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
Anaphylactic shock is sometimes accompanied by local interstitial edema due to increased vascular permeability. We performed magnetic resonance imaging (MRI) to compare edema in the larynx and brain of anesthetized rats during anaphylactic hypotension versus vasodilator-induced hypotension.
Male Sprague Dawley rats were subjected to hypotension induced by the ovalbumin antigen (n=7) or a vasodilator sodium nitroprusside (SNP; n=7). Apparent diffusion coefficient (ADC) and T2-relaxation time (T2RT) were quantified on MRI performed repeatedly for up to 68 min after the injection of either agent. The presence of laryngeal edema was also examined by histological examination. Separately, the occurrence of brain edema was assessed by measuring brain water content using the wet/dry method in rats with anaphylaxis (n=5) or SNP (n=5) and the non-hypotensive control rats (n=5). Mast cells in hypothalamus were morphologically examined.
Mean arterial blood pressure similarly decreased to 35 mmHg after an injection of the antigen or SNP. Hyperintensity on T2-weighted images (as reflected by elevated T2RT) was found in the larynx as early as 13 min after an injection of the antigen, but not SNP. A postmortem histological examination revealed epiglottic edema in the rats with anaphylaxis, but not SNP. In contrast, no significant changes in T2RT or ADC were detectable in the brains of any rats studied. In separate experiments, the quantified brain water content did not increase in either anaphylaxis or SNP rats, as compared with the non-hypotensive control rats. The numbers of mast cells with metachromatic granules in the hypothalamus were not different between rats with anaphylaxis and SNP, suggesting the absence of anaphylactic reaction in hypothalamus.
Edema was detected using the MRI technique in the larynx during rat anaphylaxis, but not in the brain.
Anaphylactic shock; brain edema; laryngeal edema; mast cell
Allergen extracts from the house dust mite (HDM, Dermatophagoides pteronyssinus) are widely utilized for diagnosis and treatment of allergic diseases. It is known that allergen extracts degrade and lose potency when stored over time.
This study aimed to determine the optimal conditions for stability of allergen extracts. This study was undertaken to investigate the optimal storage conditions for HDM extracts, the effects of adding 0.03% human serum albumin (HSA) and 50% glycerol were evaluated at -20℃, 4℃, and room temperature (RT). Changes in protein and group 1 major allergen (Der p 1) concentration, as well as allergenicity were measured over a 1 year period using the Bradford assay, two-site ELISA, and ELISA inhibition.
Protein concentrations decreased by 86%, 51%, and 6% at RT, 4℃, and -20℃, respectively, when stored in distilled water. Overall allergenicity remained high (89.9%) when the extracts was reconstituted in 50% glycerol solution, and was 93.1% when reconstituted in 50% glycerol and 0.03% HSA at RT. Allergenicity was decreased to 36.6% and 33.3%, however, reconstitution in DW or 0.03% HSA solution at RT, respectively. Allergenicity was remained high as 92.0%-97.0% when stored at 4℃ regardless of the buffer conditions.
Storage temperature is the most important factor in preserving allergenicity of HDM extracts, which is ideal at 4℃. The addition of 50% glycerol to the storage buffer was also found to play an important role in increasing the shelf-life of HDM extracts at RT.
Allergen; house dust mite; stability
The lipid entities of cell membranes are components of the immune system and important mediators of inflammation. Despite increasing interest in the function of epithelial cells in inflammation, the role of cholesterol in this process has not been described. Here, we investigated the effect of cholesterol depletion on the inflammatory process in airway epithelial cells via the expression of interleukin (IL)-8 as a marker of inflammation.
A 549 cells were treated with 0.5% methyl-β-cyclodextrin as a selective cholesterol extractor. The IL-8 level was assessed by enzyme-linked immunosorbent assay and reassessed after cholesterol repletion. Mitogen-activated protein kinase (MAPK) inhibitors were used to determine the upstream signaling pathway for IL-8 production in cholesterol-depleted cells.
