Asthma and rhinosinusitis.

Allergic rhinoconjunctivitis and asthma are becoming more common in industrialized societies, particularly in the second and third decades of life, when those affected are at a vital stage of their education and career. It is therefore of paramount importance that the treatment options available be effective, improve quality of life, and above all, they must be without any significant unwanted effects. National and international guidelines for the treatment of both allergic rhinitis and asthma have been released recently that put forward recommendations based on an extensive evidence-based review of the literature for the care of these diseases that would meet these goals of disease management.

Effect of ozone and nitrogen dioxide on the permeability of bronchial epithelial cell cultures of non-asthmatic and asthmatic subjects.

Background: Although epidemiological as well as in vivo exposure studies suggest that ozone (O3) and nitrogen dioxide (NO2) may play a role in airway diseases such as asthma, the underlying mechanisms are not clear.

Objective: Our aim was to investigate the effect of O3 and NO2 on the permeability of human bronchial epithelial cell (HBEC) cultures obtained from non-atopic non-asthmatic (non-asthmatics) and atopic mild asthmatic (asthmatics) individuals.

Methods: We cultured HBECs from bronchial biopsies of non-asthmatics and asthmatics, and exposed these for 6 h to air, 10 to 100 parts per billion (p.

Anaphylaxis and anaphylactoid reactions. A guide to prevention, recognition, and emergent treatment.

Anaphylaxis and anaphylactoid reactions are adverse immunologic responses that require early intervention to prevent life-threatening consequences. The initial symptoms, such as nasal congestion or pruritus, can quickly progress to cardiac collapse or asphyxiation. In this article, Drs Rusznak and Peebles discuss the mechanisms of these reactions, common causative agents, preventive strategies, recognition, and treatment.

Interaction of cigarette smoke and house dust mite allergens on inflammatory mediator release from primary cultures of human bronchial epithelial cells.

Several studies have shown that exposure to cigarette smoke and/or house dust mite (HDM) can lead to increased airway inflammation in susceptible individuals. The underlying mechanisms, however, are not defined. To investigate the interaction between cigarette smoke and HDM allergen on mediator release from primary cultures of human bronchial epithelial cells.

Cigarette smoke decreases the expression of secretory component in human bronchial epithelial cells, in vitro.

Epithelial secretory component (SC) is thought to be essential for immunologic protection of the respiratory tract from viral and bacterial infection, since it transports polymeric IgA from the basolateral to the luminal surface of epithelial cells. We have hypothesized that recurrent infection in airways of cigarette smokers is at least partly a consequence of cigarette smoke-induced downregulation of the expression and/or release of SC from airway epithelial cells, subsequently resulting in decreased transcytosis of secretory IgA to the airway lumen. To test this hypothesis, we have cultured human bronchial epithelial cells (HBEC) from surgical tissues and exposed these for 20 minutes to either air or cigarette smoke.

Effect of cigarette smoke on the permeability and IL-1beta and sICAM-1 release from cultured human bronchial epithelial cells of never-smokers, smokers, and patients with chronic obstructive pulmonary disease.

Although cigarette smoking is of paramount importance in the development of chronic obstructive pulmonary disease (COPD), only a small proportion of smokers develop the disease. We tested the hypothesis that the response of the bronchial epithelium to cigarette smoke (CS) differs in patients with COPD. Such a difference might explain in part why only some cigarette smokers develop the disease.

Functional effects of the inhibition of the cysteine protease activity of the major house dust mite allergen Der p 1 by a novel peptide-based inhibitor.

Background: The house dust mite (HDM) Dermatophagoides pteronyssinus is an important source of allergens, which can cause allergic conditions. The cysteine protease activity of Der p 1 may enhance the potency of this major mite allergen through cleavage of CD23 and CD25 from the surface of immune cells, IgE independent mast cell activation, increases in epithelial cell permeability and inactivation of an endogenous serine protease inhibitor. Inhibition of the enzymatic activity of Der p 1 may therefore be of therapeutic benefit.

