Environmental exposures as risk factors for idiopathic inflammatory myopathies.

Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of rare autoimmune diseases, with increasing incidence rates observed in the recent years. The pathogenesis of IIM remains not fully understood, and the interaction of genetic and environmental factors is suspected. It is unclear whether the observed upward trend in the IIM incidence is solely due to improved access to effective diagnostics or perhaps due to increased exposure to external risk factors. The PUBMED database was thoroughly searched for articles describing environmental exposures potentially triggering the onset of IIM. The article summarizes the current knowledge available on this subject, taking into account various environmental factors, including among others UV radiation, infectious agents with SARS-CoV-2, inhaled particles, or iatrogenic effects. Limitations and unmet needs requiring further studies were highlighted.

miRNA expression in serum and PBMCs isolated from middle-aged and elderly patients during asthma exacerbation.

microRNAs are short, noncoding RNA molecules involved in many inflammatory processes including bronchial asthma. Rhinoviruses are the main cause of acute asthma attack and may be involved in miRNA profile dysregulation. The aim of the study was to investigate the serum miRNA profile during asthma exacerbation in middle-aged and elderly patients. We also evaluated in this group in vitro response to rhinovirus 1b exposure. Seventeen middle-aged and elderly asthmatics were admitted to an outpatient clinic during asthma exacerbation and within a period of 6-8 weeks later. Blood samples were collected from the subjects and PBMCs were isolated. Cells were cultured in the presence of Rhinovirus 1b and with the medium only, and, after 48 h. miRNA expression (miRNA-19b, -106a, 126a, and -146a) isolated from serum and PBMCs (cultures) was evaluated with RT-PCR. Cytokines (INF-γ, TNF-α, IL6, and Il-10) in culture supernatants were evaluated with flow cytometry. On exacerbation visit patients demonstrated higher expression of serum miRNA-126a and -146a as compared to follow-up visit. There was a positive correlation between asthma control test results and miRNA-19, -126a, -146a. There was no other significant association between patient characteristics and the miRNA profile. Rhinovirus exposure did not changed miRNA expression in PBMCs as compared to medium on both visits. Cytokine production in culture supernatants significantly increased after rhinovirus infection. The group of middle-aged and elderly patients demonstrated changed levels serum miRNA during asthma exacerbation as compared to follow-up visit; however, correlations between their expression and clinical features were hardly noticeable. Rhinovirus did not affect expression of miRNA in PBMCs; yet, it induced cytokine production.

Polymorphisms in DNA Repair Genes and Association with Rheumatoid Arthritis in a Pilot Study on a Central European Population.

Rheumatoid arthritis (RA) is a chronic, multifactorial autoimmune disease characterized by chronic arthritis, a tendency to develop joint deformities, and involvement of extra-articular tissues. The risk of malignant neoplasms among patients with RA is the subject of ongoing research due to the autoimmune pathogenesis that underlies RA, the common etiology of rheumatic disease and malignancies, and the use of immunomodulatory therapy, which can alter immune system function and thus increase the risk of malignant neoplasms. This risk can also be increased by impaired DNA repair efficiency in individuals with RA, as reported in our recent study. Impaired DNA repair may reflect the variability in the genes that encode DNA repair proteins. The aim of our study was to evaluate the genetic variation in RA within the genes of the DNA damage repair system through base excision repair (BER), nucleotide excision repair (NER), and the double strand break repair system by homologous recombination (HR) and non-homologous end joining (NHEJ). We genotyped a total of 28 polymorphisms in 19 genes encoding DNA repair-related proteins in 100 age- and sex-matched RA patients and healthy subjects from Central Europe (Poland). Polymorphism genotypes were determined using the Taq-man SNP Genotyping Assay. We found an association between the RA occurrence and rs25487/XRCC1, rs7180135/RAD51, rs1801321/RAD51, rs963917/RAD51B, rs963918/RAD51B, rs2735383/NBS1, rs132774/XRCC6, rs207906/XRCC5, and rs861539/XRCC3 polymorphisms. Our results suggest that polymorphisms of DNA damage repair genes may play a role in RA pathogenesis and may be considered as potential markers of RA.

Update on Malignancy in Myositis-Well-Established Association with Unmet Needs.

