Apolipoprotein A1 potentiates lipoxin A4 synthesis and recovery of allergen-induced disrupted tight junctions in the airway epithelium.

BACKGROUND: Asthma is characterized by chronic airway inflammation triggered by various allergens in the environment. Defects in the bronchial epithelial interface with the external environment are the hallmark of asthma. Apolipoprotein A-1 (ApoA1) or ApoA1 mimetics have demonstrated anti-inflammatory activity and preventive effects in mouse models. OBJECTIVE: We investigated airway levels of ApoA1 in asthmatics and the possible role of ApoA1 in protection of the bronchial epithelium and in resolution of inflammation in cellular and animal models of asthma. METHODS: ApoA1 levels were measured in bronchoalveolar lavage fluid (BALF) from asthmatics and healthy controls. With treatment of ApoA1, mouse model of house dust mite (HDM)-driven asthma and cultured primary bronchial epithelial cells obtained from asthmatics were examined. Tight junction (TJ) expression in the bronchial epithelial cells was assessed by using confocal microscopy and immunoblot. RESULTS: Asthmatics showed significantly lower ApoA1 levels in bronchoalveolar lavage fluid than did healthy controls. Local ApoA1 treatment significantly decreased lung IL-25, IL-33, and thymic stromal lymphopoietin levels in HDM-challenged mice and inhibited allergen-induced production of these cytokines in cultured primary bronchial epithelial cells. ApoA1 promoted recovery of disrupted TJ proteins zonula occludens-1 and occludin in cultured primary bronchial epithelium obtained from asthmatics. ApoA1-induced increases in the TJ proteins were dependent on increased production of lipoxin A4 (LX A4). CONCLUSIONS AND CLINICAL RELEVANCE: ApoA1 enhances resolution of allergen-induced airway inflammation through promoting recovery of damaged TJs in the bronchial epithelium. ApoA1 could be a therapeutic strategy in chronic airway inflammatory diseases that are associated with a defective epithelial barrier, including asthma.

The impact of total antioxidant capacity on pulmonary function in asthma patients.

BACKGROUND: Oxidative stress, mediated by an imbalance between oxidants and antioxidants, contributes significantly to the pathogenesis of asthma. OBJECTIVE: To evaluate the impact of serum total antioxidant capacity (TAC) on the pulmonary function of Korean asthma patients. METHOD: A total of 104 adult asthma patients enrolled from the COREA (Cohort for Reality and Evolution of Adult Asthma in Korea) programme participated in the study. Baseline clinical parameters at enrolment, and the results of pulmonary function tests at baseline and 1 and 2 years after enrolment were collected. TAC at baseline was measured using a Trolox-equivalent antioxidant capacity assay. Patients were divided into two groups based on TAC levels, and various clinical parameters were compared. RESULT: Serum TAC levels correlated with forced expiratory volume in 1 second (FEV(1)) at baseline (r = 0.22, P = 0.03). The group with higher baseline TAC levels maintained greater mean FEV(1) both 1 and 2 years after enrolment, even after adjusting for sex, age, height, weight, body mass index and smoking status. CONCLUSION: These results suggest an important link between serum TAC levels and pulmonary function, indicating that higher TAC levels may be a biomarker for favourable prognosis in asthma patients.

A possible association between ZNRD1 and aspirin-induced airway bronchoconstriction in a Korean population.

BACKGROUND: The etiology of aspirin-exacerbated respiratory disease (AERD) has been attributed to the combination of environmental and genetic risk factors. Although widely investigated in various diseases associated with immune dysfunction, the human zinc ribbon domain containing 1 (ZNRD1) gene is thought to play a role in the pathogenesis of AERD by altering the mechanisms involved in disease development. METHODS: We selected 6 single-nucleotide polymorphisms (SNPs) for genotyping from the International HapMap database in order to analyze the association between polymorphisms in ZNRD1 and AERD in a Korean asthma cohort. Genotyping was carried out using the TaqMan assay, and differences in genotype frequency distributions were analyzed using logistic regression models. RESULTS: Nominal associations were found between ZNRD1 rs1150740 and risk ofAERD via codominant and dominant genetic inheritance (P=.03; odds ratio, 1.14 [1.14-10.16]). The same polymorphism was found to be significantly associated with a decrease in forced expiratory volume in the first second of expiration, an important diagnostic marker of AERD, even after multiple testing corrections (P=.006, P(corr)=.03 in codominant and dominant models). CONCLUSIONS: These preliminary findings suggest a possible relationship between ZNRD1 and aspirin-induced respiratory dysfunctions in a Korean population and provide essential information on the etiology of AERD.

