobronchial biopsy

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

2008 ◽  
Vol 104 (2) ◽  
pp. 394-403 ◽  
Author(s):  
Ronald L. Sorkness ◽  
Eugene R. Bleecker ◽  
William W. Busse ◽  
William J. Calhoun ◽  
Mario Castro ◽  
...  
Keyword(s):  
Airway Obstruction ◽  
Severe Asthma ◽  
Forced Expiratory Volume ◽  
Pathological Process ◽  
Airflow Limitation ◽  
Care Utilization ◽  
Air Trapping ◽  
Asthma Phenotype ◽  
Blood Institute ◽  
National Heart Lung

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 (FEV1)/FVC]. Severe asthma had prominent air trapping, evident as reduced FVC over the entire range of FEV1/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 FEV1/FVC <75% predicted. Air trapping also was associated with increases in TLC and functional reserve capacity. After maximal bronchodilation, FEV1 reversed similarly from baseline in severe and nonsevere asthma, but the severe asthma classification was an independent predictor of residual reduction in FEV1 after maximal bronchodilation. An increase in FVC accounted for most of the reversal of FEV1 when baseline FEV1 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.

scholarly journals Oral Corticosteroids Dependence and Biologic Drugs in Severe Asthma: Myths or Facts? A Systematic Review of Real-World Evidence

2021 ◽  
Vol 22 (13) ◽  
pp. 7132
Author(s):  
Luigino Calzetta ◽  
Marina Aiello ◽  
Annalisa Frizzelli ◽  
Giuseppina Bertorelli ◽  
Paola Rogliani ◽  
...  
Keyword(s):  
Systematic Review ◽  
Severe Asthma ◽  
Real World ◽  
Symptom Control ◽  
Airflow Limitation ◽  
Biologic Drugs ◽  
Asthmatic Patients ◽  
Severe Asthmatic ◽  
Oral Corticosteroids ◽  
Sparing Effect

Airway inflammation represents an important characteristic in asthma, modulating airflow limitation and symptom control, and triggering the risk of asthma exacerbation. Thus, although corticosteroids represent the cornerstone for the treatment of asthma, severe patients may be dependent on oral corticosteroids (OCSs). Fortunately, the current humanised monoclonal antibodies (mAbs) benralizumab, dupilumab, mepolizumab, omalizumab, and reslizumab have been proven to induce an OCS-sparing effect in randomized controlled trials (RCTs), thus overcoming the problem of OCS dependence in severe asthma. Nevertheless, a large discrepancy has been recognized between selected patients enrolled in RCTs and non-selected asthmatic populations in real-world settings. It is not possible to exclude that the OCS-sparing effect of mAbs resulting from the RCTs could be different than the real effect resulting in clinical practice. Therefore, we performed a systematic review and correlation analysis to assess whether mAbs are effective in eliciting an OCS-sparing effect and overcoming the OCS dependence in severe asthmatic patients in real-world settings. Overall, real-world studies support the evidence that OCS dependence is a real condition that, however, can be found only in a small number of really severe asthmatic patients. In most patients, the dependence on OCS can be related to modifying factors that, when adequately modulated, may lead to a significant reduction or suspension of OCS maintenance. Conversely, in severe asthmatics in whom OCS resistance is proved by a high daily dose intake, mAbs allow reversion of the OCS dependence, leading to the suspension of OCS therapy in most patients or >50% reduction in the daily OCS dose.

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