Repeated histamine inhalation tests in asthmatic patients

Histamine inhalation tests were performed in 12 asthmatic patients using a 2-min tidal breathing inhalation technique. The tests were repeated on separate days with 30-, 60-, and 120-min intervals between inhalation tests. On another day the inhalation tests were repeated four times with 40-min intervals between tests. The geometric mean provocative concentrations of histamine needed to cause a 20% fall in forced expiratory volume in 1 sec (PC₂₀) for the group on the latter study day were 1.67, 1.57, and 1.55 mg/ml (p > 0.25) indicating no change in sensitivity to inhaled histamine with repeated testing. The results suggest that cumulative dose-response curves for drugs potentially affecting the airways or antagonizing histamine can be constructed within 1 day using histamine inhalation tests. The data also suggested that an individual PC₂₀result may be sensitively assessed by comparing it to a ±2 SD range from the mean of a series of control or placebo PC₂₀ values.     

Effect of disodium cromoglycate on antigen-evoked histamine release from human skin

The effect of disodium cromoglycate (DSCG) on antigen-evoked histamine release from IgE-sensitized human skin in vitro has been studied using breast skin from six donors. Concentrations of DSCG ranging from 10–200 μM did not produce any consistent effect on histamine release, the results ranging from moderate inhibition to moderate enhancement. With higher concentrations of DSCG (400–500 μM) enhancement of release occurred in nearly all experiments. Variation of antigen concentration did not modify the response to DSCG. These results do not support the possibility that DSCG may be effective in the treatment of immediate hypersensitivity reactions in human skin.     

Effect of sodium cromoglycate on asthmatic reactions to environmental temperature changes

Immediate asthmatic reactions, with falls in FEV₁ of 16–42.5% were elicited by exposure in a cold room at 3°C in five out of eight subjects with histories of asthma provoked by falls in environmental temperature. In four of the subjects pretreatment by inhalation of sodium cromoglycate gave complete inhibition of the asthmatic reaction in two, partial inhibition in one and had no effect in one case.     

Topical levocabastine protects better than sodium cromoglycate and placebo in conjunctival provocation tests

Levocabastine is a new H1 receptor blocking antihistamine which is intended for topical use in the treatment of allergic conjunctivitis. The protective effect of the drug in conjunctival provocation test (CPT) was evaluated in a double blind study of 25 children aged 9-17 years with confirmed pollen allergy. One drop of levocabastine, cromoglycate or placebo was instilled into the conjunctival sac of both eyes. After 15 min CPT was performed, starting with 320 BU of pollen extract. The allergen dose was increased every 10 min in half 10-log steps in the right eye until a positive reaction occurred, or the top dose 320,000 BU was reached. The lowest dose resulting in a positive CPT reaction, i.e. at least 50% of the conjunctiva with erythema, was defined as the allergenic threshold dose (ATD). Pretreatment with levocabastine resulted in a median ATD of 32,000 BU, compared with 10,000 after cromoglycate (P less than 0.001) or placebo (P less than 0.01). Levocabastine was also superior in reducing subjective itch in the eyes. Determination of the ATD can be used as a relatively quick assessment of drugs intended for the treatment of allergic conjunctivitis.     

The effects of inhaled beclomethasone dipropionate (Becotide) and sodium cromoglycate on asthmatic reactions to provocation tests

A comparison was made between the effects of prior inhalation of sodium cromogly-cate or beclomethasone dipropionate on immediate, late and dual asthmatic reactions to provocation challenge tests with a range of allergens. Whereas sodium cromoglycate inhibited immediate and dual asthmatic reactions, beclomethasone dipropionate had no effect on immediate asthmatic reactions, but consistently inhibited late asthmatic reactions.     

The effect of sodium cromoglycate on analgesic-induced asthmatic reactions

The onset of increased airways obstruction after analgesic ingestion by asthmatics with analgesic idiosyncrasy suggests an immediate type 1 allergic response. The effect of sodium cromoglycate (DSCG) on this response was assessed in nineteen patients with this syndrome. DSCG prevented asthmatic attacks in only three patients, all non-atopic, suggesting that analgesic idiosyncrasy is not an allergic disorder. The effectiveness of DSCG in preventing asthmatic attacks in some patients with analgesic idiosyncrasy would suggest that a trial of this preparation should be undertaken before commencing continuous corticosteroid therapy.     

Effect of chinese herbal medicines and disodium cromoglycate on IgE-dependent histamine release from mouse cultured mast cells

We examined the effect of anti-allergic Chinese herbal medicines such as Ma-Xing-Gan-Shi-Tang (MXGST) and Xiao-Feng-San (XFS), and a mast cell stabilizer, disodium cromoglycate (DSCG) on histamine release from mouse cultured mast cells. The mast cells (ILMCMC) were obtained by culturing mouse bone marrow cells for 3–6 weeks in the presence of IL-3. Some of the cells (FMCMC) were further cultured with a fibroblast cell line, 3T3 for 3 weeks. FMCMC had safranin-positive granules and released histamine in response to compound 48/80, whereas ILMCMC failed to do so. MXGST and XFS at 4–40 μg/ml inhibited IgE-dependent histamine release from ILMCMC but not from FMCMC. On the contrary, DSCG at 10−4 M inhibited histamine release from FMCMC but not from ILMCMC. Chinese herbal medicines and DSCG may act on different types of mast cells.     

