A fishy cause of sudden near fatal hypotension.

Seafood-borne illnesses are a common but under recognised source of morbidity. We report the case of an 80-year-old woman who presented to hospital after collapsing in a restaurant following lunch consisting of mackerel fish. A detailed food history and clinical exclusion helped diagnose the condition as scombroid poisoning. The patient made a complete recovery following antihistamine therapy.

Therapeutic modulation of allergic airways disease with leukotriene receptor antagonists.

Although asthma is one of the most common chronic respiratory conditions, it often remains unrecognized and undertreated, while patients are often reluctant to comply with regular inhaled anti-inflammatory and bronchodilator therapy. Allergic rhinitis co-exists with asthma in as many as 40% of patients, and can be regarded as a continuum of the same inflammatory disease process. Corticosteroids are the 'gold standard' first-line treatment for both conditions, and have a significant impact upon underlying inflammation, symptoms and long-term outcome. Cysteinyl leukotrienes are potent airway inflammatory mediators, suggesting that treatment antagonizing their effects could play a role in disease management. In recent years, leukotriene receptor antagonists have provided a further therapeutic option in the management of allergic airways disease. These drugs are orally active, can be administered once daily, and provide a systemic approach to the management of patients with asthma and allergic rhinitis. We review the pharmacology of leukotriene receptor antagonists, their potential role in clinical practice in patients with allergic airways disease, and likely areas for further research.

Montelukast protects against nasal lysine-aspirin challenge in patients with aspirin-induced asthma.

Aspirin-induced asthma (AIA) is associated with increased production of cysteinyl leukotrienes (CysLT). Although leukotriene CysLT1-receptor antagonists improve lower airway outcomes in AIA, their effects and dose-response in the upper airway is less well documented. The present study evaluated the dose-response for montelukast (ML) against nasal lysine-aspirin challenge in patients with AIA. A total of 12 patients with a clear-cut history of AIA were randomised in double-blind cross-over fashion to receive single doses of ML 10 mg, ML 40 mg, or placebo (PL), with nasal lysine-aspirin challenge performed 12 h after dosing. Measurements of peak nasal inspiratory flow (PNIF), nasal blockage visual analogue scale (VAS) and forced expiratory volume in one second (FEV1) were made over 120 min after nasal lysine-aspirin challenge. Prechallenge values for mean+/-SEM PNIF (L x min(-1)) were not significantly different comparing all groups: ML 10 mg (132+/-10), ML 40 mg (125+/-12) and PL (132+/-11). There was no significant difference comparing the maximum % PNIF fall from baseline between screening (46+/-6) and PL (45+/-6). The maximum % PNIF fall from baseline was significantly greater with PL (45+/-6) compared to either ML 10 mg (34+/-6) or ML 40 mg (32+/-5). There was also a significantly greater mean % PNIF response over 120 min after lysine-aspirin challenge for PL (26+/-7) compared to either ML 10 mg (14+/-6) or ML 40 mg (17+/-6). There were no significant differences for the maximum or mean % PNIF fall from baseline comparing ML 10 mg and ML 40 mg. A significant increase in nasal blockage VAS score was observed between baseline and 60 min or 120 min with PL but not with ML 10 mg or ML 40 mg. There were no significant differences for either the maximum or mean % FEV1 over 120 min as change from baseline comparing all groups. A single 10 mg dose of montelukast partially protected against the local effects of nasal lysine-aspirin challenge, with no further benefit at 40 mg. Nasal lysine-aspirin challenge appeared to be a reproducible and safe method in assessing patients with aspirin-induced asthma.

Cross tolerance to salbutamol occurs independently of beta2 adrenoceptor genotype-16 in asthmatic patients receiving regular formoterol or salmeterol.