Idiopathic inflammatory myopathies are a group of rare connective tissue diseases with a well-documented association with malignancy. The mechanisms underlying the increased risk of neoplasms in the course of myositis are not fully understood. The Pubmed database has been thoroughly screened for articles concerning cancer-associated myositis (CAM). The article summarizes the current state of knowledge on the epidemiology and pathogenesis of CAM. Furthermore, it analyses potential risk and protective factors for developing CAM, with particular emphasis on the association with distinct serological profiles. The review summarizes recommendations proposed so far for the management of CAM and presents a novel scheme for cancer screening proposed by the authors. Moreover, promising areas requiring further research were indicated.

Circulating MicroRNAs and T-Cell Cytokine Expression Are Associated With the Characteristics of Asthma Exacerbation.

PURPOSE: Immunological mechanisms underlying asthma exacerbation have not been elucidated. The aim of this study was to assess the associations of various asthma exacerbation traits with selected serum microRNA (miRNA) expression and T-cell subpopulations. METHODS: Twenty-one asthmatics were studied during asthma exacerbation (exacerbation visit [EV] and the follow-up visit [FV] at 6 weeks). At both visits, spirometry was performed, fractional exhaled nitric oxide (FeNO) was measured, and nasopharyngeal and blood samples were collected. In nasopharyngeal samples, respiratory viruses were assayed by multiplex polymerase chain reaction (PCR), and bacterial cultures were performed. Serum miRNAs were assayed with real-time PCR. T-cell surface markers, eosinophil progenitors and intracellular cytokines were assessed by flow cytometry. RESULTS: Two-thirds of patients had moderate or severe exacerbation and the FV, overall improvement in asthma control was observed. The mean expression of serum miRNA-126a, miRNA-16 and miRNA-21 was significantly lower at the EV than at the FV. At EV, miRNA-29b correlated with FeNO (r = 0.44, P < 0.05), and 5 of 7 miRNA tested correlated with pulmonary function tests. The number of cluster of differentiation (CD)45+CD4+interleukin (IL)4+ cells was significantly higher at the EV than at the FV, and positive correlations of T-regulatory cells and eosinophil progenitors with asthma control was found. At the EV, serum miRNAs negatively correlated with the number of T cells expressing IL-4, IL-17, IL-22 and interferon gamma, while at the FV both positive and negative correlations with T-cell subsets were observed. No association of detected pathogen (viruses and bacteria) in nasopharyngeal fluid with clinical, functional and immunological parameters was found. CONCLUSIONS: Epigenetic dysregulation during asthma exacerbation could be related to respiratory function, airway inflammation and T-cell cytokine expression.

The profile of respiratory pathogens in induced sputum of elderly and non-elderly asthmatics.

INTRODUCTION: Respiratory pathogens are thought to be involved in the pathogenesis and exacerbations of asthma at all ages; however, little is known about the airway microbiome in the elderly. AIM OF THE STUDY: To identify respiratory pathogens in the induced sputum (IS) of elderly asthmatics, and to determine the association between pathogens and the markers of asthma activity. MATERIAL AND METHODS: Twenty-nine subjects with stable asthma, 15 above 65 years of age and 14 aged 30-49 years, underwent clinical evaluation, fractional exhaled nitric oxide measurement, and sputum induction. Pathogens were detected by multiplex reverse transcription polymerase chain reaction. The periostin concentration of IS supernatants was measured by enzyme-linked immunosorbent assay. Serum eosinophil cationic protein and total IgE levels were measured by ImmunoCAP. RESULTS: Elderly patients, as compared to non-elderly, had significantly higher eosinophilia in IS, although other markers of eosinophilic inflammation were comparable. Half of the subjects were positive for Haemophilus influenzae. Chlamydophila pneumoniae was found in two subjects. Respiratory viruses were detected in more than 70% of patients. The detection rates and profiles of atypical bacteria and respiratory viruses were similar in both groups. Only in the elderly asthmatics was influenza A positivity associated with lower predicted FVC%, RSV A positivity connected with decreased tIgE concentration, and RSV B positivity related to a lower percentage of lymphocytes in IS. CONCLUSIONS: Despite the existence of differences in some clinical and inflammatory characteristics of asthma between elderly and non-elderly asthmatics, the pathogen detection rates in the IS from the two groups are similar.

Obstructive Sleep Apnea: From Intermittent Hypoxia to Cardiovascular Complications via Blood Platelets.

