The objective of this study was to evaluate skills in handling inhalers and factors associated with these skills among patients with asthma who had undergone treatment at special asthma and allergy clinics in Korea.
We enrolled 78 subjects who used Turbuhaler and 145 who used Diskus for asthma control at special clinics in 10 university hospitals and visually assessed their skills in handling these inhalers. We also evaluated skills in 137 subjects who had used pressurized metered-dose inhalers (pMDIs) for symptom relief. Age, sex, duration of asthma and inhaler use, smoking status, monthly income, highest grade completed in school and previous instruction for handling inhalers were also measured to evaluate their association with overall inhaler skills.
Performance grade was inadequate for 12.8% of participants using Turbuhaler, 6.2% for Diskus, and 23.4% for pMDIs. The success rates for each step in handling the inhalers were relatively high except for the "exhale slowly to residual volume" step, in which success rates ranged from 24.2% to 28.5%. Older age, male sex, lower educational grade, and absence of previous instruction for handling inhalers were associated with inadequate inhaler technique in univariate analysis; however, only older age and absence of previous instruction remained significant independent risk factors in multivariate analysis.
Among Korean asthmatic patients in special asthma and allergy clinics, skills in handling their inhalers were mostly excellent; meanwhile, older age and absence of previous instruction for handling inhalers were associated with inadequate techniques.
Asthma; Turbuhaler; Diskus; metered-dose inhaler
Diagnosis of asthma is often challenging in primary-care physicians due to lack of tools measuring airway obstruction and variability. Symptom-based diagnosis of asthma utilizing objective diagnostic parameters and appropriate software would be useful in clinical practice. A total of 302 adult patients with respiratory symptoms responded to a questionnaire regarding asthma symptoms and provoking factors. Questions were asked and recorded by physicians into a computer program. A definite diagnosis of asthma was made based on a positive response to methacholine bronchial provocation or bronchodilator response (BDR) testing. Multivariate logistic regression analysis was used to evaluate the significance of questionnaire responses in terms of discriminating asthmatics. Asthmatic patients showed higher total symptom scores than non-asthmatics (mean 5.93 vs. 4.93; p<0.01). Multivariate logistic regression analysis identified that response to questions concerning the following significantly discriminated asthmatics; wheezing with dyspnea, which is aggravated at night, and by exercise, cold air, and upper respiratory infection. Moreover, the presence of these symptoms was found to agree significantly with definite diagnosis of asthma (by kappa statistics). Receiver-operating characteristic curve analysis revealed that the diagnostic accuracy of symptom-based diagnosis was high with an area under the curve of 0.647±0.033. Using a computer-assisted symptom-based diagnosis program, it is possible to increase the accuracy of diagnosing asthma in general practice, when the facilities required to evaluate airway hyperresponsiveness or BDR are unavailable.
Asthma; Diagnosis; Questionnaires
Fractional exhaled nitric oxide (FeNO) is widely used as an inflammatory marker for asthma. However, reference values and influencing factors of FeNO using Niox Mino, which is the only device achieving US FDA approval, are not well described in healthy Asian adults. This study aimed to suggest the reference values and influencing factors of FeNO in healthy Korean adults.
Subjects who were over 19 years old and did not have any history of rhinitis, asthma or recent respiratory symptoms were enrolled. FeNO levels were measured using Niox Mino. Age, gender, body mass index (BMI), smoking status and lung function were also measured to analyze factors associated with FeNO levels.
The mean value of FeNO was 16.14 ± 10.04 ppb. The reference value of FeNO, which was defined as the value of 95% in distribution curve, was same or less than 34 ppb. In a univariate analysis, FeNO levels were not associated with age, BMI and smoking history. However, atopy status (18.2 ± 11.8 for atopy and 15.1 ± 8.5 for nonatopy groups, P = 0.008) and gender (17.8 ± 10.2 for male and 14.8 ± 9.8 for female groups, P < 0.001) were positively associated with FeNO levels. In stratified analysis, the significance of both variables remained unchanged (P < 0.001).
