Inflammatory and structural changes in the airways of patients with asthma.
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Asthma↗
Biomedical subjects
S T Holgate
Publications and source records attributed to S T Holgate.
Persistent airway T-lymphocyte activation in chronic corticosteroid-treated symptomatic asthma.
BACKGROUND: A small proportion of patients with asthma have persistent symptoms despite regular treatment with high-dose inhaled and/or oral corticosteroids. There is little information regarding immunopathology in such patients. OBJECTIVE: To compare airway inflammatory changes in subjects with chronic corticosteroid-dependent symptomatic asthma (n = 5) and subjects with asthma that was clinically well controlled on inhaled corticosteroid therapy (n = 9). Subjects in the corticosteroid-dependent group were receiving long-term treatment with oral prednisolone and high-dose inhaled corticosteroids. METHODS: Subjects underwent fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) and bronchial biopsy. T-lymphocytes subsets and activation markers in BAL fluid and peripheral blood were determined by FACS analysis. Bronchial biopsies were stained immunohistochemically, and numbers of inflammatory cells quantitated. Inflammatory mediators in BAL fluid were measured by immunoassay. RESULTS: There was significantly greater expression of CD25 (P = .02) and HLA-DR (P = .04) by BAL fluid T-lymphocytes in corticosteroid-treated symptomatic asthmatics. In bronchial biopsies there were no significant differences between the two groups in the numbers of AA1+ cells (mast cells), EG2+ cells (eosinophils) or MT1+ T-lymphocytes. Levels of albumin, histamine, tryptase, and eosinophil cationic protein in BAL fluid did not differ significantly between groups. CONCLUSIONS: Chronic corticosteroid-treated symptomatic asthma is associated with persistent airway T-lymphocyte activation. This, however, is not necessarily accompanied by the recruitment and activation of inflammatory cells within the airways.
Administration, Inhalation↗
Prevention of allergy and asthma: interim report.
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Asthma↗
Bronchial angiogenesis in severe glucocorticoid-dependent asthma.
To examine the role of the bronchial microvasculature and adhesion molecule expression in severe asthma, the authors have performed an immunohistochemical study on bronchial biopsies comparing 15 glucocorticoid-dependent asthmatics, 15 mild asthmatics and eight control subjects. Serially cut glycol methacrylate-embedded sections were stained with monoclonal antibodies identifying the vessel marker EN-4, intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, E- and P-selectin. Sections were also stained for lymphocyte function associated antigen (LFA)-1 and very late antigen (VLA)-4. By comparison with mild asthma and nonasthma, severe asthma was characterized by increased numbers of submucosal vessels (p=0.009) which was associated with increased numbers of vessels expressing ICAM-1 (p=0.005). A highly significant correlation was found between the total number of EN-4+ vessels and the vessels expressing ICAM-1 (r=0.85, p=0.01). In contrast, E-selectin expression was lower in severe as compared with mild asthma (p=0.01) but not different from normal. No differences were found between the three groups in the expression of VCAM-1 and P-selectin nor in numbers of LFA-1+ and VLA-4+ cells. The results of this study support the notion that mucosal neovascularization is an important feature of airways remodelling in severe asthma. This is associated with a relatively higher density of vessels expressing intercellular adhesion molecule-1, although the expression of this adhesion molecule per vessel was not raised.
Adolescent↗
Low-dose methotrexate treatment in severe glucocorticoid-dependent asthma: effect on mucosal inflammation and in vitro sensitivity to glucocorticoids of mitogen-induced T-cell proliferation.
