Asthma with Irreversible Airway Obstruction in Smokers and Nonsmokers: Links between Airway Inflammation and Structural Changes

Respiration ◽  
2020 ◽  
pp. 1-11
Author(s):  
Louis-Philippe Boulet ◽  
Marie-Eve Boulay ◽  
Harvey O. Coxson ◽  
Cameron J. Hague ◽  
Joanne Milot ◽  
...  
Keyword(s):  
Lung Function ◽  
Airway Obstruction ◽  
Airway Inflammation ◽  
Wall Thickness ◽  
Structural Changes ◽  
Smoking History ◽  
Airway Wall ◽  
Tobacco Exposure ◽  
Airway Wall Thickness ◽  
Irreversible Airway Obstruction

<b><i>Background:</i></b> The development of irreversible airway obstruction (IRAO) in asthma is related to lung/airway inflammatory and structural changes whose characteristics are likely influenced by exposure to tobacco smoke. <b><i>Objective:</i></b> To investigate the interplay between airway and lung structural changes, airway inflammation, and smoking exposure in asthmatics with IRAO. <b><i>Methods:</i></b> We studied asthmatics with IRAO who were further classified according to their smoking history, those with ≥20 pack-years of tobacco exposure (asthmatics with smoking-related IRAO [AwS-IRAO]) and those with &#x3c;5 pack-years of tobacco exposure (asthmatics with nonsmoking-related IRAO [AwNS-IRAO]). In addition to recording baseline clinical and lung function features, all patients had a chest computed tomography (CT) from which airway wall thickness was measured and quantitative and qualitative assessment of emphysema was performed. The airway inflammatory profile was documented from differential inflammatory cell counts on induced sputum. <b><i>Results:</i></b> Ninety patients were recruited (57 AwS-IRAO and 33 AwNS-IRAO). There were no statistically significant differences in the extent of emphysema and gas trapping between groups on quantitative chest CT analysis, although Pi10, a marker of airway wall thickness, was significantly higher in AwS-IRAO (<i>p</i> = 0.0242). Visual analysis showed a higher prevalence of emphysema (<i>p</i> = 0.0001) and higher emphysema score (<i>p</i> &#x3c; 0.0001) in AwS-IRAO compared to AwNS-IRAO and distribution of emphysema was different between groups. Correlations between radiological features and lung function were stronger in AwS-IRAO. In a subgroup analysis, we found a correlation between airway neutrophilia and emphysematous features in AwS-IRAO and between eosinophilia and both airway wall thickness and emphysematous changes in AwNS-IRAO. <b><i>Conclusions:</i></b> Although bronchial structural changes were relatively similar in smoking and nonsmoking patients with asthma and IRAO, emphysematous changes were more predominant in smokers. However, neutrophils in AwS-IRAO and eosinophils in AwNS-IRAO were associated with lung and airway structural changes.

scholarly journals Airway remodeling in asthma

2001 ◽  
Vol 41 (3) ◽  
pp. 125
Author(s):  
Roni Naning ◽  
MTS Darmawan
Keyword(s):  
Lung Function ◽  
Combination Therapy ◽  
Airway Obstruction ◽  
Chronic Inflammation ◽  
Structural Changes ◽  
Airway Remodeling ◽  
Airway Wall ◽  
Inhaled Corticosteroid ◽  
Irreversible Airway Obstruction

Airway remodeling is the term given to a series of structural changes characterized by chronic, irreversible airway obstruction. Structural changes in the airway wall caused by chronic inflammation of asthma. Evidence for asthma airway remodeling demonstrating an accelerated decline of lung function that cannot be completely reversed with therapy. Combination therapy produced at least as much protection against inflammation as theuse of the higher dose of the inhaled corticosteroid.

