Csaba Rusznak

The impact of pollution on allergic disease

Evidence suggests that allergic disease is becoming more common, particularly in industrialized societies. Two studies of schoolchildren from Aberdeen, Scotland aged 8–13 years were undertaken in 1964 and 1989 using identical questionnaires, and found that the reported prevalence of asthma had risen from 4.1% to 10.2% during this period, hay fever from 3.2% to 11.9% and eczema from 5.3% to 12%. Indication that air pollution may contribute to this increase has come from several studies. In Japan, allergic rhinoconjunctivitis was found to be more prevalent in individuals living near motorways than in cedar forests. Severe asthma also occurs more commonly than mild asthma in children living in polluted areas. Exercise‐induced asthma and the use of asthma medication were twice as high in a town near two power stations compared with a non‐polluted town. A recent study in Finland showed that admissions to hospital with severe asthma correlated with atmospheric levels of nitrogen dioxide. Deterioration in peak flow recordings in asthmatics and exacerbations of symptoms in hay fever sufferers correlate with ambient levels of ozone. Elucidation of the mechanisms by which exposure to air pollutants may influence the frequency of allergic disease or exacerbate symptoms has come from in vitro and in vivo experiments in animals and man. Animals exposed to ozone, sulphur dioxide, nitrogen dioxide and particles from diesel exhaust, together with allergens, show more ready development of allergic sensitization compared with those exposed to allergen alone. The dose of allergen necessary to produce a 20% fall in FEV1 (forced expiratory volume in 1 second) in mild asthmatics is reduced by previous exposure to ozone or a mixture of nitrogen dioxide and sulphur dioxide. It has also been suggested that the allergic potency of pollen grains may be increased when they are coated in pollutants. Bronchial and nasal lavage studies have shown that air pollutants can induce an influx of inflammatory cells and proinflammatory cytokines into the respiratory tract. Studies on human epithelial cells cultured to confluence in vitro have indicated that exposure to nitrogen dioxide can decrease ciliary beat frequency which would, in theory, reduce allergen clearance and increase the risk of sensitization. Further, exposure of these cells to either ozone or nitrogen dioxide induces the release of inflammatory mediators, such as leukotriene C4, and proinflammatory cytokines, including granulocyte‐macrophage colony‐stimulating factor, tumour necrosis factor‐α and interleukin‐8. This effect can be attenuated by the use of anti‐inflammatory drugs.

The effects of salmeterol and salbutamol on ciliary beat frequency of cultured human bronchial epithelial cells, in vitro

Studies investigating mechanisms of mucociliary clearance have suggested that beta 2-adrenergic agents may significantly influence ciliary activity of epithelial cells and therefore play a vital role in the maintenance of functional integrity of the airways. We have cultured human bronchial epithelial cells, from surgical explants and investigated the effects of salbutamol and salmeterol, in a time- and dose-dependent manner, on the ciliary beat frequency (CBF) of these cells. Prior to and at several times after exposure to either salbutamol (10(-8) to 10(-3) M) or salmeterol (10(-8) to 10(-4) M), the epithelial cells were monitored for CBF and on the basis of data obtained from these studies, the effect of 10(-6) M propranolol was investigated in the presence of optimal concentrations of salbutamol and salmeterol. Salbutamol was optimally active at a concentration of 10(-4) M and caused a transient but significant increase in the CBF from baseline level of 8.6 +/- 0.4 to 9.6 +/- 0.5 Hz (P < 0.05), after 2 h incubation. In contrast, salmeterol was maximally active at a concentration of 10(-6) M and caused a significantly rapid and prolonged increase in CBF from a baseline value of 9.2 +/- 0.4 to 10.9 +/- 0.6 Hz (P < 0.02) and 10.6 +/- 0.8 Hz (P < 0.05) after 15 min and 24 h incubation, respectively. Propranolol (10(-6) M) abrogated the salbutamol- but not the salmeterol-induced increases in CBF.(ABSTRACT TRUNCATED AT 250 WORDS)

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. Studies investigating the putative mechanisms underlying the effects of these pollutants suggest that exposure to these agents may lead to perturbation of the airway epithelium and release of pro-inflammatory mediators from the epithelial cells, which then influence the activity of inflammatory cells, such as eosinophils.