The authors have investigated whether the steroid-sparing effect of methotrexate (MTX) in severe orally glucocorticoid-insensitive asthmatics may be accounted for by the ability of this drug to increase the T-cell responsiveness sensitivity to dexamethasone in vitro. In addition the authors have investigated whether low-dose MTX treatment is associated with anti-inflammatory effects in peripheral blood and the bronchial mucosa. In eight patients with severe atopic asthma, using > or =15 mg x day(-1) prednisolone, the inhibitory effect of dexamethasone on mitogen stimulated peripheral blood mononuclear cells (PBMC) in vitro was tested before and after 8 weeks of uncontrolled treatment with MTX. Endobronchial biopsies were taken before and after MTX therapy in seven subsequent patients, and analysed using immunohistochemistry. In eight patients, serum was drawn for measuring levels of free interleukin (IL)-8. The in vitro sensitivity of PBMC to dexamethasone (at 1.6 x 10(-9) and 3.2 x 10(-10) mol x L(-1)) was significantly lower in the asthmatics before treatment when compared with the control subjects (p=0.03 and =0.001) but increased significantly after MTX treatment (p=0.04 and =0.02) to normal responsiveness. This was not associated with a decrease in peripheral blood T-cell numbers or activation. Except for a significant increase in the numbers of CD3+ (p=0.04), no significant numerical changes in activated T-cells, eosinophils, or mast cells were found (p>0.05). However, MTX treatment was associated with a significant fall in serum levels of free IL-8 (p=0.03). It is hypothesized that the steroid-sparing effect of methotrexate originates from increased sensitivity of lymphocytes to the inhibitory effects of glucocorticoids. The absence of an inhibitory effect on inflammatory cells in blood and mucosa suggests that this effect is achieved by modulating cell function rather than cell number.
Adolescent↗
Phosphodiesterase and cyclic adenosine monophosphate-dependent inhibition of T-lymphocyte chemotaxis.
There is abundant evidence for T-lymphocyte recruitment into the airways in allergic inflammatory responses. This study has tested the hypothesis that T-cell chemotaxis induced by platelet-activating factor (PAF) and human recombinant interleukin-8 (hrIL-8) can be attenuated by inhibition of phosphodiesterase activity and raised intracellular 3',5'-cyclic adenosine monophosphate (cAMP) levels. This study used theophylline, a nonselective phosphodiesterase (PDE) inhibitor, and rolipram, a selective PDE4 inhibitor, to study the effect of PDE inhibition on T-cell chemotaxis. The beta2-adrenoceptor agonist, salbutamol, the adenylyl cyclase activator, forskolin, and the cAMP analogue, dibutyryl cAMP (db-cAMP), were used to demonstrate a role for raised cAMP levels. T-cells were obtained from 10 atopic asthmatics, and the phenotype of migrating cells was examined by flow cytometry. Theophylline caused an inhibition of both PAF-and hrIL-8-induced chemotaxis (mean+/-SEM maximum inhibition at 1 mM: 73+/-4% and 48+/-8% for hrIL-8 and PAF, respectively) that was not specific for the CD4+, CD8+, CD45RO+ or CD45RA+ T-cell subsets. T-cell chemotaxis was more sensitive to treatment with rolipram whose effect was already significant from 0.1 microM on hrIL-8-induced chemotaxis. Both a low concentration of salbutamol (0.1 mM) and forskolin (10 microM) potentiated the inhibitory effect of a low concentration of theophylline (25 microM) on responses to PAF but not to hrIL-8. Finally, T-cell chemotaxis was also inhibited by db-cAMP. It is concluded that attenuation of T-cell chemotaxis to two chemoattractants of relevance to asthma pathogenesis can be achieved via phosphodiesterase inhibition and increased intracellular 3', 5'-cyclic monophosphate using drugs active on cyclic nucleotide phosphodiesterase. This action may explain the anti-inflammatory effects of theophylline and related drugs in asthma.
Albuterol↗
The role of mast cells and basophils in inflammation.
Mast cells are positioned in the asthmatic airways so that they are able to respond to the inhaled environment. During active disease, the cells are primed to secrete an array of preformed and newly generated inflammatory mediators including histamine, neutral proteases and heparin sulphate, prostaglandins and cysteinyl leukotrienes as well as an array of cytokines and chemokines that are involved in leucocyte recruitment and activation. These cells are a potent source of mediators in both allergen- and exercise-induced asthma and possibly in asthma provoked by other stimuli such as adenosine and inhaled air pollutants. The important role played by mast cells in maintaining airway dysfunction in asthma is underpinned by the efficacy of mediator inhibitors, such as those interfering with the release or action of the leukotrienes, agents that inhibit mast cell activation such as sodium cromoglycate and the recently studied E-20 humanized monoclonal antibody that binds to and removes IgE. The recent discovery of novel inhibitory pathways involving inhibitory motifs (ITIMS) on critical cell surface signalling molecules has opened up new possibilities for preventing mast cell activation. Future research will focus on more effective ways for inhibiting the mast cell's contribution to asthma and understanding what role this unique cell has in the pathogenesis of airway wall remodelling.
