Chronic urticaria (CU) is a common allergic skin disease that requires long-term pharmacological treatment. Some patients with severe CU suffer a poor quality of life. Although the pathogenic mechanisms of CU are not clearly understood, several groups have suggested that genetic mechanisms are involved in various CU cohorts. To further understand the molecular genetic mechanisms of CU, we summarize recent genetic data in this review. Although a few HLA alleles were suggested to be candidate markers in different ethnic groups, further replication studies that apply the recent classification are needed. Genetic polymorphisms in histamine-related genes, including FcεRI and HNMT, were suggested to be involved in mast cell activation and histamine metabolism. Several genetic polymorphisms of leukotriene-related genes, such as ALOX5, LTC4S, and the PGE2 receptor gene PTGER4, were suggested to be involved in leukotriene overproduction, a pathogenic mechanism. Further investigations using candidate gene approaches and genome-wide association studies (GWAS) will provide new insights into the molecular genetic mechanisms of CU, which will provide new marker genes for differentiation of CU phenotypes and identification of potential therapeutic targets.
Chronic urticaria; genetic association; leukotriene; mast cell
Mycoplasma pneumoniae (M. pneumoniae) is one of the most common causes of community-acquired pneumonia in children. The clinical course is typically self-limited and benign; however, rare cases of severe pneumonia can develop despite appropriate antibiotic therapy. We studied the effects of methylprednisolone pulse therapy on severe refractory M. pneumoniae pneumonia in children.
The clinical effects of methylprednisolone therapy were evaluated retrospectively in 12 children with severe refractory M. pneumoniae pneumonia, which was diagnosed serologically. All patients developed respiratory distress, high fever, and initial lobar pneumonic consolidation based on radiological findings. All clinical symptoms deteriorated despite appropriate antibiotic therapy. Thus, children were treated with intravenous methylprednisolone pulse therapy in addition to antibiotics.
The average febrile period before admission was 4.9±1.7 days, and fever persisted in all children until steroid administration. Methylprednisolone pulse therapy (30 mg/kg) was given 5.4±2.5 days after admission. After methylprednisolone pulse therapy, clinical symptoms improved in all patients without adverse events. The fever subsided 0-2 h after initiation of corticosteroid therapy. The abnormal radiological findings resolved within 2.6±1.3 days, and the high C-reactive protein levels (6.7±5.9 mg/dL) on admission decreased to 1.3±1.7 mg/dL within 3.0±1.1 days after starting corticosteroid therapy.
Three-day methylprednisolone pulse therapy could be applied to treatment of refractory M. pneumoniae pneumonia despite appropriate antibiotic therapy and appeared to be efficacious and well-tolerated.
Children; methylprednisolone; Mycoplasma pneumoniae; pneumonia
Airway inflammation, bronchial hyper-responsiveness (BHR), and bronchodilator response
(BDR) are representative characteristics of asthma. Because allergic rhinitis (AR) is a
risk factor for asthma development, we evaluated these 3 characteristics in AR using
measurement of fractional exhaled nitric oxide (FeNO), a methacholine challenge test
(MCT), and impulse oscillometry (IOS).
This study included 112 children with asthma (asthma group), 196 children with AR (AR
group), and 32 control subjects (control group). We compared pulmonary function
parameters and FeNO levels among the 3 groups. The AR group was subdivided into 2
categories: the AR group with BHR and the AR group without, and again pulmonary function
and FeNO levels were compared between the 2 subgroups.
FeNO levels were more increased in the AR and asthma groups than in the control group;
within the AR group, FeNO was higher in the AR group with BHR than in the AR group
without. The BDR was more increased in the AR group than in the control group when
percent changes in reactance at 5 Hz (Δ X5) and reactance area (Δ AX) were
compared. In the AR group, however, there was no difference in Δ X5 and Δ
AX between the AR group with BHR and the AR group without.
Reversible airway obstruction on IOS and elevated FeNO levels were observed in children
with AR. Because elevated FeNO levels can indicate airway inflammation and because
chronic inflammation may lead to BHR, FeNO levels may be associated with BHR in AR. IOS
can be a useful tool for detecting lower airway involvement of AR independent of BHR
assessed in the MCT.
