Healthcare use and prescription patterns associated with adult asthma in Korea: analysis of the NHI claims database.

BACKGROUND: National Health Insurance (NHI) claim records could provide valuable data for epidemiological studies of asthma in Korea. The aim of this study is to estimate the prevalence of adult asthma and to investigate asthma-related healthcare use and prescription patterns in Korea over 5 years. METHODS: National Health Insurance claim records from January 1, 2006 to December 31, 2010 were analyzed in a retrospective, population-based study. Outcome measures included asthma prevalence, healthcare use, and prescription patterns over time, by type of hospital, and by medical specialty. Additionally, we assessed differences in healthcare use between newly diagnosed and previously diagnosed patients in 2009. RESULTS: Over 5 years, the prevalence of asthma among Korean adults increased from 4944 to 5707 cases per 100,000 population (from 3760 to 4445 in men and from 6108 to 6951 in women). Asthma-related outpatient visits decreased from 4.82 ± 8.02 to 3.44 ± 5.50. Approximately 3% of all patients were hospitalized and 2.4% received asthma-related emergency treatment each year. Pulmonary function tests were performed in 10-11% of patients an average of 1.3 times per year. Newly diagnosed patients experienced fewer asthma-related hospitalizations (1.78% vs 4.35%) and emergency department visits (0.80% vs 2.11%) than the previously diagnosed group. Prescriptions of inhaled corticosteroids-based inhalers were maintained with about 20% of average of all types of hospitals. CONCLUSIONS: The prevalence of asthma in Korea has increased over a recent 5-year period, and asthma is still suboptimally controlled. Public health strategies are needed to improve the management of asthma in adults.

Validation of the cephalosporin intradermal skin test for predicting immediate hypersensitivity: a prospective study with drug challenge.

BACKGROUND: Cephalosporin is a major offending agent in terms of drug hypersensitivity along with penicillin. Cephalosporin intradermal skin tests (IDTs) have been widely used; however, their validity for predicting immediate hypersensitivity has not been studied. This study aimed to determine the predictive value of cephalosporin intradermal skin testing before administration of the drug. METHODS: We prospectively conducted IDTs with four cephalosporins, one each of selected first-, second-, third-, or fourth-generation cephalosporins: ceftezol; cefotetan or cefamandole; ceftriaxone or cefotaxime; and flomoxef, respectively, as well as with penicillin G. After the skin test, whatever the result, one of the tested cephalosporins was administered intravenously and the patient was carefully observed. RESULTS: We recruited 1421 patients who required preoperative cephalosporins. Seventy-four patients (74/1421, 5.2%) were positive to at least one cephalosporin. However, none of responders had immediate hypersensitivity reactions after a challenge dose of the same or different cephalosporin, which were positive in the skin test. Four patients who suffered generalized urticaria and itching after challenge gave negative skin tests for the corresponding drug. The IDT for cephalosporin had a sensitivity of 0%, a specificity of 97.5%, a negative predictive value of 99.7%, and a positive predictive value (PPV) of 0%, when challenged with the same drugs that were positive in the skin test. CONCLUSION: Routine skin testing with a cephalosporin before its administration is not useful for predicting immediate hypersensitivity because of the extremely low sensitivity and PPV of the skin test (CRIS registration no. KCT0000455).

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.

Lessons from two cases of anaphylaxis to proton pump inhibitors.

WHAT IS KNOWN AND OBJECTIVE: Proton pump inhibitors (PPIs), which are widely used for the treatment of peptic ulcers and gastroesophageal diseases, reduce both basal and stimulated gastric acid secretion by inhibiting the parietal cell enzyme H(+)-K(+)-adenosine triphosphatase. There have been several reports of hypersensitivity reactions to PPIs but anaphylaxis is very rare. We report on two cases of anaphylaxis to PPIs. CASE SUMMARY: Our two interesting and instructive cases of anaphylaxis to PPIs relate to the orally disintegrating form of lansoprazole and omeprazole. The first patient had taken esomeprazole 20 mg/day for 1 month without any side effects before experiencing anaphylaxis to lansoprazole. To our knowledge, this is the first report of anaphylaxis to the orally disintegrating form of lansoprazole. In the second case, the patient was misdiagnosed with penicillin allergy which she suffered from earlier. WHAT IS NEW AND CONCLUSION: Physicians need to be more aware of the possibility of hypersensitivity to PPIs.