We found a relationship between the amount of cholesterol in A 549 cells and inflammation of the airway. IL-8 production was increased in cholesterol-depleted A 549 cells and restored by cholesterol repletion. IL-8 production was decreased by pretreatment with the extracellular signal-regulated kinase (ERK) inhibitor U0126 but not with JNK inhibitor II or the p38 MAPK inhibitor SB202190.
Our findings suggest that inflammatory responses are increased in cholesterol-depleted epithelial cells via the MAPK signaling system, predominantly by the ERK pathway. We conclude that the lipid components of airwayepithelial cells may play a role in the inflammatory process.
Cholesterol; epithelial cell; inflammation; interleukin-8; MAP kinase signaling system
The mast cell plays a pivotal role in the human immune response. Crosslinking of 2 IgE molecules bound to the high affinity IgE receptor (FcεRI) on the surface of the mast cell results in mast cell degranulation and the release of several proinflammatory mediators. Patients with type-I allergy have increased levels of IgE in the blood compared to healthy individuals.
In a 6-week culture system of stem cells to human mast cells we investigated the effect of the concentration of IgE. The mast cells were cultured with different concentrations of IgE for the last 10 days of the maturation period. It was observed how the IgE concentration affects the histamine release, FcεRI density on the mast cell surface and the concentration of other mediators.
A clear correlation between IgE concentration in culture medium and the release of histamine upon activation was observed. It showed a bell-shaped dose response curve, with maximal response around an IgE-concentration of 250 ng/mL. Furthermore, the sensitivity of the mast cells and surface density of FcεRI on mast cell surface was also influenced by the IgE concentration in the culture medium.
IgE in the culture medium during the last 10 days of mast cell maturation influences the release of the preformed mediator histamine after mast cell activation and the density of FcεRI on the mast cell surface. The release of the de novo synthetized mediator prostaglandin D2 and the expression of chymase and tryptase are not influenced by IgE in culture medium.
Human mast cell; FcεRI; histamine; prostaglandin D2; IgE; allergy; parasite infection; hygiene hypothesis
A 24-year-old male with a history of spondyloarthropathy presented with high fever, cervical lymphadenopathy and generalized maculopapular rash. He was treated with prednisolone for chronic uveitis before being switched to sulfasalazine 3 weeks prior to admission. Laboratory findings revealed marked leukocytosis with frequent atypical lymphocytes. Sulfasalazine was discontinued and the etiology of mononucleosis syndrome explored. During admission, he developed acalculous cholecystitis and hypotension. All symptoms quickly improved following administration of systemic corticosteroids. The investigation for infectious mononucleosis yielded negative results and a diagnosis of sulfasalazine-induced hypersensitivity syndrome was confirmed using enzyme-linked immunospot assays.
Drug hypersensitivity; enzyme-linked immunospot assay; sulfasalazine
Asia-Pacific is one of the most densely populated regions of the world and is experiencing rapid economic changes and urbanization. Environmental pollution is a significant problem associated with the rapid modernization of many cities in South Asia. It is not surprising that the prevalences of asthma and allergies are increasing rapidly, although the underlying reasons remain largely unknown. Many studies from this region have documented the changing prevalence of allergic diseases in various parts of the world. However, the methodologies used were neither standardized nor validated, making the results difficult to evaluate. The International Study of Asthma and Allergies in Childhood (ISAAC) has provided a global epidemiology map of asthma and allergic diseases, as well as the trend of changes in the prevalence of these diseases. Allergic sensitization is extremely common in many Asian communities. However, the prevalence of allergic diseases remains relatively rare. The rapid urbanization in the region, which increases environmental pollution and can affect the rural environment, will likely increase the prevalence of asthma and allergies in Asia.
