Bibliothek

Notizen: This case presentation describes a young woman who developed generalized urticaria after receiving the human anti-RhD(D) preparation, WinRho, intravenously. Allergy skin tests and the radioallergosorbent test (RAST) for IgE antibodies to the human anti-D immunoglobulin preparation were positive. Further studies using high-pressure liquid chromatography and protein A column chromatography implicated a nonimmunoglobulin low-molecular-weight contaminant. This case report illustrates an allergic reaction to a highly purified human immunoglobulin preparation, and demonstrates approaches to assessment of such a reaction.

Notizen: Airway provocation tests such as the methacholine inhalation test or histamine inhalation test are commonly used for the quantitation of the airway hyperresponsiveness characteristic of asthma. The reduced provocation concentration of methacholine (PC20M) or histamine (PC20H) required to produce a 20% fall in FEV1 may be due to a number of underlying mechanisms, particularly airway mucosal inflammation. The characteristic eosinophilic mucosal inflammation of asthma apparently contributes to hyperresponsiveness through an enhancement of neuromuscular responses to methacholine and histamine in addition to increased responses to various stimuli through the release of inflammatory mediators. Methacholine airway hyperresponsiveness and airway mucosal inflammation usually are both present in asthma, but these findings do not always coexist. Patients with chronic cough and a normal PC20M may have eosinophilic airway inflammation; treatment with inhaled steroid can reduce the cough, sputum production and the number of eosinophils and mast cells in the sputum. Airway responses in provocation tests with histamine or methacholine seem to depend, at least in part, upon direct stimulation of airway smooth muscle and have been referred to as direct tests of airway responsiveness. In contrast, tests with stimuli such as allergen or adenosine, which elicit mediator release, have been referred to as indirect tests of airway hyperresponsiveness. There are complex interrelationships and an interdependence between methacholine airway hyperresponsiveness and airway inflammation; progress in the assessment of underlying mechanisms has been greatly enhanced by biochemical, immunologic and pathologic-type measurements in various types of specimens from the airways to directly assess the pathogenetic processes. Some features of asthma such as exercise and nocturnal symptoms correlate well with the level of methacholine airway hyperresponsiveness. Conversely, the occurrence of cough or the occurrence of asthmatic attacks are not predicted accurately by a measurement of methacholine airway hyperresponsiveness. The assessment of asthma severity seems to require the consideration of a number of types of parameters including the level of ongoing symptoms, need for inhaled B2-agonist, frequency and severity of acute attacks, level of treatment required to maintain control of asthma, baseline airflow rates and tests of variability of airflow such as serial measurements of variability of PEF or of PC20M. Measurement of the PC20M is a sensitive test of changes in airway responsiveness and can be useful in serial measurements. In some instances, airway reactions can be identified by serial measurements of PC20M but not by serial measurement of airway calibre such as the FEV1.

Notizen: In recent studies, sputum smear cell counts were found to be reproducible and usefully applied to research in asthma and other airway conditions. However, cell definition on the smears is poor, and the procedure is tedious and has limited utility. The objective of this study is to improve the methods of sputum examination. The subjects used in this study were people with bronchitis or asthma from whom sputum could be obtained. By inverted microscopy, portions of fresh sputum were selected to exclude salivary contamination. These portions were exposed to different volumes of dithiothreitol for varied lime intervals. We used the resulting cell suspensions to perform total cell counts and prepare cytospins for differential cell counts and immunohistochemical stains for GM-CSF, EG2, TNFα and IL-8. Cytospins were compared with smears for differential cell counts on the same sputum specimens. Excellent cell dispersion and definition in cytospins could be observed. The time required for differential cell counting on cytospins was reduced and cytospin counts were more reproducible than smears. Greater duration of treatment of sputum with dithiothreitol tended to increase total cell counts and significantly decreased EG2 staining hut had no effect on differential cell counts or the cytokine cell components. Therefore the proposed method of sputum examination involving cell dispersion and use of cytospins overcomes a number of the disadvantages of the examination of smears.

Notizen: Non-allergic bronchial hyper-reactivity is a feature of most patients with asthma. We have measured non-allergic bronchial reactivity to inhaled histamine and methacholine in thirteen asthmatic subjects before and after allergen inhalation in the laboratory. The allergen inhalation produced mild early asthmatic responses (19–40% FEV1 fall) in all thirteen, additional definite late asthmatic responses (17–29% FEV1 fall) in four, and equivocal late asthmatic responses (5–11% FEV1 fall) in five. Following allergen inhalation, non-allergic bronchial reactivity increased in seven for up to 7 days. The seven included all four with definite late asthmatic responses and three of the five with equivocal late asthmatic responses. We conclude that allergens make asthma worse, partly through non-allergic mechanisms, and that avoidance of allergens is important in reducing non-allergic bronchial hyper-reactivity.