Obstructive sleep apnea is a chronic condition characterized by recurrent episodes of apneas or hypopneas during sleep leading to intermittent hypoxemia and arousals. The prevalence of the sleep disordered breathing is estimated that almost 50% of men and 24% of women suffer from moderate to severe form of the disorder. Snoring, collapse of upper airways and intermittent hypoxia are main causes of smoldering systemic inflammation in patients suffering from obstructive sleep apnea. The systematic inflammation is considered one of the key mechanisms leading to significant cardiovascular complications. Blood platelets, formerly not even recognized as cells, are currently gaining attention as crucial players in the immune continuum. Platelet surface is endowed with receptors characteristic for cells classically belonging to the immune system, which enables them to recognize pathogens, immune complexes, and interact in a homo- and heterotypic aggregates. Platelets participate in the process of transcellular production of bioactive lipids by delivering both specific enzymes and substrate molecules. Despite their lack of nucleus, platelets synthetize proteins in a stimuli-dependent manner. Atherosclerosis and consequent cardiovascular complications result from disruption in homeostasis of both of the platelet roles: blood coagulation and inflammatory processes modulation. Platelet parameters, routinely evaluated as a part of complete blood count test, were proposed as markers of cardiovascular comorbidity in patients with obstructive sleep apnea. Platelets were found to be excessively activated in this group of patients, especially in obese subjects. Persistent activation results in enhanced spontaneous aggregability and change in cytokine production. Platelet-lymphocyte ratio was suggested as an independent marker for cardiovascular disease in obstructive sleep apnea syndrome and continuous positive air pressure therapy was found to have an impact on platelet parameters and phenotype. In this literature review we summarize the current knowledge on the subject of platelets involvement in obstructive sleep apnea syndrome and consider the possible pathways in which they contribute to cardiovascular comorbidity.

Periostin in Exhaled Breath Condensate and in Serum of Asthmatic Patients: Relationship to Upper and Lower Airway Disease.

PURPOSE: Periostin is considered a biomarker for eosinophilic airway inflammation and have been associated with NSAID-Exacerbated Respiratory Disease (NERD) and chronic rhinosinusitis (CRS). In this study, we aimed to evaluate periostin in exhaled breath condensate (EBC) and in serum of patients with various asthma phenotypes. METHODS: The study included 40 asthmatic patients (22 with NERD) and 17 healthy controls. All the procedures (questionnaire, spirometry, FeNO, nasal swabs, EBC collecting, and blood sampling) were performed on the same day. Periostin concentrations were measured using an ELISA kit. RESULTS: Periostin was detected in EBC from 37 of 40 asthmatics and in 16 from 17 of controls. The concentration of periostin in EBC did not differ between the study groups and was not associated with NERD or asthma severity. However, the EBC periostin was significantly higher in asthmatics with CRS as compared to those without (3.1 vs 2 ng/mL, P=0.046). Patients with positive bacterial culture from nasal swabs had higher EBC periostin concentrations than those without (3.2 vs 2.1 ng/mL; P=0.046). The mean serum periostin level was higher in asthmatics with a 1-year history of exacerbation than in those without (3.2 vs 2.3 ng/mL, P=0.045). Asthmatics with skin manifestation of NSAIDs hypersensitivity had higher serum periostin levels as compared to those without (3.5 vs 2.3 ng/mL; P=0.03). CONCLUSIONS: EBC periostin levels seem to reflect intensity of upper airway disease in asthmatics, while serum levels of periostin are associated with asthma activity (exacerbations or FeNO) or NERD subphenotypes.

Clinical Trials of Aspirin Treatment After Desensitization in Aspirin-Exacerbated Respiratory Disease.

The clinical efficacy of aspirin treatment after desensitization in patients with respiratory disease exacerbated by nonsteroidal anti-inflammatory drugs has been documented in observational studies and in double-blind placebo-controlled trials. There is no general agreement with regard to the optimal maintenance dose or duration of treatment with acetylsalicylic acid after desensitization, thus further studies are necessary to offer clear guidelines to clinicians. This article summarizes data from noncontrolled, active-control, and placebo-controlled trials assessing clinical effectiveness and reporting on safety of treatment with acetylsalicylic acid in desensitized patients with respiratory disease exacerbated by nonsteroidal anti-inflammatory drugs.

Clinical benefits of aspirin desensitization in patients with nonsteroidal anti-inflammatory drug exacerbated respiratory disease are not related to urinary eicosanoid release and are accompanied with decreased urine creatinine.