Our data suggested that the reference value of FeNO in healthy Korean adults seemed to be same or less than 34 ppb. Reference values of FeNO in Korean adults are influenced by gender and atopy status.
AIM: To evaluate the effect of proton pump inhibitors (PPIs) on the development of gastrointestinal tuberculosis.
METHODS: All patients who were more than 20 years old and who had received a prescription for PPIs among those who visited Seoul National University Hospital from January 1, 2005 to December 31, 2009 were identified. Due to the low sensitivity of the microbiologic test and the nonspecific pathologic findings, the diagnosis of gastrointestinal tuberculosis was confirmed through the presence of active ulcerations and the responses to anti-tuberculosis medications. The patients were divided into two groups according to treatment duration (group 1: ≤ 3 mo; group 2: > 3 mo) and were followed up from the time they took the first prescription of PPIs until their last visit. Logistic regression analysis was used to calculate the relative risks (RR) and 95%CI, adjusting for covariates.
RESULTS: Among the 61 834 patients exposed to PPIs (50 534 in group 1; 11 300 in group 2), 21 patients were diagnosed with PPI-associated gastrointestinal tuberculosis during 124 274 person-years of follow-up. Of 21 patients, the 12 who revealed only scar changes in the colonoscopy were excluded from the statistical analyses. Of those who remained, 2 were excluded because they underwent gastrointestinal endoscopy within 4 wk of the first prescription for PPIs. Longer exposure to PPI was associated with a higher mean age (55.0 ± 14.5 in group 1 vs 58.2 ± 13.3 in group 2, P < 0.001) and a higher Charlson co-morbidity index (0.50 ± 0.93 in group 1 vs 0.77 ± 1.14 in group 2, P < 0.001). The true incidence of active gastrointestinal tuberculosis was 0.65 per 1000 person-years in group 1 and 0.03 per 1 000 person-years in group 2. Like the less-than-three-month PPI treatment period in group 1, the over-three-month PPI therapy period in group 2 was not associated with increased risk of acquiring gastrointestinal tuberculosis, after adjusting for age and co-morbidities, whereas the Charlson co-morbidity index was associated with increased risk of acquiring gastrointestinal tuberculosis based on the score [RR: (reference 1) in group 1 vs 1.518 in group 2; 95% CI: 1.040-2.216, P = 0.03].
CONCLUSION: Long-term PPI therapy does not seem to be associated with increased risk of acquiring gastrointestinal tuberculosis, but a higher Charlson co-morbidity index is associated with such.
Proton pump inhibitor; Acid suppression; Tuberculosis; Gastrointestinal tuberculosis; Tuberculous colitis
Many international and national asthma guidelines are now available in large parts of the world, but they are not yet implemented appropriately. There is a gap between scientific evidence-based medicine and real clinical practice. Implementation of guidelines is highly complex. Special strategies are needed to encourage guideline-based, high-quality care. It is important to understand the contents, the format, and the learning strategies which physicians prefer for the dissemination of guidelines. Physicians prefer more concise and immediately available guidelines that are practical to use. Thus, asthma guidelines should be disseminated as convenient and easily accessible tools. Various education programs and decision-support tools have been designed and applied to the clinical management of asthma to solve these challenging problems. Many of them have been shown to be effective at increasing physicians' knowledge and adherence to asthma guidelines and improving patients' clinical outcomes. These educational and decision-support tools are expected to contribute to a narrowing of the gap between asthma guidelines and practice/implementation of the guidelines.