Asthma↗
Epithelial damage and response.
Epithelial damage is a characteristic feature of asthma. The epithelium is not merely a passive barrier but can generate a range of mediators that may play a role in the inflammatory and remodelling responses that occur in the lungs in asthma. For example, the cytokine granulocyte macrophage colony-stimulating factor (GM-CSF), whose principal source is the epithelium, can prolong eosinophil survival while transforming growth factor is a potent profibrogenic cytokine. Deposition of collagen in the epithelial subbasement membrane is a characteristic feature of the remodelling response in asthma. This may be due to abnormal associations between myofibroblasts and epithelium, both of which are involved in early lung development (epithelial-mesenchymal trophic unit). In asthma, there may be a primary defect in the epithelium such that it responds abnormally to various stimuli and cannot undergo the normal repair response. Epidermal growth factor (EGF) appears to be a key factor in bronchial epithelial repair; it stimulates epithelial cell proliferation and migration. The 3v isoform of the adhesion molecule CD44 is overexpressed in damaged epithelium and seems to regulate the repair response by presenting EGF more efficiently to its receptor. Although EGF receptor expression is increased in asthma, it does not lead to an appropriate proliferative response and restitution of normal epithelium. Other factors such as transforming growth factor (TGF)beta which are generated by inflammatory cells and epithelium are also upregulated in asthma. An epithelial/fibroblast co-culture system has shown that following epithelial damage various growth factors are released from the underlying myofibroblasts and are responsible for the proliferative response. The TGFbeta family are most likely responsible for collagen production. In an in vitro study, an EGF receptor inhibitor slowed epithelial repair but enhanced TGFbeta production by the slowly repairing epithelial cells. In conclusion, the interaction between epithelial cells and myofibroblasts, i.e. reactivation of the epithelial-mesenchymal trophic unit appears to be central to the airway wall remodelling response.
Asthma↗
Localization of interleukin (IL) -4 but not IL-5 to human mast cell secretory granules by immunoelectron microscopy.
BACKGROUND: Human mast cells synthesize and secrete many cytokines of relevance to the pathogenesis of allergic diseases such as asthma and rhinitis. In particular, interleukin (IL) -4 and IL-5 are likely to play key roles in the development of the inflammatory response that characterizes these diseases. Immunohistochemical studies on human nasal and bronchial mucosal biopsies suggest that IL-4 and IL-5 may be stored preformed in mast cells. OBJECTIVE: To identify whether IL-4 and IL-5 are stored within mast cell secretory granules. METHODS: We used immunogold electron microscopic analysis on bronchial mucosa and lung parenchyma from resected lung specimens, and a nasal mucosal biopsy from a patient with active allergic rhinitis. Samples were fixed in 4% paraformaldehyde plus 0.5% glutaraldehyde and processed into Lowicryl K4M resin by the 'Progressive Lowering of Temperature' technique. Ultrathin sections were stained immunohistochemically by an indirect immunogold method. RESULTS: Immunoreactivity for IL-4, but not IL-5, was localized to the granules of mast cells in all tissue samples. IL-5 was localized to the matrix of eosinophil granules in these samples, but neither cytokine was detected in T cells. IL-4 immunoreactivity increased in the granules of mast cells 24 h after immunoglobulin (Ig) E-dependent activation (mean 17.5 +/- 1.4 gold particles per granule) compared with nonactivated mast cells (mean 6.8 +/- 0.8 gold particles per granule, P < 0.001), suggesting replenishment of stores by newly generated protein. Immunoreactive IL-5 remained undetectable in mast cells 24 h after activation, a time point at which they are known to secrete large quantities of this cytokine. CONCLUSION: Human mast cells store IL-4 within the matrix of their granules. Very few, if any, lung or nasal mast cells store IL-5. A store of preformed IL-4 within mast cell granules is likely to have an important influence during the initiation and maintenance of the allergic immunological response.
Cytoplasmic Granules↗
Glucocorticoids enhance IgE synthesis. Are we heading towards new paradigms?
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Antibodies, Anti-Idiotypic↗
Human mast cell tryptase stimulates the release of an IL-8-dependent neutrophil chemotactic activity from human umbilical vein endothelial cells (HUVEC).