Asthma; allergies; Asia; pollution; International Study of Asthma and Allergies in Childhood
Although aspirin-exacerbated respiratory disease (AERD) has attracted a great deal of attention because of its association with severe asthma, it remains widely under-diagnosed in the asthmatic population. Oral aspirin challenge is the best method of diagnosing AERD, but this is a time-consuming procedure with serious complications in some cases. Thus, development of non-invasive methods for easy diagnosis is necessary to prevent unexpected complications of aspirin use in susceptible patients. For the past decade, many studies have attempted to elucidate the genetic variants responsible for risk of AERD. Several approaches have been applied in these genetic studies. To date, a limited number of biologically plausible candidate genes in the arachidonate and immune and inflammatory pathways have been studied. Recently, a genome-wide association study was performed. In this review, the results of these studies are summarized, and their limitations discussed. In addition to the genetic variants, changes in methylation patterns on CpG sites have recently been identified in a target tissue of aspirin hypersensitivity. Finally, perspectives on application of new genomic technologies are introduced; these will aid our understanding of the genetic pathogenesis of aspirin hypersensitivity in asthma.
Aspirin; hypersensitivity; asthma; single nucleotide polymorphism; genome-wide association study; methylation
Allergen immunotherapy (AIT) has been used as a curative and specific treatment of allergic diseases. However, no data on the prescription patterns of AIT in Korea is available. Therefore, we surveyed the prescription patterns of AIT by allergy specialists in Korea.
We emailed a questionnaire on AIT prescription patterns to the 690 members of the Korean Academy of Asthma, Allergy and Clinical Immunology with clinical practice experience. All returned answers were evaluated.
The response rate was 21.0%. Only 69.0% of the respondents performed AIT in practice. Hindrance factors for performing AIT in the practice included a lack of facilities (21%), lack of practical experience during their subspecialty or postgraduate educational training programs (15.8%), no need for AIT because of sufficient pharmacotherapy (14.5%), insufficient economic profits (14.5%), and risks for adverse reactions (13.2%). Ninety-two allergy specialists (82%) performed AIT subcutaneously subcutaneous immunotherapy (SCIT) and 20 allergy specialists (18%) performed it sublingually sublingual immunotherapy (SLIT). Only 8 specialists performed both SCIT and SLIT. The allergens used for SCIT were house dust mites (98.9%), pollens (72.8%), and animal dander (23.9%). SLIT was prescribed only for house dust mites. Twenty-eight physicians (30.4%) observed anaphylactic reactions during SCIT. Eight physicians (40.0%) who prescribed SLIT observed adverse reactions, including local reactions, but none of them observed anaphylactic reactions.
In this survey, 69.0% of the respondents performed AIT in clinical practice. SCIT prescription is more popular than SLIT. The Lack of facilities and clinical education is a critical barrier to performing AIT. Therefore, proper clinical education of AIT is necessary for Korean allergists.
Allergen immunotherapy; allergic rhinitis; asthma; survey
Non-classical actions of vitamin D as a cytokine are related to the immunopathology of asthma. Few studies have examined vitamin D levels and asthma severity in adults. The aim of this research was to assess the relationship between vitamin D levels, atopy markers, pulmonary function, and asthma severity.
We analyzed 25-hydroxyvitamin D levels in serum collected from 121 asthmatic adults from Costa Rica to investigate the association between vitamin D levels (categorized as sufficient, ≥30 ng/mL, or insufficient, <30 ng/mL), allergic rhinitis, total IgE and peripheral blood eosinophils (as markers of atopy), asthma severity, baseline forced expiratory volume in 1 second (FEV1), and forced vital capacity (FVC). Univariate and multivariate analyses were performed to assess these relationships.
When the population was stratified by vitamin D status, 91% of asthmatic patients with vitamin D levels below 20 ng/mL (n=36) and 74% of patients with vitamin D levels between 20 and 30 ng/mL (n=73) had severe asthma versus 50% of those with vitamin D sufficiency (n=12; P=0.02). Vitamin D insufficiency was associated with a higher risk of severe asthma (odds ratio [OR], 5.04; 95% Confidence interval [CI], 1.23-20.72; P=0.02). High vitamin D levels were associated with a lower risk of hospitalization or emergency department visit during the last year (OR, 0.90; 95% CI, 0.84-0.98; P=0.04). Although there appeared to be a direct relationship between vitamin D levels and FEV1 (regression coefficient=0.48; r2=0.03), it did not reach statistical significance (P=0.07).
