Characteristics of Specialist-Diagnosed Asthma-COPD Overlap in Severe Asthma: Observations from the Korean Severe Asthma Registry (KoSAR).

BACKGROUND: While the clinical characteristics and outcomes of asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) have been frequently compared with those of COPD or asthma, the prevalence and features of ACO in patients with severe asthma are unclear. OBJECTIVES: Evaluation of the prevalence and clinical features of ACO using the Korean severe asthma registry. METHODS: At the time of registration, ACO was determined in patients with severe asthma by attending specialists. Patients were classified into ACO and non-ACO groups, and the demographic and clinical characteristics of these two groups were compared. RESULTS: Of 482 patients with severe asthma, 23.7% had ACO. Patients in the ACO group were more likely to be male (P < .001), older (P < .001), and ex- or current smokers (P < .001) compared with those in the non-ACO group. Patients in the ACO group had lower mean forced expiratory volume in 1 second (P < .001) and blood eosinophil percentage (P = .006), but higher blood neutrophil percentage (P = .027) than those in the non-ACO group. The ACO group used more inhaled long-acting muscarinic antagonist (P < .001), methylxanthine (P = .001), or sustained systemic corticosteroid (P = .002). In addition, unscheduled emergency department visits due to exacerbation were more frequent in the ACO group (P = .006). CONCLUSION: Among patients with severe asthma, those with ACO were older, predominantly male, and were more likely to have a smoking history than those with asthma only. Patients with ACO used more systemic corticosteroid and had more frequent exacerbations related to emergency department visits than those with severe asthma only.

The first case of tegoprazan-induced urticaria.

WHAT IS KNOWN AND OBJECTIVE: Tegoprazan induces adverse drug reactions during clinical trials; however, tegoprazan-induced urticaria has not been reported. Here, we describe the first case of this. CASE DESCRIPTION: A 55-year-old woman presented with acute urticaria with pruritus after taking the gastro-oesophageal reflux disease medication, tegoprazan. Urticaria disappeared after tegoprazan discontinuation. In an oral provocation test, after taking 10% of tegoprazan, she developed pruritus, and after taking 30%, she developed urticaria on her back. WHAT IS NEW AND CONCLUSION: This is the first case of urticaria induced by tegoprazan. Physicians should understand the possibility of a tegoprazan-induced hypersensitivity reactions.

Variation of clinical manifestations according to culprit drugs in DRESS syndrome.

PURPOSE: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare but serious condition that systematically damages various internal organs through T-cell-mediated immunological drug reactions. We aimed to investigate whether clinical manifestations of DRESS syndrome differ according to culprit drugs. METHODS: We retrospectively analyzed data from 123 patients with probable/definite DRESS syndrome based on the RegiSCAR criteria (January 2011 to July 2016). The data were obtained from the Korean Severe Cutaneous Adverse Reaction Registry. Causality was assessed using the World Health Organization-Uppsala Monitoring Centre criteria. The culprit drugs were categorized as allopurinol, carbamazepine, anti-tuberculosis drug, vancomycin, cephalosporins, dapsone, and nonsteroidal anti-inflammatory drugs. RESULTS: Differences were observed among culprit drugs regarding the frequencies of hepatitis (P < 0.01), renal dysfunction (P < 0.0001), lymphadenopathy (P < 0.01), and atypical lymphocyte (P < 0.01). Latency period differed among culprit drugs (P < 0.0001), being shorter in vancomycin and cephalosporin. In terms of clinical severity, admission duration (P < 0.01) and treatment duration (P < 0.05) differed among culprit drugs, being longer in vancomycin and anti-tuberculosis drugs, respectively. CONCLUSIONS: Based on the findings, clinical manifestations, including latency period and clinical severity, may differ according to culprit drugs in DRESS syndrome.

Clinical Features of Hereditary Angioedema in Korean Patients: A Nationwide Multicenter Study.

BACKGROUND: Hereditary angioedema (HAE) is a genetically heterogeneous autosomal dominant disorder characterized by recurrent episodes of nonpruritic, nonpitting edema increasing after puberty. It can be fatal due to laryngeal or gastrointestinal (GI) involvement with varied and changing frequency of mortality according to studies published from the Western countries. Epidemiological and clinical data of HAE in Asian countries are sparse. We sought to examine the clinical characteristics of HAE patients in Korea. METHODS: Patients diagnosed with HAE at 15 tertiary hospitals across the country until 2016 were retrospectively reviewed. RESULTS: A total of 65 patients diagnosed with HAE by 2016 were identified. The prevalence of HAE was estimated at 1.3/1,000,000 in Korea. Of the 65 patients, 21 (32.3%) were males. A total of 90.8% patients had type I HAE, while the remaining 9.2% patients had type II HAE. The first symptom developed after 20 years in 73.8% of patients, with a mean age 28.4 ± 14.1 years. The age at diagnosis was 36.5 ± 15.8 years, with a mean time delay of 7.8 ± 10.5 years. While the face (82.3%) and extremities (upper 71.0%, lower 62.9%) were the most frequently involved, the GI tract was affected in 40.5% of Korean HAE patients. Prophylaxis was maintained in 62.5% of patients. There was no reported case of death from HAE so far. CONCLUSIONS: The clinical manifestation and severity of HAE may vary according to ethnicity. HAE is more infrequent and GI involvement is less likely in Korea compared with Western countries.

Flagellin suppresses experimental asthma by generating regulatory dendritic cells and T cells.