Tryptase, the major product of human mast cell activation, is a potent stimulus of vascular leakage and neutrophil accumulation in vivo in animal studies, but the mechanisms of action remain unclear. Using HUVEC cultures we have sought to investigate the potential of tryptase to alter monolayer permeability or induce the release of neutrophil chemotactic activity. Tryptase (1-100 mU/ml) failed to alter the permeability of endothelial cell monolayers as assessed by albumin flux over 1 h. However, supernatants from endothelial cells treated with tryptase (1-50 mU/ml) for a 24-h period induced neutrophil migration across Transwell filters, with maximal migration observed at 10 mU/ml tryptase. Pretreatment of tryptase with the protease inhibitor leupeptin abolished the chemotactic activity, indicating a dependence on the catalytic site. Moreover, this effect was abolished by addition of an IL-8 neutralizing antibody, suggesting that IL-8 release makes an important contribution to the chemotactic activity. The interaction of mast cell tryptase with endothelial cells could be important in stimulating the ingress of neutrophils following mast cell activation in inflammatory disease.
Cell Movement↗
Smoking habits in a cohort of U.K. adolescents.
Active smoking is an increasing problem amongst U.K. teenagers. The smoking habits of a cohort of 14-16-year-olds were determined and the association between regular active smoking and domestic and social factors investigated. Current smoking habits of a cohort of 2289 14-16-year-olds were assessed using a simple postal questionnaire. Data concerning potential factors associated with active smoking were collected from questionnaire completed by parents. Nine hundred and sixty-nine (44.8%) children admitted to having smoked at some time, with 562 (30.0%) having smoked in the previous 12 months. Three hundred and six (14.1%) children were regular smokers and 158 (51.6% of regular smokers, 7.3% of total cohort) smoked daily. Age, number of other children in the household, parental smoking, smoking sibling(s) and living in a single parent household were all independently associated with regular smoking. Regular smoking was a significant problem amongst this cohort of teenagers. Living with other smokers, age, household size and living with one parent all predicted a regular smoking habit.
Adolescent↗
Montelukast or salmeterol combined with an inhaled steroid in adult asthma: design and rationale of a randomized, double-blind comparative study (the IMPACT Investigation of Montelukast as a Partner Agent for Complementary Therapy-trial).
Asthma patients who continue to experience symptoms despite taking regular inhaled corticosteroids represent a management challenge. Leukotrienes play a key role in asthma pathophysiology, and since pro-inflammatory leukotrienes are poorly suppressed by corticosteroids it seems rational to add a leukotriene receptor antagonist (LTRA) when a low to moderate dose of inhaled corticosteroids does not provide sufficient disease control. Long acting beta2-agonist (LABA) treatment represents an alternative to LTRAs and both treatment modalities have been shown to provide additional disease control when added to corticosteroid treatment. To compare the relative clinical benefits of adding either a LTRA or a LABA to asthma patients inadequately controlled by inhaled corticosteroids, a randomized, double-blind, multi-centre, 48-week study will be initiated at approximately 120 centres throughout Europe, Latin America, Middle East, Africa and the Asia-Pacific region in early 2000. The study will compare the oral LTRA montelukast with the inhaled LABA salmeterol, each administered on a background of inhaled fluticasone, on asthma attacks, quality of life, lung function, eosinophil levels, healthcare utilization, and safety, in approximately 1200 adult asthmatic patients. The requirements for study enrollment include a history of asthma, FEV1 or PEFR values between 50% and 90% of the predicted value together with > or = 12% improvement in FEV1 after beta-agonist administration, a minimum pre-determined level of asthma symptoms and daily beta-agonist medication. The study will include a 4-week run-in period, during which patients previously taking inhaled corticosteroids are switched to open-label fluticasone (200 microg daily), followed by a 48-week double-blind, treatment period in which patients continuing to experience abnormal pulmonary function and daytime symptoms are randomized to receive montelukast (10 mg once daily) and salmeterol placebo, or inhaled salmeterol (100 microg daily) and montelukast placebo. All patients will continue with inhaled fluticasone (200 microg daily). During the study, asthma attacks, overnight asthma symptoms, and morning peak expiratory flow rate will be assessed using patient diary cards; quality of life will also be assessed using an asthma-specific quality-of life questionnaire. The results of this study are expected to provide physicians with important clinical evidence to help them make a rational and logical treatment choice for asthmatic patients experiencing breakthrough symptoms on inhaled corticosteroids.
