Topical tacrolimus for the management of acute allergic conjunctivitis in a mouse model.

BACKGROUND: Acute allergic conjunctivitis is a constantly challenging condition that often requires steroids for effective management. Alternative treatment options are needed due to the potential side effects of steroids. Tacrolimus has been used for vernal/atopic conjunctivitis. The aim of our study was to investigate the therapeutic effect of topical administration of 0.03 % tacrolimus (eye drops or ointment) in comparison to 0.1 % dexamethasone in a mouse model of acute allergic conjunctivitis. METHODS: BALB/c mice were sensitized by an intraperitoneal injection of 10 µg/0.2 ml ovalbumin (OVA) absorbed on ALUM (2.0 mg) on days 1 and 8. They were challenged by topical instillation of 2 µl of 15 % OVA (absorbed in 10 % glycerol) twice daily, on days 15-21. Treatment was administered twice daily on days 17-21. Mice were randomly assigned topical treatment groups: Group 1, 0.1 % dexamethasone drops; Group 2, 0.03 % tacrolimus drops; Group 3, 0.03 % tacrolimus ointment; Group 4 PBS drops (control). On day 22 all mice underwent clinical evaluation, blood sampling for IgE levels, and conjunctivas were removed for eosinophil counting. RESULTS: IgE and OVA-specific IgE levels were similar among all groups, demonstrating induction of allergic reaction in all mice. Significantly lower clinical scores were found among all treated groups as compared to controls (P < 0.001), while no significant difference was found among the three treatment groups (P > 0.05). Conjunctival eosinophil counts were significantly lower in Group 1 (P < 0.05) as compared to the other groups. CONCLUSIONS: The clinical efficacy of topical 0.03 % tacrolimus was similar to 0.1 % dexamethasone for acute allergic conjunctivitis.

Expression of Th17 and Treg lymphocyte subsets in hypertrophied adenoids of children and its clinical significance.

Adenoid hypertrophy is the most common cause of upper airway obstruction and sleep-disordered breathing in children, yet its pathogenesis remains unclear. The identification of the novel helper T cell subsets, Th17 cells and regulatory T cells (Tregs) could provide new insight into our understanding of the mechanisms involved in the development of this condition. The purpose of this study is to evaluate the adenoidal lymphocyte subsets to describe the percentage of various lymphocyte subsets in hypertrophied adenoids and correlate them with symptom severity. Twenty consecutive children undergoing adenoidectomy were included, and lymphocytes were isolated from their adenoids. T cell subpopulations were detected by flow cytometry using a fluoresceinated monoclonal antibody directed against a number of cell markers (CD4+, CD8+, CD25+, FOXP3 IL17+, and others). We found a significant negative linear correlation between the Th17/Treg ratio and the patients' clinical scores (R = -0.71 p < 0.005). The correlation was independent of age and gender. Decreased ratios of Th17/Treg subpopulations may play a role in the pathogenesis of adenoid hypertrophy.

Sensitization to Dermatophagoides, Blomia tropicalis, and other mites in atopic patients.

BACKGROUND: House dust mites (HDMs) are important causes of persistent allergic diseases, such as asthma and rhinitis. Various types of mites are found in the house dust of many countries, including Israel. OBJECTIVE: To evaluate the prevalence of sensitization to various HDMs in patients with perennial allergic rhinitis and asthma. METHODS: Sensitization of 117 patients with persistent rhinitis who attended the Allergy and Asthma Center in Tel Aviv (Israel) was evaluated by a skin prick test (SPT) using standardized allergenic extracts. The tested mites were Dermatophagoides farinae (DF), Dermatophagoides pteronyssinus (DP), Lepidoglyphus destructor (LD), Blomia tropicalis (BT), Tyrophagus putrescentiae (TP), Acarus siro (AS), Glycyphagus domesticus (GD), Blomia kulagini (BK), and Tetranychus urticae (TU). RESULTS: Most patients (n = 95, 81%) had a positive SPT to at least one mite extract. The three most frequent positive reactions were to DF (78%), DP (75%), and, unexpectedly, BT (77%). The correlation between DF and DP sensitization was higher than the correlation between DF or DP to BT (r = .78 versus r = .60, p < .05). Six patients had positive skin reactions to at least one mite species other than DF, DP or BT, mainly LD (n = 2, 2.1%) and BK (n = 4, 3.8%). CONCLUSIONS: The findings of this study identified the most ubiquitous mites to which Israeli patients with allergic rhinitis were sensitized and indicated the importance of BT as an allergen. Extracts of these mites may provide a more accurate diagnosis and effective treatment of respiratory diseases due to mite allergy in Israel and probably in other countries with similar climes.

