Impact of Polyvalent Mechanical Bacterial Lysate on lymphocyte number and activity in asthmatic children: a randomized controlled trial.

BACKGROUND: Polyvalent Mechanical Bacterial Lysate (PMBL®) contains antigens of bacteria responsible for respiratory infections. PMBL® has been proven to reduce the number of respiratory infections, and in its use, immunological benefits have been seen in allergic patients. PMBL® activates both innate and specific immune responses. The lysate induces dendritic cells, T and B lymphocytes and IgA secretion, as well as the production of antibodies directed against administered bacterial antigens. Moreover, it increases the response against other bacteria and viruses. The immunologic mechanism of lysate's action is not yet clearly determined. The objective of this study was to assess the effect of PMBL® on T cells in children with allergic asthma. METHODS: This study was a part of the EOLIA study. Herein, 49 children with allergic asthma and house dust mites allergy were included: 21 in PMBL® and 28 in the Placebo group, both, drug and placebo were administered sublingually. The tests were done at baseline and 12 weeks after the last tablet intake. The lymphocytes CD45+, lymphocytes T CD3+, CD3+CD25+, CD3+CD69+, Th CD3+CD4+, CD4+CD25+, CD4+CD25+ high, CD4+CD69+, Treg CD4+CD25+FOXP3, Tc CD3+CD8+, CD8+CD25+, CD8+CD69+, NK-like T CD3+CD16+CD56+ and NK cells CD3-CD16+CD56+ were described. RESULTS: At baseline, no significant differences between groups relative to blood count cells were observed, except for eosinophils. After 12 weeks, we observed an increase of T lymphocytes count. In addition, CD4+CD25+FOXP3+, CD8+ and CD3-CD16+CD56+ and (insignificantly) Th count increased. However, CD69+ and CD25+ subset of CD3+ significantly decreased. CONCLUSIONS: The EOLIA study demonstrated that PMBL® administration 10 days per month for 3 months changed the panel of T lymphocytes. Trial registration Clinical Trial Registration: This study was a part of the EOLIA (Efficacy Of mechanical bacterial Lysate In Allergic children), a clinical study NCT02541331. Frederic Durmont, MD Lallemand Pharma International AG. Date of registration 09/08/2013. URL of trial registry record: https://clinicaltrials.gov/ct2/show/study/NCT02541331.

Demographic and medical factors affecting short-term changes in subjective evaluation of asthma control in adolescents.

INTRODUCTION: Asthma control is an important measure of disease stabilization, which is linked to the treatment and lifestyle recommendations. AIM: To assess the impact of selected factors on asthma control in adolescents, as assessed using the Asthma Control Test (ACT™). MATERIAL AND METHODS: The prospective study included 100 asthma patients aged between 12 and 19. Asthma was assessed in three consecutive follow-up visits spaced 3 months apart, using the standardized ACT™ questionnaire. RESULTS: Asthma was fully controlled (ACT score = 25 points) in more than half of the patients in all follow-up visits (53.0%, 54.0%, and 56.0%, respectively). More than one third of the participants scored between 20 and 24 points (37.0% vs. 39.0% vs. 40.0%). A minority of patients had uncontrolled asthma (scores below 20), and the group consistently diminished in subsequent visits (10% vs. 7% vs. 4%). Uncontrolled asthma was found significantly more often in female patients (33.33%; p < 0.001) and those living in rural areas (20.59%; p < 0.01). Treatment with a combination of inhaled corticosteroids (ICS) and LABAs was associated with worse asthma control (14.81%; p < 0.05). Better asthma control was found in patients with a family history of allergies (73.85% vs. 75.38% vs. 78.46%; p < 0.001) and in those with concurrent allergies (66.67% vs. 68.00% vs. 70.67%; p < 0.001). CONCLUSIONS: Asthma control in adolescents differs by sex and residence. Concurrent allergies and family history of allergies improve asthma self-control in adolescents.

Persistence of Vaccine-Induced Immunity in Preschool Children: Effect of Gestational Age.