Acetates↗
Mometasone furoate antagonizes AMP-induced bronchoconstriction in patients with mild asthma.
BACKGROUND: Mometasone furoate (MF) is a new potent corticosteroid for use in treating asthma. OBJECTIVE: To test the lower range of the dose-response curve, effects of MF delivered by dry powder inhaler (DPI) on AMP-induced bronchoconstriction were compared with those of placebo. METHODS: In a placebo-controlled, 3-phase cross-over, single-center, double-blind study, 15 patients with mild asthma were randomized to three 2-week treatment phases (separated by 4-week washout phases) with MF DPI 50 microg twice daily, MF DPI 100 microg twice daily, or placebo. AMP challenge was performed before and at the end of each treatment phase. RESULTS: Thirteen patients completed all 3 phases and were included in the primary efficacy analysis. Treatment with MF DPI 50 microg twice daily or with MF DPI 100 microg twice daily significantly reduced the bronchoconstrictor response to AMP, displacing the dose-response curve to the right by 2.81 and 3.11 doubling dilutions, respectively, compared with placebo (P <.001). The improvement in FEV(1) over the 2-week treatment phase was significantly (P < or =.033) greater during treatment with MF DPI 50 microg or 100 microg twice daily than with placebo. Peak expiratory flow rate, wheezing scores, difficulty breathing scores, nocturnal awakenings requiring salbutamol, and puffs of salbutamol per day also indicated a greater improvement in respiratory function and symptoms of asthma with MF DPI 50 or 100 microg twice daily than with placebo. Both doses of MF DPI were well tolerated. CONCLUSIONS: Treatment with low doses of MF DPI decreased airway responsiveness to AMP challenge and improved secondary measures of pulmonary function and asthma symptoms.
Adenosine Monophosphate↗
Tear and conjunctival changes during the allergen-induced early- and late-phase responses.
BACKGROUND: Allergic eye disease is common, but little is known about the underlying disease mechanisms. Conjunctival allergen challenge causes symptoms similar to those of seasonal allergic conjunctivitis and is a useful model to study. OBJECTIVE: We have used allergen challenge to investigate the course of the ocular response, tear inflammatory mediators, tissue adhesion protein expression, and cellular infiltration. METHODS: Eighteen atopic patients and 4 nonatopic control subjects were challenged with extracted mixed grass or Dermatophagoides pteronyssinus in one eye and control vehicle in the other. The clinical response was recorded, and tears were collected over a 6-hour period. Conjunctival biopsy specimens were taken from the challenged eye at 6 or 24 hours. RESULTS: An early-phase response (maximal at 20 minutes) showed a significant increase in tear histamine and tryptase levels, reducing to control levels again by 40 minutes. At 6 hours, a late-phase response occurred with increased symptoms, a second peak of tear histamine and eosinophil cationic protein but not tryptase, upregulation of the adhesion molecules E-selectin and intercellular adhesion molecule, and a cellular infiltrate of mast cells, neutrophils, eosinophils, macrophages, and basophils, with T cells increased only in bulbar biopsy specimens. CONCLUSIONS: The early peaks of tear histamine plus tryptase indicate that the mast cell is responsible for the early-phase response, but basophils may be involved in the late-phase response. Both tear and biopsy findings underline the significance of the late-phase response as the transition between a type I response and clinical disease.
Adolescent↗
Expression of c-erbB receptors and ligands in human nasal epithelium.