Notizen: Five nurses aged 31–55 years old had a history of asthmatic symptoms after being exposed to psyllium that they prepared and distributed to patients. They had been nurses for 9–20 years and had reported asthmatic symptoms related to work in the past 3–12 months. They reported symptoms of rhinoconjunctivitis and all were atopic but only one had a previous history of asthma. Four of the five tested subjects had an immediate skin reaction to a commercial psyllium extract. All had IgE antibodies to psyllium. At the time that they were investigated, four out of the five had a significant increase in bronchial responsiveness to methacholine (PC 20 〈8 mg/ml). Inhalation challenges with psyllium caused isolated immediate (one subject) and dual reactions (three subjects). One subject exposed for only 1 min to the psyllium powder experienced a severe immediate bronchospastic reaction, which required intubation for 3 h with complete functional recovery thereafter. This experience illustrates the precautions necessary, with the inclusion of a cautious dose-response approach, even with an‘occupation-type’challenge in the laboratory.

Notizen: Oxatomide is an H1, receptor antagonist, which also inhibits antigen-induced mediator release from sensitized mast cells and basophils. The effects of ingested oxatomide (30 mg/capsule) were compared with those of chlorpheniramine (5 mg/capsule) in a double-blind non-crossover study in two groups of twenty-five subjects with ragweed pollen-induced hay fever during the pollen season. Oxatomide or chlorpheniramine was started when symptoms became troublesome and was used in a dose of two to four capsules daily according to severity. Other medications were added, in a standardized way, if hay fever symptoms were not controlled by the test capsules. Forty-one subjects completed the study; nineteen received oxatomide and twenty-two chlorpheniramine. Mean symptom scores, number of test capsules and number of doses of additional medication were not significantly different between the two groups. Drowsiness was reported by subjects in both groups but was worse in the chlorpheniramine group (P〈0.05). We conclude that, in the studied doses, oxatomide is as effective for the treatment of allergic rhinoconjunctivitis as chlorpheniramine and produces less drowsiness.

Notizen: Local exudation at the sites of allergic and histamine-induced cutaneous reactions, was measured with an in vivo double-labelling procedure, based upon local serial simultaneous measurements of indium-113 m (113mIn) labelled transferrin and technitium-99m labelled red blood cells (99mTc RBC). Analyses depended upon the reaction index i.e. comparison of the ratio of 113mIn/99mTc counts at the reaction site with the ratio of 113mIn/99mTc at the corresponding unreacted site in the skin of the opposite arm.Reaction indices were initially significantly elevated at the sites of histamine and allergic reactions. After the first hour, there was a progressive reduction at histamine sites indicating a tapering of the local accumulation of indium-labelled transferrin. By contrast allergic reaction sites showed a continuing increase in the reaction index after one hour. During the first hour the curves were comparable, but they diverge and were significantly different after one hour (0.05 〉 P 〉 0.02). This is consistent with the known occurrence of late cutaneous responses at the site of allergic but not histamine reactions.

Notizen: Chronic eosinophilic rhinosinusitis underlies a range of respiratory disorders including nasal polyposis. Surgical and medical methods are used to control polyps, with topical steroids commonly being used for their anti-inflammatory properties. Fluticasone propionate nasal drops (FPND) is a formulation developed specifically for an effective and well tolerated corticosteroid treatment of nasal polyposis.〈section xml:id="abs1-2"〉〈title type="main"〉ObjectivesTo assess efficacy and tolerability of FPND in the treatment of bilateral nasal polyposis in adults.〈section xml:id="abs1-3"〉〈title type="main"〉MethodsThis multicentre, randomized, parallel-group study compared FPND 400 μg once daily (o.d.) with placebo for 12 weeks in adult patients with mild to moderate bilateral polyposis. The primary efficacy endpoint was visual assessment of polyp size by the physician at monthly clinic visits. Nasal blockage, rhinitis, peak nasal inspiratory flow (PNIF), olfactory function and requirement for polypectomy were also assessed at visits. The patients kept diary card records of symptoms, PNIF, and use of rescue antihistamine. Additional safety data were provided by a 12-week open extension, when all patients received FPND 400 μg o.d.〈section xml:id="abs1-4"〉〈title type="main"〉ResultsAfter 12 weeks double-blind treatment with FPND (n = 52) or placebo (n = 52), polyp size was reduced in 27% and 16% of patients, respectively; clinical reduction of nasal blockage significantly favoured FPND over placebo (55% vs 22%; P = 0.002), and clinic PNIF had increased significantly with FPND (by 52 L/min vs −3 L/min for placebo; P 〈 0.001). Diary card measurements showed significant benefits of FPND vs placebo for daily PNIF, nasal blockage, rhinitis and use of loratadine rescue medication. Both treatments were well tolerated and no serious adverse events occurred during randomized treatment. Epistaxis was more frequent with FPND than placebo but was generally mild and did not result in withdrawals. Mean serum cortisol levels did not change significantly with either treatment.〈section xml:id="abs1-5"〉〈title type="main"〉ConclusionThis study showed FPND 400 μg o.d. to be an effective and well tolerated treatment for bilateral nasal polyposis in adults.