Andrzej Bozek

The effect of pimecrolimus on expression of genes associated with skin barrier dysfunction in atopic dermatitis skin lesions

Abstract:  The mechanism of action of pimecrolimus (PIM) on atopic lesions is still under consideration. Thus far, we have evidence of its anti‐inflammatory and immunomodulatory activity, and recent papers focus on its effect on epidermal barrier function. This study analysed changes in the expression of genes associated with skin barrier dysfunction in atopic dermatitis (AD) skin lesions after 2 weeks of exposure to PIM 1% cream. A real‐time quantitative PCR analysis of selected epidermal differentiation complex genes and three alternative pathway keratins was performed in skin biopsies from 11 individuals with AD before and after PIM exposure. The real‐time quantitative PCR analysis was compared to non‐lesional skin in the same patients. Involucrin, a small proline‐rich region (SPRR) 2C gene, and alternative pathway keratin 16 showed significant over‐expression in lesional skin followed by significant decrease after PIM therapy. The SPRR1A gene, S100A9, and keratin 6A were also increased; however, the decrease after PIM treatment was not significant. The changes in S100 A2, A7 and A8 followed a similar course with borderline significance. SPRR4 had a significant decrease in expression in lesional versus non‐lesional skin, which persisted after PIM treatment. No significant changes were detected in mRNA expression levels of filaggrin and loricrin. Our results suggest that PIM can be effective in restoring the epidermal barrier in patients with AD at least in part by its impact on expression of genes, which are important for the normal barrier function of skin.

Pre-seasonal, subcutaneous immunotherapy: a double-blinded, placebo-controlled study in elderly patients with an allergy to grass

BACKGROUND There is limited evidence indicating that specific immunotherapy in elderly patients is safe and effective. OBJECTIVE To evaluate the safety and efficacy of pre-seasonal specific subcutaneous immunotherapy (SCIT) against grass pollen allergens in patients older than 65 years with seasonal allergic rhinitis and to measure the prime outcome of area under the curve for the combined symptoms and medication score during grass pollen season after 3 years of SCIT in a double-blinded, placebo-controlled trial. METHODS This study included 60 65- to 75-year-old patients with seasonal allergic rhinitis and grass pollen allergy. Patients were individually randomized to the active or placebo group. Thirty-three subjects in the SCIT group and 27 subjects in the placebo group were monitored for 3 years. Patients were required to record each use of anti-allergy medication. RESULTS Thirty-one patients completed 3 years of pre-seasonal SCIT and 24 subjects finished placebo treatment. The median area under the curve for the combined symptoms and medication score after the third grass pollen season after SCIT was significantly decreased from 7.85 (range 3.67-8.98) to 4.63 (range 3.56-7.80) in the active group and did not significantly change in the placebo group. In the active group, the combined symptoms and medication score was decreased by 41%, the symptoms score was decreased by 55%, and the medication score was decreased by 64% after 3 years of immunotherapy. CONCLUSION Pre-seasonal SCIT in the elderly is safe and efficacious and elicits an immune response comparable to what is found in studies of younger patients.

HLA Status in Patients with Chronic Spontaneous Urticaria

Chronic spontaneous urticaria (CSU) is the most common form of chronic urticaria. A considerable amount of data supports an immunological basis for CSU. Some research has focused on the association between chronic urticaria and specific human leukocyte antigen (HLA) alleles. The aim of this study was to investigate the HLA status of Polish patients diagnosed with CSU. Methods: The standard complement-dependent microlymphocytotoxicity assay and PCR amplification with sequence-specific primers were used to analyze HLA alleles in 115 patients diagnosed with CSU, and the results were compared to those from 162 healthy, genetically unrelated individuals. Results: Among the HLA-A alleles, A-33 occurred significantly more often in the control group (p < 0.01). Analysis of the HLA-B allele frequencies revealed the prevalence of the B44 antigen in the study group (p < 0.0001). Frequencies of HLA-C alleles and HLA-DQ did not differ significantly between the groups. Among the HLA class II alleles, DRB1*04 was observed significantly more often in the study population (p < 0.001), mainly in the autoimmunological subtype of urticaria. Conclusion: HLA alleles may be involved in CSU development or play a protective role in CSU.

The influence of hospitalizations due to exacerbations or spontaneous pneumothoraxes on the quality of life, mental function and symptoms of depression and anxiety in patients with COPD or asthma.