Variations in the STK10 gene and possible associations with aspirin-intolerant asthma in a Korean population.

BACKGROUND AND OBJECTIVE: Lymphocyte-oriented kinase deficiency encoded by the serine/threonine kinase 10 (STK10) gene correlates with the intracellular adhesion molecule 1 (ICAM-1)/lymphocyte function associated antigen 1 (LFA-1) complex in aspirin hypersensitivity. This study investigated the association between single nucleotide polymorphisms (SNPs) of STK10 and aspirin-intolerant asthma (AIA). METHODS: A total of 54 SNPs were genotyped in 163 AIA patients and 429 aspirin-tolerant asthma (ATA) controls. RESULTS: Logistic regression revealed that a synonymous variant (rs2306961G>A) had the most significant association with AIA (P = .008 under the codominant model; P = .004 under the dominant model), suggesting that tissue-specific codon usage between Lys_TTT and Lys_CTT could play a role in regulating expression of STK10 in airway epithelium. Haplotype analysis revealed that 4 haplotypes, including STK10_BL4-ht1, which is unique to rs2306961G>A, were significantly associated with aspirin hypersensitivity in asthmatics (P < .05). CONCLUSIONS: Although replications in independent cohorts and further functional evaluations are needed, our preliminary findings suggest that STK10 polymorphisms might be susceptible genetic markers of AIA and that gene expression could be mediated by tissue-specific codon usage.

Reliability and validity of the St George's Respiratory Questionnaire for asthma.

BACKGROUND: The St George's Respiratory Questionnaire (SGRQ) is a self-administered questionnaire that has been used to evaluate the health-related quality of life of patients with chronic respiratory diseases. OBJECTIVE: To assess the validity and reliability of the SGRQ for a large population with asthma. DESIGN: We used the previously developed Korean version of the SGRQ (SGRQ-K) to assess 676 asthma patients enrolled from the Cohort for Reality and Evolution of Adult Asthma in Korea study. Cronbach's α was used to assess test reliability and Pearson's correlation coefficient was used to assess the correlation between SGRQ scores and various clinical factors. RESULTS: The total SGRQ-K score had acceptable reliability (Cronbach's α = 0.92). The total SGRQ-K score was significantly correlated with symptom duration (r = 0.157, P < 0.001), pulmonary function (% FEV(1) of predicted r = -0.314, P < 0.001; % FVC of predicted r = -0.224, P < 0.001; FEV(1)/FVC r = -0.224, P < 0.001), asthma severity (r = 0.278, P < 0.001) and history of asthma exacerbation. CONCLUSION: With the exception of the SGRQ-K symptoms, SGRQ-K is a reliable and valid test for evaluation of the quality of life of patients with asthma. Scores were well correlated with duration of symptoms, lung function and previous history of asthma exacerbation.

Genetic effect of single-nucleotide polymorphisms in the PPARGC1B gene on airway hyperreactivity in asthmatic patients.