The effect of exposure to ozone and nitrogen dioxide on the airway response of atopic asthmatics to inhaled allergen: dose- and time-dependent effects.

Eleven mild atopic asthmatic patients were exposed for 6 h, in randomized order, to air, 100 ppb O3, 200 ppb NO2, and 100 ppb O3 + 200 ppb NO2, followed immediately by bronchial allergen challenge. Subsequently 10 of these patients were exposed for 3 h to air, 200 ppb O3, 400 ppb NO2, and 200 ppb O3 + 400 ppb NO2, followed immediately by bronchial allergen challenge. All exposures were carried out in an environmental chamber, with intermittent moderate exercise, and a minimal interval of 2 wk.

Cigarette smoke potentiates house dust mite allergen-induced increase in the permeability of human bronchial epithelial cells in vitro.

Although studies have suggested that exposure to cigarette smoke (CS) may be associated with the development of atopy, the mechanisms underlying this are not clearly understood. It has been suggested that CS impairs the barrier function of the airway epithelium, leading to increased access of allergens such as those of the house dust mite (HDM) Dermatophagoides pteronyssinus (Der p) to antigen-presenting cells, with subsequent allergic sensitization. In order to test this hypothesis, we established primary explant cultures of human bronchial epithelial cells (HBEC) in cell culture inserts, and exposed these for 20 min, 1 h, 3 h, and 6 h to CS or air in the absence or presence of 300 ng/ml Der p, and then further incubated the cultures over a period of 24 h.

Effect of fluticasone propionate aqueous nasal spray on allergen-induced inflammatory changes in the nasal airways of allergic rhinitics following exposure to nitrogen dioxide.

Background: The authors have recently demonstrated that prior exposure for 6 h to 400 p.p.b.

Why is allergy increasing?--environmental factors.

Data from epidemiological studies have shown that allergic conditions have increased over the last 30-40 years, particularly in developed countries, despite a decrease in the severity of grass pollen seasons. Other epidemiological studies suggest an interaction between allergic diseases and traffic pollution, and laboratory findings indicate that diesel exhaust particles enhance sensitivity to allergens. In an in vitro study, we found evidence to suggest that cigarette smoke may render the airway epithelium more susceptible to adverse effects of allergens.

The effect of nedocromil sodium on human airway epithelial cell-induced eosinophil chemotaxis and adherence to human endothelial cell in vitro.

Although some studies have shown that long-term treatment of asthmatics with nedocromil sodium can reduce airway hyperresponsiveness and improve symptoms and lung function, the mechanisms underlying its effects are not well understood. We have investigated the effect of nedocromil sodium on eosinophil chemotaxis, eosinophil adherence to human endothelial cells and release of soluble intercellular adhesion molecule-1 (sICAM-1) from endothelial cells, induced by conditioned medium collected from cultured human bronchial epithelial cells. Conditioned medium significantly increased eosinophil chemotaxis from a baseline median value of 2.

New insights into the understanding of asthma.

The prevalence of asthma is increasing, despite better understanding of its pathogenesis and improved treatments. During the past 10 years, the perception of asthma has shifted from a disease primarily characterized by altered smooth muscle function to one mainly characterized by chronic inflammation. This article reviews the evidence supporting the relationship of inflammation in both the upper and lower airways, focusing on intermittent seasonal disease as well as on the more chronic and severe forms of asthma, including that associated with aspirin intolerance.

Allergen-irritant interaction and the role of corticosteroids.

Studies of exposure to air pollutants, such as ozone and nitrogen dioxide (NO2) +/- sulphur dioxide (SO2), have demonstrated that these agents, either individually or in combination, increase the airway response of both asthmatics and allergic rhinitics to inhaled allergen. Other studies have demonstrated that exposure to these pollutants significantly increased the levels of eosinophil cationic protein (ECP) in the nasal secretions of both asthmatics and allergic rhinitics, suggesting that pollutants may prime eosinophils for subsequent activation by allergen. More recently, our studies have demonstrated that treatment with inhaled corticosteroids, such as fluticasone propionate, significantly attenuated pollution+ allergen-induced release of ECP in allergic rhinitics.

