New millennium: The conquest of allergy
Tissue remodeling as a feature of persistent asthma,☆☆

https://doi.org/10.1067/mai.2000.107195Get rights and content

Abstract

A chronic inflammatory process is almost invariably associated with tissue damage and healing. Healing results in repair and replacement of dead or damaged cells by viable cells. Repair usually involves 2 distinct processes: regeneration, which is the replacement of injured tissue by parenchymal cells of the same type, and replacement by connective tissue and its eventual maturation into scar tissue. In many instances both processes contribute to the healing response. Chronic inflammatory disease can therefore lead to a wide variety of consequences, from complete or partial restitution of organ structure and function to fibrosis. Asthma is characterized by a chronic inflammatory process of the airways. The ensuing healing process results in structural alterations referred to as a remodeling of the airways. The mechanisms underlying these structural alterations are still largely unknown. They are likely to be heterogeneous, leading—through the highly dynamic process of cell de-differentiation, migration, differentiation, and maturation—to changes in connective tissue deposition and to the altered restitution of airways structure, resulting in mucus gland hyperplasia, neovascularization, fibrosis, and an increase in smooth muscle mass. (J Allergy Clin Immunol 2000;105:1041-53.)

Section snippets

Origin and fate of the inflammatory infiltrate in asthma

Accumulation of inflammatory cells in the bronchial mucosa is characteristic of asthma. The tissue infiltration of cells may involve both recruitment of mature cells from the blood stream and proliferation of their progenitors in the submucosa. The survival of these cells is influenced to a large extent by the micro-environment within the airway wall. As in most organ systems, superfluous and damaged cells are removed by programmed cell death or “apoptosis.”5 In contrast with necrosis, which

DEMONSTRATION OF AIRWAY REMODELING IN ASTHMA

The airways in asthma display various structural alterations, which can all contribute to an overall increase in airway wall thickness66, 67 (Fig 2).

. Relationships between airway wall thickness and baseline airway caliber. Airways in asthma display various structural alterations, all of which can contribute to an overall increase in airway wall thickness, leading to a reduced airway caliber.

CLINICAL CONSEQUENCES OF AIRWAY REMODELING IN ASTHMA

The pathophysiologic consequences of the aforementioned structural airway changes remain to be fully established. As already mentioned, the various components of the ECM have a range of biologic effects. Changes in the composition of the ECM could therefore profoundly influence the characteristics of airway inflammation in asthma. In addition, airway remodeling could have an important effect on lung function. This latter aspect has been most extensively investigated to date.

RADIOGRAPHIC FINDINGS

High-resolution computed tomography (HRCT) scans provide indirect information about airway remodeling in asthma. Anatomic pulmonary changes including bronchial wall thickening, emphysema, and bronchiectasis have been demonstrated by HRCT scan in many patients with asthma.147, 148, 149, 150, 151 Bronchiectasis in asthma is usually not extensive and is rarely associated with clear-cut symptoms of sputum production. Asthma may therefore lead to physiologic features of chronic obstructive pulmonary

IMPLICATIONS FOR TREATMENT

Although the exact clinical relevance of airway remodeling is not completely clear, it is proposed that treatment or prevention of remodeling is a crucial element in asthma management.

β2-Agonists and CysLT antagonists have been shown to reduce smooth muscle proliferation in vitro.154, 155, 156 However, their effect on remodeling in asthma is largely unknown.

The role of inhaled corticosteroids in airway remodeling needs to be better assessed. The broad in vitro pharmacologic profile of

CONCLUSION

Remodeling of the airways is a proven structural concept, but is remodeling of the airways a proven clinical concept? It is clear that changes in the ECM, smooth muscle, and mucous glands have the capacity to influence airway function and reactivity in asthma. However, it is not known how each of the many structural changes that occur in the airway wall contributes to altered airway function in asthma. In asthma, remodeling is almost always present in biopsy specimens (eg, collagen deposition

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    Supported by a grant from Novartis Pharamaceutical Corp., East Hanover, NJ

    ☆☆

    Reprint requests: Jean Bousquet, MD, PhD, Cliniques des Maladies Respiratoires, Hopital Arnaud de Villeneuve, Centre Hospitalier Universitaire, 34295 Montpellier Cedex 5, France.

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