Our findings suggest that vitamin D insufficiency is common among our cohort of asthmatic adults. Lower vitamin D levels are associated with asthma severity.
Adult; asthma; vitamin D
In the USA and Europe, hypovitaminosis D is associated with increased asthma severity, emergency department (ED) visit, and impaired pulmonary function in asthmatic patients. However, in tropical countries, data on the effect of vitamin D status on asthma is limited. This study evaluates the relationship between vitamin D status and the level of asthma control as well as other asthmatic parameters.
Asthmatic children were evaluated for serum 25-hydroxyvitamin D, pulmonary function tests, a skin prick test, and the level of asthma control.
A total of 125 asthmatic children were recruited (boys, 66.4%). Their mean age±SD was 10.8±3.0 years. Vitamin D statuses were: deficiency (<20 ng/mL) in 19.2% of the patients, insufficiency (20-30 ng/mL) in 44.8%, and sufficiency (>30 ng/mL) in 36%. The vitamin D levels were 25.9±9.4 ng/mL in uncontrolled patients, 29.2±8.6 ng/mL in partly controlled patients, and 27.9±8.0 ng/mL in controlled patients (P>0.05). There were no significant differences in pulmonary function, asthma exacerbation, inhaled-corticosteroid (ICS) dose, anti-inflammatory drugs, or ED visit or hospitalization between different vitamin D statuses. Vitamin D deficiency patients were older and had a delayed onset of asthma than insufficiency or sufficiency patients. There was no significant correlation between serum vitamin D and pulmonary function/doses of ICS.
High prevalences of vitamin D deficiency and insufficiency were found in asthmatic children in Thailand; however, there was no significant relationship between vitamin D status and the level of asthma control or other asthma parameters.
Asthma; children; corticosteroid; 25-hydroxyvitamin D; vitamin D
As pet ownership increases, sensitization to animal allergens due to domestic exposure is a concern. Sensitization to animal allergens may occur from indirect exposure, as well as direct ownership of animals. However, there have been conflicting results regarding the association between pet ownership and sensitization to animal allergens in adults.
In total, 401 patients with various allergic diseases were enrolled in this study. We performed skin prick tests with 55 common inhalant and food allergens, including dog, cat, and rabbit allergens. A mean wheal diameter of 3 mm or greater was considered a positive reaction. The exposure modality to each animal allergen was investigated using a questionnaire and included present ownership, past ownership, occupational exposure, occasional exposure, contact with pet owner, and no contact. Present ownership, past ownership, occupational, and occasional exposure were regarded as direct exposure.
The sensitization rate for animal allergens was 20.4% for dog, 15.0% for cat, and 9.0% for rabbit. Direct exposure to dogs (72.0%) was significantly higher than that of other animals (18.4% for cats and 16.7% for rabbits), whereas 'no contact' with cats (78.3%) and rabbits (83.3%) was significantly higher than with dogs (26.8%; P<0.0001). Independent risk factors for sensitization to animal allergens were sensitization to Dermatophagoides pteronyssinus (OR=2.4, P=0.052), Dermatophagoides farinae (OR=5.1, P<0.001), cat (OR=4.4, P<0.0001), and direct exposure to dogs (OR=1.5, P=0.029) for dog, and sensitization to dog (OR=4.4, P<0.0001) and rabbit (OR=2.6, P=0.036) for cats. Finally, for rabbits, the independent risk factor was sensitization to Alternaria (OR=6.0, P<0.002).
These results suggest that direct exposure to dogs contributes to the sensitization to dog allergens in patients with allergic diseases, whereas indirect exposure to cats and rabbits may induce sensitization to each animal's allergen.
Cats; dogs; rabbits; pets; ownership; sensitization
We previously demonstrated seasonal variation in sensitization to aeroallergens in a small group of patients with exercise-induced asthma. This study was performed to confirm the relationship in a much larger population.