Asthma; Guideline; Education; Decision-support; Implementation
Major classes of medication in asthma management include bronchodilating β2-agonists, anti-inflammatory inhaled corticosteroids, leukotriene modifiers and theophyllines. However, all asthmatics do not respond to the same extent to a given medication. Available data suggest that a substantial range of individual variability, as much as 70%, may be due to genetic characteristics of each patient. Pharmacogenomics offers the potential to optimize medications for individual asthmatics by using genetic information to improve efficacy or avoid adverse effects. The best-studied case of the potential contribution of pharmacogenomics to treatment response in asthma comes from studies on human β2 adrenergic receptors. In addition, genetic variation in β2-adrenergic receptor (Arg16Gly) may predict response to anticholinergics for the treatment of asthma. In case of inhaled corticosteroids, a recent investigation using a traditional SNP-based approach identified a gene for corticotropin releasing hormone receptor 1 as a potential marker of response. Another major pathway that has been investigated is the pathway underlying response to cysteinyl leukotriene receptor antagonist. It is likely that in the near future, pharmacogenomic approaches based on individual genetic information will be introduced into an asthma treatment guideline and this guideline will allow us to identify those who have the best chance to respond to a specific medication.
Asthma; pharmacogenomics; treatment response
Atopy is considered to be a complex genetic trait and does not follow a simple mendelian pattern of inheritance. It is now well recognised that gene–gene interactions are important in complex genetic disease.
To analyse the influence of gene–gene interactions in the development of atopy.
A total of 2055 ethnically identical participants aged 10–18 years living in rural areas on Jeju Island, Korea, were randomly recruited. Atopy was defined as a positive skin prick test response to one or more common inhalant allergens. Gene–gene interactions among 12 polymorphic loci were analysed in the seven candidate genes of atopy using the multidimensionality‐reduction method.
A significant interaction was found between V297I in the gene coding vascular endothelial growth factor receptor 2 (KDR) and −308G→A in the gene coding tumour necrosis factor (TNF)α on the risk of atopy, with a cross‐validation consistency of 10 out of 10 and a prediction error of 35.9% (p = 0.001). Conventional logistic regression also revealed significant interactions between KDR and TNF for atopy. Individuals with the variant allele of −308G→A in TNF (GA or AA) and V297I in KDR (VI or II) had a significantly higher risk of atopy (OR 2.23; 95% CI 1.48 to 3.57).
KDR and TNF may synergistically influence the development of atopy through gene–gene interaction in Korean children and adolescents.
A systematic review of English and Korean articles published between 1990 and 2004 and a search of database and various online resources was conducted to determine the prevalences, mortality rates, socioeconomic burden, quality of life, and treatment pattern of asthma in Korean adults and children. Asthma morbidity and mortality in Korea are steadily increasing. The prevalence of asthma in Korea is estimated to be 3.9% and its severity is often underestimated by both physicians and patients. Mortality resulting from chronic lower respiratory diseases including asthma increased from 12.9 to 22.6 deaths per 100,000 of the population between 1992 and 2002. Disease severity, level of control, and symptom state were all found to negatively impact the quality of life of asthmatics. Although international and Korean asthma management guidelines are available, familiarity with and implementation of these guidelines by primary care physicians remain poor.
Asthma; Prevalence; Mortality; Cost of Illness; Quality of Life; Korea
Despite the substantial amount of asthma-related information available on the internet, little is known about the quality of such information. We assessed asthma-related information on the Korean internet intended as an educational material for asthma patients. By entering the key word, 'asthma', into 4 popular search engines, 32 web sites were identified and categorized with respect to authorship. The core asthma educational concepts and Health On the Net Code of Conduct principles were used to evaluate informational value and justifiability of unreliable information. Eight of 32 web sites were categorized as western physician, seventeen as oriental physician, four as commercial, and three as others. The mean number of core asthma educational concepts on the whole web sites was 2.7 out of 8. By type of authorship, 1.7 on the commercial sites, 2.1 on the oriental physician sites, 3.5 on the western physician sites, and 5.0 on the others sites in decreasing order. One of the western physician sites, two of the commercial sites, and all of the oriental physician and others sites contained unreliable information. However all of them except one site failed to satisfy our criteria of justifiability. Asthma-related information currently available on the Korean internet is highly variable in quality and lacks core asthma educational concepts and justifiability.
