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We have examined in vitro cell-mediated lymphocyte responses to Concanavalin A, (Con. A), and the effects of histamine and indomethacin upon these responses, in normal subjects, and patients with extrinsic and intrinsic asthma, and chronic bronchitis. Lymphocytes from both intrinsic and extrinsic asthmatics are particularly sensitive to histamine-induced suppression of their response to Con. A, and this increased sensitivity was reversed by indomethacin. In these respects, lymphocytes from intrinsic and extrinsic asthmatics behave in an identical fashion, but differ significantly from lymphocytes from both normal subjects and patients with fixed airways obstruction (chronic bronchitis). It is suggested that there is a common immunological mechanism in extrinsic asthma and intrinsic asthma.

Bronchoalveolar lavage (BAL) mast cells provide a useful tool with which to screen potential therapeutic agents for human airway diseases. This study was therefore designed to compare the activity of nedocromil sodium and sodium cromoglycate in inhibiting anti-IgE induced histamine release from human mast cells obtained by BAL and from dispersed lung (DL) fragments. After 10 min pre-incubation with the mast cell preparations, both drugs displayed greater inhibition of histamine release from BAL than from DL mast cells. Under optimal conditions of 10 min pre-incubation with BAL and none with DL mast cells, nedocromil sodium showed significantly more activity than sodium cromoglycate on both BAL and DL mast cells.

The differential diagnosis of asthma in farm workers is between a type I hypersensitivity to a pollen or dust allergen and a type III hypersensitivity to mould antigens. We describe asthma and rhinitis, and not farmer's lung, in a farming population due to the non-pyroglyphid grain storage mite. Before a diagnosis of farmers' lung due to mouldy hay is made in any patient whether or not precipitins to Micropolyspora faeni are present, skin tests for storage mite should be made. If these are positive a diagnosis of 'barn allergy' should be considered and a trial of sodium cromoglycate be given.

After ingestion of food, immune complexes containing food proteins as antigens were demonstrated in the serum of normal and atopic subjects. In the atopic patients challenged with the food to which they were sensitive, abnormal levels were detected. The same atopic patients pretreated with oral sodium cromoglycate had less antigen entry, diminished immune-complex formation, and no atopic symptoms. Tests for antigen entry and immune-complex formation after oral challenge may permit objective assessment of food allergy and may show whether drugs such as oral sodium cromoglycate are likely to benefit individual patients.

Nedocromil sodium and sodium cromoglycate inhibited histamine release from rat peritoneal mast cells. Tachyphylaxis was observed with both drugs. The 2 compounds were extremely selective in their action, being less active against peritoneal mast cells from the hamster and completely ineffective against mast cells from the mouse. Human basophil leucocytes, tissue mast cells of the guinea-pig and rat intestinal mast cells were also unresponsive. Both drugs inhibited immunological histamine release from human pulmonary mast cells obtained by bronchoalveolar lavage (BAL) and, less effectively, from lung parenchyma. Nedocromil sodium was about 1 order of magnitude more potent than sodium cromoglycate in each case. Tachyphylaxis was observed with the dispersed lung, but not with the cells obtained by BAL, and the degree of inhibition varied inversely with the magnitude of the secretory response. The possible clinical significance of these observations is discussed.

Specific IgE complexes and symptoms of asthma and eczema were produced in two allergic patients by oral challenge with food allergen. Both symptoms and IgE complexes could be prevented by pre-treatment with oral sodium cromoglycate. The IgE complexes can fix complement and may therefore provide the vehicle of the "late" responses seen in immediate hypersensitivity. The central role of gut sensitivity is emphasised by the protection afforded by sodium cromoglycate both when given acutely, against the effects of an oral challenge, and when given continuously for asthma and eczema due to food allergy.

We have studied the effect of depleting human peripheral blood lymphocytes (PBL) on plates coated with histamine-rabbit serum albumin (H-RSA) or control (E-RSA) conjugates, on the concanavalin A (Con A) response and the histamine suppression of Con A responses. Low H10-RSA-substituted conjugate depletion had little effect on [3H]-thymidine incorporation of Con A-stimulated cells compared to control (E10-RSA) conjugates and unseparated cells, but significantly increased unstimulated cell counts, therefore reducing stimulation index (SI). Highly histamine-substituted (H30-RSA) and control (E30-RSA) conjugates decreased SI in a similar way, but also decreased the [3H]-thymidine incorporation of Con A-stimulated cells. Histamine suppression of Con A responses was reduced by both E10- and H10-RSA-coated plates at suboptimal but not optimal mitogen concentrations. The induction of Con A-induced suppressor cells was unaffected by prior depletion of cells on H10- or E10-RSA conjugate-coated plates. Addition of H10- and E10-RSA to Con A cultures had a slight enhancing effect on transformation, but no effect on histamine suppression of the Con A response. Thus, whilst it is clear from other studies in vitro that functional histamine receptors are present on suppressor T cells, the results presented here show that histamine-protein conjugates do not specifically bind to histamine receptor-bearing human peripheral blood suppressor T lymphocytes.

We have studied patients with the diagnoses of asthma, eczema, and arthralgia by monitoring the formation of immune complexes containing IgE after antigen egress from the gut before and after challenge with food. Following challenge, immune complexes containing IgE, IgG, and antigen are detectable in the circulation. Their appearance correlates with the production of symptoms. The effect of sodium cromoglycate was to prevent the appearance of complexes. This was associated with absence of symptoms. It is suggested that a local IgE-mediated mechanism acts as a "trigger" for the entry of antigen and the formation of immune complexes by altering the permeability of the gut mucosa. The resulting delayed onset symptoms could be viewed as a form of serum sickness with few or many target organs affected.

Patients with well defined reactions to foods were examined for their ability to carry out both sulphur and carbon oxidation reactions by using carbocisteine and debrisoquine as probe compounds. The proportion of poor sulphoxidisers (58 of 74) was significantly greater than that of a previously determined normal control population (67 of 200; p less than 0.005). The proportion of poor carbon oxidisers was not significantly different from the controls. Metabolic defects may play a part in the pathogenesis of adverse reactions to foods.

Evidence of circulating high-molecular-weight forms of IgE was found in 16 patients with hayfever and/or atopic eczema. This finding of what appears to be complexed IgE in the serum of atopic patients may help to elucidate the aetiology of atopy.

A group of patients with cutaneous sensitivity was compared with another group with cement dermatitis who showed sensitivity to chromate. HLA typing for A and B locus antigens demonstrated a 29% incidence of B21 in the nickel sensitive group (control population 4.9%) and the antigen was not found in 16 patients with chromium sensitivity. It is suggested that this may represent a hapten specific HLA dependent immune response in man.

Human pulmonary mast cells were obtained by bronchoalveolar lavage (BAL) and by enzymic dissociation of whole lung. The cells released histamine on immunological stimulation or on exposure to a hyperosmolar environment. Cell suspensions similarly released newly generated products of arachidonic acid metabolism. Increased numbers of mast cells were recovered by BAL of asthmatic subjects and patients suffering from sarcoidosis and these cells were hyperresponsive to immunological challenge. Mast cells recovered by BAL and enzymic dissociation were differentially inhibited by antiasthmatic drugs. These data emphasize the potential role of BAL mast cells in pulmonary diseases of diverse origin.