The charts of 1,891 patients who received allergy skin prick tests were reviewed retrospectively. The test results from subjects aged ≤60 years were compared between the groups classified according to the season when the patients received the tests (spring: March-May, summer: June-August, fall: September-November, winter: December-February). The data from 25 respiratory allergy patients who received the tests two or more times and showed a positive response at least once were analyzed longitudinally.
The most prevalent among 29 tested aeroallergens were house dust mites (HDMs) Dermatophagoides pteronyssinus and D. farinae. The skin sensitization rates to D. pteronyssinus (23.2% vs. 32.1%, P=0.004) and D. farinae (22.2% vs. 30.2%, P=0.009) were significantly lower in the summer and higher in the fall (38.3% vs. 26.6% and 35.6% vs. 25.3%; P=0.001 respectively) than those in other seasons in patients with a respiratory allergy (n=1,102). The sensitization rates to weed pollens in the fall (13.9% vs. 8.3%, P=0.006) and to Aspergillus fumigatus in the winter (2.9% vs. 0.7%, P=0.005) were significantly higher. In patients with non-respiratory allergy such as urticaria/anaphylaxis (n=340), the D. farinae sensitization rate was significantly lower in the summer also but higher in the spring. The trend of the HDM sensitization rate being lower in the summer and higher in the fall was observed in the longitudinal study.
Skin sensitivity to aeroallergens such as HDMs, pollens, and molds demonstrates seasonal variation in respiratory allergy patients. Non-respiratory allergy patients also showed seasonal variation in sensitivity to aeroallergens, which might be related to the "priming" effect of allergens.
Seasonal variation; skin sensitivity; aeroallergens; allergy
The sensitization rate to Japanese Hop (Hop J) in respiratory allergy patients has increased in recent years in Korea. We evaluated changes in the allergenic potency of Hop J pollen collected in 1998 and 2009.
Thirty-five patients with allergic rhinitis and/or asthma were enrolled. Group I included 21 subjects sensitized to Hop J at an initial visit and group II included 14 subjects who developed a new sensitization. Hop J pollens were collected in 1998 and 2009 (98 and 09 extracts) and both urban and suburban environments (urban and suburban extracts). Serum specific IgE levels to Hop J pollen extracts were compared using an enzyme-linked immunosorbent assay (ELISA). IgE binding components were compared by IgE immunoblot analysis.
Serum specific IgE levels to the 09 and urban extracts in both groups increased significantly compared to those of the 98 and suburban extracts. IgE immunoblot demonstrated that the major 10 kDa allergen was intensified in group I, while it was newly generated in group II with additional components ranging from 12-95 kDa. When the 98 and 09 extracts were compared, intensification of the major allergen of 09 extract had occurred in both groups. The IgE binding components of the urban extract was stronger than those of suburban one.
The allergenic potency of Hop J pollen may be increased with environmental changes.
Allergens; environment; Japanese Hop pollen
The aim of the present study was to investigate the relationship between three major allergic diseases, asthma, allergic rhinitis (AR), and atopic dermatitis (AD), and psychological and behavioural problems in preschoolers based on a community survey.
A cross-sectional survey was conducted using a modified International Study of Asthma and Allergies in Childhood questionnaire to determine the prevalence of symptoms and diagnosed allergic diseases, and a Korean version of the Child Behaviour Checklist to assess internalizing, externalizing, and sleep problems among 780 preschoolers. Five-hundred and seventy-five preschoolers with valid data were included in this study.
The prevalence of lifetime diagnosis and treatment in the past 12 months was 8.7% and 4.4% for asthma, 24.4% and 19.2% for AR, and 35.1% and 16.6% for AD, respectively. Scores for internalizing and sleep problems were significantly higher in those diagnosed with AR. Preschoolers who had been treated for AD in the past 12 months had higher attention problem and attention-deficit/hyperactivity disorder scores. Sleep problems were more severe in moderate to severe AD compared to control and mild AD groups, categorised according to SCOring index of AD. The severity of sleep problems correlated positively with the percentage of eosinophils in peripheral blood.