BACKGROUND A program of immunization that ensures optimal development of acquired immunity should be carried out in all healthy newborns. The aim of the present study was to verify, at 2.5-3 years after the last dose of basic vaccination, if preschool children who have been delivered preterm and at term differ in their levels of post-vaccination protective antibodies. MATERIAL AND METHODS Humoral response was assessed in 352 children (mean age: 5.22±0.34 years) who received a series of obligatory vaccinations in the period from birth to 2.5-3 years of age. Antibodies (in IgG class) against vaccine antigens - diphtheria (D), tetanus (T), pertussis (P), Haemophilus influenzae type b (Hib), poliomyelitis (IPV), measles, mumps, and rubella (MMR) - were measured using ELISA. The level of antibodies against hepatitis B (HBV) was assessed by chemiluminescence. RESULTS All children had been immunized according to the Polish National Vaccination Program. The group of 352 children eligible for the study included 46 (13.1%) preschoolers delivered preterm (32-36 weeks of gestation), and 306 (86.9%) born at term (37-42 weeks of gestation). All children maintained seroprotective antibody levels against polioviruses type 1, 2, and 3 (>12 mIU/mL), and against measles antigens (>300 U/mL). No statistically significant differences were found in the proportions of preschoolers born preterm and at term who were seroprotected against other vaccine antigens. CONCLUSIONS Among preschool children who were immunized according to chronological age, those we were born late preterm do not seem to differ in vaccine-induced immunity from those who were born full-term.

Relationship between the expression of CD25 and CD69 on the surface of lymphocytes T and B from peripheral blood and bone marrow of patients with chronic lymphocytic leukemia and established prognostic factors of this disease.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is a condition characterized by the accumulation of morphologically mature monoclonal lymphocytes B with the CD19+/CD5+/CD23+ phenotype in lymphoid tissue, peripheral blood and bone marrow. The clinical course of patients with CLL is heterogeneous, ranging from indolent to aggressive. The role of lymphocyte activation in the natural history of CLL is still a matter of discussion. OBJECTIVES: The aim of this study was to determine the percentages and absolute numbers of lymphocytes B and T in peripheral blood and bone marrow of CLL patients. Moreover, we analyzed the relationship between the number of CD25-positive and CD69-positive lymphocytes and the established prognostic factors in CLL. MATERIAL AND METHODS: The study included 80 untreated patients with CLL and 20 healthy subjects. The immunophenotype of peripheral blood mononuclear cells (in both groups) and bone marrow cells (solely in the CLL group) was determined by means of flow cytometry. RESULTS: Patients with CLL showed a higher absolute number of activated lymphocytes B with phenotypes CD19+CD25+ and CD19+CD69+, as well as a higher absolute number of CD3+CD25+ lymphocytes T than the controls. The enhanced activation of peripheral blood and bone marrow lymphocytes was associated with higher Rai stages, an increased concentration of lactate dehydrogenase and beta-2 microglobulin and the progression of the disease. The number of lymphocytes B CD19+ZAP-70+ correlated positively with the number of CD19+CD25+ B cells and CD3+CD69+ T cells. CONCLUSIONS: The study confirmed the association between an unfavorable prognosis and a high expression of activation markers in CLL patients. The determination of CD25+ and CD69+ lymphocytes T and B constitutes a valuable diagnostic tool, completing the cytometric evaluation of CLL.

Mechanical bacterial lysate administration prevents exacerbation in allergic asthmatic children-The EOLIA study.

BACKGROUND: Despite progress in asthma management, prevention of asthma exacerbation remains challenging in school-aged children with allergic asthma. New therapeutic approaches are needed. Previously, a chemical bacterial lysate has been successfully used in preschool children to reduce wheezing attacks. We assessed the effect of Polyvalent Mechanical Bacterial Lysate (PMBL® ) Tablet on asthma clinical course and control in 6- to 16-year-old children with partly controlled or uncontrolled allergic asthma. METHODS: A randomized, double-blind, placebo-controlled, parallel-group study was performed in 152 patients exhibiting allergic asthma assigned to receive Placebo or PMBL® . Eligible patients underwent four visits during the 9-month study. Asthma control level was assessed by ACT/C-ACT score. RESULTS: The main criterion was not achieved as ACT/C-ACT changes were similar in both groups at the end of the 3-month treatment period. However, the mean number (±SD) of asthma exacerbations was significantly lower with PMBL® Tablet than with Placebo at Week 12 (0.3 ± 0.6 vs 0.8 ± 1.1, P = .009) and over the total study period (1.1 ± 1.3 vs 1.9 ± 2.0, P = .01). Consistently, the mean number of days with exacerbation per patient was significantly lower with PMBL® Tablet (13.3 ± 11.2 vs 19.8 ± 15.7 over the whole study, P = .009). Treatment with PMBL® Tablet prolonged the time to second exacerbation by 55% (Hazard Ratio [HR]=0.45; 95% Confidence Interval [CI] 0.27 to 0.77, P = .002) and to third exacerbation by 74% (HR=0.26; 95% CI 0.12 to 0.58, P < .001). No serious adverse event related to PMBL® Tablet administration was recorded. CONCLUSION: Administration of PMBL® Tablet represents a safe and effective means for significantly reducing the rate of exacerbations in school-aged allergic asthmatic children. (EudraCT 2013-000737-12 and NCT02541331).

