Sarcoidosis and calcium homeostasis disturbances-Do we know where we stand?

The majority of cases involving hypercalcemia in the setting of sarcoidosis are explained by the overproduction of calcitriol by activated macrophages. Vitamin D takes part in the regulation of granuloma formation. However, using vitamin D metabolites to assess the activity of the disease is still problematic, and its usefulness is disputable. In some cases, though, a calcium metabolism disorder could be a valuable tool (i.e. as a marker of extrathoracic sarcoidosis). Although sarcoidosis does not cause a decrease in bone mineral density, increased incidence of vertebral deformities is noted. Despite increasing knowledge about calcium homeostasis disorders in patients with sarcoidosis, there is still a need for clear guidelines regarding calcium and vitamin D supplementation in these patients.

Histamine type 2 receptor expression on peripheral blood regulatory lymphocytes in patients with allergic rhinitis treated with specific immunotherapy.

BACKGROUND: Both histamine H1- and H2-receptors (H2R) were found on regulatory T (Treg) cells; however, there is a paucity of information regarding the role of H2R in Treg function. This study aimed to investigate the effects of natural allergen stimulation and specific immunotherapy (SIT) on H2R expression in Treg cells in patients with allergic rhinitis (AR). METHODS: In this prospective, double-blind, placebo-controlled study 41 patients with AR were screened for 1 year and treated with SIT (n = 21) or placebo (n = 20) for the next 2 years. Fifteen healthy subjects were included as a control. Subsets of Treg cells that expressed H2R were assessed annually in the blood by flow cytometry: before, at the height of the pollen season, and after, at the end of the pollen season. In addition, total nasal symptom score, the use of rescue medication, and nasal eosinophilia were evaluated. RESULTS: Treg cells of AR patients slightly up-regulate H2R out of the pollen season. Natural allergen stimulation results in prompt up-regulation of H2R within these cells. SIT significantly decreased the number of Treg cells with increased expression of H2R in the blood exclusively at the height of pollen season, which, however, had no impact on the expression of H2R in Treg cells. SIT improved significantly the symptom score, rescue medication use, and decreased nasal eosinophilia. CONCLUSION: Natural pollen exposure results in up-regulation of H2R in Treg cells. Immunotherapy might transiently decrease the number of Treg-H2R(+) cells in the blood, which may be associated with their migration to the peripheral tissues. This study was part of the clinical trial registered in www.clinicaltrials.gov.

Orally exhaled nitric oxide in patients with seasonal allergic rhinitis during natural pollen season.

BACKGROUND: Nitric oxide (NO) is the endogenous molecule involved in regulatory, protective, and defensive mechanisms. Although exhaled NO (ENO) has been used to monitor patients with asthma, possible usage of ENO in allergic rhinitis (AR) still needs to be evaluated. The authors wanted to determine the levels of NO exhaled orally both out of the pollen season and during the natural pollen exposure in patients with AR without asthma. METHODS: Forty-six patients without asthma, with seasonal AR (SAR) and 15 healthy, nonreactive, nonatopic subjects as a control group were investigated. ENO, congestion score, and peak nasal inspiratory flows (PNIFs) were measured in all subjects 6 weeks before the pollen season, at the height of the pollen season, and 6 weeks after the end of the pollen season. RESULTS: Patients with SAR had significantly higher basal ENO values compared with healthy control. The number of parts of NO increased in both groups during the pollen season but only in AR patients was the increase significant compared with the levels before the pollen season. Those with SAR and high levels of NO in exhaled air at the height of the pollen season had significantly lower PNIF rates and higher obstruction scores than out of the pollen season and in the healthy group. CONCLUSION: Natural exposure may lead to an elevation of ENO in the patients with SAR without asthma. We estimate that the increased ENO may result from subclinical allergic inflammation present within the lower airways of nonasthmatic patients with SAR.

[Effect of natural allergens exposure on serum concentration of soluble form of intercellular adhesion molecule 1 in patients with seasonal airway allergy]. / Wplyw naturalnej ekspozycji na alergeny na stezenie rozpuszczalnej formy czasteczki adhezji miedzykomórkowej 1 w surowicy chorych z sezonowa alergia dróg oddechowych.

UNLABELLED: Chronic inflammation is a feature of bronchial asthma and allergic rhinitis. Intercellular adhesion molecules, especially ICAM-1 and its soluble form sICAM-1 present in systemic liquids play an important role in allergic inflammation. The aim of this study was to assess the effect of natural pollen exposure to plants on serum sICAM-1 concentration in patients with different clinical expression of seasonal allergy and to determine the relation between concentrations of these molecules to clinical symptom score and nonspecific bronchial hyperresponsiveness (BHR). MATERIAL AND METHODS: The study comprised 48 patients with isolated seasonal allergic rhinitis (SAR), 26 patients with seasonal asthma (SA) and 16 healthy volunteers. Serum s/CAM-1 concentration using an immunoenzymatic ELISA method and BHR to methacholine were measured twice, before grass season and during symptomatic period of SAR and SA. Clinical symptoms severity were evaluated by pointing method from patients diary cards. RESULTS: The study revealed no differences in mean concentration of serum sLCAM-1 between patients with SAR and SA but significant increase of serum sICAM-1 level during natural allergen exposure in all patients was observed. CONCLUSION: Serum concentration of sICAM-1 was not correlated to symptom score and BHR in both SAR and SA patients in and out of season.

The effect of montelukast (10mg daily) and loratadine (10mg daily) on wheal, flare and itching reactions in skin prick tests.

UNLABELLED: Antileukotriene agents are widely used for the treatment of allergic conditions including bronchial asthma and allergic rhinitis. The influence of montelukast on skin reactivity has not been clearly evaluated. The aim of this study was to determine the effect of montelukast on wheal, flare and itching in skin prick tests (SPTs). METHODS: Fifteen atopic patients (5 women and 10 men) with average age 28.04 (SD+/-8.24) were tested with histamine, codeine, negative control solution and allergen extract (grasses). Montelukast (10mg), loratadine (10mg) or placebo were given to the volunteers for 5 days in a double-blind manner, followed by SPT, with 14 days of wash-out period. RESULTS: There was no differences in wheal, flare and itching (p=0.205; 0.086 and 0.069, respectively, Wilcoxon rank-sum test) between SPT performed after placebo and wash-out period. The analysis revealed a statistically significant suppression of wheal and flare by loratadine (p<0.05 for all tested solutions). Pre-treatment with montelukast did not influence wheal size (p=0.099, 0.21, 0.066 for histamine, codeine and allergens, respectively), but significantly reduced flare (p=0.005; 0.003; 0.02 for histamine, codeine and allergens, respectively). We found a significant suppression of itching produced by montelukast (p=0.02) and loratadine (p=0.03) as compared to placebo (p=0.068 vs. wash out). CONCLUSIONS: Our data show a tendency to suppressive effect of montelukast on flare and itching but not on wheal which is basic for SPT interpretation. We conclude that found suppression have little impact on clinical effectiveness of SPT as a diagnostic tool.