Vitamin D, asthma prevalence and asthma exacerbations: a large adult population-based study.

BACKGROUND: The impact of low vitamin D status on asthma, asthma morbidity and control is unclear. We aimed to investigate in adults the associations between serum 25-hydroxyvitamin D level and prevalent asthma as well as asthma exacerbations. METHODS: A cohort of Israeli adults aged 22-50 years with documented vitamin D status were extracted from Clalit Health Services (HMO) between July 1, 2008 and July 1, 2012. Among this population, those with physician-diagnosed asthma and asthma exacerbations were identified. Asthma exacerbations were defined as any of the following: prescription for oral corticosteroids, >5 prescriptions for short acting beta agonists and more than four visits to a physician for asthma. Logistic regression models assessed the associations between vitamin D and both asthma and asthma exacerbations. RESULTS: Approximately 308 000 members with at least one vitamin D measurement were included in the cohort. Among them, 6.9% (21 237) had physician-diagnosed asthma vs 5.7% in the general population. Serum 25-OHD levels across both groups were similar. However, among those with vitamin D deficiency, the odds of having an exacerbation were 25% greater compared to those with levels in the normal range. This association remained significant after controlling for known confounders. CONCLUSION: While there was no significant association between vitamin D status and physician-diagnosed asthma, there was a strong association with asthma exacerbations. The presented evidence supports vitamin D screening in the subgroup of asthmatics that are uncontrolled and experience recurrent exacerbations.

Medical clowns ease anxiety and pain perceived by children undergoing allergy prick skin tests.

BACKGROUND: Intervention of medical clowns (MC) during various medical procedures performed in children has been used to relieve anxiety and pain. Their role in allergy skin testing has never been evaluated. OBJECTIVE: To evaluate whether MC can diminish pain and anxiety perceived by children undergoing allergy skin prick tests (SPT). METHODS: In a prospective, randomized, controlled, and blinded study, children undergoing SPT were or were not accompanied by MC. All parents and children ≥8 years completed the State-Trait Anxiety Inventory (STAI) before and after SPT. Videotapes recorded during the procedure were scored for anxiety (m-YPAS) for all children and for pain (FLACC) for children 2-7 years old by a psychologist who was unaware of the MC's presence. After SPT, children ≥8 years completed a visual analog score (VAS) for pain. RESULTS: Ninety-one children (mean age 8.2 years, M/F = 54/37) were recruited of whom 45 were accompanied by clowns. A significant reduction in state-STAI was found in the clowns group, in both parents and children, when compared with the regular group (26.9 ± 6.6 and 32.3 ± 10.0; P = 0.004, and 27.1 ± 4.2 and 34.3 ± 7.6; P = 0.002, respectively). Both m-YPAS and FLACC were reduced in the clowns group compared with the regular one. In the clowns group, m-YPAS positively correlated with both VAS and FLACC (P = 0.000 and 0.002, respectively). m-YPAS was positively correlated with FLACC in the regular group (P = 0.000). CONCLUSION: Medical clowns significantly decrease the level of anxiety perceived by both children undergoing allergy SPT and their parents, as well as the pain perceived by young children.

Bee venom immunotherapy - how early is it effective?

BACKGROUND: Although the effectiveness of venom immunotherapy (VIT) in bee venom (BV) allergy has been well established over the past 30 years, no previous study has demonstrated its efficacy immediately after reaching the maintenance dose (MD). We examined the effectiveness of bee VIT within a week after the MD was achieved. METHODS: Bee venom allergic patients underwent conventional or rush VIT. Within 1 week after reaching the 100 microg MD, patients were challenged with a live bee sting. RESULTS: Seventy-nine of 107 patients (73.8%) who reached the MD agreed to be challenged. Seventy patients (88.6%) tolerated the sting uneventfully. Four patients (5.1%) developed a very mild local transient rash and continued to receive the 100 microg MD. In five patients (6.3%), the sting resulted in a mild-moderate systemic reaction. In four of these, the MD was increased to 200-250 microg. All four patients uneventfully tolerated a repeated sting that was performed within 1 week after achieving the increased MD in three patients and after 14 months in the fourth patient. CONCLUSIONS: Bee VIT is effective in most patients immediately after the conventional MD has been reached. In the minority of patients who are not protected with this dose, an increased MD will provide appropriate protection immediately after it is achieved. Thus, the dosage of the MD seems to be the major factor affecting protection from re-stings rather than the accumulated venom dose or the duration on the MD.