Asthma; Patient Education; Internet; Quality Assurance, Health Care; Quality Indicators, Health care
Neuropilin 1 (NP1) is a part of essential receptor complexes mediating both semaphorin3A (SEMA3A) and vascular endothelial growth factor (VEGF) which is one of important mediators involved in the pathogenesis of asthma. Therefore, it is possible that SEMA3A plays a role in the pathogenesis of asthma through attenuation of VEGF-mediated effects. In the present study, we aimed to evaluate expression levels of SEMA3A and NP1 using induced sputum of asthmatics and a murine model of asthma. Firstly, SEMA3A and NP1 expressions in induced sputum of asthmatics and SEMA3A and NP1 expression on bronchoalveolar lavage (BAL) cells and lung homogenates of asthmatic mice were determined. Then we evaluated the immunolocalization of VEGF receptor 1 (VEGFR1), VEGF receptor 2 (VEGFR2), and NP1 expressions on asthmatic mice lung tissue and their subcellular distributions using fibroblast and BEAS2B cell lines. Sputum SEMA3A and NP1 expressions were significantly higher in asthmatics than controls. Similarly, SEMA3A and NP1 expressions on BAL cells and lung homogenates were significantly elevated in asthmatic mice compared to control mice. Immunohistochemical analysis showed that VEGFR1, VEGFR2, and NP1 expressions were also uniformly increased in asthmatic mice. Our observations suggest that SEMA3A and NP1 may play important roles in the pathogenesis of asthma.
Asthma; Neuropilin; Semaphorin-3A (SEMA3A); Vascular Endothelial Growth Factor
Immunoglobulin E (IgE) is one of the central players in asthma and allergic diseases. Although the serum IgE level, a useful endophenotype, is generally increased in patients with asthma, genetic factors influencing IgE regulation in asthma are still not fully understood. To identify the genetic variations associated with total serum and mite-specific IgEs in asthmatics, a genome-wide association study (GWAS) of 657,366 single nucleotide polymorphisms (SNPs) was performed in 877 Korean asthmatics. This study found that several new genes might be associated with total IgE in asthmatics, such as CRIM1 (rs848512, P = 1.18×10−6; rs711254, P = 6.73×10−6), ZNF71 (rs10404342, P = 7.60×10−6), TLN1 (rs4879926, P = 7.74×10−6), and SYNPO2 (rs1472066, P = 8.36×10−6; rs1038770, P = 8.66×10−6). Regarding the association of specific IgE to house dust mites, it was observed that intergenic SNPs nearby to OPRK1 and LOC730217 might be associated with Dermatophagoides pteronyssinus (D.p.) and Dermatophagoides farinae (D.f.) in asthmatics, respectively. In further pathway analysis, the phosphatidylinositol signaling system and adherens junction pathways were estimated to play a role in the regulation of total IgE levels in asthma. Although functional evaluations and replications of these results in other populations are needed, this GWAS of serum IgE in asthmatics could facilitate improved understanding of the role of the newly identified genetic variants in asthma and its related phenotypes.
Sputum eosinophilia is observed frequently in patients with rhinitis. Sputum eosinophilia in patients with non-asthmatic allergic rhinitis has been suggested to be related to nonspecific airway hyperresponsiveness (AHR). However, the clinical significance of sputum eosinophilia in patients with non-asthmatic rhinitis without AHR has not been determined. We conducted a retrospective study examining the influence of sputum eosinophilia in patients with non-asthmatic rhinitis without AHR on pulmonary function and expression of fibrosis-related mediators.