Efficacy of the Plasma Cluster device in asthmatic and/or allergic rhinitis patients with house dust mite allergy: a prospective observational pilot study.

BACKGROUND: Mite allergy is an indoor allergen responsible for most respiratory allergies in the western world. Environmental control can modify disease activity in these patients. OBJECTIVES: To examine the benefit of the Plasma Cluster device (Sharp, Japan) for inactivating and removing mites from the environment of patients diagnosed with either mite-sensitive perennial allergic rhinitis or mite-sensitive allergic asthma. METHODS: Patients with AR (n=30) or AA (n=10) were enrolled into a prospective open observational 8 week study. The first 2 weeks involved initial evaluation, the following 4 weeks consisted of active usage of the device, and the last 2 weeks were designated for follow-up. Symptom scores (recorded daily by patients and during visits by physicians) were recorded and analyzed. RESULTS: Patients with AR experienced a significant (P < 0.05) reduction in nasal discharge, post-nasal drip, nasal congestion, nasal itching, watery eyes, itchy eyes, headache, itchy ears, night disturbances and an improvement in general well-being during the last 2 days of the study compared to baseline. Patients with AA reported significant (P < 0.05) reduction in dyspnea, wheezing and the need to avoid dust mites. There was a significant (P < 0.05) improvement in mean peak expiratory flow rate at study closure compared to baseline. CONCLUSIONS: Short-term usage of the Plasma Cluster device resulted in considerable clinical improvement and increased peak expiratory flow rate in patients with AR or AA. The findings of this pilot study warrant longer and controlled studies to determine the value of this device in the treatment of various allergic disorders.

Eosinophilia: A study of 100 hospitalized patients.

BACKGROUND: Eosinophilia accompanies a large number of diseases and conditions, but information is lacking about the clinical characteristics of patients who are hospitalized due to this abnormality. Our aim was to determine the clinical profile and most informative diagnostic tests in patients hospitalized in a tertiary hospital because of hypereosinophilia. METHODS: A retrospective review was done of the medical records of all patients hospitalized in a large urban medical center due to hypereosinophilia. All relevant clinical, laboratory, and imaging data were analyzed. RESULTS: A total of 100 patients were included in the study (58 males and 42 females, mean age 55.2+/-29 years). The blood eosinophil blood count was 4107+/-7254/mul (mean+/-SD) and this usually persisted for a few months. The cause of the eosinophilia was asthma or other atopic disease in 13% of the cases, allergic drug reaction in 6%, eosinophilic pneumonia in 10%, neoplastic diseases in 10%, idiopathic hypereosinophilic syndrome in 8%, Churg-Strauss Syndrome in 4%, infections in 10%, allergic fungal disease in 2%, and skin diseases in 3%; the cause remained unknown in 34% of cases. CONCLUSION: Guidelines are suggested for the investigation of patients with eosinophilia, including the level of the eosinophilia associated with specific diseases and the most informative diagnostic tests.

[Asthma and scuba diving: can asthmatic patients dive?].

Self-contained underwater breathing apparatus (scuba) diving has grown in popularity, with millions of divers enjoying the sport worldwide. This activity presents unique physical and physiological challenges to the respiratory system, raising numerous concerns about individuals with asthma who choose to dive. Asthma had traditionally been a contraindication to recreational diving, although this caveat has been ignored by large numbers of such patients. Herein we review the currently available literature to provide evidence-based evaluation of the risks associated with diving that are posed to asthmatics. Although there is some indication that asthmatics may be at an increased risk of pulmonary barotrauma, the risk seems to be small. Thus, under the right circumstances, patients with asthma can safely participate in recreational diving without any apparent increased risk of an asthma-related event. Decisions on whether or not diving is hazardous must be made on an individual basis and be founded upon an informed decision shared by both patient and physician.

Effect of montelukast on basophil releasability in patients with asthma.

