Remodelling and Inflammation in Bronchial Asthma

Chronic stable asthma is characterized by inflammation of the airway wall, with abnormal accumulation of basophils, eosinophils, lymphocytes, mast cells, macrophages, dendritic cells and myofibroblasts. The airway inflammation is not confined to severe asthma, but is also found in mild and moderate asthma. This inflammation results in a peculiar type of lymphocytic infiltration whereby Th2 lymphocytes secrete cytokines that orchestrate cellular inflammation and promote airway hyperresponsiveness. The term “airway remodelling” in bronchial asthma refers to structural changes that occurr in conjunction with, or because of, chronic airway inflammation. Airway remodelling results in alterations in the airway epithelium, lamina propria, and submucosa, leading to thickening of airway wall. The consequences of airway remodelling in asthma include incompletely reversible airway narrowing, bronchial hyperresponsiveness (BHR), smooth muscle contraction, airway edema, and mucus hypersecretion which may predispose persons with asthma to exacerbations and even death from airway obstruction.

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The extracellular matrix of the lung and airway responsiveness in asthma

Monaldi Archives for Chest Disease ◽

10.4081/monaldi.2009.373 ◽

2016 ◽

Vol 71 (1) ◽

Author(s):

F.G. Salerno ◽

M.P. Foschino Barbaro ◽

O. Toungoussova ◽

E. Carpagnano ◽

P. Guido ◽

...

Keyword(s):

Extracellular Matrix ◽

Smooth Muscle ◽

Mechanical Load ◽

Bronchial Hyperresponsiveness ◽

Lung Parenchyma ◽

Smooth Muscle Contraction ◽

Airway Remodelling ◽

Airway Narrowing ◽

Matrix Deposition ◽

Airways Smooth Muscle

The extracellular matrix is the main determinant of the structure and of mechanical behaviour of the lung. The extracellular matrix is also responsible for the mechanical interdependence between airway and parenchyma due to the alveolar attachments to the airways. Asthma is characterized by bronchial hyperresponsiveness, airway remodelling and inflammation, and an altered extracellular matrix may play a role in all these functional and structural abnormalities. The excessive airway narrowing observed in asthma may be related to the altered viscoelastic properties of lung parenchyma and airway wall, determining a decrease in the mechanical load opposing the airways’ smooth muscle contraction. Indeed, an altered extracellular matrix deposition in asthma in humans, has been demonstrated. In addition, in the asthmatic lung, the matrix seems to contribute to airway inflammation, airway remodelling, and to those alterations of the smooth muscle function of the airway and morphology typical of asthma.

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

Respiration ◽

10.1159/000508163 ◽

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

Background: 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. Objective: To investigate the interplay between airway and lung structural changes, airway inflammation, and smoking exposure in asthmatics with IRAO. Methods: 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 <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. Results: 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 (p = 0.0242). Visual analysis showed a higher prevalence of emphysema (p = 0.0001) and higher emphysema score (p < 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. Conclusions: 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.

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Decreased airway narrowing and smooth muscle contraction in hyperresponsive pigs

Journal of Applied Physiology ◽

10.1152/japplphysiol.00150.2002 ◽

2002 ◽

Vol 93 (4) ◽

pp. 1296-1300 ◽

Cited By ~ 12

Author(s):

Debra J. Turner ◽

Peter B. Noble ◽

Matthew P. Lucas ◽

Howard W. Mitchell

Keyword(s):

Smooth Muscle ◽

Airway Hyperresponsiveness ◽

Porcine Model ◽

Smooth Muscle Contraction ◽

Airway Wall ◽

Muscle Contractility ◽

Smooth Muscle Contractility ◽

Airway Narrowing

Increased smooth muscle contractility or reduced smooth muscle mechanical loads could account for the excessive airway narrowing and hyperresponsiveness seen in asthma. These mechanisms were investigated by using an allergen-induced porcine model of airway hyperresponsiveness. Airway narrowing to electric field stimulation was measured in isolated bronchial segments, over a range of transmural pressures (0–20 cmH2O). Contractile responses to ACh were measured in bronchial segments and in isolated tracheal smooth muscle strips isolated from control and test (ovalbumin sensitized and challenged) pigs. Test airways narrowed less than controls ( P < 0.0001). Test pigs showed reduced contractility to ACh, both in isolated bronchi ( P < 0.01) and smooth muscle strips ( P < 0.01). Thus isolated airways from pigs exhibiting airway hyperresponsiveness in vivo are hyporesponsive in vitro. The decreased narrowing in bronchi from hyperresponsive pigs may be related to decreased smooth muscle contractility. These data suggest that mechanisms external to the airway wall may be important to the hyperresponsive nature of sensitized lungs.