Abstract Background: Patients with bronchial asthma or chronic obstructive pulmonary disease (COPD) frequently have a low quality of life (QoL) in addition to depression symptoms. The aim of this study was to compare the QoL, depression symptoms, mental function and anxiety in patients with asthma or COPD exacerbations or spontaneous pneumothoraxes (SP) to patients with stable disease. Materials and methods: Patients with a confirmed diagnosis of severe (III degree) bronchial asthma or COPD were included in this study. Prospective observations of asthma or COPD exacerbations or SP were performed over a three-year period. QoL was assessed using St. George’s Respiratory Questionnaire (SGRQ). In addition, the AQ20 questionnaire (AQ20), the Hospital Anxiety and Depression Scale (HADS) and the Mini-Mental State Examination (MMSE) were administered. Results: A total of 233 patients (112 with asthma and 121 with COPD; mean age 57.9 ± 11.9 years) were included in the study. Patients with COPD or asthma had a low QoL as estimated by the SGRQ (mean ± SD: 27.5 ± 12.9 and 25.1 ± 10.2 for asthma and COPD, respectively). Asthma exacerbations, COPD exacerbations or SP requiring hospitalization were associated with lower SGRQ scores over the three-year observation period (41.5 ± 11.7, 57.9 ± 14.3 and 65.3 ± 11.4, respectively). The mean MMSE score significantly decreased after an asthma exacerbation compared to the baseline (29.9 ± 2.1 versus 27.2 ± 3.1; p < 0.05). The mean MMSE score decreased after COPD exacerbations (28.5 ± 0.9 versus 26.9 ± 1.2; p < 0.05) and after COPD with an SP event (28.8 ± 1.2 versus 24.1 ± 2.2; p < 0.05). Conclusion: Low QoL and mental impairment were observed in patients with asthma and COPD. In addition, the QoL significantly decreased following hospitalizations due to exacerbations or SP.

Local Allergic Rhinitis to Pollens is Underdiagnosed in Young Patients

Background Local allergic rhinitis (LAR) has been observed in patients without atopy. However, LAR is still underdiagnosed in patients with perennial or seasonal nasal symptoms. Objective The aim of this study was to determine the prevalence of LAR in young patients with a previous diagnosis of nonallergic rhinitis or suspicion of allergy. Methods A total of 121 patients, ages 12–18 years old, with confirmed nonallergic rhinitis and typical seasonal nasal symptoms were examined. Skin-prick tests; serum and nasal specific immunoglobulin E (IgE) measurements; and nasal provocation tests by using grass (Phleum partense), Artemisia, and birch pollens were performed. A control group of age-matched patients with a diagnosis of seasonal allergic rhinitis underwent the same procedures as the test group. Results LAR to grass pollen (P. partense), Artemisia, and birch was confirmed in 17 (16.6%), 6 (5.9%), and 9 (8.9%) of patients, respectively. Polyvalent allergy was established in 21 subjects (20.8%): grass and Artemisia, 11 patients (10.9%); and grass and birch, 10 patients (9.9%). The remaining 48 patients (47.5%) were diagnosed with nonallergic rhinitis. The results of the nasal provocation tests and the concentrations of nasal IgE were similar among the analyzed groups. Furthermore, the concentration of nasal IgE increased faster in patients with LAR than in patients with allergic rhinitis; however, this difference was not statistically significant. Conclusion LAR is a serious problem in young patients; however, its significance is still unappreciated.

Asthma, COPD and comorbidities in elderly people

Abstract Co-morbidities are a significant problem in the elderly population but are rarely presented and analyzed for interdependencies among the various coexisting chronic diseases. Objective: The aim of this study was to present a profile of comorbidities in elderly patients with and without asthma and COPD. Methods: Respondents were recruited at 20 sites in Poland. Stratified random sampling from patient databases resulted in 15,973 patients older than 60 years of age. A retrospective analysis of medical history and ICD-10 codes was performed. In addition, patients underwent a spirometry test with a bronchial reversibility test and were administered questionnaires on the prevalence of chronic diseases by doctors. Results: The study population consisted of 1023 asthmatic patients, 1084 patients with COPD and 1076 control subjects without any signs of bronchoconstriction and with correct spirometry. Patients with asthma exhibited a similar distribution of cardiovascular and metabolic co-morbidities as the control group. However, asthmatic patients had a higher prevalence of arterial hypertension and depression with an odds ratio (OR) = 1.48 (95% CI: 1.38–1.62) and OR = 1.52 (95% CI: 1.44–1.68), respectively. Coronary disease (OR = 2.12; 95% CI: 1.97–2.33), cor pulmonale (OR = 3.1; 95% CI: 2.87–3.22) and heart failure (OR = 2.71; 95% CI: 2.64–3.11) were predominantly observed in patients with COPD. Patients with severe asthma exhibited a greater predisposition to cardiovascular and neuropsychiatric diseases. Conclusion: Asthma coexisted frequently with arterial hypertension and depression in elderly patients. Patients with COPD have a more exaggerated profile of coexisting diseases, specifically cardiovascular problems.

