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
2008 ◽  
Vol 104 (2) ◽  
pp. 394-403 ◽  
Author(s):  
Ronald L. Sorkness ◽  
Eugene R. Bleecker ◽  
William W. Busse ◽  
William J. Calhoun ◽  
Mario Castro ◽  
...  

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.


2021 ◽  
Vol 11 (4) ◽  
pp. 240
Author(s):  
Seung Han Baek ◽  
Dinah Foer ◽  
Katherine N. Cahill ◽  
Elliot Israel ◽  
Enrico Maiorino ◽  
...  

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.


2021 ◽  
Vol 2 ◽  
Author(s):  
Siti Farah Rahmawati ◽  
Maurice te Velde ◽  
Huib A. M. Kerstjens ◽  
Alexander S. S. Dömling ◽  
Matthew Robert Groves ◽  
...  

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.


2018 ◽  
Vol 107 ◽  
pp. 33-38 ◽  
Author(s):  
Philip Konietzke ◽  
Oliver Weinheimer ◽  
Mark O. Wielpütz ◽  
Willi L. Wagner ◽  
Philine Kaukel ◽  
...  

2017 ◽  
Vol 50 (3) ◽  
pp. 1602298 ◽  
Author(s):  
Pieter-Paul Hekking ◽  
Matthew J. Loza ◽  
Stelios Pavlidis ◽  
Bertrand De Meulder ◽  
Diane Lefaudeux ◽  
...  

2018 ◽  
Vol 15 (1) ◽  
pp. 33-41 ◽  
Author(s):  
Satoshi Konno ◽  
Natsuko Taniguchi ◽  
Hironi Makita ◽  
Yuji Nakamaru ◽  
Kaoruko Shimizu ◽  
...  

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

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

2014 ◽  
Vol 21 (8) ◽  
pp. 986-993 ◽  
Author(s):  
Chad A. Witt ◽  
Ajay Sheshadri ◽  
Luke Carlstrom ◽  
Jaime Tarsi ◽  
James Kozlowski ◽  
...  

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