Prevalence of asthma in a large group of Israeli adolescents: influence of country of birth and age at migration.

BACKGROUND: The occurrence of asthma has geographic variations and is lower in developing compared with industrialized countries. Both environmental and genetic factors may influence its prevalence. We aimed to evaluate the importance and effect of immigration (country of birth and age at immigration to Israel) on the prevalence of asthma in a large group of Israeli adolescents. METHODS: Computerized medical records of 17-year-old adolescents, who underwent routine examination before military recruitment, were studied. The sample comprised both native-born Israelis (NBI) and immigrants from Ethiopia, the Former Soviet Union (FSU), and Western countries (WC). Asthma was defined as clinical symptoms and signs compatible with the disease accompanied by abnormal spirometry or documented chronic use of inhaled steroids. RESULTS: Our cohort consisted of 1 466 654 adolescents, including 1 317 556 (89.8%) NBI and 149 098 (10.2%) immigrants. The prevalence of asthma at age 17 was higher in NBI compared with Ethiopian immigrants [4.7% (61 921) vs 2.6% (418), respectively, P < 0.0005], lower compared with immigrants from WC [5.6% (2177), P < 0.0005], and similar to immigrants from the FSU. Further analysis of the association between age at immigration and the risk for developing asthma showed that the younger immigrants from the FSU and Ethiopia arrived to Israel, the higher their prevalence of asthma at the age of 17 was. CONCLUSIONS: Both environmental and genetic factors seem to influence the prevalence of asthma in 17-year-old adolescents. However, the higher risk for developing asthma associated with young age of immigration points toward an environmental predominance.

Effective desensitization protocol to paclitaxel following hypersensitivity reaction.

The objective of this paper is to describe our experience with a desensitization protocol to paclitaxel using the original paclitaxel solution in patients following severe hypersensitivity reactions. A retrospective review of 75 consecutive patients with ovarian cancer who received intravenous paclitaxel-based chemotherapy between January 1996 and May 1998 at the Gynecologic Oncology Unit at Meir Hospital-Sapir Medical Center, Kfar-Saba, Israel. All patients who developed a hypersensitivity reaction to paclitaxel were treated with a desensitization protocol. The protocol included serial 10-fold dilutions (up to 1:100,000) of the actual paclitaxel infusate, delivered in successive volumes of 1, 2, 4, and 8 ml. These escalating doses of paclitaxel were given intravenously at 15-min intervals for each dilution. Following administration of the last diluted dose, the patient received a 1-ml dose of the undiluted solution. If no side effects were recorded, the rest of the actual dose was delivered at a 3-h infusion rate. Vital signs were monitored and recorded throughout the course of treatment. Six patients with a previous paclitaxel-associated hypersensitivity reaction were successfully treated with the desensitization protocol. In conclusion, we demonstrate that the desensitization protocol is feasible and safe without compromising cytotoxic activity. Our results show that this strategy is a reasonable choice in this clinical setting and potentially avoids paclitaxel-based regimen interruption.

Insect sting-inflicted systemic reactions: attitudes of patients with insect venom allergy regarding after-sting behavior and proper administration of epinephrine.