Asthma; allergic rhinitis; bronchial hyper-responsiveness; bronchodilator effect; child; nitric oxide
Calprotectin is a cytosolic protein with immunomodulatory, antimicrobial, and antiproliferative actions. The concentration of calprotectin increases in infection, inflammation, and malignancy. We determined if calprotectin can be used as a marker for the diagnosis and follow-up of bowel inflammation in cow's milk protein allergy (CMPA).
In total, 32 patients newly diagnosed with CMPA were included (24 IgE-mediated, 8 non-IgE-mediated). In all subjects, a complete blood count, total IgE, cow's milk-specific IgE, and fecal calprotectin (FC) were assessed before and after a cow's milk protein (CMP) elimination diet was started. The results were compared with those of 39 healthy children.
The mean FC value before the CMP elimination diet was 516±311 µg/g in the 32 patients with CMPA and 296±94 µg/g in the control group (P=0.011). The mean FC value after the diet in these patients was 254±169 µg/g, which was significantly different from the mean value before the CMP elimination diet (P<0.001). When we compared FC levels before the CMP elimination diet in the IgE-mediated group with the control group, we found no significant statistical difference (P=0.142). The mean FC value before the CMP elimination diet was 886±278 µg/g in the non-IgE-mediated group and 296±94 µg/g in the control group; this difference was statistically significant (P<0.001). In the IgE-mediated and non-IgE-mediated groups, FC values after CMP elimination diet were 218±90 µg/g and 359±288 µg/g, respectively, and FC values before CMP elimination diet were 392±209 µg/g and 886±278 µg/g, respectively; these differences were statistically significant (P=0.001 and P=0.025, respectively).
FC levels may be a useful marker for follow-up treatment and recurrence determination in CMPA.
Milk hypersensitivity; milk protein; fecal calprotectin
Sensitization to specific allergens may be important in the development of allergic airway inflammation and airway hyperresponsiveness (AHR). We evaluated the effect of specific aeroallergen sensitization on eosinophilic airway inflammation and AHR.
We reviewed retrospectively the clinical data of subjects who underwent skin prick tests to aeroallergens, induced sputum analysis, and methacholine bronchial provocation tests to evaluate lower airway symptoms as well as analyzed the associations between the pattern of aeroallergen sensitization and sputum eosinophilia or AHR.
Of the 1,202 subjects be enrolled, 534 (44.4%) were sensitized to at least one aeroallergen in skin tests. AHR was demonstrated in 23.5% and sputum eosinophilia in 38.8%. Sputum eosinophilia was significantly associated with sensitization to perennial allergens (OR, 1.9; 95% CI, 1.4-2.5), house dust mite (OR, 1.7; 95% CI, 1.3-2.3), dog (OR, 1.9; 95% CI, 1.1-3.3), and cat (OR, 2.1; 95% CI, 1.4-3.4). AHR was associated with sensitization to perennial allergens (OR, 2.7; 95% CI, 2.0-3.7), house dust mite (OR, 2.2; 95% CI, 1.6 3.2), Alternaria (OR, 2.3; 95% CI, 1.2-4.7), and cat (OR, 2.7; 95% CI, 1.7-4.3). Sensitization to more perennial allergens increased the risk for sputum eosinophilia and AHR. There was no relationship with individual seasonal allergens.
The development of airway eosinophilic inflammation and AHR in an adult Korean population was associated with sensitization to perennial allergens rather than seasonal allergens.
Aeroallergen; airway eosinophilia; airway hyperresponsiveness
This study evaluates offending allergens in patients with allergic rhinitis (AR) according to age that establish a minimal panel for skin prick test (SPT) allergens required to identify if a patient is sensitized.
We retrospectively analyzed SPT results according to age to determine the minimum test battery panel necessary to screen at least 93%-95% of AR patients. Allergic skin tests (common airborne indoor and outdoor allergens) were performed on 7,182 patients from January 2007 to June 2011. All patients were classified into 9 groups according to age; subsequently, we investigated offending allergens by age group.