BACKGROUND: Peroxisome proliferator-activated receptor gamma coactivator 1 beta (PPARGC1B) is a co-activator for intracellular receptors such as the estrogen receptor, PPAR, and glucocorticoid receptor, which are involved in asthma development. OBJECTIVES: Genetic association of single-nucleotide polymorphisms (SNPs) in the PPARGC1B gene with the risk of asthma and airway hyperreactivity (AHR) was investigated, as well as the functional effects of these SNPs on PPARGC1B gene and protein expression. METHODS: Direct sequencing of DNA from 24 Korean was performed to identify PPARGC1B SNPs. Genotyping was done in 264 controls and 949 asthmatics using single-base extension methods. PPARGC1B mRNA levels were measured using real-time PCR methodology. Luciferase and electrophoretic mobility shift assays (EMSA) were performed to functionally analyse PPARGC1B SNPs on promoter. RESULTS: Eighteen SNPs and one insertion/deletion polymorphism were identified, and seven SNPs were genotyped. No significant difference existed in the distribution of SNPs and haplotypes between the asthmatics and controls. However, the allele frequency of -427C>T and +102525G>A;R265Q showed a significant association with log-transformed PC(20) methacholine values in the asthmatics (P=0.005-0.0004). Real-time PCR demonstrated higher PPARGC1B mRNA levels in asthmatics having -427CC allele than in those having -427TT or CT alleles (P=0.048). The ratio of the mRNA expression for each PPARGC1B exon4-mRNA compared with the wild type was similar in peripheral blood mononuclear cells carrying the +102525G>A allele. Luciferase reporter assays revealed that -427C allele caused higher promoter activity than -427T allele. EMSA demonstrated that -427C allele exhibited stronger binding activity to a nuclear protein in 293T cells than did the -427T allele. CONCLUSIONS AND CLINICAL RELEVANCE: Polymorphisms of -427C>T on the promoter and those of +102525G>A on exon 5 of the PPARGC1B gene may affect the development of AHR through the modulation of PPARGC1B gene products. The PPARGC1B genotypes may serve as genetic markers for AHR.

Asp-Tyr-Leu-Lys tetrapeptide inhibits airway inflammation in toluene-2,4-diisocyanate-induced asthma mice.

BACKGROUND: Airway inflammation and remodelling contribute to chronic airway obstruction of asthma. Currently, no medication effectively controls airway remodelling and related vascular changes. Therefore, new strategies need to be developed. The kringle 5 domain has anti-angiogenic activity resulting from the tetrapeptide Lys-Leu-Tyr-Asp (KLYD). OBJECTIVE: To investigate the therapeutic effect of KLYD and its inverse form Asp-Tyr-Leu-Lys (DYLK) on the inflammation and remodelling of toluene-2,4-diisocyanate (TDI)-sensitization/challenged mice. METHODS: Cell numbers were measured in the presence of various concentrations of KLYD and DYLK using in vitro endothelial cell proliferation assay. The changes of cell number and the level of vascular endothelial growth factor (VEGF) in bronchoalveolar lavage (BAL) fluid and response to methacholine (MCh) were measured using the in vivo TDI-sensitized/challenged mice model. Muc5ac, smooth muscle actin (SMA) and proliferating cell nuclear antigen (PCNA) protein expression was analysed on trachea and intrapulmonary bronchi using immunohistochemical stain. RESULTS: Compared with KLYD, DYLK had a greater inhibitory effect on endothelial cell proliferation (P<0.05). Pre-treatment of DYLK showed dose-dependent reduction in the response to MCh (P<0.05) and numbers of inflammatory cells in BAL fluids of TDI-sensitized/challenged mice. TDI induced increases in Muc5ac, SMA and PCNA protein expression and VEGF levels, which were also abolished by DYLK treatment. CONCLUSIONS: Local administration of DYLK effectively inhibits the airway inflammation and airway remodelling of TDI-sensitized/challenged mice via down-regulation of VEGF. These findings suggest that anti-angiogenic peptide therapies, such as local administration of DYLK, are an effective strategy for the treatment of remodelling in asthma.

A promoter nucleotide variant of the dendritic cell-specific DCNP1 associates with serum IgE levels specific for dust mite allergens among the Korean asthmatics.

Dendritic cells (DCs), the most abundant antigen-presenting cells in the lung, have been drawing attention for their roles in specific allergic responses to aeroallergens with support of Th lymphocytes, and in persistent inflammatory changes in allergic asthma. To identify genetic factors that may be involved in the asthma susceptibility and development of the disease phenotypes, we examined association of DC-specific DCNP1 polymorphisms with the disease risk. The case-control study revealed association of the nucleotide variants with serum immunoglobulin E (IgE) levels specific for Dermatophagoides farinae (Der f 1) and Dermatophagoides pteronyssinus (Der p 1), major aeroallergens of dust mites, among subjects with asthma. In particular, the T-allele-carrying genotype frequencies for one of the variants (c.-1289C>T) located in the promoter region were found increased in the asthmatic group with low levels of the mite-specific IgE (odds ratio (OR)=0.63 (0.48-0.83) for Der p 1). Results from functional analyses indicated that the promoter variant would affect the gene expression by modulating DNA-protein interaction. We propose that the genetic polymorphism of DCNP1 may influence production of specific IgE by altering DC functions in the mite allergen presenting and/or processing. The functional relevance of the genetic variation would provide an important insight into the genetic basis of allergic response to the mite antigens.