BACKGROUND: Treatment with acetylsalicylic acid (ASA) after desensitization may be a therapeutic option in patients with nonsteroidal anti-inflammatory drug exacerbated respiratory disease (NERD). The mechanisms that lead to improvement in rhinosinusitis and asthma symptoms remain unknown. AIM: To attribute the documented clinical effects of ASA treatment of chronic rhinosinusitis and/or asthma to the release of eicosanoid metabolites in urine. METHODS: Fourteen patients with NERD were successfully desensitized, and, eventually, eight patients were treated with 650 mg of ASA daily for 3 months. In addition to clinical assessments, nuclear magnetic resonance imaging and smell test were performed before and after treatment with ASA. Venous blood and urine were collected before desensitization and after 1 and 3 months of treatment. The levels of urinary leukotrienes (LT) (cysteinyl LT and LTE4) and tetranor PGDM (metabolite of prostaglandin D2) were measured by enzyme-linked immunosorbent assay. RESULTS: Treatment with ASA after desensitization alleviated symptoms of rhinosinusitis, improved nasal patency (mean, 50% decrease in peak nasal inspiratory flow) and sense of smell (fourfold increase in smell test score) in as early as 4 weeks. Clinical improvements were not accompanied by any change in sinonasal mucosa thickness as assessed with nuclear magnetic resonance. Urinary cysteinyl LTs, LTE4, and prostaglandin D2 metabolite remained relatively stable during ASA treatment and did not correlate with clinical improvements. Desensitization was associated with a progressive decrease of urinary creatinine. CONCLUSION: Clinical improvement in rhinosinusitis and/or asthma after ASA desensitization was not related to concentrations of urinary eicosanoid metabolites. A decrease of urinary creatinine requires further study to determine the renal safety of long-term treatment with ASA after desensitization.

Angiopoietin-2 concentration in serum is associated with severe asthma phenotype.

BACKGROUND: Several proangiogenic molecules have been implicated in the pathogenies of asthmatic inflammation and remodeling. The aim of the study was to compare the concentration of proangiogenic factors in the sera of asthmatic patients and in healthy subjects (HS), and to refer the concentrations to both clinical and inflammatory markers of the disease severity. METHODS: Serum was collected from 45 patients with severe/refractory asthma (SRA) and 51 patients with non-severe asthma (nSA). The control group included 30 HS. Serum concentrations of Angiopoietin-1, Angiopoietin-2, vascular endothelial growth factor (VEGF) and osteopontin were assessed by the enzyme-linked immunosorbent assay. RESULTS: The levels of Angiopoietin-1 (68.8 ± 2.7 vs 56.4 ± 9.3 ng/ml; p < 0.05), Angiopoietin-2 (4.9 ± 0.35 vs 1.38 ± 0.14 ng/ml; p < 0.0001) and VEGF were significantly higher in asthmatic patients (n = 94) as compared to HS (255 ± 45.4 vs 424.5 ± 27.8 pg/ml; p < 0.01). The mean serum level of Angiopoietin-2 was found to be significantly higher in patients with SRA as compared to nSA patients (6.04 ± 0.46 vs 3.84 ± 0.43; p < 0.001). Angiopoietin-2 serum level correlated with respiratory function and with parameters of asthma severity: the mean number of asthma exacerbations in the preceding 12 months (R = 0.21; p < 0.05), mean number of emergency visits due to severe asthma exacerbation (R = 0.24; p < 0.04) and mean number of hospitalizations (R = 0.21; p < 0.05) or dose of inhaled glucocorticosteroids taken by the patients (R = 0.36; p < 0.001). CONCLUSION: Angiopoietin-2 seems to be a crucial proangiogenic cytokine overproduced in patients with SRA characterized by repeated exacerbations and Angiopoietin-2 serum levels can serve as a biomarker of severe asthma.

Environmental factors affecting seasonality of ambulance emergency service visits for exacerbations of asthma and COPD.