A total of 5,032 (70.1%) patients were found sensitized to at least one of the 55 aeroallergen extracts tested. The annual ranking of offending allergens was not significantly different from each other over the past 5 years. House dust mites (HDM) were the most prevalent allergens ranked from first to third for all 5 years. The allergens in the minimum test panel differed slightly among all age groups; in addition, the types of sensitized allergen sources were more diverse in the older versus younger age group. HDM covered a larger proportion of the sensitized allergens in the younger age group versus the older age group. Testing with 5 allergens (Dermatophagoides farinae, Tetranychus urticae, oak, mugwort and cockroach) adequately identified over 90% of the sensitized patients.
A SPT with around 5-7 allergens adequately detected most of the sensitization in the majority of the age groups in Korea. However, this study suggests that physicians perform the SPT with appropriately selected allergens in each age category for the screening of AR.
Allergic rhinitis; aeroallergen; skin prick test; sensitization
Eosinophils function as an effector cell in the development of asthma and allergic disease. Eotaxins are cytokines that promote pulmonary eosinophilia via the receptor CCR3. Single-nucleotide polymorphisms (SNPs) in CCR3 and eotaxin genes are associated with asthma. In this study, genetic interactions among SNPs of several eotaxin genes and CCR3 were assessed and their relationship with blood eosinophilia in asthma was examined.
A total of 533 asthmatics were enrolled in this study. Asthmatics with eosinophilia (>0.5×109/L) were compared with those without eosinophilia (≤0.5×109/L). Chi-square tests were used to compare SNP frequencies. Two different models were used to evaluate gene-gene interactions: logistic regression and generalized multifactor dimensionality reduction (GMDR).
EOT2+304C>A (29L>I) was significantly associated with 3 of the 4 CCR3 SNPs among asthmatics with eosinophilia (P=0.037-0.009). EOT2+304C>A (29L>I) and the CCR3 SNPs were also significantly associated with blood eosinophilia in an interaction model constructed by logistic regression (P=0.0087). GMDR analysis showed that the combination of EOT2+304C>A (29L>I) and CCR3-174C>T was the best model (accuracy=0.536, P=0.005, CVC 9/10).
The epistatic influence of CCR3 on eotaxin gene variants indicates that these variants may be candidate markers for eosinophilia in asthma.
Asthma; epistasis; polymorphisms; CCR3; eotaxin
Factors that can induce the release of histamine from basophils have been studied for more than 30 years. A protein termed histamine-releasing factor (HRF) was purified and molecularly cloned in 1995. HRF can stimulate histamine release and IL-4 and IL-13 production from IgE-sensitized basophils and mast cells. HRF-like activities were found in bodily fluids during the late phase of allergic reactions, implicating HRF in allergic diseases. However, definitive evidence for the role of HRF in allergic diseases has remained elusive. On the other hand, we found effects of monomeric IgE on the survival and activation of mast cells without the involvement of a specific antigen, as well as heterogeneity of IgEs in their ability to cause such effects. The latter property of IgE molecules seemed to be similar to the heterogeneity of IgEs in their ability to prime basophils in response to HRF. This similarity led to our recent finding that ~30% of IgE molecules can bind to HRF via their Fab interactions with two binding sites within the HRF molecule. The use of peptide inhibitors that block HRF-IgE interactions revealed an essential role of HRF to promote skin hypersensitivity and airway inflammation. This review summarizes this and more recent findings and provides a perspective on how they impact our understanding of allergy pathogenesis and potentially change the treatment of allergic diseases.
Asthma; allergy; histamine-releasing factor; IgE; mast cell; basophil
Asthma is a chronic inflammatory disease of the airways, and is associated with upregulation of phospholipase A2 (PLA2), the enzyme that hydrolyzes phosphatidylcholine, producing lysophosphatidylcholine (LPC) and free fatty acids. LPC is a lipid mediator with known pro-inflammatory and pro-atherogenic properties, and is believed to be a critical factor in cardiovascular diseases. We postulate that asthmatic subjects have an elevated content of LPC in the lung lining fluids.