BACKGROUND: Patients with insect venom allergy are at higher risk for development of a recurrent systemic reaction after re-sting. This risk significantly decreases with venom immunotherapy. Patients with insect venom allergy should be able to distinguish a life-threatening systemic reaction from all other various reactions after an insect sting. Accidental epinephrine injection by EpiPen has been reported in the past. Therefore patients with venom allergy should also be well trained in self-administration of their epinephrine when needed. OBJECTIVE: Our objective was to assess patients' attitudes regarding after-sting behavior and their capability to correctly self-administer the epinephrine autoinjector. METHODS: All patients with venom allergy attending our allergy unit either before commencement of or during venom immunotherapy answered a questionnaire addressing various aspects of their intended after-sting behavior. Using an EpiPen trainer device, patients' performance of EpiPen self-administration was evaluated. RESULTS: Ninety-six patients participated in the study. Seventy-six of them were equipped with an EpiPen device. Less than 30% of these patients carried it at all times. After re-sting, 50 (54%) patients planned to wait for the development of other symptoms before taking any further action. Twenty-two percent of the patients said that after re-sting they would immediately administer their EpiPen. Proper EpiPen administration technique was demonstrated by 44% of the patients. Having not reached the maintenance dose correlated with a better compliance with carrying of the EpiPen. EpiPen instruction provided by an allergist correlated with a better EpiPen administration technique by the patients. CONCLUSION: Many patients with venom allergy hold wrong ideas about after-sting behavior. Compliance with carrying EpiPen at all times and the ability to correctly administer it are both poor in most patients. Thorough and probably repeated instruction, both written and oral, provided by knowledgeable physicians is mandatory.

Maintenance venom immunotherapy administered at 3-month intervals is both safe and efficacious.

BACKGROUND: Maintenance venom immunotherapy (MVIT) is usually administered to patients with venom allergy at 4- to 6-week intervals for at least 3 to 5 years. The small number of studies assessing the possibility of extending the maintenance interval (MI) included either too small a population and patients with only vespid and not bee venom (BV) allergy or relied on reaction to field stings only. OBJECTIVE: We sought to assess the safety and efficacy of MVIT given at 3-month intervals to a large population of patients allergic to both yellow jacket venom and BV. METHODS: In all patients undergoing venom immunotherapy, MI was gradually extended to 3 months. Systemic reactions (SRs) to immunotherapy injections or to field stings were regularly recorded. Some of the patients were also deliberately sting challenged during the 3-month interval. Patients discontinuing MVIT were interviewed regarding their responses to field re-stings, and in some of them, an in-hospital sting challenge was performed. RESULTS: One hundred sixty patients mostly allergic to BV were enrolled in the study. Failure to reach the 3-month interval was observed in 6 (3.8%) patients, originating in failure to reach the full maintenance dose in most of them. SRs to MVIT administered at 3-month intervals were observed in 2.6% of the patients. One of 36 patients who experienced a field sting during the 3-month interval had an objective mild SR (2.8%). Two (4.5%) of 44 patients who were deliberately stung during the 3-month interval had mild SRs. After discontinuation of MVIT, 2 (8.3%) of 24 patients who experienced a field sting had an SR. Both were allergic to yellow jacket venom. Three to 82 months after discontinuation of MVIT, 22 patients allergic to BV were sting challenged. Only one (4.5%) patient had a mild objective SR. CONCLUSIONS: The conventional 4- to 6-week MI can easily be extended to 3 months in most patients without any adverse events. MVIT given at a 3-month interval is safe and effective while being administered, as well as after its discontinuation. This fact should be applied to almost every patient allergic to insect venom.

Cost-effectiveness of in-hospital evaluation of patients with syncope.

In order to assess the utility of in-hospital evaluation of syncope we reviewed the records of 134 consecutive patients admitted within 6 h of a true syncopal episode, and obtained follow-up information on 130 of them 3 years later. All threatened cardiac rhythm and conduction disturbances were detected on the initial ECG recording. Prolonged ECG monitoring did not contribute additional diagnoses. Other diagnostic tests and procedures performed during the mean 7.5-day hospital stay only confirmed the findings of the initial history, physical and ECG examinations. Diagnostic evaluation was followed by therapeutic intervention in only 33 patients (24%); all interventions were clearly mandated by the initial admission evaluation. There were no cases of sudden death and no association between causes of death, the index syncope episode or prior history of syncope. We therefore propose that the evaluation of patients presenting within hours of a syncopal episode include only history taking, physical examination and the initial ECG recording. Further in-hospital evaluation should be limited to confirming initial positive findings. This approach may allow an estimated 85% reduction in costs involved in the management of similar patients, with probable negligible adverse effects on prognosis.