Efficacy and safety of birch pollen immunotherapy for local allergic rhinitis

BACKGROUND Local allergic rhinitis (LAR) is a relatively new disease. OBJECTIVE To ascertain the effects of allergen-specific immunotherapy in LAR. METHODS A randomized, double-blind, placebo-controlled trial of birch subcutaneous allergen immunotherapy (AIT) for LAR was performed in 28 patients. The therapy was performed for 24 months in 15 patients with AIT and 13 patients given placebo. The primary end point was decrease in symptom medication score (SMS). In addition, we monitored serum-specific immunoglobulin E (IgE), serum-specific immunoglobulin G4, nasal-specific IgE to Bet v 1, and safety and quality-of-life parameters. RESULTS After 24 months of treatment, there was a significant decrease in the median area under the curve for SMS of the active group vs the placebo group: 2.14 (range, 1.22-4.51) vs 6.21 (range, 5.12-7.89), at the P < .05 level. During AIT, the active group showed a significant decrease in SMS of up to 65% vs baseline. A significant increase in immunoglobulin G4 and decrease in nasal-specific IgE were observed in the active group during AIT compared with the placebo group. AIT was well-tolerated and without systemic reactions. CONCLUSION This study demonstrates that AIT for birch pollen in patients with LAR was clinically effective and exhibited good tolerance. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT03157505.

The clinical differences of asthma in patients with molds allergy

INTRODUCTION Bronchial asthma is an increasing problem worldwide. The course of bronchial asthma is dependent on the type of inducing allergens. The differences between the clinical features of asthma in patients with monovalent allergies to molds and with other allergies were explored. MATERIAL AND METHODS Randomly selected 1910 patients (924 women and 986 men) between 18-86 years in age were analyzed according to type of allergy and asthma. The diagnosis of asthma was confirmed on the basis of GINA criteria, physical examination and spirometry. Allergy diagnosis was confirmed on the basis of medical history, a positive skin prick test and the measurement of serum-specific IgE to inhalant allergens, using an extended profile of mold allergens. RESULTS Patients with monovalent allergies to molds (4% of analyzed group) had significantly more frequent diagnoses of asthma than patients in the other group (53% vs. 27.1-32.4%, p < 0.05). Patients with allergies to Alternaria alternata had an odds ratio of 2.11 (95%CI: 1.86-2.32) for receiving a diagnosis of bronchial asthma. They had less control over their asthma, which was more severe compared to patients with other allergies. Patients with asthma and allergies to mold had significantly more frequent exacerbation of asthma requiring systemic corticosteroids and/or hospitalization. They used a significantly greater mean daily dose of inhaled steroids compared to other patients. CONCLUSION Patients with monovalent IgE allergies to molds are at a higher risk for asthma than patients with other allergies. Their asthma is often more intense and less controlled compared to that of patients with other types of allergies.

Immunotherapy of mold allergy: A review

ABSTRACT Mold allergies are common, mainly target the respiratory tract and present as allergic rhinitis and/or bronchial asthma. Molds include a large group of different allergens that induce all types of allergic reactions. Allergen specific immunotherapies (AITs) to molds are common; however, at the present time, they are limited to Alternaria. This review presents not only the benefits but also the problems with such types of AIT based on the literature and our experience.

The relationship between autoimmunity and specific immunotherapy for allergic diseases

The aim of this study was to perform a 20-year post-specific immunotherapy (SIT) observational evaluation for an assessment of any manifestations of autoimmune disease or the appearance of autoantibodies in serum. In total, 1,888 patients (902 women and 986 men) were observed. The mean age of the patients was 34.1±12.4 y at the start of the prospective observation after finishing SIT. New incidences of autoimmune disease and/or the presence of autoantibodies in serum were monitored. The SIT group was compared with control groups consisting of allergic patients who had very received SIT and with non-allergic subjects. There were no significant differences in the autoimmune disease prevalence between the allergic patients with or without SIT. However, significantly higher prevalence of 4 different autoimmune diseases (AID) were observed in the non-allergic patients during the same period. Additionally, the incidence of 8 different autoantibodies was significantly higher in non-allergic patients than in control subjects. Hashimoto disease was the most common autoimmune disease observed. The results of this long-term observational study indicated a lack of a significant prevalence of new instances of autoimmune disease during 20 y of observation post-SIT and at a rate lower than that of non-allergic control subjects, suggesting that SIT is safe in this regard in the long term.