Eight non-asthmatic controls and seven asthmatic subjects were recruited for broncho-alveolar lavage fluids (BALF) collection for analysis of LPC by high performance liquid chromatography-tandem mass spectrometry.
LPC16:0 and LPC18:0 were significantly elevated in the BALF of asthmatics with impaired lung function characteristic of moderate asthma, but not mild asthma. The increased LPC content in BALF was accompanied by increased PLA2 activity. Furthermore, qRT-PCR analysis of the BALF cell fraction indicated increased secretory PLA2-X (sPLA2-X).
The increased LPC content in the lung lining fluids is a potential critical lipid mediator in the initiation and/or progression of airway epithelial injury in asthma.
Lysophosphatidylcholine; asthma; phospholipase A2
In human subjects and animal models with acute and chronic lung injury, the bioactive lysophosphatidylcholine (LPC) is elevated in lung lining fluids. The increased LPC can promote an inflammatory microenvironment resulting in lung injury. Furthermore, pathological lung conditions are associated with upregulated phospholipase A2 (PLA2), the predominant enzyme producing LPC in tissues by hydrolysis of phosphatidylcholine. However, the lung cell populations responsible for increases of LPC have yet to be systematically characterized. The goal was to investigate the LPC generation by bronchial epithelial cells in response to pathological mediators and determine the major LPC species produced.
Primary human bronchial epithelial cells (NHBE) were challenged by vascular endothelial growth factor (VEGF) for 1 or 6 h, and condition medium and cells collected for quantification of predominant LPC species by high performance liquid chromatography-tandem mass spectrometry (LC-MS-MS). The cells were analyzed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) for PLA2. The direct effects of LPC in inducing inflammatory activities on NHBE were assessed by transepithelial resistance as well as expression of interleukin-8 (IL-8) and matrix metalloproteinase-1 (MMP-1).
VEGF stimulation of NHBE for 1 or 6 h, significantly increased concentrations of LPC16:0, LPC18:0, and LPC18:1 in condition medium compared to control. The sPLA2-selective inhibitor (oleyloxyethyl phosphorylcholine) inhibited the VEGF-induced release of LPC16:0 and LPC18:1 and PLA2 activity. In contrast, NHBE stimulated with TNF did not induce LPC release. VEGF did not increase mRNA of PLA2 subtypes sPLA2-X, sPLA2-XIIa, cPLA2-IVa, and iPLA2-VI. Exogenous LPC treatment increased expression of IL-8 and MMP-1, and reduced the transepithelial resistance in NHBE.
Our findings indicate that VEGF-stimulated bronchial epithelial cells are a key source of extracellular LPCs, which can function as an autocrine mediator with potential to induce airway epithelial inflammatory injury.
Bronchial epithelium; phospholipase A2; lysophosphatidylcholine
To evaluate airway changes in ovalbumin-induced asthmatic mice in terms of postmortem micro-CT images and pathological findings.
Asthma was induced in mice by intraperitoneal injection and nasal instillation of ovalbumin aluminium hydroxide into mice (experimental group, n=6), and another group of mice received intraperitoneal injection and nasal instillation of distilled phosphate-buffered saline (control group, n=6). Bronchial lumen area was measured in the main bronchial lumen of the distal third bronchial branch level (6 parts per each mouse) on axial scans of Micro-CT, using a Lucion's smart pen (semi-automated) and a curve pen (manual). Bronchial wall thickness was obtained in 4 sections (2 levels on either side) after the third bronchial branch by measuring the diameter which was perpendicular to the longitudinal axis of the main bronchus on curved Multi-planar reconstruction (MPR) images. Histologic slides were obtained from the lesion that was matched with its CT images, and bronchial wall thicknesses were determined.
The mean bronchial lumen area was 0.196±0.072 mm2 in the experimental group and 0.243±0.116 mm2 in the control group; the difference was significant. Bronchial wall thickness on micro-CT images (mean, 0.119±0.01 vs. 0.108±0.013 mm) and in pathological specimens (mean, 0.066±0.011 vs. 0.041±0.009 mm) were thicker in the experimental group than in the control group; bronchial wall thickness on micro-CT images correlated well with pathological thickness (for the experimental group, r=0.712; for the control group, r=0.46). The thick bronchial wall in the experimental group demonstrated submucosal hypertrophy along with goblet cell hyperplasia and smooth muscle hyperplasia.
