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Year : 2016  |  Volume : 33  |  Issue : 1  |  Page : 1-2  

Remodeling in asthma and COPD—recent concepts

Jindal Clinics; Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India

Date of Web Publication4-Jan-2016

Correspondence Address:
Surinder Kumar Jindal
Jindal Clinics; Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0970-2113.173074

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How to cite this article:
Jindal SK. Remodeling in asthma and COPD—recent concepts. Lung India 2016;33:1-2

How to cite this URL:
Jindal SK. Remodeling in asthma and COPD—recent concepts. Lung India [serial online] 2016 [cited 2020 Oct 1];33:1-2. Available from: http://www.lungindia.com/text.asp?2016/33/1/1/173074

Remodeling in airway diseases, such as asthma and chronic obstructive pulmonary disease (COPD), is defined as structural alterations of both small and large airways due to subepithelial fibrosis, increased smooth muscle mass of airways, neovascularization, and glandular hypertrophy. Unlike the true remodeling or renovation of a structure which should result in improvement, the airway remodeling causes further functional and clinical deterioration due to thickening of bronchial walls and narrowing of the lumina.

Airway remodeling in occurring in asthma patients, which was first documented in 1922, is now a recognized entity.[1] However, it is not commonly appreciated that airway remodeling also occurs in patients with COPD, although the structural damage to the airways and the lung parenchyma is known to occur. Further, remodeling is not limited to the airways alone. It is also the pulmonary vascular remodeling that adds to the complications, especially in COPD patients.

Airway remodeling in asthma patients has been documented in all degrees of asthma severity and types of airways.[2] It is not necessarily related to the duration of the illness since it may also occur in children with early asthma when it may act as a precursor to a chronic and debilitating respiratory disease.[3] It possibly occurs as a result of ongoing inflammation and activation of different inflammatory cells. The inflammatory cells such as the mast cells, eosinophils, and CD8 + lymphocytes correlate with airway hyperresponsiveness.[4] Some important inflammatory mediators with significant remodeling action are transforming growth factor (TGF)-beta, interleukin (IL) 11, IL-17, and histamine.[5],[6]

In asthma, airway remodeling is responsible for significant clinical effects such as greater asthma symptomatology, higher aryl hydrocarbon receptor (AHR), excessive use of rescue medication, and an accelerated decline in lung function. However, it is not clear if it results in permanent alterations in lung function.

Remodeling also occurs in patients with COPD, typically involving the peripheral airways causing thickening of walls and narrowing of bronchial lumen.[7],[8] In the recent years, it has been shown that the larger and central airways are also involved.[9] This happens apparently due to deposition of extracellular matrix in subepithelial layer and hypertrophy of smooth muscles in the airway walls. Of various pathobiological mechanisms, the proteolytic enzymes matrix metalloproteinases (MMPs), especially MMP-9, play an important role in remodeling in patients suffering from asthma and COPD.[10] Integrins, a group of transmembrane proteins, are also likely to cause AHR and remodeling.[11]

Vascular remodeling is another common pathological consequence of inflammation in patients suffering from COPD and asthma. Pulmonary hypertension is known to occur as a complication of COPD that is responsible for chronic cor pulmonale. It has been recently recognized that airway remodeling not only results in severity of airway obstruction but also correlates with mean pulmonary artery pressure (mPAP) and pulmonary hypertension.[12]

The exact mechanism to link pulmonary hypertension with bronchial obstruction is not clear. Pulmonary vascular remodeling may also occur in chronic asthma although to a lesser extent than in COPD.

It has been observed recently that mPAP >25 mmHg used to define pulmonary hypertension is not a good indicator to suggest the development of symptoms and severity of COPD. Pulmonary artery stiffness is a more important marker for early detection of pulmonary vascular disease and right ventricular failure.[13]

Some of these findings have an important bearing on early diagnosis and treatment of remodeling as well as prevention of development of severe airway obstruction and pulmonary hypertension. Role of inhaled corticosteroids that constitute the cornerstone of treatment of asthma and acute exacerbations of COPD is not clearly understood for prevention of remodeling and chronic structural changes in the airways.[14] Same holds true regarding the role of antileukotriene.[14] There is little effect of beta-agonists and anti-immunoglobulin E (IgE) treatment on airway remodeling.