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Longitudinal shape irregularity of airway lumen assessed by CT in patients with bronchial asthma and COPD

Thorax ◽

10.1136/thoraxjnl-2014-206651 ◽

2015 ◽

Vol 70 (8) ◽

pp. 719-724 ◽

Cited By ~ 14

Author(s):

Tsuyoshi Oguma ◽

Toyohiro Hirai ◽

Motonari Fukui ◽

Naoya Tanabe ◽

Satoshi Marumo ◽

...

Keyword(s):

Bronchial Asthma ◽

Ct Images ◽

Wall Thickening ◽

Airway Remodelling ◽

Healthy Controls ◽

Airway Wall ◽

Cross Sectional ◽

Airway Lumen ◽

Luminal Area ◽

Shape Irregularity

BackgroundAirway remodelling in bronchial asthma (BA) and COPD has been quantitatively assessed by analysing the airway wall area and the luminal area on cross-sectional CT images. To date, there have been no reports on assessment of the longitudinal structure of the airway lumen.MethodsQuantitative airway analysis using CT was performed on three groups consisting of 29 patients with BA, 58 patients with COPD and 59 healthy controls. To assess the longitudinal shape irregularity of the airway lumen, new quantitative CT parameters, validated by a phantom study, were established. The internal radii of imaginary inscribed spheres in the airway lumen were measured as a function of distance from the level of the carina to the fifth-order branches of the right posterior basal bronchus. The gaps of these radii from the regression line were calculated as parameters to reflect the longitudinal airway lumen shape irregularity. These new parameters were compared among the study groups as well as with the conventional parameters of airway wall thickening and luminal area.ResultsLongitudinal airway lumen shape irregularity was significantly greater in patients with COPD than in those with BA and healthy controls. Wall thickening was significantly greater, and luminal area smaller, in patients with BA than in those with COPD and healthy controls. These results were consistent even among the BA and COPD subgroups with similar airflow limitation.ConclusionsThe combination of cross-sectional and longitudinal airway structure analyses using CT images may suggest differences in the characteristics of airway remodelling between COPD and asthma.

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Lung Sound Analysis Provides A Useful Index For Both Airway Narrowing And Airway Inflammation In Patients With Bronchial Asthma

Journal of Asthma and Allergy ◽

10.2147/jaa.s216877 ◽

2019 ◽

Vol Volume 12 ◽

pp. 323-329

Author(s):

Terfumi Shimoda ◽

Yasushi Obase ◽

Yukio Nagasaka ◽

Reiko Kishikawa ◽

Sadahiro Asai

Keyword(s):

Airway Inflammation ◽

Bronchial Asthma ◽

Lung Sound ◽

Sound Analysis ◽

Airway Narrowing

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Structural basis for exaggerated airway narrowingThis article is one of a selection of papers published in the Special Issue on Recent Advances in Asthma Research.

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y07-051 ◽

2007 ◽

Vol 85 (7) ◽

pp. 653-658 ◽

Cited By ~ 23

Author(s):

Peter D. Paré ◽

Brent E. McParland ◽

Chun Y. Seow

Keyword(s):

Airway Hyperresponsiveness ◽

Structural Changes ◽

Airway Remodeling ◽

Structural Basis ◽

Airway Wall ◽

Special Issue ◽

Airway Narrowing ◽

Quantitative Changes ◽

Or Organization ◽

Selection Of

Airway hyperresponsiveness, particularly the ability of airways to narrow excessively in response to stimuli that normally cause little airway narrowing in nonasthmatic subjects, is a characteristic feature of asthma and the basis of its symptoms. Although airway hyperresponsiveness may be partly the result of alterations in the contractile phenotype of the airway smooth muscle, there is evidence that it may also be caused by structural changes in the airway wall, collectively termed airway remodeling. Airway remodeling is defined as changes in composition, quantity, and (or) organization of cellular and molecular constituents of the airway wall. Airway wall remodeling that occurs in asthma can result in functional alterations because of quantitative changes in airway wall compartments, and (or) because of changes in the biochemical composition or material properties of the various constituents of the airway wall. This brief review summarizes the quantitative changes in the dimensions and organization of the airway wall compartments that have been described and explains how structural alterations may lead to the exaggerated airway narrowing.

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Lung parenchymal shear modulus, airway wall remodeling, and bronchial hyperresponsiveness

Journal of Applied Physiology ◽

10.1152/jappl.1997.83.1.140 ◽

1997 ◽

Vol 83 (1) ◽

pp. 140-147 ◽

Cited By ~ 54

Author(s):

Rodney K. Lambert ◽

Peter D. Paré

Keyword(s):