Deliberate bee sting challenge of patients receiving maintenance venom immunotherapy at 3-month intervals.

BACKGROUND: A large part of the cost and inconvenience associated with venom immunotherapy (VIT) is related to the need for monthly treatments. Since VIT is advocated for at least 3 to 5 years, and occasionally longer, reducing the number of venom injections may cut down significantly on both cost and inconvenience. OBJECTIVE: We evaluated whether maintenance VIT given every 3 months is both safe and effective regarding reactions to treatment injections or field re-stings and lack of systemic reaction (SR) to deliberate challenge sting. METHODS: The standard 1-month interval was gradually extended to 3 months in 28 patients (mean age 26 years, range 7 to 76) allergic to bee venom (BV), yellow jacket venom, or both venoms. Nineteen patients allergic to BV were deliberately challenged by a live bee sting. In 15 patients the original SR in the field was moderate; in one patient it was mild; and in three patients it was severe. RESULTS: Mean duration receiving standard maintenance VIT before extending the 1-month interval was 17 months. No patient had an SR while receiving the 3-month VIT therapy. Two patients experienced four field re-stings while receiving the 3-month therapy with no reaction. After the live challenge, there was mild urticaria in a single patient; no SR developed in the rest of the patients. CONCLUSION: For young patients allergic to BV whose initial SR is mild to moderate and who have already received 1-month VIT for longer than 17 months, the maintenance interval may safely be extended to 3 months while preserving its protective activity against re-stings.

Deliberate hymenoptera sting challenge as a diagnostic tool in highly selected venom-allergic patients.

BACKGROUND: Open environment and working conditions close to abundant insects of the order Hymenoptera should be avoided as much as possible by patients allergic to Hymenoptera venom who do not receive venom immunotherapy. After having experienced accidental field re-stings not resulting in a systemic reaction, some of these patients may be willing to resume normal life and working habits. Since venom-specific IgE usually remains elevated in these patients, repeated skin tests or RASTs are not helpful in identifying disappearance of their venom allergy. OBJECTIVE: The purpose of this study was to evaluate the usefulness of deliberate live sting challenge as a diagnostic tool in highly selected venom-allergic patients who had initially refused venom immunotherapy. METHODS: Two cases are reported of bee venom-allergic patients who had previously refused venom immunotherapy and subsequently experienced honeybee field re-stings not resulting in systemic reactions. Two to three years later, their skin tests remained positive for bee venom. A third patient allergic to Vespa orientalis who had negative skin tests to all available venoms was denied venom immunotherapy due to lack of proper commercial venom. Because none of the patients was receiving venom immunotherapy the military service personnel concluded they still had venom allergy and rejected them from the highly prestigious service. All three patients were anxious to confirm the disappearance of their venom allergy and we used deliberate live sting challenges for that purpose. RESULTS: Two to three years after their initial systemic reactions live sting challenges were well tolerated by the three patients. They felt free to resume their normal life habits and were allowed to begin military service without further limitations. CONCLUSION: Deliberate insect stings using appropriate safety precautions should be considered a diagnostic tool in selected allergic patients who do not receive venom immunotherapy but in whom a reliable history of negative field re-stings can be obtained despite positive skin tests and in those who continue to have inconclusive venom skin tests.

Debilitating beliefs, emotional distress and quality of life in patients given immunotherapy for insect sting allergy.