BACKGROUND: The epidermal growth factor (EGF) family of growth factors plays an important role in maintenance and repair in a variety of epithelial tissues. However, very little is known about coexpression of these factors and their receptors, the c-erbB family of receptor tyrosine kinases, in human nasal epithelium. OBJECTIVE: We sought to investigate the expression of these molecules in cultured nasal epithelial cells and nasal mucosa from healthy individuals. METHODS: Identification of c-erbB receptors and their ligands was sought by using reverse transcription PCR, Western blotting, and immunohistochemistry. RESULTS: Messenger RNA encoding the EGF receptors (EGFR) c-erbB2 and c-erbB3, but not c-erbB4, was detected in primary cultures of human nasal epithelial cells. Transcripts encoding EGF, heparin-binding EGF, transforming growth factor (TGF) alpha, and amphiregulin were also detected. Receptor and ligand expression was confirmed by using immunocytochemical staining of the cells and Western blotting of the cell lysates. Immunohistochemical analysis of tissue sections obtained from biopsy specimens of nasal mucosa revealed intense membrane staining for the EGFR within the respiratory nasal epithelium, which was predominantly localized at the level of the columnar epithelial layers. Similar staining patterns were observed for c-erbB2 and c-erbB3 in the respiratory nasal epithelium. Evidence for EGF, transforming growth factor alpha, heparin-binding EGF, amphiregulin, and betacellulin immunostaining in the nasal epithelium was also obtained; their staining patterns paralleled that of EGFR immunostaining. CONCLUSION: Colocalization of c-erbB receptors and ligands establishes a basis on which to investigate c-erbB receptor- mediated effects in human nasal epithelium.
Cells, Cultured↗
Evaluation of the accuracy and precision of lung aerosol deposition measurements from single-photon emission computed tomography using simulation.
Single-photon emission computed tomography (SPECT) imaging is being increasingly used to assess inhaled aerosol deposition. This study uses simulation to evaluate the errors involved in such measurements and to compare them with those from conventional planar imaging. SPECT images of known theoretical distributions of radioaerosol in the lung have been simulated using lung models derived from magnetic resonance studies in human subjects. Total lung activity was evaluated from the simulated images. A spherical transform of the lung distributions was performed, and the absolute penetration index (PI) and a relative value expressed as a fraction of that in a simulated ventilation image were calculated. All parameters were compared with the true value used in the simulation, and the errors were assessed. An iterative method was used to correct for the partial volume effect, and its effectiveness in improving errors was evaluated. The errors were compared with those of planar imaging. The precision of measurements was significantly better for SPECT than planar imaging (2.8 vs 6.3% for total lung activity, 6 vs 20% for PI, and 3 vs 6% for relative PI). The method of correcting for the influence of the partial volume effect significantly improved the accuracy of PI evaluation without affecting precision. SPECT is capable of accurate and precise measurements of aerosol distribution in the lung, which are improved compared with those measured by conventional planar imaging. A technique for correcting the SPECT data for the influence of the partial volume effect has been described. Simulation is demonstrated as a valuable method of technique evaluation and comparison.
Aerosols↗
Involvement of the epidermal growth factor receptor in epithelial repair in asthma.
Epithelial damage and airway remodeling are consistent features of bronchial asthma and are correlated with disease chronicity, severity, and bronchial hyperreactivity. To examine the mechanisms that control bronchial epithelial repair, we investigated expression of the epidermal growth factor receptor (c-erbB1, EGFR) in asthmatic bronchial mucosa and studied repair responses in vitro. In biopsies from asthmatic subjects, areas of epithelial damage were frequently observed and exhibited strong EGFR immunostaining. EGFR expression was also high in morphologically intact asthmatic epithelium. Using image analysis, EGFR immunoreactivity (% of total epithelial area, median (range) was found to increase from 9.4 (4.1-20.4) in normal subjects (n=10) to 18.4 (9.3-28.9) in mild asthmatics (P<0.01, n=13) and 25.4 (15.4-31.8) in severe asthmatics (P<0.00, n=5). Epithelial EGFR immunoreactivity remained elevated in patients treated with corticosteroids and was positively correlated with subepithelial reticular membrane thickening. Using 16HBE 14o- bronchial epithelial cells, we found that EGF accelerated repair of scrape-wounded monolayers and that the EGFR-selective inhibitor, tyrphostin AG1478, inhibited both EGF-stimulated and basal wound closure whereas dexamethasone was without effect. Intrinsic activation of the EGFR was confirmed by analysis of tyrosine phosphorylated proteins, which revealed a rapid, damage-induced phosphorylation of the EGFR, irrespective of the presence of exogenous EGF. To assess the relationship between EGFR-mediated repair and tissue remodeling, release of the profibrogenic mediator TGF-beta2 was also measured. Scrape wounding increased release of TGF-beta2 from epithelial monolayers and EGF had no additional stimulatory effect. However, when repair was retarded with AG1478, the amount of TGF-beta2 increased significantly. These data indicate that the EGFR may play an important role in bronchial epithelial repair in asthma and that impairment of this function may augment airway remodeling.
Adult↗