Psychological and behavioural problems differed among the three major allergic diseases, weaker association for asthma and stronger association for AR and AD. The results of this study may lead to the identification of potential underlying shared mechanisms common to allergic diseases and psychological and behavioural problems.
Preschool child; psychometrics; asthma; allergic rhinitis; atopic dermatitis
Recently, the clinical application of the forced oscillation technique (FOT) has progressed with the spread of commercially available FOT devices, including the impulse oscillation system and MostGraph. We investigated the usefulness of color 3D imaging of respiratory impedance in asthma using MostGraph.
Whole-breath and within-breath respiratory system resistance (Rrs) and reactance (Xrs) were measured in 78 patients with asthma. Color 3D images were classified into three patterns: the chronic obstructive pulmonary disease (COPD)-like pattern (high values of Rrs and Xrs with a marked respiratory cycle and frequency dependence), the asthma pattern (moderately high Rrs over the entire frequency and a respiratory cycle with slight Xrs changes), and a normal-like pattern (low Rrs and Xrs with few within-breath changes). The classification was performed by three researchers, who were unaware of the clinical information, and the clinical characteristics were compared among the three groups.
Color 3D imaging provided a COPD-like pattern in 25 patients, an asthma pattern in 39 patients, and a normal-like pattern in 14 patients. Patients with the COPD-like pattern were predominantly female with a higher body mass index, lower forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC), and higher Rrs and Xrs values (whole-breath and within-breath variation). Those with the normal pattern had higher FEV1 and FVC, and a lower single-breath nitrogen washout slope. There were no differences in asthma control or exhaled nitric oxide levels among the three groups.
These results suggest that color 3D imaging of respiratory impedance may show asthma phenotypes.
Forced oscillation technique; multi-frequency; phenotype; whole-breath; within-breath
Prostaglandin (PG) E2 is an immunomodulatory lipid mediator generated mainly via the cyclooxygenase-2 (COX-2) pathway from arachidonic acid at sites of infection and inflammation. A positive feedback loop of PGE2 on COX-2 expression is critical for homeostasis during toll-like receptor (TLR)-mediated inflammatory processes. The mechanism of PGE2-regulated COX-2 expression remains poorly understood. The low-molecular-weight stress protein heme oxygenase-1 (HO-1) contributes to the anti-inflammatory, anti-oxidant and anti-apoptotic response against environmental stress.
We explored the involvement of HO-1 on PGE2 regulation of LPS-induced COX-2 expression in RAW 264.7 macrophages.
LPS-induced COX-2 expression in RAW 264.7 macrophages was enhanced by exogenous PGE2 or cyclic AMP (cAMP) analogue and was suppressed by a COX inhibitor (indomethacin), a protein kinase A (PKA) inhibitor (KT5720), and A kinase anchoring protein (AKAP) disruptors (Ht31 and RIAD). This result suggests that the stimulatory effects of endogenous and exogenous PGE2 on COX-2 expression are mediated by a cAMP-PKA-AKAP-dependent pathway. The induction of HO-1 was observed in LPS-stimulated RAW 264.7 macrophages. This induction was suppressed by exogenous PGE2 and enhanced by blockage of the endogenous PGE2 effect by the PKA inhibitor or AKAP disruptors. In addition, HO-1 induction by the HO activator copper protoporphyrin suppressed LPS-induced COX-2 expression, which was restored by the addition of exogenous PGE2. The induction of HO-1 inhibited LPS-induced NF-κB p-65 nuclear expression and translocation.
AKAP plays an important role in PGE2 regulation of COX-2 expression, and the suppression of HO-1 by PGE2-cAMP-PKA-AKAP signaling helps potentiate the LPS-induced COX-2 expression through a positive feedback loop in RAW 264.7 macrophages.
Cyclooxygenase-2; heme oxygenase-1; lipopolysaccharide; prostaglandin E2; macrophages