The assessment of nasal mucociliary clearance and the effect of drugs

Mucociliary clearance provides an important protective function in the nose. A variety of topically and systemically administered drugs are used to treat nasal pathologies and there is evidence that these therapies may modify nasal mucociliary clearance (NMCC). This review describes the methods of assessing NMCC and the effects upon it of therapeutic agents. Overall, mucociliary clearance is dependent on an adequate quantity of mucus of appropriate viscosity and elasticity, and on adequately functioning cilia. The nasal mucus blanket consists of two layers. The outer mucus layer (gel phase) is relatively viscous and moves over the surface of the cilia, which are surrounded by a serous periciliary fluid layer (sol phase) (1). The ciliated cells have between 120 and 200 cilia that project from the luminal surface of the cell into the mucus. In the anterior part of the nose, there is a paucity of cilia and the mucus moves slowly at about l-2 mm h‘. In the posterior part of the nose, mucus moves more rapidly at 10 mm min‘. The beat of cilia is quick and forceful in a forward propulsive stroke that is followed by a slower recovery stroke, and beat frequency in man is about 13 Hz in vitro at 37°C. Beating activity is coordinated so that it appears to move from one region to another adjacent posterior one in a metachronous fashion. Fine particulate matter, including bacteria, that enters with inspired air is filtered by adherence to the mucus film. This occurs both by impaction and as the result of an electrostatic surface charge. Most particles, including microorganisms, trapped by this moving carpet of mucus in the nose are propelled towards the pharynx where they are swallowed (2). A defect in any part of this system such as occurs in primary or secondary

ABC of allergies: Diagnosing allergy

Allergy to environmental agents can affect almost every organ of the body. Although allergic rhinitis is the commonest manifestation, the lower respiratory tract, the conjunctiva, the skin, and the gastrointestinal tract are frequently affected by allergic disease. #### Age when certain allergies are likely to occur for first time Allergic diseases are common, and their prevalence is increasing. Accurate diagnosis of triggering or causative allergens is essential for appropriate advice for avoidance and environmental control measures. Although allergic diseases can occur at almost any age, some allergies are most likely to develop for the first time in particular age groups. #### Taking a clinical history An immediate relation between exposure to potential allergens and the development of symptoms makes both the diagnosis and identification of allergy straightforward. In …

Circadian rhythms in ciliary beat frequency of human bronchial epithelial cells, in vitro

Introduction Studies of ciliated airway epithelial cells have suggested that these play a vital role in mucociliary clearance and consequently in maintenance of airways integrity. Studies of the mechanism/s underlying this process have demonstrated that efficient mucus clearance is dependent on the total number of cilia and the coordination and frequency of their beat, of which the latter is significantly influenced by neurohormones and neurotransmitters (1). Sanderson and Dirksen ( 2 ) a n d Tamaoki and colleagues (3) have investigated the mechanism/s influencing the ciliary beat frequency of rabbit tracheal epithelium explants, in vitro, and suggested that two independent mechanisms, one utilizing calcium and the other utilizing cAMP, may be operative. Whilst studies of plasma concentrations of agents such as cAMP and epinephrine, which modulate ciliary activity, have suggested that these may be influenced by circadian rhythms (4,5), to date there are no such reports of the influence of circadian rhythms on ciliary activity of human bronchial epithelial cells. Investigations of ciliary activity of cultured human bronchial epithelial cells, in our laboratory, have suggested that the ciliary beat frequency of these cells may also be influenced by circadian rhythms, since this was attenuated in the early morning hours each day, irrespective of the experimental condition under investigation (6,7). In view of these findings, the aim of the present study was to elucidate whether ciliary beat frequency (CBF) of human bronchial epithelial cells, in vitro, was influenced by circadian rhythms and to see if changes in CBF correlated with changes in generation of cAMP in these cultures.