Eighty-nine patients with moderate-to-severe perennial rhinitis without AHR were included. All underwent lung function tests (forced expiratory volume in 1 second [FEV1] and forced vital capacity [FVC]), skin tests to inhalant allergens, methacholine bronchial challenge tests, and hypertonic saline-induced sputum to determine eosinophil counts. Sputum mRNA levels for transforming growth factor-β (TGF-β), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinase-1 (TIMP-1) were also examined. Patients were divided into two groups according to the presence of sputum eosinophilia (≥3%, eosinophilia-positive [EP] and <3%, eosinophilia-negative [EN] groups).
FEV1 was significantly lower (P=0.04) and FEV1/FVC tended to be lower (P=0.1) in the EP group than in the EN group. In sputum analyses, the MMP-9 mRNA level (P=0.005) and the ratio of MMP-9 to TIMP-1 expression (P=0.01) were significantly higher in the EP group than in the EN group. There was no significant difference in TGF-β mRNA expression between the two groups.
Sputum eosinophilia in patients with moderate-to-severe perennial rhinitis without AHR influenced FEV1 and the expression pattern of fibrosis-related mediators.
Sputum; eosinophil; rhinitis; forced expiratory volume; matrix metalloproteinase-9
The prevalence of allergic diseases has been increasing rapidly, especially in developing countries. Various adverse health outcomes such as allergic disease can be attributed to rapidly increasing air pollution levels. Rapid urbanization and increased energy consumption worldwide have exposed the human body to not only increased quantities of ambient air pollution, but also a greater variety of pollutants. Many studies clearly demonstrate that air pollutants potently trigger asthma exacerbation. Evidence that transportation-related pollutants contribute to the development of allergies is also emerging. Moreover, exposure to particulate matter, ozone, and nitrogen dioxide contributes to the increased susceptibility to respiratory infections. This article focuses on the current understanding of the detrimental effects of air pollutants on allergic disease including exacerbation to the development of asthma, allergic rhinitis, and eczema as well as epigenetic regulation.
Allergy; Air pollution; Tobacco smoke pollution; Environmental exposure
We reported that level of lipopolysaccharide (LPS) exposure determined the type of airway inflammation in a murine model of asthma.
The purpose of this study is to evaluated the role of IL-13 in low dose LPS induced murine model of asthma using IL-13 and signal transducer and activator of transcription 6 (STAT6) deficient mice.
Mice were sensitized with an intranasal application of LPS-depleted ovalbumin (OA) and different doses of LPS (0.1 and 10 µg), and then challenged intranasally with OA alone. The phenotype changes between wild type (WT) and IL-13-/- mice and between WT and STAT6-/- mice were evaluated.
We confirmed again that low and high dose LPS resulted in different phenotypes of murine asthma. In the present study, we observed that phenotypes of murine asthma induced by low dose LPS were abolished in the homozygous null mutation of the IL-13 and STAT6 gene. However, those changes were not shown in mice sensitized OA plus high dose LPS.
IL-13 plays an important role in low dose LPS induced murine model of asthma. Our results provided a new insight in understanding of the potential role of IL-13 in innate immunity in human allergic asthma.
Asthma; Animal model; IL-13; STAT6; Lipopolysaccharide
Airway remodeling and exacerbated airway narrowing in asthma have been attributed to the regulation of intracellular Ca2+ by sarcoplasmic reticulum (SR) of the airway smooth muscle cells. The protein encoded by obscurin, cytoskeletal calmodulin and titin-interacting RhoGEF (OBSCN) is a crucial factor in determining the SR architecture in Obscn−/− mice. This study genotyped a total of 55 common single-nucleotide polymorphisms (SNPs) in 592 Korean asthmatics including 163 aspirin exacerbated respiratory disease (AERD) cases and 429 aspirin-tolerant asthma (ATA) controls. Eight SNPs, including two nonsynonymous polymorphisms rs1188722C>T (Leu2116Phe) and rs1188729G>C (Cys4642Ser), and one haplotype BL2_ht1 showed statistically significant associations with AERD development (p=0.003–0.03). Two variants, rs1188722C>T (Leu2116Phe) and rs369252C>A, also revealed nominal association with FEV1 decline by aspirin provocation in asthmatics (p=0.03–0.04). Intriguingly, rs1188722C>T (Leu2116Phe) is a highly conserved amino acid residue among species, suggesting its functional relevance to AERD. In addition, the A allele of rs369252C>A, which was more prevalent in AERD than in ATA, was predicted as a potential branch point (BP) site for alternative splicing (BP score=4.29). Although further functional evaluation is required, our findings suggest that OBSCN polymorphisms, in particular, highly conserved nonsynonymous Leu2116Phe variant, might contribute to aspirin hypersensitivity in asthmatics.