Effect and mechanism of lipopolysaccharide on allergen-induced interleukin-5 and eotaxins production by whole blood cultures of atopic asthmatics.

Interleukin (IL)-5 and eotaxin families regulate the development of eosinophilic inflammation of asthma in a co-operative manner. The exposure to airborne lipopolysaccharide (LPS) induces varying degrees of airflow obstruction and neutrophilic airway inflammation. Production of IL-5 and eotaxin subfamily chemokines was analysed in response to Dermatophagoides pteronyssinus allergen (D.p.) according to the presence of specific IgE to D.p., and investigated the mechanism underlying their LPS-mediated regulation of these cytokines in response to the specific allergen. Peripheral blood cells (PBCs) from asthmatics with (group 1) or without (group 2) specific IgE to D.p. and from non-asthmatics with (group 3) or without (group 4) were stimulated with D.p. or LPS. For LPS-mediated inhibition of IL-5 and eotaxin-2 production, LPS-induced cytokines were added to the D.p.-stimulated PBCs. IL-5 and eotaxin-2, but not eotaxin-1 and 3, were significantly increased by D.p.-stimulated-PBCs from group 1, while only eotaxin-2 was elevated in group 3. Eotaxin-2 production was found in monocytes and correlated with the level of specific IgE to D.p. LPS treatment resulted in the decrease in eotaxin-2 and IL-5 production by the D.p.-stimulated PBCs. LPS-induced IL-10 completely inhibited D.p.-stimulated production of eotaxin-2 and IL-5. The differential responses of the eotaxin family to specific antigens suggest that the predominant role of eotaxin-2 and LPS may attenuate eosinophilic inflammation by inhibiting IL-5 and eotaxin-2 synthesis through IL-10 production.

Differences in radiological/HRCT findings in eosinophilic bronchitis and asthma: implication for bronchial responsiveness.

BACKGROUND: Airway hyperresponsiveness in asthmatics is considered to be one of the major consequences of airway inflammation and remodelling. Airway responsiveness is normal in patients with eosinophilic bronchitis (EB), despite eosinophilic inflammation of the airways comparable to that which occurs in asthmatics. Comparisons between asthma and EB should clarify the changes in airway morphology that are related specifically to AHR in asthmatics. METHODS: Eighteen asthmatic patients, 15 patients with EB, and 11 healthy subjects were recruited. Airway wall area percentage (WA%), centrilobular prominence, and air trapping were compared using thin slice section computed tomography. RESULTS: WA% was significantly greater in asthmatics than in patients with EB (72 (3.1)% v 54 (2.1)%, p = 0.032) and was similar in EB patients and controls (54 (2.1)% v 57 (1.8)%, p>0.05). Centrilobular prominence and air trapping were similar in EB patients and asthmatics and were significantly greater than in controls. CONCLUSION: WA% rather than air trapping or centrilobular prominence may be associated with the airway hyperresponsiveness that occurs in asthmatics but not in patients with EB.

ADAM33 polymorphism: association with bronchial hyper-responsiveness in Korean asthmatics.

