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Chronic inflammation and remodeling may follow acute inflammation or may begin insidiously as a low-grade smoldering response, especially in the case of immune reactions. The histologic hallmarks of chronic inflammation and remodeling are as follows: (1) infiltration by macrophages and lymphocytes; (2) proliferation of fibroblasts that may take the form of myofibroblasts; (3) angiogenesis; (4) increased connective tissue (fibrosis); and (5) tissue destruction. It is clear that changes in the extracellular matrix, smooth muscle, and mucous glands have the capacity to influence airway function and reactivity in asthma patients. 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 on basement membrane) but is not always clinically demonstrated. Destruction and subsequent remodeling of the normal bronchial architecture are manifested by an accelerated decline in FEV[sub 1] and bronchial hyperresponsiveness. This irreversible component of airway obstruction is more prominent in patients with severe disease and even persists after aggressive anti-inflammatory treatment. Airway remodeling appears to be of great importance for understanding the long-term follow-up of asthmatic patients, but there are major gaps in our knowledge. Physiologic correlations with pathology represent a major missing link that should be filled. More long-term studies are needed to appreciate the prevention and treatment of remodeling. Future research therefore should provide better methods for limiting airway remodeling in asthma patients. [ABSTRACT FROM AUTHOR]

Bronchial epithelial cells are activated in asthma but the mechanisms underlying this activation are poorly understood. We tested the possibility that bronchial epithelial cells recovered by brushing from 15 asthmatic and 11 control subjects may be activated by an IgE-dependent mechanism. The expression of the low-affinity IgE receptor (CD23) was studied by immunocytochemistry using the alkaline phosphatase anti-alkaline phosphatase technique and immunofluorescence using confocal microscopy. Four of eight allergic asthmatic patients and none of the seven non-allergic asthmatic or control subjects had a positive expression of CD23. The functional activity of CD23 was examined in the cells recovered from these subjects by stimulating them with IgE/anti-IgE. 15HETE was not released but endothelin was released in the three of four asthmatic patients who had a positive expression of CD23. None of the other subjects released any endothelin. This study suggests that bronchial epithelial cells of asthmatic patients may be directly activated by an IgEmediated mechanism. [ABSTRACT FROM AUTHOR]

Background: Inflammation in chronic obstructive pulmonary disease (COPD) is characterised by increased neutrophilic infiltration of the airways. Cilomilast, a novel selective phosphodiesterase 4 inhibitor in clinical development for COPD treatment, exerts anti-inflammatory effects. The ability of cilomilast to inhibit the release of neutrophil chemoattractants such as tumour necrosis factor (TNF)-α, interleukin (IL)-8, and granulocyte-macrophage colony stimulating factor (GM-CSF) by bronchial epithelial cells and sputum cells isolated from 10 patients with COPD, 14 normal controls, and 10 smokers was investigated. Methods: Bronchial epithelial cells obtained by bronchial brushing and sputum cells isolated from induced sputum samples were cultured for 24 hours in the presence or absence of cilomilast (1 µM). After incubation the supernatants were harvested and the levels of mediators measured by ELISA. Chemotactic activity in supernatants was also measured using a Boyden chamber. Results: TNF-α and IL-8 release by bronchial epithelial cells and sputum cells was higher in patients with COPD than in controls (p < 0.0001) and smokers (p < 0.0001). GM-CSF was only detectable in sputum cell supernatants and its level was higher in patients with COPD than in controls and smokers (p < 0.0001, respectively). Cilomilast significantly reduced TNF-α release by bronchial epithelial cells and sputum cells (p = 0.005) and GM-CSF release by sputum cells (p = 0.003), whereas IL-8 release was not statistically inhibited. Supernatants of sputum cells and bronchial epithelial cells treated with cilomilast significantly decreased neutrophil chemotaxis (p < 0.006 and p < 0.008, respectively). Conclusions: Cilomilast inhibits the production of some neutrophil chemoattractants by airway cells. This drug may play a role in the resolution of neutrophilic inflammation associated with COPD and cigarette smoke. [ABSTRACT FROM AUTHOR]