OBJECTIVE: The aim of this study was to assess the association of severe exacerbations of asthma and Chronic Obstructive Pulmonary Disease (COPD) requiring ambulance emergency service (AES) visits with meteorological parameters and influenza outbreaks. METHODS: The records of patients calling the AES in 2007 and 2008 in the urban area of Lodz due to dyspnea were analyzed. Information on 25 daily reported meteorological parameters was obtained from the local meteorological service and data on influenza outbreaks obtained from the national surveillance service. RESULTS: During the winter months, a significantly higher mean daily number of AES visits for both COPD and asthma were noticed when compared to the summer. Interestingly, the number of daily AES visits correlated with several weather parameters, and the multiple regression analysis confirmed a negative correlation with minimum temperature, mean temperature and the dew point for both diseases (R = 0.526; p < 0.01; R = 0.577; p < 0.01 and R = 0.589; p < 0.01). Furthermore, the increased number of AES visits also correlated with a new number of cases of influenza infections as reported by local influenza surveillance system (rs = 77.6%; p < 0.001 and rs = 80.8%; p < 0.001 for asthma and COPD, respectively). CONCLUSION: Seasonality of AES visits for asthma and COPD are similar and seems to be related to specific weather conditions and to influenza outbreaks.

Seven steps to the diagnosis of NSAIDs hypersensitivity: how to apply a new classification in real practice?

Frequent use of non-steroidal anti-inflammatory drugs (NSAIDs) has been paralleled by increasing occurrence of adverse reactions, which vary from mild local skin rashes or gastric irritation to severe, generalized symptoms and even life-threatening anaphylaxis. NSAID-induced hypersensitivity reactions may involve both immunological and non-immunological mechanisms and should be differentiated from type A adverse reactions. Clinical diagnosis and effective management of a hypersensitive patient cannot be achieved without identifying the underlying mechanism. In this review, we discuss the current classification of NSAID-induced adverse reactions and propose a practical diagnostic algorithm that involves 7 steps leading to the determination of the type of NSAID-induced hypersensitivity and allows for proper patient management.

Association of serum Clara cell protein CC16 with respiratory infections and immune response to respiratory pathogens in elite athletes.

BACKGROUND: Respiratory epithelium integrity impairment caused by intensive exercise may lead to exercise-induced bronchoconstriction. Clara cell protein (CC16) has anti-inflammatory properties and its serum level reflects changes in epithelium integrity and airway inflammation. This study aimed to investigate serum CC16 in elite athletes and to seek associations of CC16 with asthma or allergy, respiratory tract infections (RTIs) and immune response to respiratory pathogens. METHODS: The study was performed in 203 Olympic athletes. Control groups comprised 53 healthy subjects and 49 mild allergic asthmatics. Serum levels of CC16 and IgG against respiratory viruses and Mycoplasma pneumoniae were assessed. Allergy questionnaire for athletes was used to determine symptoms and exercise pattern. Current versions of ARIA and GINA guidelines were used when diagnosing allergic rhinitis and asthma, respectively. RESULTS: Asthma was diagnosed in 13.3% athletes, of whom 55.6% had concomitant allergic rhinitis. Allergic rhinitis without asthma was diagnosed in 14.8% of athletes. Mean CC16 concentration was significantly lower in athletes versus healthy controls and mild asthmatics. Athletes reporting frequent RTIs had significantly lower serum CC16 and the risk of frequent RTIs was more than 2-fold higher in athletes with low serum CC16 (defined as equal to or less than 4.99 ng/ml). Athletes had significantly higher anti-adenovirus IgG than healthy controls while only non-atopic athletes had anti-parainfluenza virus IgG significantly lower than controls. In all athletes weak correlation of serum CC16 and anti-parainfluenza virus IgG was present (R = 0.20, p < 0.01). In atopic athletes a weak positive correlations of CC16 with IgG specific for respiratory syncytial virus (R = 0.29, p = 0.009), parainfluenza virus (R = 0.31, p = 0.01) and adenovirus (R = 0.27, p = 0.02) were seen as well. CONCLUSIONS: Regular high-load exercise is associated with decrease in serum CC16 levels. Athletes with decreased CC16 are more susceptible to respiratory infections. Atopy may be an additional factor modifying susceptibility to infections in subjects performing regular high-load exercise.

Stem cell factor and its soluble receptor (c-kit) in serum of asthmatic patients- correlation with disease severity.