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.

Polymorphisms in the neurokinin-2 receptor gene are associated with angiotensin-converting enzyme inhibitor-induced cough.

BACKGROUND AND OBJECTIVE: Treatment with angiotensin-converting enzyme (ACE) inhibitors can induce chronic cough in many patients. Genetic variations in the neurokinin 2 receptor gene (NK2R) are significantly associated with cough sensitivity to capsaicin. METHODS: This study assessed the relationship between genetic polymorphisms in the NK2R gene and chronic cough in 91 patients taking ACE inhibitors. Patients included in the study did not have chest abnormalities, postnasal drip, gastroesophageal reflux or a recent history of upper respiratory infection. RESULTS: We detected two single nucleotide polymorphisms in the NK2R gene (i.e., Gly231Glu and Arg375His). The allelic frequencies at amino acid 231 were 36.3% for Gly/Gly, 49.5% for Gly/Glu and 14.3% for Glu/Glu. The allelic frequencies at amino acid 375 were 74.7% for Arg/Arg, 24.2% for Arg/His and 1.1% for His/His. The prevalence of chronic cough in patients with the amino acid 231 genotype was 33.3% in Gly/Gly homozygotes, 24.4% in Gly/Glu heterozygotes and 0% in Glu/Glu homozygotes. There was a statistically significant association between chronic cough and the Glu/Glu allele (P = 0.028) when the data were analyzed with a recessive model. In addition, there was a significant inverse linear association between the number of Glu231 alleles and ACE inhibitor-related cough (P = 0.026). The prevalence of chronic cough in patients with the amino acid 375 genotype was 22.1% in Arg/Arg homozygotes, 31.8% in Arg/His heterozygotes and 0% in His/His homozygotes, although none of these association were statistically significant. CONCLUSION: Our findings indicate that the Gly231Glu polymorphism is associated with a lower prevalence of ACE inhibitor-related cough.

Additive role of tiotropium in severe asthmatics and Arg16Gly in ADRB2 as a potential marker to predict response.

BACKGROUND: Recent findings have raised new interests about the use of anticholinergics, especially tiotropium, for the treatment of asthma. This study was performed to determine whether an additional improvement in lung function is obtained when tiotropium is administrated in addition to conventional therapies in severe asthmatics, and to identify factors capable of predicting the response to tiotropium, using a pharmacogenetic approach. METHODS: A total of 138 severe asthmatics on conventional medications and with decreased lung function were randomly recruited. Tiotropium 18 microg was added once a day and lung functions were measured every 4 weeks. Responders were defined as those with an improvement of > or = 15% (or 200 ml) in the forced expiratory volume in 1 s (FEV1) that was maintained for at least 8 successive weeks. Eleven single nucleotide polymorphisms (SNPs) in CHRM1-3 (coding muscarinic receptors one to three) which were identified by re-sequencing, and Arg16Gly and Gln27Glu in ADRB2 (coding beta(2) adrenoreceptor) were scored in 80 of the 138 asthmatics. RESULTS: Forty-six of the 138 asthmatics (33.3%) responded to tiotropium treatment. Logistic regression analyses (controlled for age, gender, and smoking status) showed that Arg16Gly in ADRB2 [P = 0.003, OR (95% CI) = 0.21 (0.07-0.59) in a minor allele-dominant model] was significantly associated with response to tiotropium. CONCLUSIONS: As many as 30% of severe asthmatics on conventional medications with reduced lung function were found to respond to adjuvant tiotropium. The presence of Arg16Gly in ADRB2 may predict response to tiotropium.

Corticotomy-/osteotomy-assisted tooth movement microCTs differ.