Several potential therapies have emerged which are still undergoing further tests for their place in clinical prescriptions. Prostanoids such as prostacyclins (i.e. prostaglandin E-2 and I-2), which elevate cyclic AMP, constitute an attractive target.[15] MMP-9 inhibition is another potential line of approach to therapy.[10] Anti-IL-5 molecules and Bacillus Calmette–Guérin (BCG) vaccinations are also under investigation.[14] Similarly, the integrin antagonists may find their role as a potential target for treatment.[11]

In summary, one can conclude that a lot of progress has been made in the understanding of pathological alterations and mechanisms of airway and vascular remodeling in patients suffering from asthma and COPD. A number of new and potential therapeutic targets have been also found. One can only hope that one or more of them find place in the clinical armamentarium.

   References Top

Redington AE, Howarth PH. Airway wall remodelling in asthma. Thorax 1997;52:310-2.  Back to cited text no. 1
James AL, Maxwell PS, Pearce-Pinto G, Elliot JG, Carroll NG. The relationship of reticular basement membrane thickness to airway wall remodeling in asthma. Am J Respir Crit Care Med 2002;166:1590-5.  Back to cited text no. 2
Payne DN, Rogers AV, Adelroth E, Bandi V, Guntupalli KK, Bush A, et al. Early thickening of the reticular basement membrane in children with difficult asthma. Am J Respir Crit Care Med 2003;167:78-82.  Back to cited text no. 3
Sont JK, Han J, van Krieken JM, Evertse CE, Hooijer R, Willems LN, et al. Relationship between the inflammatory infiltrate in bronchial biopsy specimens and clinical severity of asthma in patients treated with inhaled steroids. Thorax 1996;51:496-502.  Back to cited text no. 4
Molet S, Hamid Q, Davoine F, Nutku E, Taha R, Pagé N, et al. IL-17 is increased in asthmatic airways and induces human bronchial fibroblasts to produce cytokines. J Allergy Clin Immunol 2001;108:430-8.  Back to cited text no. 5
Chakir J, Shannon J, Molet S, Fukakusa M, Elias J, Laviolette M, et al. Airway remodeling-associated mediators in moderate to severe asthma: Effect of steroids on TGF-beta, IL-11, IL-17, and type I and type III collagen expression. J Allergy Clin Immunol 2003;111:1293-8.  Back to cited text no. 6
Jeffery PK. Remodeling in asthma and chronic obstructive lung disease. Am J Respir Crit CareMed 2001;164:S28-38.  Back to cited text no. 7
Hogg JC, Chu F, Utokaparch S, Woods R, Elliott WM, Buzatu L, et al. The nature of small-airway obstruction in chronic obstructive pulmonary disease. N Engl J Med 2004;350:2645-53.  Back to cited text no. 8
Pini L, Pinelli V, Modina D, Bezzi M, Tiberio L, Tantucci C. Central airways remodeling in COPD patients. Int J Chron Obstruct Pulmon Dis 2014;9:927-32.  Back to cited text no. 9
Grzela K, Litwiniuk M, Zagorska W, Grzela T. Airway remodeling in chronic obstructive pulmonary disease and asthma: The role of Matrix Metalloproteinase-9. Arch Immunol Ther Exp (Warsz) 2015. [Epub ahead of print].  Back to cited text no. 10
Wright DB, Meurs H, Dekkers BG. Integrins: Therapeutic targets in airway hyperresponsiveness and remodelling? Trends Pharmacol Sci 2014;35:567-74.  Back to cited text no. 11
Dournes G, Laurent F, Coste F, Dromer C, Blanchard E, Picard F, et al. Computed tomographic measurement of airway remodeling and emphysema in advanced chronic obstructive pulmonary disease. Correlation with pulmonary hypertension. Am J Respir Crit Care Med 2015;191:63-70.  Back to cited text no. 12
Weir-McCall JR, Struthers AD, Lipworth BJ, Houston JG. The role of pulmonary arterial stiffness in COPD. Respir Med 2015. [Epub ahead of print].  Back to cited text no. 13
Bergeron C, Tulic MK, Hamid Q. Airway remodelling in asthma: From benchside to clinical practice. Can Respir J 2010;17:e85-93.  Back to cited text no. 14
Zaslona Z, Peters-Golden M. Prostanoids in Asthma and COPD: Actions, dysregulation, and therapeutic opportunities. Chest 2015;148:1300-6.  Back to cited text no. 15


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