LEICESTER, UK—A comparative, two-center study has produced the unexpected finding that patients with asthma have substantially more mast cells in airway smooth muscle (ASM) than do either patients with eosinophilic bronchitis or healthy controls.[1]

Patients with eosinophilic bronchitis are known to have higher sputum concentrations of histamine and prostaglandin D2 than do patients with asthma, which should mean that such patients also have a greater number of mast cells. Christopher Brightling, PhD, MRCP, a clinical lecturer in the Department of Respiratory Medicine at the Institute for Lung Health in Leicester, United Kingdom, told RESPIRATORY REVIEWS that before this study, he and his colleagues had “thought that there may be more superficial, perhaps epithelial, mast cells in [patients with] eosinophilic bronchitis.” Finding more mast cells in asthma patients was an unexpected result.

A STRIKING DIFFERENCE

The study included 17 patients with asthma, 13 patients with eosinophilic bronchitis, and 11 healthy controls. All participants visited the study centers twice. At the first visit, spirometry, skin prick testing, and methacholine challenge were performed. At the second visit, bronchoscopy was used to obtain bronchial mucosa biopsy specimens. Two observers who were unaware of the participants’ disease status examined the specimens and identified areas of smooth muscle and subepithelial mucosa. Immunohistochemical analysis was performed on all samples.

The number of mast cells in ASM was markedly greater in the group with asthma (median, 5.1 cells/mm2) than in the other two groups (median for both, 0 cells/mm2). There was also a significant correlation between the number of mast cells infiltrating the ASM of patients with asthma and the degree of airway hyperresponsiveness.

In an editorial commentary that accompanied Dr. Brightling’s study, Judith Black, MBBS, PhD, a Professor of Pharmacology at the University of Sydney, Australia, noted that a greater number of mast cells have been found in the ASM of patients who have allergies than in the ASM of patients who don’t have allergies, despite similar numbers of lymphocytes and eosinophils in both groups.[2] (None of the patients had asthma.)

In the present study, the marked difference in the number of mast cells found in the ASM of patients with asthma versus either healthy controls or those with eosinophilic bronchitis may help clarify the role that mast cells play in the development of asthma.

According to the investigators, mast cells may also be present in the ASM of patients with obstructive lung diseases other than asthma. Including a group of these patients in future studies could potentially provide useful information. However, they note that selecting such a group would be difficult because obstructive lung disease and asthma share many clinical and pathophysiologic features.

MAST CELLS AND ASM

Many theories exist as to why more mast cells are present in the ASM of asthma patients and what it means to the progression and development of asthma. Dr. Black speculated that the reason for the increased presence of mast cells is the secretion of stem-cell factor by the muscle. Stem-cell factor attracts mast cells and regulates their growth, function, and survival. Whether a greater amount of stem-cell factor is released by the ASM of patients with asthma requires further research, however.

Some mast-cell products, such as histamine and prostaglandin D2, may adversely affect the growth and function of ASM. In lung resection and postmortem studies, mast cells were the predominant type of inflammatory cell localized in the ASM in samples from patients with asthma. The argument for selective recruitment of mast cells in these samples is supported by the absence of eosinophils and T lymphocytes.[1]

Dr. Brightling and his colleagues have concluded that the interaction between ASM and mast cells is a key element in the development of airway dysfunction in asthma. In light of these findings, they are pursuing their study of mast cells in asthma. “We have begun a program of research investigating mast-cell chemotaxis into the ASM, mast-cell ASM adhesion, and the functional consequences of [these] interactions,” Dr. Brightling said.

He also noted that the findings of the present study suggest new directions in asthma management. “We would anticipate that blocking mast-cell traffic into the ASM or inhibiting the functional interactions would attenuate the development of airway hyperresponsiveness and improve the symptoms of asthma,” observed Dr. Brightling.

—Gale Jurasek