The results of this study suggest that asthma may induce thickening of bronchial wall and narrowing of the lumen area on micro-CT images and that these results may significantly correlate with pathological findings.
Bronchial asthma; mice Laboratory; x-ray Micro-CT scans; airway remodeling; quantitative evaluation; histopathology; case comparison studies
Recognition of microbes is important to trigger the innate immune system. Mycolic acid (MA) is a component of the cell walls of mycobacteria such as Mycobacterium bovis Bacillus Calmette-Guerin. MA has immunogenic properties, which may modulate the innate and adaptive immune response. This study aimed to investigate whether a novel synthetic MA (sMA) inhibits allergic inflammatory responses in a mouse model of asthma.
BALB/c mice were injected intraperitoneally with sMA followed by sensitization and challenge with ovalbumin (OVA). Mice were examined for bronchial hyperresponsiveness (BHR), the influx of inflammatory cells into the lung tissues, histopathological changes in the lungs and CD4+CD25+Foxp3+ T cells in the spleen, and examined the response after the depleting regulatory T cells (Tregs) with an anti-CD25mAb.
Treatment of mice with sMA suppressed the asthmatic response, including BHR, bronchoalveolar inflammation, and pulmonary eosinophilic inflammation. Anti-CD25mAb treatment abrogated the suppressive effects of sMA in this mouse model of asthma and totally depleted CD4+CD25+Foxp3+ T cells in the spleen.
sMA attenuated allergic inflammation in a mouse model of asthma, which might be related with CD4+CD25+Foxp3+ T cell.
Mycolic acid; asthma; allergic inflammation; regulatory T cells; mice
The management of severe recalcitrant atopic dermatitis (AD) is a challenging issue for clinicians and patients. We hypothesized that repeated intramuscular injections of autologous immunoglobulin (autologous immunoglobulin therapy: AIGT) might induce clinical improvements in patients with AD by stimulation of the active immune response to antigen-binding-site of pathogenic antibodies. We tried AIGT in 3 adult patients with severe recalcitrant AD whose clinical conditions could not be effectively controlled by medical treatments (including oral cyclosporine) for more than 2 years. Autologous immunoglobulin was purified from the autologous plasma by affinity chromatography using Protein A. The patients were treated by an intramuscular injection of 50 mg of autologous immunoglobulin twice a week for 4 weeks. A clinical severity score of AD (SCORAD value) showed a decrease greater than 30% at 8 weeks after the initiation of AIGT compared with the baseline before the initiation of AIGT in all 3 patients with severe recalcitrant AD. No significant side effects from treatment were observed. Further studies with larger numbers of patients are required to evaluate the clinical usefulness of AIGT for AD.
Dermatitis; atopic; immunoglobulin; treatment
Codeine is widely prescribed in clinical settings for the relief of pain and non-productive coughs. Common adverse drug reactions to codeine include constipation, euphoria, nausea, and drowsiness. However, there have been few reports of serious adverse reactions after codeine ingestion in adults. Here, we present a case of severe anaphylaxis after oral ingestion of a therapeutic dose of codeine. A 30-year-old Korean woman complained of the sudden onset of dyspnea, urticaria, chest tightness, and dizziness 10 minutes after taking a 10-mg dose of codeine to treat a chronic cough following a viral infection. She had previously experienced episodes of asthma exacerbation following upper respiratory infections, and had non-atopic rhinitis and a food allergy to seafood. A skin prick test showed a positive response to 1-10 mg/mL of codeine extract, with a mean wheal size of 3.5 mm, while negative results were obtained in 3 healthy adult controls. A basophil histamine release test showed a notable dose-dependent increase in histamine following serial incubations with codeine phosphate, while there were minimal changes in the healthy controls. Following a CYP2D6 genotype analysis, the patient was found to have the CYP2D6*1/*10 allele, indicating she was an intermediate metabolizer. An open label oral challenge test was positive. To the best of our knowledge, this is the first report of a patient presenting with severe anaphylaxis after the ingestion of a therapeutic dose of codeine, which may be mediated by the direct release of histamine by basophils following exposure to codeine.