BACKGROUND: The anti-inflammatory effect of montelukast, a leukotriene receptor antagonist, in patients with bronchial asthma is not entirely clear. Basophils can release a variety of mediators, including histamine and leukotriens, which most likely play an active role in the late allergic response. OBJECTIVES: To study the effect of montelukast (10 mg/day) on histamine and cysteinyl leukotriene release from basophils taken from 12 mild atopic asthmatic patients who took the drug for 4 weeks. METHODS: Basophils were withdrawn at baseline, and after 48 hours, 1 week, and 4 weeks of therapy. Histamine was measured by a radioenzymatic method and leukotrienes by immunologic assay. Histamine and cysLT release was measured spontaneously and following stimulation with interleukin-3 and anti-immunoglobulin E. Spirometry and symptom score were measured before and during treatment. RESULTS: During the treatment with montelukast there were no significant changes in spontaneous, IL-3 and anti-IgE-induced histamine release. cysLT release decreased significantly only after 4 weeks of treatment (from 2899 +/- 550 pg/ml at baseline to 2225 +/- 430 pg/ml at 4 weeks, P= 0.02). CONCLUSIONS: Montelukast does not seem to affect the release of histamine from basophils but mildly inhibits the cysLT release seen after 4 weeks of treatment.

Middle cerebral artery flow velocity decreases and electroencephalogram (EEG) changes occur as acute hypercapnia reverses.

OBJECTIVE: To define the changes in middle cerebral artery flow velocity (Vmca) and the electroencephalogram (EEG) during rapid reduction in arterial carbon dioxide (PCO2) from acute hypercapnia. DESIGN. Human volunteer study. SETTING: University-affiliated hospital experimental laboratory. PARTICIPANTS: Nine healthy volunteers aged 25-35 years. INTERVENTIONS: Subjects rebreathed exhaled gas from a bag pre-filled with 5% carbon dioxide (CO2) in oxygen, up to an end-tidal CO2 of 10% or to the limit of discomfort, when they were disconnected. MEASUREMENTS AND RESULTS: Middle cerebral artery blood flow velocity was continuously measured by transcranial Doppler ultrasound, quantitative EEG was recorded and hemodynamics were monitored non-invasively. Vmca closely correlated with end-tidal CO2 changes (r=0.65, p<0.001). When rebreathing ceased, there was a rapid decline in end-tidal CO2 and in Vmca to baseline within 42+/-14 s, followed by a rapid further decline in both variables to below baseline. End-tidal CO2 reached a nadir of 4.4+/-1.1% at 146+/-79 s, with Vmca decreasing to 37+/-10 cm/s at 104+/-65 s (a 40% reduction and 31% below basal values). Electroencephalogram alpha activity significantly decreased and delta activity increased during hypercapnia. During subsequent hypocapnia, delta activity decreased back to baseline, while alpha activity increased, but remained below baseline. CONCLUSIONS: These findings demonstrate the rapid changes occurring in cerebral blood flow during rapid declines in arterial CO2 and the consequent potential for producing brain ischemia and hemodynamic alterations if inadvertent hyperventilation occurs following institution of mechanical ventilation for acute hypercapnia.

Knowledge and expectations of patients receiving aeroallergen immunotherapy.

BACKGROUND: Patients receiving aeroallergen immunotherapy frequently have poor knowledge and unfounded expectations of various important aspects of their treatment. OBJECTIVE: To evaluate patients' knowledge about the content, benefit, and risk related to the aeroallergen immunotherapy that they were receiving. METHODS: A self-administered questionnaire was distributed to all patients older than 16 years who had undergone aeroallergen immunotherapy for allergic rhinitis at 3 university-affiliated allergy clinics. RESULTS: A total of 132 patients (77 males and 57 females; mean +/- SD age, 30 +/- 13 years) participated in the study. The mean +/- SD duration of treatment was 30 +/- 60 months. Complete recovery of their allergies was expected by 39% of the patients. One fifth of the study group did not know when improvement should be expected, and 18% anticipated improvement to occur within days or weeks from the initiation of treatment. Only 32% were aware that immunotherapy might have some potential risk or adverse effects, and 24.2% failed to identify at least one of the allergens they were receiving. Patients who were interviewed during their first 6 months of aeroallergen immunotherapy had more knowledge about it than those who had been undergoing long-term treatment. CONCLUSIONS: There is a grave lack of knowledge and numerous misconceptions among substantial numbers of patients receiving aeroallergen immunotherapy. More educational effort is needed to increase patients' knowledge about immunotherapy before and during aeroallergen immunotherapy to improve their compliance and the success and safety of this therapeutic modality.