BACKGROUND: Patients who receive immunotherapy for systemic reaction to insect stings are told that once they reach maintenance dose they are almost 100% protected against future systemic reactions. However, we have observed that some patients continued to perceive themselves as highly debilitated by the allergy, and this perception had a significant impact on their quality of life. OBJECTIVE: To validate this clinical observation and to explore possible reasons for such an undesired psychological reaction. METHODS: The study group consisted of 97 patients who regularly attended an allergy outpatient clinic for venom immunotherapy, and who had been under medical surveillance for up to 8 years. They completed a questionnaire measuring debilitating beliefs, preoccupation with the systemic reaction event, emotional distress, perceived restriction by allergy, and perceived quality of life. We also recorded the duration of immunotherapy, physician-graded severity of the systemic reaction and the frequency at which immunotherapy was administered. The reference group consisted of patients who had not reached maintenance dose and were still at risk of recurrent systemic reactions. RESULTS: As many as one-third of the patients held self-imposed debilitating beliefs, were preoccupied with the systemic reaction event, perceived a moderate to severe impairment in their quality of life, and manifested symptoms of emotional distress. These psychological responses did not correlate with the immunotherapy dosage that had been reached. Patients who reached a full maintenance dose were doing no better psychologically than those in the reference group. Moreover, the length of time on immunotherapy did not result in attenuation of the psychological responses. CONCLUSION: This study demonstrates for the first time, the long-lasting psychological impact of a threatening systemic reaction. It suggests a need for intervention aimed at dispelling patients' unfounded and persisting debilitating beliefs.

Allergic responses to pollen of ornamental plants: high incidence in the general atopic population and especially among flower growers.

BACKGROUND: The incidence of allergy to pollen of ornamental plants has not been deeply investigated, and its extent has remained obscure. Most of such studies have concentrated only on pollen of ornamental plants from the Asteraceae family (Compositae). In this study an attempt was made to clarify whether various other ornamental plants may also cause skin responses and allergic symptoms among allergic urban dwellers and among rural flower growers. METHODS: Two hundred ninety-two patients were referred for allergic evaluation by their primary physicians; 75 flower growers and 44 university students were evaluated. For all participants, a detailed health record was obtained, and skin prick tests (SPTs) were performed. Extracts for SPTs included commercial common airborne allergens and autochthonous pollen extracts of 11 species of plants belonging to the Asteraceae, Ranunculaceae, Liliaceae, Scrophulariaceae, and Genetianaceae families. RESULTS: Fifty-one of the 292 patients (17%) referred for allergic evaluation had positive SPT responses to pollen of various ornamental plants. A similar incidence was found among the students (23%). However, the incidence among flower growers was significantly higher, reaching 52%. Higher incidence (83%) of positive SPT responses to ornamental plants was found among flower growers also sensitive to the common allergens. All the tested plants, not only those belonging to the Asteraceae family, provoked positive SPT responses in all 3 groups of participants. None of the participants from the general population or the group of students reported exacerbation of allergic symptoms on exposure to the tested plants. In contrast, almost half of the flower growers (45%) described nasal, ocular, or respiratory symptoms associated with occupational exposure to the tested plants. Some 15% of the growers were eventually compelled to change their profession. CONCLUSIONS: The incidence of positive SPT responses to ornamental plants was 17% to 23% among the general public but 52% among flower growers. Thus the effects of ornamental plant pollen on atopic patients should be seriously contemplated.

Anaphylaxis to cisplatin: diagnosis and value of pretreatment in prevention of recurrent allergic reactions.

Two patients, who developed anaphylaxis to cisplatin, are described. This phenomenon was preceded by mild allergic symptoms, which were overlooked, in previous treatment courses. Intradermal skin tests were both sensitive and specific in the diagnosis of cisplatin allergy. Pretreatment with antihistamines and corticosteroids was ineffective in preventing recurrent anaphylaxis. Thus, a trial of desensitization is mandatory among those patients whose disease responds to the administration of this agent.

Trisomies 9 and 8 detected by fluorescence in situ hybridization in patients with systemic mastocytosis.