Anaphylaxis; basophil degranulation test; codeine
Although idiopathic hypereosinophilic syndrome(IHES) commonly involves the lung, it is rarely associated with acute respiratory distress syndrome (ARDS). Here we describe a case of IHES presented in conjunction with ARDS. A 37-year-old male visited the emergency department at Samsung Medical Center, Seoul, Korea, with a chief complaint of dyspnea. Blood tests showed profound peripheral eosinophilia and thrombocytopenia. Patchy areas of consolidation with ground-glass opacity were noticed in both lower lung zones on chest radiography. Rapid progression of dyspnea and hypoxia despite supplement of oxygen necessitated the use of mechanical ventilation. Eosinophilic airway inflammation was subsequently confirmed by bronchoalveolar lavage, leading to a diagnosis of IHES. High-dose corticosteroids were administered, resulting in a dramatic clinical response.
Idiopathic hypereosinophilic syndrome; eosinophilia; acute respiratory distress syndrome; pulmonary thromboembolism
My research career has focused on the causes of asthma and its treatment. After establishing the key role that mast cells play in the inflammatory response in asthma, attention was turned towards understanding disease chronicity and variability across the lifecourse. Through a combination of studies on airway biopsies and primary cell cultures we have established that asthma is primarily an epithelial disease driven by increased environmental susceptibility to injury and an altered repair response as depicted by sustained activation of the epithelial mesenchymal trophic unit (EMTU) that is invoked in foetal branching morphogenesis. Varied activation of the EMTU connects the origins of asthma to its progression over time with involvement of epithelial susceptibility through impaired barrier and innate immune functions and altered mesenchymal susceptibility as exemplified by polymorphisms of the metalloprotease gene, ADAM33. Taken together these observations have led to a fundamental re-evaluation of asthma pathogenesis. Rather than placing allergic inflammation as the prime abnormality, it is proposed that the airway epithelium lies at the center of asthma pathogenesis, and that in conjunction with the underlying mesenchyme, it is the principle orchestrator of both the induction of asthma and its evolution over the lifecourse. This concept has provided 'the basis for a new preventative and therapeutic approach focused more on increasing the airways resistance to environmental insults rather than suppressing downstream inflammation once it is established.
Asthma; management; prevention; treatment
Grain-induced asthma is a frequent occupational allergic disease mainly caused by inhalation of cereal flour or powder. The main professions affected are bakers, confectioners, pastry factory workers, millers, farmers, and cereal handlers. This disorder is usually due to an IgE-mediated allergic response to inhalation of cereal flour proteins. The major causative allergens of grain-related asthma are proteins derived from wheat, rye and barley flour, although baking additives, such as fungal α-amylase are also important. This review deals with the current diagnosis and treatment of grain-induced asthma, emphasizing the role of cereal allergens as molecular tools to enhance diagnosis and management of this disorder. Asthma-like symptoms caused by endotoxin exposure among grain workers are beyond the scope of this review. Progress is being made in the characterization of grain and bakery allergens, particularly cereal-derived allergens, as well as in the standardization of allergy tests. Salt-soluble proteins (albumins plus globulins), particularly members of the α-amylase/trypsin inhibitor family, thioredoxins, peroxidase, lipid transfer protein and other soluble enzymes show the strongest IgE reactivities in wheat flour. In addition, prolamins (not extractable by salt solutions) have also been claimed as potential allergens. However, the large variability of IgE-binding patterns of cereal proteins among patients with grain-induced asthma, together with the great differences in the concentrations of potential allergens observed in commercial cereal extracts used for diagnosis, highlight the necessity to standardize and improve the diagnostic tools. Removal from exposure to the offending agents is the cornerstone of the management of grain-induced asthma. The availability of purified allergens should be very helpful for a more refined diagnosis, and new immunomodulatory treatments, including allergen immunotherapy and biological drugs, should aid in the management of patients with this disorder.