Smooth Muscle ◽

Shear Modulus ◽

Airway Remodeling ◽

Bronchial Hyperresponsiveness ◽

Lung Parenchyma ◽

Wall Thickening ◽

Forced Expiration ◽

Airway Wall ◽

Airway Narrowing ◽

Muscle Shortening

Lambert, Rodney K., and Peter D. Paré. Lung parenchymal shear modulus, airway wall remodeling, and bronchial hyperresponsiveness. J. Appl. Physiol.83(1): 140–147, 1997.—When airways narrow, either through the action of smooth muscle shortening or during forced expiration, the lung parenchyma is locally distorted and provides an increased peribronchial stress that resists the narrowing. Although this interdependence has been well studied, the quantitative significance of airway remodeling to interdependence has not been elucidated. We have used an improved computational model of the bronchial response to smooth muscle agonists to investigate the relationships between airway narrowing (as indicated by airway resistance), parenchymal shear modulus, adventitial thickening, and inner wall thickening at lung recoil pressures of 4, 5, and 8 cmH2O. We have found that, at low recoil pressures, decreases in parenchymal shear modulus have a significant effect that is comparable to that of moderate thickening of the airway wall. At higher lung recoil pressures, the effect is negligible.

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Bronchoconstriction: a potential missing link in airway remodelling

Open Biology ◽

10.1098/rsob.200254 ◽

2020 ◽

Vol 10 (12) ◽

pp. 200254

Author(s):

Michael J. O'Sullivan ◽

Thien-Khoi N. Phung ◽

Jin-Ah Park

Keyword(s):

Deleterious Effect ◽

Structural Changes ◽

Ex Vivo ◽

Airway Remodelling ◽

Mechanical Forces ◽

Airway Wall ◽

Comprehensive Understanding ◽

Missing Link

In asthma, progressive structural changes of the airway wall are collectively termed airway remodelling. Despite its deleterious effect on lung function, airway remodelling is incompletely understood. As one of the important causes leading to airway remodelling, here we discuss the significance of mechanical forces that are produced in the narrowed airway during asthma exacerbation, as a driving force of airway remodelling. We cover in vitro , ex vivo and in vivo work in this field, and discuss up-to-date literature supporting the idea that bronchoconstriction may be the missing link in a comprehensive understanding of airway remodelling in asthma.

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Airway Remodelling in Asthma: From Benchside to Clinical Practice

Canadian Respiratory Journal ◽

10.1155/2010/318029 ◽

2010 ◽

Vol 17 (4) ◽

pp. e85-e93 ◽

Cited By ~ 121

Author(s):

Céline Bergeron ◽

Meri K Tulic ◽

Qutayba Hamid

Keyword(s):

Structural Changes ◽

Small Airways ◽

Airway Remodelling ◽

Airway Narrowing ◽

Asthmatic Patients ◽

Clinical Consequences ◽

Characteristic Features ◽

Airway Walls ◽

The Relationship ◽

Subepithelial Fibrosis

Airway remodelling refers to the structural changes that occur in both large and small airways relevant to miscellaneous diseases including asthma. In asthma, airway structural changes include subepithelial fibrosis, increased smooth muscle mass, gland enlargement, neovascularization and epithelial alterations. Although controversial, airway remodelling is commonly attributed to an underlying chronic inflammatory process. These remodelling changes contribute to thickening of airway walls and, consequently, lead to airway narrowing, bronchial hyper-responsiveness, airway edema and mucous hypersecretion. Airway remodelling is associated with poor clinical outcomes among asthmatic patients. Early diagnosis and prevention of airway remodelling has the potential to decrease disease severity, improve control and prevent disease expression. The relationship between structural changes and clinical and functional abnormalities clearly deserves further investigation. The present review briefly describes the characteristic features of airway remodelling observed in asthma, its clinical consequences and relevance for physicians, and its modulation by therapeutic approaches used in the treatment of asthmatic patients.

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Airway Remodelling in Asthma and COPD: Findings, Similarities, and Differences Using Quantitative CT

Pulmonary Medicine ◽

10.1155/2012/670414 ◽

2012 ◽

Vol 2012 ◽

pp. 1-8 ◽

Cited By ~ 17

Author(s):

Gaël Dournes ◽

François Laurent

Keyword(s):

Structural Changes ◽

Chronic Obstructive Lung Disease ◽

Pathological Examination ◽

Chronic Obstructive ◽

Airway Remodelling ◽

Airway Wall ◽

Quantitative Ct ◽

Similarities And Differences ◽

3D Evaluation

Airway remodelling is a well-established feature in asthma and chronic obstructive lung disease (COPD), secondary to chronic airway inflammation. The structural changes found on pathological examination of remodelled airway wall have been shown to display similarities but also differences. Computed tomography (CT) is today a remarkable tool to assess airway wall morphologyin vivosince submillimetric acquisitions over the whole lung volume could be obtained allowing 3D evaluation. Recently, CT-derived indices extracted from CT images have been described and are thought to assess airway remodelling. This may help understand the complex mechanism underlying the remodelling process, which is still not fully understood. This paper summarizes the various methods described to quantify airway remodelling in asthma and COPD using CT, and similarities and differences between both diseases will be emphasized.

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