BACKGROUND: The development of tolerance following the use of long acting beta(2) agonists in asthmatic patients with either the homozygous arginine (Arg-16) or glycine (Gly-16) genotypes is poorly documented, especially in relation to the acute reliever response to salbutamol in constricted airways. A study was undertaken to evaluate the Arg-16 and Gly-16 genotypes for the acute salbutamol response following methacholine bronchial challenge between the first and last doses of formoterol (FM) and salmeterol (SM) combination inhalers. METHODS: Parallel groups of 10 matched homozygous Arg-16 and 10 homozygous Gly-16 patients completed a randomised, double blind, double dummy, crossover study. Following a 1 week washout period, patients received treatment for 2 weeks with either inhaled budesonide (BUD) 200 micro g + FM 6 micro g (two puffs twice daily) or inhaled fluticasone propionate (FP) 250 micro g + SM 50 micro g (one puff twice daily). After washouts and randomised treatments (1 hour after the first and last inhalation) a methacholine challenge was performed followed by salbutamol 200 micro g, with recovery over 30 minutes (the primary outcome). RESULTS: Washout values for forced expiratory volume in 1 second (FEV(1)), methacholine hyperreactivity, and salbutamol recovery were similar for both treatments and genotypes. Pre-challenge FEV(1) values for both genotypes did not differ significantly between the first and last doses of each treatment. Salbutamol recovery as mean (SE) area under the 30 minute time-response curve was significantly delayed (p<0.05) equally in both genotype and treatment groups. There were no differences in salbutamol recovery in either genotype or treatment group. CONCLUSION: Acute salbutamol recovery in methacholine constricted airways was significantly delayed to a similar degree in both genotypes due to cross tolerance induced by FM or SM.

A placebo-controlled evaluation of butterbur and fexofenadine on objective and subjective outcomes in perennial allergic rhinitis.

BACKGROUND: There are presently no placebo-controlled data regarding the effects of butterbur (BB) on subjective and objective outcomes in patients with perennial allergic rhinitis. OBJECTIVE: We performed a placebo-controlled evaluation of the effects of BB and fexofenadine (FEX) on subjective and objective outcomes in patients with perennial allergic rhinitis. METHODS: Sixteen patients with perennial allergic rhinitis and house dust mite sensitization were randomized in double-blind cross-over fashion to receive for 1 week either BB 50 mg twice daily, FEX 180 mg once daily and placebo (PL) once daily, or PL twice daily. The peak nasal inspiratory flow (PNIF) response to adenosine monophosphate (AMP) challenge administered as a single 400 mg/mL dose was measured over a 60-min period after challenge, and domiciliary total nasal symptom score was recorded. RESULTS: Pre-challenge values for mean+/-SEM PNIF (L/min) were not significantly different comparing all groups; BB (138+/-8), FEX (140+/-9), and PL (138+/-8). The maximum % PNIF fall from baseline after nasal AMP challenge was significantly attenuated (P<0.05) compared to PL (46+/-3), with BB (34+/-3) and FEX (39+/-3). The area under the 60-min time-response curve (%.min) was also significantly attenuated (P<0.05) compared to PL (1734+/-156), with BB (1052+/-258) and FEX (1194+/-161). There was also a significant reduction (P<0.05) in total nasal symptom score with BB (1.8+/-0.4) and FEX (1.8+/-0.4), compared to PL (2.8+/-0.5). There were no significant differences between BB and FEX for any outcomes. CONCLUSION: BB and FEX, in comparison to PL, were equally effective in attenuating the nasal response to AMP and in improving nasal symptoms, highlighting a potential role for BB in the treatment of allergic rhinitis.

Comparative effects of desloratadine, fexofenadine, and levocetirizine on nasal adenosine monophosphate challenge in patients with perennial allergic rhinitis.

Summary Background There are no data directly comparing the relative efficacy of modern H(1)-antihistamines in allergic rhinitis using nasal provocation challenge. Objective We elected to study the comparative effectiveness of usual clinically recommended doses of desloratadine (DES), fexofenadine (FEX), and levocetirizine (LEV), on nasal adenosine monophosphate (AMP) challenge in patients with perennial allergic rhinitis (PAR). Methods 16 patients with PAR were randomized in double-blind cross-over fashion to receive single doses of DES 5 mg, FEX 180 mg, LEV 5 mg, or placebo (PL), with nasal AMP challenge performed 12 h after dosing. Measurements of peak nasal inspiratory flow (PNIF) were made over 60 min after nasal AMP challenge. Results Pre-challenge values (mean+/-SEM) for PNIF (L/min) were not significantly different comparing all groups; DES (129+/-9), FEX (128+/-11), LEV (128+/-13), and PL (128+/-12). The maximum % PNIF fall from baseline over 60 min after nasal AMP challenge was significantly attenuated (P<0.05) compared to PL (50+/-4), with DES (32+/-5), FEX (36+/-4), and LEV (36+/-4). The area under the 60-min time-response curve (%.min) was also significantly attenuated (P<0.05) compared to PL (2110+/-268), with DES (1126+/-285), FEX (1225+/-255), and LEV (1261+/-194). There were no significant differences between the three H(1)-antihistamines for any outcomes. Conclusion DES, FEX, and LEV were equally effective in attenuating the response to nasal AMP challenge. However, further long-term studies will be required to study their comparative effects on nasal symptoms, quality of life, as well as on nasal inflammatory cells.