Baker's asthma; cereals; wheat allergens; soya flour; fungal enzymes; allergen immunotherapy
Long-term asthma management is recommended to asthmatics; however, many patients do not adhere to follow-up treatment. It is unclear why many asthmatics do not adhere to follow-up treatment and long-term clinical course after discontinuation of asthma management. This study investigates the factors associated with loss to follow-up and observes the clinical course in asthmatics who discontinued asthma treatment.
A retrospective investigation was conducted after reviewing medical records of adult patients who were newly diagnosed with asthma at a university hospital in Seoul, South Korea from January 2005 to March 2007. We compared baseline demographics and the clinical and laboratory profiles of patients to see if they successfully adhered to the treatment at an outpatient clinic for at least 3 years. The clinical course and asthma control status were surveyed by telephone for patients who were lost to follow-up within 3 years.
A total of 351 (73.9%) out of 475 patients were lost to follow-up within 3 years of asthma diagnosis. Patients lost to follow-up were younger and had clinical features of less severe asthma at time of diagnosis (higher FEV1 and PC20, and lower grade treatments) compared to patients who adhered to the follow-up for longer than 3 years (all P<0.05). Among the 198 responders to the telephone survey, 124 responders (62.6%) answered that they eventually discontinued asthma medication. A significantly higher proportion of the 124 responders who discontinued asthma treatment maintained symptom improvement compared to the 74 responders who continued asthma medication (77.4% vs. 55.4%, P=0.003).
Almost three quarters of newly diagnosed asthmatics discontinued asthma medication within 3 years despite a medical recommendation. There are considerable numbers of asthmatics who can maintain long-term asthma control status without medication.
Asthma; medication adherence; lost to follow-up; surveys; telephone; questionnaires
The oil spill from the Heibei Spirit in December 2007 contaminated the Yellow Coast of South Korea. We evaluated the respiratory effects of that spill on children who lived along the Yellow Coast.
Of 662 children living in the area exposed to the oil spill, 436 (65.9%) were enrolled as subjects. All subjects completed a modified International Study of Asthma and Allergies in Childhood questionnaire. A health examination, including a skin prick test, pulmonary function test, and methacholine bronchial provocation test (MBPT), was administered. The children were assigned to two groups: those who lived close to the oil spill area and those who lived far from the oil spill area.
The children who lived close to the oil spill area showed a significantly lower forced expiratory volume in one second (FEV1), an increased prevalence of 'asthma ever' (based on a questionnaire), and 'airway hyperresponsiveness' (based on the MBPT) than those who lived far from the oil spill area (FEV1; P=0.011, prevalence of 'asthma ever' based on a questionnaire; P=0.005, prevalence of 'airway hyperresponsiveness' based on the MBPT; P=0.001). The onset of wheezing after the oil spill was significantly higher in children who lived close to the oil spill area than in those who lived far from the oil spill area among the 'wheeze ever' group (P=0.002). In a multiple logistic regression analysis, male sex, family history of asthma, and residence near the oil spill area were significant risk factors for asthma (sex [male/female]: odds ratio [OR], 2.54; 95% confidence interval [CI], 1.31-4.91; family history of asthma [No/Yes]: OR, 3.77; 95% CI, 1.83-7.75; exposure group [low/high]; OR, 2.43; 95% CI, 1.27-4.65).
This study suggests that exposure to an oil spill is a risk factor for asthma in children.
Asthma; airway hyperresponsiveness; prevalence; industrial oils
The IL-4 and IL-4 receptor α (IL-4Rα) genes are the key candidate genes for atopy and asthma susceptibility. Exposure to wheat flour can cause IgE sensitization and respiratory symptoms in bakery workers. Therefore, we hypothesized that IL-4 and IL-4Rα single nucleotide polymorphisms (SNPs) may be involved in the pathogenic mechanism of baker's asthma.