Sublingual immunotherapy (SLIT)--indications, mechanism, and efficacy: Position paper prepared by the Section of Immunotherapy, Polish Society of Allergy.

SLIT (sublingual immunotherapy,) induces allergen-specific immune tolerance by sublingual administration of a gradually increasing dose of an allergen. The mechanism of SLIT is comparable to those during SCIT (subcutaneous immunotherapy), with the exception of local oral dendritic cells, pre-programmed to elicit tolerance. In the SLIT dose, to achieve the same efficacy as in SCIT, it should be 50-100 times higher with better safety profile. The highest quality evidence supporting the efficacy of SLIT lasting 1-3 years has been provided by the large scale double-blind, placebo-controlled (DBPC) trials for grass pollen extracts, both in children and adults with allergic rhinitis. Current indications for SLIT are allergic rhinitis (and conjunctivitis) in both children and adults sensitized to pollen allergens (trees, grass, Parietaria), house dust mites (Dermatophagoides pteronyssinus, Dermatophagoides farinae), cat fur, as well as mild to moderate controlled atopic asthma in children sensitized to house dust mites. There are positive findings for both asthma and new sensitization prevention. Severe adverse events, including anaphylaxis, are very rare, and no fatalities have been reported. Local adverse reactions develop in up to 70 - 80% of patients. Risk factors for SLIT adverse events have not been clearly identified. Risk factors of non-adherence to treatment might be dependent on the patient, disease treatment, physician-patient relationship, and variables in the health care system organization.

Five-grass pollen 300IR SLIT tablets: efficacy and safety in children and adolescents.

The efficacy and safety of five-grass pollen 300IR sublingual immunotherapy (SLIT) tablets (Stallergènes SA, France) have previously been demonstrated in paediatric patients. This report presents additional data concerning efficacy at pollen peak, efficacy and safety according to age, nasal and ocular symptoms, use of rescue medication, satisfaction with treatment and compliance. Children (5-11 yr) and adolescents (12-17 yr) with grass pollen-allergic rhinoconjunctivitis were included in a multinational, randomized, double-blind, placebo-controlled study and received either a 300IR five-grass pollen tablet or placebo daily in a pre- (4 months) and co-seasonal protocol. The severity of six symptoms (sneezing, rhinorrhoea, nasal congestion, nasal and ocular pruritis, and tearing) was scored, and rescue medication use was recorded daily during the pollen season. Patient satisfaction was recorded at the season end. A total of 161 children and 117 adolescents were evaluated (n = 267). 300IR SLIT was effective over the whole season (p = 0.0010) and at the pollen peak (p = 0.0009). The adjusted mean difference between 300IR and placebo groups was significant for both nasal (p = 0.0183) and ocular (p < 0.0001) symptoms. Rescue medication use was statistically lower in the SLIT group during the pollen season and at the pollen peak (both p < 0.05). More patients in the SLIT group were satisfied with their treatment compared to placebo (83.2% vs. 68.1%, p = 0.0030), and compliance was high (SLIT 93.9% of patients were compliant, placebo 94.8% of patients were compliant). SLIT was well tolerated by children and adolescents. 300IR five-grass pollen tablets are effective and safe during the pollen season and at the pollen peak in children and adolescents with grass pollen rhinoconjunctivitis.

The effect of Propionibacterium acnes on maturation of dendritic cells derived from acne patients' peripherial blood mononuclear cells.

Propionibacterium acnes (P. acnes) has been implicated in the pathogenesis of acne vulgaris which is the most common cutaneous disorder. It has a proinflammatory activity and takes part in immune reactions modulating the Th1/Th2 cellular response. The exposure of dendritic cells (DCs) to whole bacteria, their components, cytokines or other inflammatory stimuli and infectious agents induces differentiation from immature DCs into antigen-presenting mature DCs. The aim of the study was to evaluate the capability of P. acnes to induce the maturation of DCs. We stimulated monocyte derived dendritic cells (Mo-DCs) from acne patients with various concetrations of heat-killed P. acnes (10(6)-10(8) bacteria/ml) cultured from acne lesions. The results showed an increase in CD80+/CD86+/DR+ and CD83+/CD1a+/DR+ cells percentage depending on the concetration of P. acnes. The expression of CD83 and CD80 (shown as the mean fluorescence intensity - MFI) increased with higher concetrations of P. acnes. There were also significant correlations between MFI of CD83, CD80, CD86 and concetration of P. acnes. The study showed that P. acnes in the concetration of 10(8) bacteria/ml is most effective in the induction of Mo-DCs maturation. Futher studies concerning the influence on the function of T cells are needed.

