Maciej Kupczyk

Efficacy and safety of immunotherapy for allergies to Alternaria alternata in children

BACKGROUND The safety and efficacy of specific immunotherapy for mold allergy are not known in children and adolescents. OBJECTIVE We evaluated the efficacy and safety of specific immunotherapy with a standardized allergen extract in a randomized, double-blind, placebo-controlled, 3-year prospective study of patients who were allergic to only Alternaria alternata. METHODS Fifty children and adolescents (25 girls; 5-18 years of age) with A alternata-induced seasonal allergic rhinoconjunctivitis and/or bronchial asthma were randomly assigned to groups given treatment (Novo-Helisen Depot, A alternata 100%) or placebo. The primary end point was the combined symptom medication score. Secondary end points included safety, quality of life, and sensitivity to allergen-specific nasal challenge. RESULTS Forty-five children completed the 3-year study. Although there was no significant change in year 1, the combined symptom medication score decreased in years 2 and 3 of the study (by 38.7% and 63.5%, respectively; P < .001 for each). The reduction in symptoms was associated with a significant improvement in quality of life (P < .05) and decrease in sensitivity after allergen-specific nasal challenge. Side effects were observed in 7 patients; the most common (edema at the site of injection) occurred after 11 injections. CONCLUSIONS Allergen-specific immunotherapy with standardized A alternata extract reduces symptoms of asthma and rhinoconjunctivitis in children and adolescents without serious side effects.

Frequent exacerbators – a distinct phenotype of severe asthma

Exacerbations represent a major source of morbidity and mortality in asthma and are a prominent feature of poorly controlled, difficult‐to‐treat disease.

Stability of phenotypes defined by physiological variables and biomarkers in adults with asthma

Although asthma is characterized by variable airways obstruction, most studies of asthma phenotypes are cross‐sectional. The stability of phenotypes defined either by biomarkers or by physiological variables was assessed by repeated measures over 1 year in the Pan‐European BIOAIR cohort of adult asthmatics.

U.S. and European severe asthma cohorts: what can they teach us about severe asthma?

Abstract. Kupczyk M, Wenzel S (Medical University of Lodz, Lodz, Poland; University of Pittsburgh Pittsburgh, PA, USA; Karolinska Institutet, Stockholm, Sweden). US and European severe asthma cohorts: what can they teach us about severe asthma? (Review). J Intern Med 2012; 272: 121–132.

Reduction of asthma burden is possible through National Asthma Plans

To cite this article: Kupczyk M, Haahtela T, Cruz AA, Kuna P. Reduction of asthma burden is possible through National Asthma. Allergy 2010; 65: 415–419.

Solution-engineered palladium nanoparticles: model for health effect studies of automotive particulate pollution.

Palladium (Pd) nanoparticles are recognized as components of airborne automotive pollution produced by abrasion of catalyst materials in the car exhaust system. Here we produced dispersions of hydrophilic spherical Pd nanoparticles (Pd-NP) of uniform shape and size (10.4 ± 2.7 nm) in one step by Bradleys reaction (solvothermal decomposition in an alcohol or ketone solvent) as a model particle for experimental studies of the Pd particles in air pollution. The same approach provided mixtures of Pd-NP and nanoparticles of non-redox-active metal oxides, such as Al(2)O(3). Particle aggregation in applied media was studied by DLS and nanoparticle tracking analysis. The putative health effects of the produced Pd nanoparticles and nanocomposite mixtures were evaluated in vitro, using human primary bronchial epithelial cells (PBEC) and a human alveolar carcinoma cell line (A549). Viability of these cells was tracked by vital dye exclusion, and apoptosis was also assessed. In addition, we monitored the release of IL-8 and PGE(2) in response to noncytotoxic doses of the nanoparticles. Our studies demonstrate cellular uptake of Pd nanoparticles only in PBEC, as determined by TEM, with pronounced and dose-dependent effects on cellular secretion of soluble biomarkers in both cell types and a decreased responsiveness of human epithelial cells to the pro-inflammatory cytokine TNF-α. When cells were incubated with higher doses of the Pd nanoparticles, apoptosis induction and caspase activation were apparent in PBEC but not in A549 cells. These studies demonstrate the feasibility of using engineered Pd nanoparticles to assess the health effects of airborne automotive pollution.

DNA Methylation in the Neuropeptide S Receptor 1 (NPSR1) Promoter in Relation to Asthma and Environmental Factors