BACKGROUND: Systemic mastocytosis is a rare disease characterized by proliferation of mast cells in one or more organs. The origin of the mast cells is still debated, although it has been recently shown that they derive from CD34+ hematopoietic progenitors. Some clinical and in vitro studies have suggested a possible link between myeloproliferative disorders and systemic mast cell disease. OBJECTIVE: This study was designed to further evaluate the association between systemic mast cell disease and other hematologic disorders by means of conventional cytogenetic analysis and fluorescent in situ hybridization. METHODS: We used cytogenetic analysis and fluorescent in situ hybridization with probes to chromosomes 8 and 9 in six patients with systemic mast cell disease. RESULTS: Fluorescent in situ hybridization helped to identify five patients with trisomy 9 and one with trisomy 8. In contrast, chromosomal analysis demonstrated an abnormal karyotype (45,XO/46,XY) in only one patient. CONCLUSION: The association between myeloproliferation disorders and systemic mast cell disease may be explained by the finding that trisomy 9 and trisomy 8 are common in both disorders. A trisomy was detected in all of the patients in our small group compared with nearly 40% of previously reported patients with myeloproliferative disorders. FISH is more sensitive than conventional cytogenetics in detecting these aberrations.

Identification of a subset of common variable immunodeficiency patients with impaired B-cell protein tyrosine phosphorylation.

The mechanisms responsible for common variable immunodeficiency syndrome (CVID) are as yet unknown. In the present study, we show that the B-cell dysfunction in a subset of CVID patients is caused by defective protein tyrosine phosphorylation (PTP). We demonstrated that the PTP level and immunoglobulin (Ig) secretion malfunctions can be successfully repaired when normal plasma membrane components are implanted into these patients' B cells. Stimulation of CVID patients' peripheral blood mononucleated cells with anti-Ig antibody revealed that 7 of 11 patients had lower PTP levels than those found in the normal donor cells. Plasma membrane implantation to the cells of these patients resulted in elevated PTP levels which reached normal levels upon stimulation with anti-human Ig antibody. The results revealed two distinct groups of CVID patients. The first group included patients whose B cells expressed low PTP levels after Ig stimulation. In these patients the plasma membrane implantation restored the normal PTP level as well as the ability to secrete IgM and/or IgG after B-cell stimulation. In the second group, patients whose B cells expressed a normal PTP level after Ig stimulation, with no restoration of their ability to secrete Ig upon plasma membrane implantation and lipopolysaccharide stimulation. We conclude that the first group has an early signal transduction defect located in the B-cell plasma membrane, while in the second group the defect is located elsewhere.

Continuous avoidance measures with or without acaricide in dust mite-allergic asthmatic children.

BACKGROUND: Improvement in the quality of life in the Western world and increased time spent indoors by children have enhanced the spread of house dust mites and increased the exposure time for sensitive children. Also, exposure to house dust mites in infancy and subsequent development of childhood asthma have been clinically linked. Recently, new acaricides have been developed. OBJECTIVE: To test the efficacy of the new acaricide (esdepallethin and piperonyl butoxide--"Acardust") combined with environmental control compared with continuous house dust mite avoidance measures. METHOD: Forty-six house dust mite-allergic, asthmatic children were evaluated for 6 months in a prospective, randomized, double-blind, and placebo-controlled study. Patients were randomly allocated to active and placebo acaricide treatment combined with avoidance measures, whereas only continuous avoidance measures were taken in the third group. Symptom score, medication usage, and peak flow measurements were recorded daily. The amount of house dust mite allergen in the dust vacuumed from the bedrooms was also measured. RESULTS: Morning and evening peak expiratory flow rates and forced expiratory volume in one second remained unchanged throughout the study period. In all groups, the symptom scores improved significantly, whereas the amount of house dust mite allergen decreased significantly at the end of the trial. CONCLUSIONS: Continuous house dust mite avoidance measures have a significant positive effect on the symptomology of children with mild or moderate asthma. "Acardust" combined with continuous house dust mite avoidance measures is not more effective than continuous house dust mite avoidance measures alone in the treatment of house dust mite-allergic, asthmatic children.