BACKGROUND: A disintegrin and metalloprotease 33 (ADAM33) is expressed in the lung by fibroblasts and bronchial smooth muscle cells. Given its structure and cellular provenance, ADAM33 may be associated with airway remodelling and bronchial hyper-responsiveness. Single nucleotide polymorphisms (SNPs) and haplotypes of the ADAM33 gene have previously been associated with asthma susceptibility in the Caucasian population. OBJECTIVE AND METHODS: To assess whether genetic variants of ADAM33 are related to asthma in a Korean population, we conducted an association study of the ADAM33 gene with asthma susceptibility, bronchial hyper-reactivity and serum IgE in Korean asthmatics (n=326) and normal controls (n=151). Five of the 14 polymorphisms originally reported to be associated with asthma development (S1 G>A, T1 T>C, V-1 C>A, V1 T>A, V4 C>G) were genotyped using single base extension and electrophoresis. Haplotypes and their frequencies were inferred using the algorithm implemented by the software Arlequin. Allele frequencies of each SNP and haplotypes were compared between the patients and the normal controls using logistic regression analysis. RESULTS: There was no significant difference in the distribution of SNPs and the six haplotypes between asthmatics and normal controls. All single SNPs and six haplotypes in ADAM33 were also analysed for the association with level of PC(20) using general linear models. The distribution of the T1 T>C SNP and one haplotype (ht4: GCGG) showed significant association with log-transformed PC(20) methacholine level in the asthma patients (P=0.03 and 0.0007, respectively, using a co-dominant model). CONCLUSION: Polymorphism of ADAM33 may contribute to development of BHR in asthma.

Epidemiologic evidence of a relationship between airway hyperresponsiveness and exposure to polluted air.

BACKGROUND: There has been an increase in allergic diseases as a result of increased air pollution emanating from traffic and various industries. OBJECTIVE: This study evaluated the association between air pollution and airway hyperresponsiveness in a cross-sectional study of a cohort of 670 children, aged 10-13 years. METHODS: We measured spirometry and conducted allergic skin tests and methacholine challenge tests in 670 schoolchildren. The methacholine concentration causing a 20% fall in FEV1 (PC20) was used as the threshold of airway hyperresponsiveness (AHR). Thresholds of 16 mg/dl or less were assumed to indicate AHR. RESULTS: All of the schoolchildren had normal pulmonary function. Of the children, 257 (38.3%) had AHR. There was a significant increase in AHR in schoolchildren living near a chemical factory [45.0% (138/306), 6.50 +/- 0.48] compared to those in rural [31.9% (52/163), 9.84 +/- 0.83] and coastal [33.3% (67/201), 7.17 +/- 0.68] areas. Atopy was significantly more prevalent near the chemical factory vs the coastal and rural areas [35.6% (109/306) vs 27.3% (55/201) and 23.3% (38/163), respectively, P < 0.007]. Schoolchildren with atopy had lower PC20 than those without atopy (5.98 +/- 0.60 vs 8.15 +/- 0.45, P < 0.001). Positive allergy skin tests and living in a polluted area were risk factors in multivariate analyses adjusted for sex, parents' smoking habits, age, body mass index, nose symptoms and lung symptoms (odds ratio for location = 2.4875, confidence interval 1.6542-3.7406, P < 0.000; odds ratio for allergy skin test = 1.5782, confidence interval 1.1130-2.2379, P < 0.0104). CONCLUSION: Our findings demonstrate that more children living in polluted areas have airway hyperresponsiveness than do those living in less polluted areas.

The relationship between alveolar epithelial proliferation and airway obstruction after ozone exposure.

BACKGROUND: Proliferating cell nuclear antigen (PCNA) is a component of multiprotein complexes that are expressed during cell proliferation. Ozone induces cell necrosis and a consequent increase in cell proliferation. METHODS: To investigate the effects of acute ozone inhalation on cell proliferation and airway obstruction in BALB/C mice, we examined enhanced pause (Penh) as an index of airway obstruction and PCNA expression by immunohistochemical staining. RESULTS: Compared with controls that received filtered air, the ozone-exposed groups had increased PCNA expression in the alveolar epithelial cells. In rank order, the highest PCNA index was found following 2.0 p.p.m. ozone exposure. In the 2.0 p.p.m. ozone group, there was a PCNA index of 16.83 +/- 0.57% (mean +/- SEM; P< 0.01), compared with 4.25 +/- 0.5% at 0.12 p.p.m., 6.83 +/- 0.60 at 0.5 p.p.m and 12.16 +/- 0.48% at 1 p.p.m. Following ozone exposure, Penh was increased in a dose-dependent manner. There was a significant correlation between the PCNA index in alveoli and Penh (r = 0.63, P< 0.01). CONCLUSIONS: These data suggest that ozone can induce alveolar epithelial cell proliferation in a dose-dependent manner, and that alveolar epithelial cell proliferation is correlated with airway obstruction.

