Library

Notes: Abstract Kay and his colleagues [1] have suggested that the neutrophil high molecular weight chemotactic factor (NCF) found in the serum of patients suffering from a variety of allergic diseases is mainly derived from mast cells and is therefore an indicator of mast cell activation. We have studied some of the properties of NCF obtained from patients with atopic extrinsic asthma and compared it withN-formyl-1-methionyl-1-leucyl-1-phenylalanine (FMLP), a chemotactic peptide [2]. A number of differences between FMLP and NCF were observed. In contrast to FMLP, checkerboard analysis showed that NCF caused random migration of neutrophils. In addition microscopic analysis of neutrophil locomotion in response to FMLP demonstrated the characteristic pseudopod formation. Furthermore, it was found that in contrast to FMLP, NCF did not cause the release of lysosomal enzymes from cytochalasin B-treated neutrophils. These results suggest that NCF has chemokinetic rather than chemotactic properties.

Notes: Standardization of allergen provocation tests of the airways requires standardization of each of the steps involved, including standardization of the extracts used. The value of international standards is emphasized and so is the determination of a clinically relevant potency. The allergen extracts used for bronchial provocation tests must be compared with qualitatively and quantitatively clinically relevant standards using complementary immunochemical and biological methods. Ideally the same extracts should be used for diagnosis (skin test, specific IgE determinations, provocations) and treatment (immuno-therapy). The importance of the biological compared with the non-biological methods is that the biological methods are established in allergenic patients in order to select a clinically relevant potency of the allergen in question, and this potency ought to be confirmed in clinical trials. Once established the biological potency of an in-house preparation can be reproduced by supplementary in vitro methods. Very few commercial allergen preparations are available which fulfil the above-mentioned criteria.

Notes: The effect of single dose topical nasal therapy with azelastine hydrochloride (azelastine) on the response of nasal airways resistance (NAR) to provocation testing was studied in 36 patients with seasonal allergic rhinitis. Nasal provocation testing (NPT) with histamine or grass pollen was performed after a single dose of azelastine, 0.28 mg to each nostril, or placebo. NAR was assessed by rhinomanometry for 10 hr following NPT. Compared to placebo the NAR response to histamine was inhibited at both 1 and 2 hr following azelastine administration, significant at 1 hr (P 〈 0.02) and 2 hr (P 〈 0.0001). No such effect was observed in relation to allergen-induced changes in NAR. Azelastine also inhibited numbers of sneezes for up to 10 hr following both histamine NPT (P 〈 0.02) and allergen NPT (P 〈 0.05), when compared to placebo. Forty-seven per cent of participants experienced bitter or unpleasant taste sensations after azelastine administration but no other unwanted effects were clearly related to azelastine therapy.

Notes: The role of pyroglyphid mites in house dust allergy is well established and the major allergens from the common house dust mites (Dermatophogoides species) have been characterized. There is, however, relatively little progress in the understanding of the human IgE response to non-pyroglyphid storage mites, allergenic crossreactivity with other mite species and extent of environmental exposure. We studied 196 individuals from an urban environment who were not occupationally exposed to storage mites and found a 24% prevalence of specific IgE antibody to Dermatophagoides pteronyssinus and a 14% prevalence of RAST positivity to at least one of three storage mites, Acarus siro, Lepidoglyphus destructor and Tyrophagus longior. All individuals with a positive RAST to storage mites had specific IgE to D.pteronyssinus. RAST inhibition studies with the eight sera with greater than 2% RAST binding to both families of mites showed considerable crossreactivity between D. pteronyssinus and the storage mites A.siro and T. longior and limited crossreactivity between D. pteronyssinus and L. destructor. This suggests that at least some of the response to storage mites observed by direct RAST is a consequence of crossreactivity with the more abundant D. pteronyssinus.

Notes: The inhibition of immediate allergen-induced airflow obstruction by lodoxamide tromethamine (LT), a new drug with properties considered to be similar to those of sodium cromoglycate, was studied in twelve young asthmatic volunteers. Single aerosolized doses of 0.01 mg LT, 0.1 mg LT or placebo were administered by inhalation 15 min prior to allergen provocation at weekly intervals, in a double-blind random order study. Following inhalation of both doses of LT a significantly greater amount of allergen had to be administered to cause a 20% fall in the forced expiratory volume in one second (FEV1) from control levels than was the case following placebo pre-treatment (P 〈 0.001). After single-dose inhalation of LT only minor unwanted effects were recorded; in particular a transient feeling of heat in the upper respiratory tract after inhalation of the higher dose of drug.

Notes: Radioallergosorbent testing was used to look for the presence of specific IgE antibody against a para-tolyl-mono-isocyanate human serum albumin conjugate in sera from five groups of subjects. The first three groups consisted of individuals exposed to toluene diisocyanate (TDI) who had been shown by bronchial provocation testing with levels of TDI below the threshold limit value of 0.02 parts/106, to have immediate asthmatic reactions, late asthmatic reactions or no respiratory changes at all. The two control groups consisted of atopic and non-atopic individuals who had no respiratory symptoms and no known exposure to TDI. Although RAST showed high ct/min in some of the sera from patients with proven TDI-induced respiratory disease, these levels were not significantly different from controls and appeared to reflect the presence in these sera of high levels of total IgE (〉 100 u ml-1). There is no evidence from this study for the presence of specific IgE antibody against a para-tolyl mono isocyanate human serum albumin conjugate in patients with TDI-induced respiratory disease. This finding may reflect absence of antibodies, or that the techniques for their detection are not always effective even when performed by experienced persons, and there is a potential source of error in the interpretation of results when sera contain large amounts of IgE.

Notes: 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.Confluent human bronchial epithelial cell cultures were exposed to cigarette smoke in the absence or presence of HDM allergen and investigated for the release of IL-8, IL-1β, and sICAM-1. Damage to the epithelial cells themselves was assessed by release of 51Cr. On separate occasions, we investigated the effect of PTL11028, a highly potent and selective Der p1 inhibitor, on HDM allergen-induced release of IL-8, following activation of HDM allergen by incubation with cysteine. The effect of cigarette smoke exposure on the stability of these released mediators in prepared solutions in the absence/presence of reduced glutathione was also studied.Both HDM allergens and short-term (20 min) cigarette smoke exposure led to a significantly increased release of IL-8, IL-1β and sICAM-1 from the epithelial cell cultures. Longer exposure (1–6 h) to cigarette smoke led to a dramatic decrease in the amount of these mediators detected in the culture medium. Whilst incubation of epithelial cultures with HDM allergen did not cause any significant change in the release of 51Cr from pre-loaded cells, cigarette smoke on its own led to a marked, exposure and incubation-time dependent increase in the release of 51Cr. Incubation with HDM allergen led to a significant, dose and time-dependent increase in the release of IL-8, which was further enhanced when the allergen extract was pre-activated with cysteine. This effect was completely abrogated by PTL11028, a novel Der p1 inhibitor. Prepared solutions of various concentrations of IL-8, IL-1β and sICAM-1 exposed to cigarette smoke demonstrated a dramatic exposure time-dependent decrease in the detectable amount of these mediators, an effect which was abrogated by GSH.HDM-induced airway inflammation may include Der p-mediated release of inflammatory mediators from epithelial cells. Additionally, short-term cigarette smoke exposure may induce airway inflammation by release of inflammatory mediators from these cells, an effect which may be potentiated by Der p allergens. Longer term cigarette smoke exposure may cause damage to epithelial cells and changes in the structure of inflammatory mediators.