The upper and lower airways have complimentary roles in the ultimate object of supplying the body with oxygen whilst removing waste products of metabolism. Pathology in one area may trigger a response in another, the physiology of which, in the case of virus-induced asthma exacerbations remains poorly characterized. Viral infection of the upper airways by common cold viruses frequently triggers a response in the lower airways leading to prolonged morbidity, especially in subjects with significant pre-existing airway disease. The induction or amplification of BHR may be an important mechanism whereby asthmatic symptoms are produced although the cellular and tissue events or reflex mechanisms activated by viral illnesses and underlying BHR changes are poorly defined and may be dependent on the type and the severity of infection. Children and asthmatics tend to develop frequent colds setting in motion a sequence of events culminating in airway obstruction and symptoms of wheezing, coughing and chest tightness. This may reflect independent inflammatory changes caused by a simply additive effect of viral damage to the mucosa superimposed upon pre-existing allergic inflammation (Fig. 1). Few if any symptoms will develop in normal subjects with a mild cold whereas significant symptoms may ensue if the cold is severe and induces marked lower airway swelling, secretions and smooth muscle contraction; pathology to which children who have small calibre airways may be particularly susceptible. In asthmatics even a mild cold frequently induces exacerbation of symptoms, while serious life-threatening asthma attacks may occur associated with a severe cold. Some studies have suggested that this effect is not only additive but also synergistic and brought about by release of the mediators already present in increased quantities, the induction of IgE synthesis, or by the potentiation of neural and epithelial damage. The combined effect of both asthma and viruses may thus be amplified and result in a sustained and refractory period of airway obstruction, severe symptoms and unstable asthma. As most hospital admissions for asthma occur over the winter months and soon after the start of the school terms [115], spread of viruses through the community to susceptible individuals may be the single most important cause of sustained exacerbations of asthma. Definition of the pathological and physiological mechanisms involved will lead to better understanding and may thus provide a basis for prevention and the development of effective forms of treatment for virus-induced asthma.

E Ex xp pe er ri im me en nt ta al l r rh hi in no ov vi ir ru us s i in nf fe ec ct ti io on n i in n v vo ol lu un nt te ee er rs sPStudies were conducted in 25 clinically healthy volunteers using a validated HRV inoculum in the first 17 and a new inoculum in the subsequent eight subjects. Severity of cold symptoms, nasal wash albumin levels and airway responsiveness were measured, and the new inoculum was prepared from nasal washes obtained during the cold. The new inoculum was tested using standard virological and serological techniques, as well as a polymerase chain reaction for Mycoplasma pneumoniae.No contaminating viruses or organisms were detected and the methods suggested were workable. Good clinical colds developed in 20 of the 25 subjects and median symptom scores were similar in the validated and new inoculum groups (18 and 17.5, respectively; p=0.19). All subjects shed virus, and there were no differences noted in viral culture scores, nasal wash albumin and rates of seroconversion in the two groups. Although airway responsiveness increased in both groups (p=0.02 and p=0.05), the degree of change was similar.We have performed experimental rhinovirus infection studies and demonstrated similar clinical disease in two inoculum groups. Amplified airway responsiveness was induced; continuing studies will define the mechanisms and suggest modes of treatment.

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increased the amount of PG D2 required to produce a fall of 20% in the forced expiratory volume in 1 s by 6-fold and 16-fold at 60 min and 90 min after ingestion respectively, and the 50 mg dose by 14-fold at 90 min after ingestion. 5 The specificity of the drug was confirmed in vivo in that there was no significant protection against histamine bronchial provocation at either dose or at either time point. 5 The time course study showed significant protection against PG D2 bronchial provocation at 1 h and at 3 h after a single 20 mg oral dose. 7 There was no correlation between subjects in plasma BAY u 3405 concentration and drug effect. Within the subjects performing the time course study there was a strong correlation in time between drug effect and plasma BAY u 3405 concentration. 8 BAY u 3405 may be useful in preventing prostanoid mediated bronchoconstriction in clinical asthma.

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