Relationship between the perception of dyspnoea and airway inflammatory markers.

Poor dyspnoea perception in asthmatic patients seems to be associated with increased risk of asthma exacerbation. We have studied the relationship between basel ne dyspnoea perception and inflammatory markers in sputum in eight patients with mild asthma and in 13 patients with moderate to severe asthma. The perception of dyspnoea was scored on the Borg scale. Eosinophilic cationic protein (ECP) was measured by fluoroimmunoassay and by an interleukin (IL)-5 sandwich ELISA. The baseline Borg score was significantly higher in patients with severe asthma than in patients with mild to moderate asthma (4.1 +/- 0.29 vs. 2.28 +/- 0.28, P<0.05). The proportion of eosinophil and ECP levels in the sputum were significantly higher in patients with moderate to severe asthma. IL-5 in sputum was significantly increased in moderate to severe asthmatic patients compared to mild asthmatic patients. A significant relationship was found between the baseline perception score and FEV1/FVC (r = -0.53, P<0.01), sputum eosinophils (r = 0.70, P<0.01) and sputum ECP (r = 0.62, P<0.01). These findings suggest that the baseline perception score is related to inflammatory markers in sputum, and that the perception of dyspnoea as well as airway inflammatory markers may be considered to evaluate asthma severity.

The association of airway hyperresponsiveness and tuberculin responses.

BACKGROUND: The balance between the two subsets of T cell is pivotal for allergic sensitization. OBJECTIVE: We conducted a cross-sectional study of 486 children vaccinated with bacillus Calmette-Guérin (BCG), aged 10-13 years, to evaluate whether tuberculin responses may contribute to airway hyperresponsiveness (AHR). METHODS: Tuberculin skin test, allergic skin test, and methacholine challenge test were done. The methacholine concentration causing a 20% fall (PC20) in forced expiratory volume in 1 second (FEV1) was used as a threshold of AHR. Atopy was defined as a reaction showing a mean wheal size of > or = 3 mm to one or more allergens on skin prick test (SPT). Two tuberculin units of polysorbate-stabilized purified protein derivatives (PPD) were injected intradermally into the volar surface of the forearm. Reactions were read at 48-72 h as the transverse diameter in millimeters of induration. RESULTS: Of the children in the study, 12.3% (60/486) had PPD induration; 7.8% (38/486) of children had PPD induration of greater than 10 mm. The PPD induration size was 10.5 +/- 1.03 mm (confidence interval (CI) 7.19-12.33) in atopic children and 11.2 +/- 0.76 mm (CI 7.89-13.1) in nonatopic children. The differences of PPD induration diameter between the two groups were not significant. There was no difference of log PC20 between PPD induration > or = 10 mm and < 10 mm (0.13 +/- 0.18 vs. 0.42 +/- 0.05). The difference of log PC20 between positive and negative tuberculin response was not significant. Children with atopy had lower log PC20 than those without atopy (0.16 +/- 0.07 vs. 0.51 +/- 0.05, P = 0.001). After adjusting for sex, age, height, weight, tuberculin response, atopy was associated with AHR in multivariate analyses (odds ratio = 1.895, CI 1.285-2.505, P = 0.002). CONCLUSION: These data suggested that a tuberculin response due to mycobacterial infection status have no effect on AHR in schoolchildren.

Relationship between sputum inflammatory markers and osmotic airway hyperresponsiveness during induction of sputum in asthmatic patients.