Corticotomy-assisted and osteotomy-assisted tooth movement involves surgical incisions through the alveolar bone. To ascertain whether teeth move by distraction osteogenesis or by regional accelerated phenomenon (RAP), we randomly assigned 30 Sprague-Dawley rats to one of 5 experimental groups: corticotomy alone, corticotomy-assisted tooth movement, osteotomy alone, osteotomy-assisted tooth movement, or tooth movement alone. Each animal was imaged by microtomography immediately after surgery, after 21 days, and after 2 months. After 21 days, regional accelerated phenomenon was observed in the alveolar bone of the corticotomy-treated animals and distraction osteogenesis in the osteotomy-assisted tooth movement animals. Pixel count data were analyzed by nested ANOVA for 5 experimental groups, split-mouth controls, 3 levels along the root, and 5 sites per level. The most demineralized sites after 21 days differed for each of the experimental groups. Our study indicates that osteotomies and corticotomies induce different alveolar bone reactions, which can be exploited for tooth movement.

Serum cholesterol in idiopathic and lupus-related protein-losing enteropathy.

Abstract The characteristics of protein-losing enteropathy were evaluated in patients with systemic lupus erythematosus. Among the patients with systemic lupus erythematosus (n=380) in a tertiary hospital, we reviewed the records of seven patients with generalized edema, hypoalbuminemia without proteinuria and positive results on 99mTc-labelled human serum albumin scintigrams. Patient characteristics and laboratory findings were compared between these seven patients and patients with lupus enteritis (n=15) or idiopathic protein-losing enteropathy (n=11). Compared with the lupus enteritis patients, the erythrocyte sedimentation rate and serum total cholesterol levels were significantly increased in patients with systemic lupus erythematosus-related protein-losing enteropathy. Compared with idiopathic protein-losing enteropathy patients, the level of serum total cholesterol was significantly increased, but the level of serum albumin was decreased in patients with systemic lupus erythematosus-related protein-losing enteropathy. Among patients with systemic lupus erythematosus-related protein-losing enteropathy, four patients had high serum total cholesterol levels (>or=248 mg/dL) and achieved complete remission after receiving high doses of steroid treatment. However, three patients who had low serum total cholesterol levels (

Effects of advanced glycation end products on the expression of COX-2, PGE2 and NO in human osteoarthritic chondrocytes.

OBJECTIVE: Advanced glycation end products (AGE) accumulate in articular cartilage with age. We investigated the effects of AGE in primary-cultured human OA chondrocytes. METHODS: Chondrocytes were cultured with/or without AGE-bovine serum albumin (AGE-BSA) and the expression levels of inducible nitric oxide (iNOS), cyclooxygenase (COX)-2 microsomal prostaglandin E synthase-1 (mPGES-1) were evaluated using RT-PCR and western blot analysis. Prostaglandin E(2) (PGE(2)) was analysed by ELISA and nitric oxide (NO) was analysed by Griess reaction assay. Pharmacological studies to elucidate the involved pathway were executed using specific inhibitors of MAPK and receptor for AGE (RAGE). RESULTS: We found that treatment of OA chondrocytes with AGE-BSA increased COX-2, mPGES-1 and iNOS mRNA and protein, as well as elevating production of PGE(2) and NO. Pre-treatment with the MAPK inhibitors SP600125 (JNK inhibitor), SB202190 (p38 inhibitor) or PD98059 (ERK inhibitor) significantly inhibited AGE-BSA induction of COX-2 expression and production of PGE(2). In contrast, SN50, a nuclear factor-kappaB (NF-kappaB) inhibitor, had no effect on levels of COX-2 and PGE(2). SB202190 and SN50, but not SP600125 and PD98059, decreased AGE-BSA-induced production of NO. Pre-treatment with soluble receptor for AGE (sRAGE) also reduced AGE-stimulated COX-2, iNOS and PGE(2), implicating the involvement of RAGE. CONCLUSIONS: These results show that AGE may augment inflammatory responses in OA chondrocytes by increasing PGE(2) and NO levels, possibly via the MAPK pathway for PGE(2) and the NF-kappaB pathway for NO.