BACKGROUND: SCF (stem cell factor) is a pleiotropic cytokine exerting its role at different stages of bone marrow development and affecting eosinophil activation, mast cells and basophil chemotaxis and survival. The aim of the study was to assess concentration of SCF and its soluble receptor c-kit (sc-kit) in peripheral blood of patients with asthma referring it to asthma severity and phenotype. METHODS: The study involved 107 patients with bronchial asthma, well characterized with respect to severity and 21 healthy controls. Concentration of SCF and sc-kit in the patients serum were measured by ELISA method. RESULTS: Mean serum SCF level in the group of asthmatics (n = 88) was significantly higher as compared to healthy controls (1010 pg/ml +/- 37 vs 799 +/- 33; p < 0,001). The level of SCF was higher in patients with severe asthma as compared to patients with non-severe asthma (1054 +/- 41 pg/ml vs 819 +/- 50; p < 0,01) and correlated with dose of inhaled glucocorticosteroids taken by the patients to achieve asthma control (R = 0,28; p < 0,01). The mean sc-kit serum level did not differ between asthmatic patients and healthy controls, however the level of sc-kit in non-severe asthmatics was significantly higher as compared to patients with severe asthma and healthy controls. In asthmatic patients (n = 63) the level of sc-kit correlated positively with FEV1% predicted value (R = 0,45; p < 0,001) and MEF25% predicted value (R = 0,33; p < 0,01). The level of sc-kit inversely correlated with the dose of inhaled glucocorticosteroids taken by the patients (R = -0,26; p < 0,01). CONCLUSION: Serum levels of SCF and its soluble receptor c-kit seem to be reflect asthma severity suggesting a role for these molecules in asthmatic inflammation.

Recruitment of CD34+ progenitor cells into peripheral blood and asthma severity.

BACKGROUND: Previous studies have suggested that the number of progenitor cells is elevated in the peripheral blood of asthmatic patients and that the number of progenitors correlate with the severity of the disease. OBJECTIVE: To evaluate the number of leukocyte progenitor and eosinophil progenitor cells in the peripheral blood of patients with bronchial asthma in relation to disease severity. METHODS: The study involved 51 patients with asthma (25 patients with a mild form and 26 with a severe form of the disease) and a group of 12 healthy controls. Using the flow cytometric method, leukocyte (CD34+ leukocytes) and eosinophil progenitors (CD34+CD125+) were detected in the peripheral blood of both asthmatic patients and healthy controls. RESULTS: Patients with asthma had significantly more leukocyte progenitor cells (median, 0.06% vs 0.016%) and eosinophil progenitor cells (median, 0.046% vs 0.004%) compared with the controls. Patients with severe asthma had more leukocyte progenitor cells (0.12% vs 0.035%) and more eosinophil progenitor cells (0.102% vs 0.019%) than patients with mild asthma. The number of circulating leukocyte and eosinophil progenitor cells inversely correlated with the forced expiratory volume in 1 second percentage of predicted value (r = -0.4 and r = -0.35, respectively) and positively correlated (r = 0.63 and r = 0.65, respectively) with the dose of inhaled steroids used to control asthma. CONCLUSION: These data suggest that the presence of leukocyte precursors and eosinophil progenitor cells in the peripheral blood of asthmatic patients may reflect ongoing airway inflammation.

Systemic responses after bronchial aspirin challenge in sensitive patients with asthma.

BACKGROUND: In aspirin-sensitive patients with asthma, bronchial obstruction induced by oral aspirin may be associated with extrabronchial symptoms, suggesting the systemic character of the response. OBJECTIVE: Go assess potential systemic effects of local aspirin challenge, hemopoietic progenitors were measured in the peripheral blood of challenged patients. METHODS: In 19 patients with a history of aspirin-induced asthma, placebo-controlled bronchial challenges with lysine-aspirin were performed. Peripheral blood was collected before and then 1 hour and 20 hours after challenge (placebo or aspirin). Using the flow-cytometric method, the numbers of leukocyte (CD34+ cells) and eosinophil (CD34+CD125+ cells) progenitors were determined. RESULTS: The challenge was positive in 13 patients; 6 patients had isolated local bronchial reaction, and 7 patients developed systemic symptoms (bronchial and extrabronchial). In patients with positive challenge (n = 13), leukocyte progenitors increased significantly at 1 hour and 20 hours after challenge (mean, 0.04% at baseline, 0.066% at 1 hour after challenge, and 0.073% at 20 hours; P < .05). Eosinophil progenitors raised significantly from mean 0.017% before challenge to 0.04% (P < .05) at 20 hours after the challenge. At 20 hours after the challenge, the increase in leukocyte and eosinophil progenitors was observed only in patients with systemic reactions. Positive aspirin challenge was associated with a significant increase in eotaxin 2 serum concentration. CONCLUSION: This study demonstrated that bronchial challenge with aspirin may involve systemic reactions and is associated with mobilization of leukocyte and eosinophil progenitor cells from the bone marrow.