Clinical and genetic data from 373 bakery workers were analyzed. A survey questionnaire, spirometry, and skin prick tests with wheat flour were performed. Serum-specific IgE, IgG1, and IgG4 to wheat flour were determined using ELISA. Five candidate IL-4 (-729 T>G, 589 T>C, and 33 T>C) and IL-4Rα (Ile75Val A>G and Gln576Arg A>G) SNPs were genotyped and analyzed.
Workers with the G allele of IL-4Rα Ile75Val A>G had a significantly higher prevalence of work-related lower respiratory symptoms than those with the AA genotype (P=0.004, 16.0% vs. 2.9%). In the skin prick test, workers with the AA genotype of IL-4Rα Gln576Arg A>G had a significantly higher positive rate to wheat flour (P=0.015, 8.2% vs. 1.1%) than those with AG/GG genotype. No significant associations were found in the three genetic polymorphisms of IL-4. For the predicted probabilities, workers with the AA genotype of Gln576Arg A>G had a higher prevalence of IgG1 and IgG4 in response to wheat flour, according to increased exposure intensity (P=0.001 for IgG1 and P=0.003 for IgG4).
These findings suggest that the IL-4Rα Ile75Val and Gln576Arg polymorphisms may be associated with work-related respiratory symptom development.
Genetic polymorphism; IL-4 Receptor α; IL-4; baker's asthma; work-related symptom
Interleukin (IL)-13, a Th2-type cytokine, plays a pivotal role in the pathogenesis of asthma through its direct effects on airway smooth muscles. A naturally occurring IL-13 polymorphism, R110Q, is strongly associated with increased total serum IgE levels and asthma. In the present study, we aimed to determine whether the IL-13 R110Q variant would display different biochemical properties or altered functions in comparison with wild-type (WT) IL-13 in cultured human bronchial smooth muscle cells (hBSMCs).
Culture supernatants and cell proteins were collected from cultured hBSMCs that were treated with 50 ng/mL IL-13 or IL-13 R110Q for 24 hours. Eotaxin released into hBSMC culture medium was determined by ELISA. The expression levels of the high-affinity IgE receptor (FcεRI) α-chain, smooth muscle-specific actin alpha chain (α-SMA), smooth muscle myosin heavy chain (SmMHC), and calreticulin in the cells were measured on Western blots.
Compared with WT IL-13, treatment with the IL-13 R110Q variant resulted in a significant increase in eotaxin release as well as significant, although modest, increases in the expression levels of α-SMA, SmMHC, calreticulin, and FcεRI α-chain.
The results of the present study suggenst that the IL-13 R110Q variant may enhance enhanced functional activities in hBSMCs.
IL-13; polymorphisms; bronchial smooth muscle cells; functional activity
Basophil activation occurs both in patients with immediate hypersensitivity reactions to anti-inflammatory drugs and in healthy controls in a dose-dependent manner. Our aims were to define the optimal basophil activation test (BAT) concentration and the threshold for BAT positivity for dipyrone.
From 45 patients with a positive history of an immediate hypersensitivity reaction to dipyrone, we found 20 patients with dipyrone-induced anaphylaxis demonstrating positive skin tests. All selected patients, as well as 10 healthy controls, were tested in vivo and in vitro. BAT was performed using Flow 2CAST technique with three low dipyrone concentrations: 25 µg/mL (c1), 2.5 µg/mL (c2) and 0.25 µg/mL (c3). The threshold for BAT positivity was established using receiver operating characteristics (ROC) curve analysis.
Using ROC curve analysis the highest area under curve, 0.79 (0.63-0.95) (P<0.01), was found for c3. When the highest stimulation indexes from the three concentrations for each patient were used, ROC curve analysis revealed an area under curve of 0.81 (0.65-0.96) (P<0.01), sensitivity and specificity were 0.70 and 1 and the optimal threshold value for BAT positivity was 1.71. Thirteen patients had a positive BAT for at least one of the tested dipyrone concentrations. All healthy controls presented negative BAT.
BAT might be a useful technique to diagnose dipyrone allergy, provided all three low dipyrone concentrations are used together. With an assay-specific threshold of 1.71, ROC curve analysis yields 70% sensitivity and 100% specificity.
Hypersensitivity; dipyrone; cytometry; basophils