Recent literature suggests that Staphylococcal enterotoxin specific IgE may be a risk factor for asthma.
To investigate the associations between Staphylococcal enterotoxin sensitization and asthma.
A systematic review and meta-analysis was performed for relevant case-control or population-based studies, published in the peer-reviewed journals until February 2013. Data were extracted on study designs, subjects, definitions and the prevalence of Staphylococcal enterotoxin sensitization.
A total of 683 studies were initially identified, of which 7 studies finally met the inclusion criteria (5 case-control and 2 population-based studies). All the included studies reported higher prevalence of the sensitization in asthmatics than in controls, despite clinical and methodological heterogeneity. In a meta-analysis, the pooled odds ratio of the sensitization for asthma was 2.95 (95% confidence intervals 2.28-3.82).
Staphylococcal enterotoxin sensitization was significantly associated with asthma. The mechanisms of associations warrant further elucidation.
Asthma; Staphylococcus; Meta-analysis
Transglutaminase 2 (TG2) is a post-translational protein-modifying enzyme that catalyzes the transamidation reaction, producing crosslinked or polyaminated proteins. Increased TG2 expression and activity have been reported in various inflammatory conditions, such as rheumatoid arthritis, inflammation-associated pulmonary fibrosis, and autoimmune encephalitis. In particular, TG2 from epithelial cells is important during the initial inflammatory response in the lung. In this study, we evaluated the role of TG2 in the pathogenesis of allergic asthma, particularly whether TG2 affects initial activation signaling leading to Th2 differentiation against antigens.
We induced allergic asthma by ovalbumin sensitization and intranasal challenge in wild-type (WT) BALB/c and TG2-deficient mice. Broncheoalveolar lavage fluid cells and intracellular cytokine production were analyzed by flow cytometry. Interleukin (IL)-33 and TG2 expression in lung epithelial cells was detected by confocal microscopy.
Airway responsiveness was attenuated in TG2-deficient mice compared to that in the WT control. In addition, recruitment of eosinophils and Th2 and Th17 differentiation decreased in TG2-deficient mice. Treatment with cysteamine, a transglutaminase inhibitor, also reduced airway hypersensitivity, inflammatory cell recruitment, and T helper cell differentiation. TG2-deficient mice showed reduced IL-33 expression following induction of allergic asthma compared to those in the WT control.
We found that pulmonary epithelial cells damaged by allergens triggered TG2-mediated IL-33 expression leading to type 2 responses by recruiting both innate and adaptive arms of the immune system.
Epithelium; IL-33; Transglutaminase 2; Asthma; Animal models
Aspirin exacerbated respiratory disease (AERD) results in a severe asthma attack after aspirin ingestion in asthmatics. The filamin A interacting protein 1 (FILIP1) may play a crucial role in AERD pathogenesis by mediating T cell activation and membrane rearrangement. We investigated the association of FILIP1 variations with AERD and the fall rate of forced expiratory volume in one second (FEV1).
A total of 34 common FILIP1 single nucleotide polymorphisms (SNPs) were genotyped in 592 Korean asthmatic subjects that included 163 AERD patients and 429 aspirin-tolerant asthma (ATA) controls.