Hypertonic saline aerosols are being used increasingly for bronchial provocation testing and induction of sputum. The aims of this study were to assess the response to challenge with 3% hypertonic saline administered via a ultrasonic nebulizer in patients with asthma, and to evaluate relationship between % fall of FEV1 during induction of sputum (osmotic airway hyperresponsiveness; osmotic AHR) and biochemical markers of induced sputum. We investigated changes in FEV1 in response to inhaling ultrasonically nebulized 3% saline in 25 patients with asthma and 10 control subjects. FEV1 was measured before, during, and after induction of sputum. We used fluoroimmunoassay to detect eosinophil cationic protein (ECP), immunohistochemical staining to detect EG2+ (secretory form of ECP) eosinophils, and a sandwich ELISA to detect interleukin (IL)-5. Protein concentration was determined by using bicinchoninic acid protein assay reagent. Asthmatics, compared with controls, had significantly higher osmotic AHR. Moderate to severe asthmatics had significantly higher osmotic AHR compared to mild asthmatics. Osmotic AHR was significantly correlated with the proportion of eosinophils, the levels of ECP, EG2+ eosinophils, IL-5, and proteins. These data suggest that osmotic AHR is closely related to the clinical status and biochemical markers of sputum supernatant in asthmatic patients.

Effects of prednisolone on eosinophils, IL-5, eosinophil cationic protein, EG2+ eosinophils, and nitric oxide metabolites in the sputum of patients with exacerbated asthma.

Corticosteroids are considered to be one of the most effective medicine for asthma by suppressing airway inflammation. This study was carried out to investigate the effects of prednisolone in the sputum of exacerbated asthmatics. Clinical severity, cell differentials, levels of interleukin (IL)-5, eosinophil cationic protein (ECP), EG2+ eosinophils, and nitric oxide (NO) metabolites were measured. Sputum was examined 2 weeks apart in 13 exacerbated asthmatics before and after prednisolone treatment, and once in 12 stable asthmatics. We used a sandwich ELISA for IL-5, fluoroimmunoassay for ECP, immunohistochemical staining for EG2+ eosinophils, a NO metabolites assay using modified Griess reaction. Exacerbated asthmatics, in comparison with stable asthmatics, had significantly higher proportion of eosinophils, higher level of ECP, higher percentage of EG2+ eosinophils, and NO metabolites. Exacerbated asthmatics after treatment with prednisolone had reduced the proportions of eosinophils, reduced level of IL-5, ECP and percentage of EG2+ eosinophils. FEV1 was correlated with the proportion of eosinophils, ECP, and IL-5 respectively. These findings suggest that prednisolone is considered to be effective medicine for asthma by suppressing eosinophil activation through IL-5.

Increase in airway hyperresponsiveness among workers exposed to methylene diphenyldiisocyanate compared to workers exposed to toluene diisocyanate at a petrochemical plant in Korea.

BACKGROUND: The purpose of this study was to investigate the prevalence of airway hyperresponsiveness induced by methylene diphenyldiisocyanate (MDI) and toluene diisocyanate (TDI) at a petrochemical industry complex in Korea. METHODS: Questionnaires, allergic skin test, and nonspecific airway hyperresponsiveness (AHR) were studied in 64 exposed workers and 27 control subjects. Questionnaires included questions about symptoms of cough, wheezing, chest tightness, dyspnea, rhinorrhea, sneezing, itching, stuffiness, tearing, urticaria, sore throat, and exacerbating time. Methacholine challenge tests were done. Bronchial responsiveness (BRindex) defined as log (% fall in FEV(1))/log (last concentration of methacholine +10). RESULTS: Prevalence of AHR (PC20 FEV(1) < 16.0 mg/mL of methacholine) was higher in MDI-exposed workers than in TDI-exposed workers [4/20 (20%) vs. 2/42 (4.7%), P<0.05]. Twenty-three workers (36%) of all subjects had respiratory symptoms. MDI-exposed workers, in comparison with control subjects, had higher BRindex (0.73+/-0.04 vs. 0.62+/-0.02, P<0.05). Workers exposed to TDI or MDI who had respiratory symptoms (n = 23), in comparison to workers exposed to TDI or MDI without respiratory symptoms (n = 41), had significantly higher BRindex (0.82+/-0.06 vs. 0.60+/-0.02, P<0.05). FEV(1) was significantly negatively correlated with BRindex (r = -0.253, P<0.05). BRindex was not correlated with atopy, smoking status, and exposure duration. CONCLUSIONS: These findings suggest that workers exposed to MDI are at a higher risk of asthma in comparison with TDI-exposed workers and control subjects at a petrochemical plant in Korea.