Delivery of sodium cromoglycate by pressurized aerosol

Sodium cromoglycate (SCG) has recently been formulated as a pressurized aerosol. Twenty-five asthmatic outpatients taking SCG via the Spinhaler were studied in a double-dummy, double-blind cross-over trial in which subjects took Spincaps containing 20 mg of SCG for 2 months, and for the alternate 2 months were treated with SCG aerosol delivering 1 mg/actuation. There was no evidence of clinical deterioration occurring during the period on aerosol SCG. During this period however cough frequency was significantly lower and when data for the 8-13 and 14-46 year age groups were analysed separately, this decrease was seen to be confined to the younger group. Furthermore, this group but not the adults, showed a significant improvement in morning peak expiratory flow rate. We conclude that the aerosol preparation of SCG is a useful alternative to delivery by Spinhaler for patients who are able to coordinate, and that it may have special advantages for children.     

Sodium cromoglycate in histamine and methacholine reactivity in asthma

The effect of increasing concentrations of inhaled sodium cromoglycate (SCG) (2, 10, 20 and 40 g/l) on histamine and methacholine bronchial reactivity was studied in nine patients with extrinsic bronchial asthma. The responses to histamine and methacholine were expressed in terms of provocative concentrations producing 20% fall in the FEV₁ (PC₂₀)- The PC₂₀ for histamine and methacholine was unaffected by all the concentrations of SCG used in the study. These results suggest that the effect of SCG on the bronchial smooth muscle or on the muscarinic receptors is minimal.     

Double-blind crossover study comparing sodium cromoglycate, reproterol, reproterol plus sodium cromoglycate, and placebo in exercise-induced asthma

Sixteen patients were included in the analysis of this double-blind crossover study comparing the effect of sodium cromoglycate, reproterol, sodium cromoglycate plus reproterol, and placebo in exercise-induced asthma. Both the sodium cromoglycate and the reproterol-containing treatment significantly inhibited exercise-induced asthma. The best protection is effected by the combination of sodium cromoglycate and reproterol. A synergistic effect of both medications could not be confirmed statistically so that their combined effect is simply additive.     

Bronchial mucosal structure after histamine inhalation

Previous studies have shown an increased number of inflammatory cells and an increased level of hyaluronan in the bronchoalveolar lavage (BAL) fluid, 24 h after the inhalation of histamine. In the present report, the influence of histamine inhalation on the bronchial mucosa was, therefore, investigated in 20 subjects. Scanning electron microscopy (SEM) revealed that small areas of the mucosal surface were altered or lacked cilia more frequently in the bronchial biopsies taken 24 h after the inhalation of histamine than in the control biopsies. In contrast, light and transmission electron microscopy revealed no increase in epithelial damage and no changes in the subepithelial morphology. The results indicate that inhalation of histamine does not significantly alter the structure of the bronchial mucosa, which means that bronchial biopsies can be taken for routine morphological examination within 24 h after a histamine test. When using the biopsies in research, one should consider the possible influence of the histamine test.     

Monitoring of maximum expiratory peak flow rates and histamine inhalation tests in the investigation of occupational asthma

A 49 year old carpenter developed asthma after he was employed in a new workshop. Specific inhalation tests carried out in a laboratory with presswood sawdust and the different glues used at work were negative. Monitoring peak expiratory flow rates (PEFR) at work revealed a progressive fall on consecutive days with recovery after periods off-work. Histamine inhalation tests showed a definite increase in bronchial hyperexcitability after working periods. Monitoring of PEFR in conjunction with histamine inhalation tests can thus help in confirming occupational asthma.     

Intestinal permeability in irritable bowel syndrome. Effect of diet and sodium cromoglycate administration

We studied 14 patients with irritable bowel syndrome for the presence of increased intestinal permeability to food antigens and their responses to diet with and without disodium cromoglycate. After a standardized oral challenge with cow milk, serum beta-lactoglobulin was increased above control values in three patients. This finding did not correlate with response to hypoallergenic diet or treatment with disodium cromoglycate for 3 weeks. However over 50% of patients improved after diet with and without DSCG (2/5 on diet only and 5/7 with disodium cromoglycate of 12 evaluable cases). Since only two patients had elevated serum IgE levels, our results suggest that intolerance rather than hypersensitivity to foods may play a role in the disease. The tests we used to identify immunologic mechanisms could not predict which patients would do better on the diet and/or the drug.