Asthma and allergy are complex disorders influenced by both inheritance and environment, a relationship that might be further clarified by epigenetics. Neuropeptide S Receptor 1 (NPSR1) has been associated with asthma and allergy and a study suggested modulation of the genetic risk by environmental factors. We aimed to study DNA methylation in the promoter region of NPSR1 in relation to asthma and environmental exposures. Electrophoretic Mobility Shift Assay (EMSA) was used to investigate potential functional roles of both genotypes and methylation status in the NPSR1 promoter. DNA methylation was analysed using EpiTYPER in blood samples from two well-characterized cohorts; the BIOAIR study of severe asthma in adults and the Swedish birth cohort BAMSE. We observed that DNA methylation and genetic variants in the promoter influenced the binding of nuclear proteins to DNA, suggesting functional relevance. Significant, although small, differences in methylation were related to both adult severe asthma (p = 0.0001) and childhood allergic asthma (p = 0.01). Furthermore, DNA methylation was associated with exposures such as current smoking in adults for two CpG sites (p = 0.005 and 0.04), parental smoking during infancy in the children (p = 0.02) and in which month the sample was taken (p = 0.01). In summary, DNA methylation levels in the promoter of NPSR1 showed small but significant associations with asthma, both in adults and in children, and to related traits such as allergy and certain environmental exposures. Both genetic variation and the methylated state of CpG sites seem to have an effect on the binding of nuclear proteins in the regulatory region of NPSR1 suggesting complex regulation of this gene in asthma and allergy.

Effects of celecoxib on major prostaglandins in asthma

Background Prostaglandin (PG) D2 is a pro‐inflammatory and bronchoconstrictive mediator released from mast cells, and is currently evaluated as a new target for treatment of asthma and rhinitis. It is not known which cyclooxygenase (COX) isoenzyme catalyses its biosynthesis in subjects with asthma.

Long-Term Deterioration of Lung Function in Asthmatic Outpatients

Background: Although the long-term deterioration of lung function in asthmatic patients has been described, the exact mechanism remains to be determined. Objectives: The aim of this study was to find correlations between age, sex, atopic status, duration of asthma, asthma severity and the decline in pulmonary function. Method: The medical histories of 1,006 randomly chosen asthmatic outpatients were studied and retrospective data on asthma duration, spirometry results, treatment and symptomatology were gathered. A screening spirometry was performed. Results: 598 women and 408 men (age: 44.59, range 12–95 years) participated in the study. Intermittent asthma was diagnosed in 35.4%, chronic mild asthma in 33.4%, moderate asthma in 23.8% and severe asthma in 7.45% of the patients. Statistically significant correlations between patient age, asthma duration and lung function measurements were found. Linear regression revealed the following differences in lung functions per year of asthma duration: FEV1: –0.882% of predicted; FVC: –0.509% of predicted; FEV1/FVC: –0.324% of predicted. The unadjusted annual decline was 80.1 ml/year (p = 0.00003) in FEV1 and 20.5 ml/year (p = 0.036) in FVC. A multiple regression model revealed that asthma severity appears to be the strongest factor influencing pulmonary function (β = –0.55, p < 0.001 for FEV1). Also, significant associations between pulmonary function measurements, patient age, atopic status and male sex were noted. Conclusions: The results of this large cohort study show that asthmatic patients develop a progressive decline in pulmonary function correlated with age, sex, duration of asthma and asthma severity. Early diagnosis and intervention is necessary to ameliorate any potential negative impact of asthma on lung function.

Increased YKL-40 and Chitotriosidase in Asthma and Chronic Obstructive Pulmonary Disease

RATIONALE Serum chitinases may be novel biomarkers of airway inflammation and remodeling, but less is known about factors regulating their levels. OBJECTIVES To examine serum chitotriosidase activity and YKL-40 levels in patients with asthma and chronic obstructive pulmonary disease (COPD) and evaluate clinically relevant factors that may affect chitinase levels, including genetic variability, corticosteroid treatment, disease exacerbations, and allergen exposure. METHODS Serum chitotriosidase (CHIT1) activity and YKL-40 (CHI3L1) levels, as well as the CHIT1 rs3831317 and CHI3L1 rs4950928 genotypes, were examined in subsets of patients with mild to moderate asthma (n = 76), severe asthma (n = 93), and COPD (n = 64) taking part in the European multicenter BIOAIR (Longitudinal Assessment of Clinical Course and Biomarkers in Severe Chronic Airway Disease) study. Blood was obtained at baseline, before and after a 2-week oral steroid intervention, up to six times during a 1-year period, and during exacerbations. Baseline chitinase levels were also measured in 72 healthy control subjects. The effect of allergen inhalation on blood and sputum YKL-40 levels was measured in two separate groups of patients with mild atopic asthma; one group underwent repeated low-dose allergen challenge (n = 15), and the other underwent high-dose allergen challenge (n = 16). MEASUREMENTS AND MAIN RESULTS Serum chitotriosidase and YKL-40 were significantly elevated in patients with asthma and those with COPD compared with healthy control subjects. Genotype and age strongly affected both YKL-40 and chitotriosidase activity, but associations with disease remained following adjustment for these factors. Correlations were observed with lung function but not with other biomarkers, including exhaled nitric oxide, blood eosinophils, periostin, and IgE. Generally, acute exacerbations, allergen-induced airway obstruction, and corticosteroid treatment did not affect circulating chitinase levels. CONCLUSIONS YKL-40 and chitotriosidase are increased in asthma and more so in COPD. The data in the present study support these substances as being relatively steroid-insensitive, non-T-helper cell type 2-type biomarkers distinctly related to chronic inflammatory disease processes.