This study found that 5 SNPs (P=0.006-0.01) and 2 haplotypes (P=0.01-0.03) of FILIP1 showed nominal signals; however, corrections for the multiple testing revealed no significant associations with the development of AERD (Pcorr>0.05). In addition, association analysis of the genetic variants with the fall rate of FEV1, an important diagnostic marker of AERD, revealed no significant evidence (Pcorr>0.05).
Although further replications and functional evaluations are needed, our preliminary findings suggest that genetic variants of FILIP1 might be not associated with the onset of AERD.
Filamin A interacting protein 1; single nucleotide polymorphism; haplotype; asthma; aspirin exacerbated respiratory disease
Immunotherapy was introduced 100 years ago and has a unique role in the treatment of allergic diseases in that only immunotherapy can induce long-term immunological tolerance. However, only a few mouse models of immunotherapy have been developed so far.
We tried to establish murine immunotherapy models that have similar findings in human using subcutaneous rush immunotherapy-like schedule.
To determine the maximal safe or maximal tolerable dose, injection dose was doubled twice a day from the dose of sensitization. Mice with established asthma using ovalbumin (OVA) were repeatedly injected with OVA from the dose of sensitization subcutaneously twice a day: after reaching to the maximal safe or maximal tolerable dose, mice were injected with each dose either 10 times or 24 times.
Short term immunotherapy (10 times) with the maximal safe and tolerable dose of OVA showed decreased IL-5 production, decreased IL-5/INF-γ ratio, and increased IgG2a/IgG1 but there was no significant difference in airway hyperresponsiveness (AHR) or airway inflammation. Prolonged immunotherapy (24 times) with the maximal tolerable dose not only decreased cytokine productions of IL-5 and even INF-γ, but also decreased IgE, IgG1 and even IgG2a production. Remarkably, the prolonged immunotherapy provided a protective effect on AHR.
This study suggested immunotherapy models with some beneficial immunological and physiological effects in murine asthma.
Asthma; Animal models; Allergy; Immunotherapy
Chronic rhinitis is a heterogeneous group of diseases that cause nasal inflammation. And the nose may be a window into the lung in the concept of "one airway one disease."
This study was conducted to evaluate differences between the different forms of chronic rhinitis in terms of lower airway inflammation.
Patients that attended the allergy clinic and presented with moderate/severe persistent rhinitis symptoms for more than 1 year were enrolled. The patients with chronic rhinitis were classified into two groups (house dust mites [HDM]-sensitive allergic rhinitis [AR] or non-allergic rhinitis [NAR]) according to the presence of atopy, and additionally according to nasal polyposis and airway hyperresponsiveness, respectively. Medical records were reviewed and the mRNA expression levels of IL-5, IFN-γ, TGF-β1, IL-17A, and IL-25 were evaluated in induced sputum samples in each group.
Induced sputum samples of 53 patients were evaluated. Patients with NAR were significantly older than patients with HDM-sensitive AR (p < 0.05). Nasal polyposis was more prevalent in NAR patients than in HDM-sensitive AR patients (10.2% vs. 62.5%, p < 0.001). The expression levels of IL-17A mRNA were higher in NAR patients, regardless of the presence of airway hyperresponsiveness (p = 0.005).
These results suggest that patients with different forms of chronic rhinitis could have different inflammatory environments in their lower airway and NAR patients might have bronchial inflammation related to the elevated levels of IL-17A compared to HDM-sensitive AR patients.