Mechanisms of pollution-induced airway disease: in vitro studies in the upper and lower airways.

Evidence from both epidemiological and laboratory-based studies suggests that increased exposure to liquid petroleum and gas-derived air pollutants [nitrogen dioxide (NO2), ozone, and respirable particulate matter] may play a role in the clinical manifestation of both allergic and non-allergic airway disease. The mechanisms and cell types involved in pollutant-mediated effects in the airways, however, are not clear. In vitro studies have suggested that human fibroblasts, B-lymphocytes, alveolar macrophages, and epithelial cells/cell lines may be involved.

Airway response of asthmatic subjects to inhaled allergen after exposure to pollutants.

Background: Recent studies have suggested that air pollutants resulting from vehicle exhaust emissions and burning of fossil fuels, either in combination or individually, may enhance the airway response of asthmatic subjects to inhaled allergen. It was hypothesised that the airway response to inhaled allergen after exposure to a combination of 400 ppb nitrogen dioxide (NO2) and 200 ppb sulphur dioxide (SO2) is increased 24-48 hours after exposure.

Methods: Thirteen mild atopic asthmatic volunteers were exposed for six hours to a single exposure of air and three exposures of the combination of 400 ppb NO2 + 200 ppb SO2 in randomised order, and then challenged with increasing concentrations of Dermatophagoides pteronyssinus allergen either immediately after exposure to air, or immediately, 24 hours or 48 hours after exposure to the combination of the two pollutants, until a 20% fall in forced expiratory volume in one second (FEV1) was recorded.

Ozone-induced mediator release from human bronchial epithelial cells in vitro and the influence of nedocromil sodium.

Although animal and human studies have demonstrated that ozone inhalation leads to airway epithelial inflammation and damage, the underlying mechanisms are not fully understood. We cultured human bronchial epithelial cells as explant cultures and investigated the effect of 6 h of exposure to 0-500 parts per billion (ppb) O3 with or without 10(-5) M nedocromil sodium on: 1) epithelial cell membrane integrity; and 2) release of inflammatory cytokines and soluble intercellular adhesion molecule-1 (sICAM-1), as assessed by enzyme-linked immunosorbent assay (ELISA). O3 exposure led to significant epithelial cell damage at concentrations of 10-500 ppb O3, as indicated by increased release of [51Cr]-labelled sodium chromate.

Nedocromil sodium and airway inflammation in vivo and in vitro.

We conducted a series of studies investigating the antiinflammatory effects of nedocromil sodium, with particular reference to its effects on human bronchial epithelial cells and eosinophils in vitro and on eosinophils in vivo. Nedocromil sodium produced a dose-related inhibition of ozone-induced IL-8 release from human bronchial epithelial cells and also attenuated the release of granulocyte macrophage colony-stimulating factor, tumor necrosis factor-alpha, and soluble intercellular adhesion molecule 1. The culture medium from human bronchial epithelial cell cultures, containing the proinflammatory cytokines IL-8, granulocyte macrophage colony-stimulating factor, "regulated on activation, normal T expressed and secreted," IL-1 beta, and tumor necrosis factor-alpha, increased eosinophil chemotaxis and eosinophil adhesion to cultured human endothelial cells.

Air pollutants and respiratory hypersensitivity.

Epidemiological evidence suggests that an increase in liquid petroleum derived pollutants is associated with exacerbation of allergic airway disease, and that the effects of pollution may occur 1-2 days later. Laboratory based studies have demonstrated that the pollutants responsible for the adverse effects on respiratory health include nitrogen dioxide (NO2), sulphur dioxide (SO2), ozone (O3) and respirable particulates (PM10). More recently, studies of asthmatic individuals exposed to O3, NO2 and a combination of NO2 and SO2 have indicated that these agents increase the airway responsiveness of these individuals to inhaled allergen, and that this effect may be maximal 24 h after exposure to the pollutants.