Five-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside attenuates poly (I:C)-induced airway inflammation in a murine model of asthma.

BACKGROUND: Asthma can frequently be induced or exacerbated by respiratory viral infections. Oxidative stress might also play an essential role in the pathogenesis of allergic airway diseases, indicating that antioxidant therapy may have a potential effect in controlling allergic airway diseases. Recent studies showed that 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR) has the potential ability to modulate NADPH oxidase activity, indicating the antioxidant activity of AICAR. This study investigated the inhibitory effects of AICAR as an anti-inflammatory modulator on allergic airway inflammation in murine animal models. METHODS: The anti-inflammatory effects of AICAR were evaluated in two experimental asthma models: (1) an ovalbumin (OVA)-induced experimental asthma model and (2) an OVA plus polyinosinic-polycytidylic acid [poly (I:C)]-induced experimental asthma model to mimic respiratory viral infections. The inhibitory effects of AICAR in poly (I:C)-mediated signalling for NF-kappaB activation and production of TNF-alpha were analysed in vitro. RESULTS: AICAR was shown to have a marginal inhibitory effect in an OVA-induced asthma model. Interestingly, AICAR significantly attenuated poly (I:C)-induced airway hyperresponsiveness and airway inflammation, as shown by the attenuation of the influx of total inflammatory cells and soluble products into bronchoalveolar lavage fluid, such as macrophages, eosinophils, IL-5, IL-13, TNF-alpha and IFN-gamma. AICAR also significantly reduced the serum levels of OVA-specific IgE and IgG2a antibodies. Histologic and flow cytometric studies showed that AICAR inhibited poly (I:C)-induced lung inflammation and the infiltration of CD11b+CD11c+ dendritic cells into the lung. Moreover, AICAR effectively inhibited poly (I:C)-mediated activation of NF-kappaB and the production of TNF-alpha. CONCLUSION: These findings suggest that AICAR may be a novel immunomodulator with promising beneficial effects for the treatment of respiratory viral infection in airway allergic diseases.

Atmospheric deposition of polycyclic aromatic hydrocarbons in an urban and a suburban area of Korea from 2002 to 2004.

Atmospheric bulk samples (wet and dry) were collected monthly during 2002 to 2004 from an urban and a suburban area in Korea for assessment of depositional flux and seasonal variations in the concentrations of polycyclic aromatic hydrocarbons (PAHs). PAH depositional flux ranged from 64.1 to 610 microg/m2/y for the urban area and from 65 to 460 microg/m2/y for the suburban area. The fluxes of PAHs measured in this study were comparable with those reported for urban and suburban areas in other countries. The fluxes of particulates and PAHs were higher in winter than in summer, consistent with the greater per capita consumption of fossil fuel in winter than in summer. Ambient temperature played a major role in the seasonal variability in PAH fluxes. Photochemical degradation of PAHs appears to occur during the summer months. The relationship of PAH depositional fluxes with major air pollutants, such as ozone, sulfur dioxide, carbon monoxide, nitrogen dioxide, and presence of particulate matter up to 10 microm in size (PM10), was also investigated. Dominant PAH compounds in both the urban and the suburban locations were benzo[g,h,i]perylene, pyrene, and indeno[1,2,3-c,d]pyrene. Based on the PAH diagnostic ratios and a factor analysis, the major sources of PAHs in the urban and the suburban regions were found to be similar. Diesel exhaust, coal combustion, and gasoline emissions contributed predominantly to atmospheric PAH contamination.

4-1 BB stimulation inhibits allergen-specific immunoglobulin E production and airway hyper-reactivity but partially suppresses bronchial eosinophilic inflammation in a mouse asthma model.