Rhinitis; Allergy; IL-17A; Nasal polyps; Sputum; Asthma
Busulfan is an antineoplastic agent with a narrow therapeutic window. A post-hoc population pharmacokinetic analysis of a prospective randomized trial for comparison of four-times daily versus once-daily intravenous busulfan was carried out to search for predictive factors of intravenous busulfan (iBu) pharmacokinetics (PK). In this study the population PK of iBu was characterized to provide suitable dosing recommendations. Patients were randomized to receive iBu, either as 0.8 mg/kg every 6 h or 3.2 mg/kg daily over 4 days prior to hematopoietic stem cell transplantation. In total, 295 busulfan concentrations were analyzed with NONMEM. Actual body weight and sex were significant covariates affecting the PK of iBu. Sixty patients were included in the study (all Korean; 23 women, 37 men; mean [SD] age, 36.5 [10.9] years; weight, 66.5 [11.3] kg). Population estimates for a typical patient weighing 65 kg were: clearance (CL) 7.6 l/h and volume of distribution (Vd) 32.2 l for men and 29.1 L for women. Inter-individual random variabilities of CL and Vd were 16% and 9%. Based on a CL estimate from the final PK model, a simple dosage scheme to achieve the target AUC0-inf (defined as median AUC0-inf with a once-daily dosage) of 26.18 mg/l·hr, was proposed: 24.79·ABW0.5 mg q24h, where ABW represents the actual body weight in kilograms. The dosing scheme reduced the unexplained interindividual variabilities of CL and Vd of iBu with ABW being a significant covariate affecting clearance of iBU. We propose a new simple dosing scheme for iBu based only on ABW.
Dosage scheme; Intravenous busulfan; Population pharmacokinetics
Cockroach (CR) is an important inhalant allergen and can induce allergic asthma. However, the mechanism by which CR induces airway allergic inflammation and the role of endotoxin in CR extract are not clearly understood in regards to the development of airway inflammation. In this study, we evaluated whether endotoxin is essential to the development of CR induced airway allergic inflammation in mice.
Materials and Methods
Airway allergic inflammation was induced by intranasal administration of either CR extract, CR with additional endotoxin, or endotoxin depleted CR extract, respectively, in BALB/c wild type mice. CR induced inflammation was also evaluated with toll like receptor-4 (TLR-4) mutant (C3H/HeJ) and wild type (C3H/HeN) mice.
Intranasal administration of CR extracts significantly induced airway hyperresponsiveness (AHR), eosinophilic and neutrophilic airway inflammation, as well as goblet cell hyperplasia in a dose-dependent manner. The addition of endotoxin along with CR allergen attenuated eosinophilic inflammation, interleukin (IL)-13 level, and goblet cell hyperplasia of respiratory epithelium; however, it did not affect the development of AHR. Endotoxin depletion in CR extract did not attenuate eosinophilic inflammation and lymphocytosis in BAL fluid, AHR and IL-13 expression in the lungs compared to CR alone. The attenuation of AHR, eosinophilic inflammation, and goblet cell hyperplasia induced by CR extract alone was not different between TLR-4 mutant and the wild type mice. In addition, heat inactivated CR extract administration induced attenuated AHR and eosinophilic inflammation.
Endotoxin in CR extracts may not be essential to the development of airway inflammation.
Cockroach; endotoxin; toll like receptor-4
Food-dependent exercise-induced anaphylaxis (FDEIA) is a type of exercise-induced anaphylaxis associated with postprandial exercise. We describe a 19-year-old man with FDEIA. Our patient complained of urticaria, angioedema, dizziness and hypotension associated with exercise after ingestion of walnut-containing foods in a warm environment. Skin prick test and prick to prick test were positive for walnut antigen. The attack didn't occur by free running outside for 10 min 2 h after taking walnuts, and the temperature was about -2℃. Food-exercise test was done again in a warm environment based on prior history. Anaphylaxis was developed after exercise for 10 min in a warm environment after taking walnuts. Some environmental factors such as high temperature and high humidity or cold temperature may influence exercise-induced anaphylaxis. In our case, the cofactor was a warm environment: the challenge test done in a cold environment was negative, but positive in a warm environment. Physicians should be aware that the challenge test of FDEIA can show different results depending on temperature.
Anaphylaxis; Exercise; Food; Heat