Airway Wall Thickness Correlates With Smoking History, Lung Function And Bronchodilator Response In COPD

2010 ◽  
Author(s):  
Bipen D. Patel ◽  
Harvey O. Coxson ◽  
Sreekumar Pillai ◽  
Alvar Agusti ◽  
Peter M. Calverley ◽  
...  
Keyword(s):  
Lung Function ◽  
Wall Thickness ◽  
Smoking History ◽  
Airway Wall ◽  
Bronchodilator Response ◽  
Airway Wall Thickness

Visualization of airway obstruction in vivo during pulmonary vascular engorgement and edema

1995 ◽  
Vol 78 (3) ◽  
pp. 1070-1078 ◽  
Author(s):  
R. H. Brown ◽  
E. A. Zerhouni ◽  
W. Mitzner
Keyword(s):  
Airway Obstruction ◽  
Wall Thickness ◽  
Fluid Challenge ◽  
Left Ventricular ◽  
Wall Thickening ◽  
Airway Wall ◽  
Volume Loading ◽  
Airway Wall Thickness ◽  
Airway Caliber ◽  
Luminal Area

Although pulmonary vascular engorgement has often been hypothesized to decrease airway caliber, leading to airway obstruction in asthma, direct evidence for this hypothesis is lacking. In the present study, we used high-resolution computed tomography to directly measure the changes in the caliber and wall thickness of conducting airways after volume loading with normal saline (NS) and homologous blood. Five anesthetized dogs received 0.2 mg/kg of atropine followed by either three sequential fluid challenges of 50 ml/kg of NS or two sequential challenges of 25 ml/kg of blood. Several weeks later, the same dogs received the other fluid challenge. Volume loading with 150 ml/kg of NS decreased the average airway luminal area to 68 +/- 3% (+/- SE) of baseline. Concomitantly, airway wall thickness increased to 150 +/- 6% of baseline. Volume loading with 50 ml/kg of blood decreased the average airway luminal area to 81 +/- 2% of baseline. Concomitantly, airway wall thickness increased to 108 +/- 2% of baseline. Therefore, for comparable changes in pulmonary vascular pressure, an infusion of NS caused a significantly greater decrease in airway luminal area and a larger increase in airway wall thickness than an infusion of blood. This suggests that the presence of edema fluid in or immediately surrounding the airway wall acts to decrease the airway lumen. However, since the degree of airway narrowing was only moderate, even with a most extreme fluid load, it seems unlikely that airway wall thickening or edema could be a primary cause of conducting airway obstruction in patients with asthma or impaired left ventricular function.(ABSTRACT TRUNCATED AT 250 WORDS)

An interferon inducible signature of airway disease from blood gene expression profiling

2021 ◽  
pp. 2100569
Author(s):  
Jeong H. Yun ◽  
Sool Lee ◽  
Pooja Srinivasa ◽  
Jarrett Morrow ◽  
Robert Chase ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Function ◽  
Wall Thickness ◽  
Airway Remodeling ◽  
Gene Expression Signature ◽  
Airway Disease ◽  
Chronic Obstructive ◽  
Airway Wall ◽  
Wall Area ◽  
Airway Wall Thickness

BackgroundThe molecular basis of airway remodeling in chronic obstructive pulmonary disease remains poorly understood. We identified gene expression signatures associated with chest CT scan airway measures to understand molecular pathways associated with airway disease.MethodsIn 2,396 subjects in the COPDGene Study, we examined the relationship between quantitative CT airway phenotypes and blood transcriptomes to identify airway disease-specific genes and to define an airway wall thickness (AWT) gene set score. Multivariable regression analyses were performed to identify associations of the AWT score with clinical phenotypes, bronchial gene expression and genetic variants.ResultsType 1 interferon induced genes were consistently associated with airway wall thickness, Pi10, and wall area percent, with the strongest enrichment in airway wall thickness. A score derived from 18 genes whose expression was associated with AWT was associated with COPD-related phenotypes including reduced lung function (FEV1% predicted −3.4, p<0.05) and increased exacerbations (incidence rate ratio 1.6, p<0.05). The AWT score was reproducibly associated with airway wall thickness in bronchial samples from 23 subjects (beta 3.22, p<0.05). The blood AWT score was associated with genetic variant rs876039, an expression quantitative trait locus (eQTL) for IKZF1, a gene which regulates interferon signaling and is associated with inflammatory diseases.ConclusionA gene expression signature with interferon stimulated genes from peripheral blood and bronchial brushings is associated with CT airway wall thickness, lung function, and exacerbations. Shared genes and genetic associations suggest viral responses and/or autoimmune dysregulation as potential underlying mechanisms of airway disease in COPD.

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