[Nasal allergen provocation test, allergic skin tests and serum allergen-specific IgE level in asthmatic children]. / Test prowokacji nosowej z alergenem, alergiczne testy skórne oraz poziom alergenowo swoistych IgE w surowicy u dzieci chorych na astme oskrzelowa.

INTRODUCTION: The important element in the asthma diagnosis is a confirmation of trigger's asthma symptoms allergens. AIM: The aim of this study was to evaluate diagnostic value of an allergic skin prick test and serum allergen-specific IgE level with reference to nasal allergen provocation test (NPT) results in asthmatic children. MATERIAL AND METHODS: Study was performed in 80 asthmatic children in 3-14 yrs aged. 118 NPTs accompanied by assessments of nasal airflow by rhinospirography, were done. In all subjects, allergic skin prick tests with mites and grasses or trees pollen allergens and serum allergen specific IgE levels with the allergen used in NPT were done. RESULTS: Concordance between SPT and TPN results was shown in 59% cases, most often in group with pollen than mites provocation. SPT's sensitivity and specificity in relation to TPN result was 71% and 53%, respectively. Concordance between asIgE level and TPN results was shown in 76% cases. asIgE results sensitivity and specificity in relation to TPN result was 71% and 82%, respectively. CONCLUSION: The usefulness of skin prick test results in allergologic diagnosis of asthma is lesser than serum allergen specific IgE determination, especially in patients with house dust mites allergens hypersensitivity. Nasal provocation test (NPT) with suspected allergen should be performed in asthmatic children with a negative or doubtful skin prick test or serum allergen specific IgE level results.

Prevalence of asthma and some respiratory symptoms in the years 1995 and 2001 in schoolchildren from rural regions of Poland.

The aim of our study was to estimate the prevalence of asthma and some respiratory symptoms and diseases in schoolchildren from rural regions of Poland in 2001 and to compare these data with previous estimations in 1995. Repeated cross-sectional epidemiological studies were performed among 594 primary schoolchildren in 1995 and 541 in 2001 using the same standardized questionnaire. Lifetime prevalence of "doctor's-diagnosed asthma" increased significantly from 3.4 % in 1995 to 9.6 % in 2001. This trend may be due to the real increase in the prevalence of asthma and also may be a result of better physician's diagnosis and/or better parents' health education. A substantial increase of asthma-related symptoms (post-exercise breathlessness, wheezing and dyspnoea) was also observed between these years (8.3-17.7 %, 6.2-13.2 % and 7.6-13.3 %, respectively). These results suggest that asthma in Polish schoolchildren is still underdiagnosed.

Progress in pediatric allergology in 2001.

The year 2001 brought much essential news in the nomenclature, pathophysiology and allergic diseases therapy, especially in children. They should soon find their own place in everyday practice of allergology. However, some of them need further research. The most important news and discoveries refer to a proposal of modified allergic nomenclature, new classification of allergic rhinitis (AR) and its links with asthma, prevention of allergic diseases (breast-feeding, probiotics) and pharmacotherapy of atopic dermatitis (AD).

Possibilities of using alefacept in the treatment of psoriasis.

Alefacept belongs to the new generation of drugs applied in the treatment of psoriasis. It is an immunomodulatory recombinant, fully human lymphocyte function associated antigen-3/immunoglobulin G1 fusion protein (LFA-3-Ig) CD2 antagonist that targets memory-effector T cells by binding CD2 on the T cell surface. It blocks the interactions of leukocyte functional antigen (LFA)-3 with CD2 interaction. This drug is used to treat moderate-to-severe chronic plaque psoriasis and there was conducted a pilot study of psoriatic arthritis. It was observed that Alefacept had reduced peripheral-blood memory effector T-lymphocyte (CD45RO+) counts, cells which are responsible for sustaining the disease. Pharyngitis, dizziness, increased cough, nausea, pruritus, myalgia, chills, injection site inflammation, and accidental injury were recorded. So far, in the conducted trials no generalised immunosuppression or increased risk of infection or malignancy were observed. The possibility of increased risk of infections and malignancies must be considered because of reduced lymphocyte counts.