BACKGROUND: 4-1 BB, a member of the tumour necrosis factor receptor superfamily, functions as a co-stimulatory molecule. Recently, stimulation of the 4-1 BB pathway was shown to suppress antigen-specific CD4(+) T cell and subsequent T cell-dependent humoral immune responses. OBJECTIVE: We examined the effect of agonistic anti-4-1 BB monoclonal antibody (mAb) treatment on allergic asthma, in which allergen-specific type 2 helper T cells (Th2) have been shown to play an important role. METHODS: BALB/c mice were systemically sensitized with intraperitoneal injections of ovalbumin (OVA) and alum on days 0 and 14, and then challenged with inhaled OVA on days 28, 29 and 30. In test groups, the agonistic anti-4-1 BB mAb was administered at the time of initial systemic sensitization with OVA. On day 31, mice were challenged with inhaled methacholine, and enhanced pause was measured as an index of airway hyper-responsiveness (AHR). Levels of OVA-specific IgE in serum, and levels of various cytokines in bronchoalveolar lavage (BAL) fluids were measured. The severity of airway inflammation was determined by differential cell counts in BAL fluids and histopathologic lung analysis. To evaluate local immunity, we cultured lymphocytes from draining perihilar lymph nodes and evaluated the proliferative response to OVA and the levels of IL-5 in the culture supernatant. In addition, the functional mechanism of 4-1 BB stimulation was evaluated in splenocytes obtained at day 7 after systemic OVA sensitization. RESULTS: We found that treatment with the anti-4-1 BB mAb significantly decreased AHR and the production of allergen-specific IgE. Bronchial inflammation, however, had only partially improved and the levels of IL-4 and IL-5 in BAL fluids showed only a small degree of reduction compared with the control Ig-treated mice. Thoracic lymphocytes from anti-4-1 BB-treated mice showed significant suppression of OVA-induced proliferation and IL-5 production. In anti-4-1 BB-treated mice, splenocytes exhibited poor proliferation and marked apoptosis 7 days after systemic OVA challenge. CONCLUSION: These results suggest that stimulation of the 4-1 BB pathway effectively suppresses some features of allergic asthma, including allergen-specific IgE production and AHR, through deletion of allergen-specific Th2 cells. However, we found that bronchial allergic inflammation was not strictly mediated by suppression of the Th2 immune response in this murine model of asthma. Despite these somewhat contradictory effects, intervention in the 4-1 BB pathway might provide a potential novel immunotherapeutic approach for treatment of allergic asthma.

Chlamydia pneumoniae infection enhances cellular proliferation and reduces steroid responsiveness of human peripheral blood mononuclear cells via a tumor necrosis factor-alpha-dependent pathway.

BACKGROUND: Although epidemiological studies have found an association between Chlamydia pneumoniae infection and severe asthma, the causality and underlying mechanism are largely unknown. We hypothesized that C. pneumoniae infection increases the proliferation and enhances the survival of immune and inflammatory cells, resulting in reduced responsiveness to corticosteroids and suggesting that the underlying mechanism is related to a TNF-alpha-dependent pathway. METHODS: Human peripheral blood mononuclear cells (PBMCs) were cultured in vitro in the presence or absence of C. pneumoniae infection. Responsiveness to corticosteroids was assayed by adding dexamethasone, and the underlying mechanism was investigated by treating cells with infliximab that is a chimeric anti-TNF-alpha monoclonal antibody. Cellular proliferation and apoptosis was assessed by thymidine uptake and counting apoptotic cells using flow cytometry. RESULTS: Cellular proliferation was significantly higher in C. pneumoniae-infected PBMCs than in uninfected PBMCs, which is more prominent in Th2-dominant microenvironment. The anti-proliferative and pro-apoptotic effect of corticosteroid were significantly reduced in C. pneumoniae-infected PBMCs compared with uninfected PBMCs. The proliferative effect of C. pneumoniae infection and the reduced response to corticosteroid were effectively reversed by blocking the TNF-alpha pathway at least partially. CONCLUSION: C. pneumoniae infection enhanced the proliferation and survival of immune and inflammatory cells, resulting in steroid resistance. The reversal of these phenomena by the TNF-alpha inhibitor suggests that TNF-alpha may play an important role in the induction of steroid dependence or resistance. A TNF-alpha inhibitor may therefore be a candidate agent for managing steroid-dependent or -resistant severe asthma.