BACKGROUND: Although the hygiene hypothesis suggests that microbial infections could subvert asthma and thus a microbial product might serve as a therapeutic adjuvant for asthma, the relationship between bacterial components and asthma is complex. Recently, low levels of flagellin, the Toll-like receptor (TLR) 5 ligand, have been reported to promote asthma. OBJECTIVE: We show that a therapeutic dose of flagellin suppresses asthma and that the effect occurs through generating regulatory dendritic cells (rDCs) and regulatory T (Treg) cells. METHODS: Ovalbumin (OVA)-induced wild-type and TLR5 knockout asthmatic mice were treated intranasally with a mixture of OVA and 10 µg of a flagellin B (FlaB; of Vibrio vulnificus). OVA/FlaB-treated rDCs were adoptively transferred to mice with OVA-induced asthma. Anti-CD25 mAb was used to deplete Treg cells. A mixture of house dust mite (HDM) and FlaB was used to treat mice with HDM-induced asthma. Blood CD14(+) monocyte-derived dendritic cells from HDM-sensitive asthmatic patients were treated with FlaB and incubated with autologous CD4(+) T cells. RESULTS: An OVA/FlaB mixture ameliorated OVA-induced asthma by inhibiting TH1/TH2/TH17 responses in a TLR5-dependent manner through generating rDCs and Treg cells. The adoptive transfer of OVA/FlaB-treated dendritic cells inhibited OVA-induced asthma, whereas the depletion of CD25(+) cells eliminated the inhibitory effect. A similar effect of FlaB was observed in mice with HDM-induced asthma. In patients with HDM-sensitive asthma, FlaB-treated rDCs inhibited HDM-stimulated TH1/TH2 responses while enhancing Treg cells in an IL-10-dependent manner. CONCLUSION: These findings collectively suggest that flagellin could be used as a tolerogenic adjuvant to treat allergic asthma.

The potential utility of iodinated contrast media (ICM) skin testing in patients with ICM hypersensitivity.

Both immediate and delayed hypersensitivity reactions to iodinated contrast media (ICM) are relatively common. However, there are few data to determine the clinical utility of immunologic evaluation of ICM. To evaluate the utility of ICM skin testing in patients with ICM hypersensitivity, 23 patients (17 immediate and 6 delayed reactions) were enrolled from 3 university hospitals in Korea. With 6 commonly used ICM including iopromide, iohexol, ioversol, iomeprol, iopamidol and iodixanol, skin prick (SPT), intradermal (IDT) and patch tests were performed. Of 10 patients with anaphylaxis, 3 (30.0%) and 6 (60.0%) were positive respectively on SPTs and IDTs with the culprit ICM. Three of 6 patients with urticaria showed positive IDTs. In total, 11 (64.7%) had positive on either SPT or IDT. Three of 6 patients with delayed rashes had positive response to patch test and/or delayed IDT. Among 5 patients (3 anaphylaxis, 1 urticaria and 1 delayed rash) taken subsequent radiological examinations, 3 patients administered safe alternatives according to the results of skin testing had no adverse reaction. However, anaphylaxis developed in the other 2 patients administered the culprit ICM again. With 64.7% (11/17) and 50% (3/6) of the sensitivities of corresponding allergic skin tests with culprit ICM for immediate and delayed hypersensitivity reactions, the present study suggests that skin tests is useful for the diagnosis of ICM hypersensitivity and for selecting safe ICM and preventing a recurrence of anaphylaxis caused by the same ICM.

Strongyloidiasis in a diabetic patient accompanied by gastrointestinal stromal tumor: cause of eosinophilia unresponsive to steroid therapy.

We report here a case of strongyloidiasis in a 72-year-old diabetic patient (woman) accompanied by gastrointestinal stromal tumor receiving imatinib therapy, first diagnosed as hypereosinophilic syndrome and treated with steroids for uncontrolled eosinophilia. She suffered from lower back pain and intermittent abdominal discomfort with nausea and diagnosed with gastrointestinal stromal tumor. After post-operative imatinib treatment eosinophilia persisted, so that steroid therapy was started under an impression of hypereosinophilic syndrome. In spite of 6 months steroid therapy, eosinophilia persisted. Stool examination was performed to rule out intestinal helminth infections. Rhabditoid larvae of Strongyloides stercoralis were detected and the patient was diagnosed as strongyloidiasis. This diagnosis was confirmed again by PCR. The patient was treated with albendazole for 14 days and her abdominal pain and diarrhea improved. This case highlights the need for thorough investigation, including molecular approaches, to test for strongyloidiasis before and during steroid therapies.

Occupational contact dermatitis caused by sodium tetradecyl sulfate in a healthcare worker: A case report.

Healthcare workers are known to be at a higher risk of experiencing occupational contact dermatitis and attention should be paid to new materials that cause contact dermatitis. Sodium tetradecyl sulfate is widely used in the treatment of small varicose veins of the legs and venous malformations. We report the case of a 42-year-old woman, a healthcare worker, who presented with contact dermatitis caused by sodium tetradecyl sulfate. The contact dermatitis induced by sodium tetradecyl sulfate resolved completely after sodium tetradecyl sulfate avoidance at the last follow-up. Thus, we recommend increased protective measures when handling this substance.

Relationship of computed tomography-based measurements with symptom perception and quality of life in patients with severe asthma.

BACKGROUND: Symptom perception and quality of life (QOL) are important domains for properly managing severe asthma. This study aimed to assess the relationship between airway structural and parenchymal variables measured using chest computed tomography (CT) and subjective symptom perception and QOL in patients with severe asthma enrolled in the Korean Severe Asthma Registry. METHODS: This study used CT-based objective measurements, including airway wall thickness (WT), hydraulic diameter, functional small airway disease (fSAD), and emphysematous lung (Emph), to assess their association with subjective symptom (cough, dyspnea, wheezing, and sputum) perception measured using the visual analog scale, and QOL measured by the Severe Asthma Questionnaire (SAQ). RESULTS: A total of 94 patients with severe asthma were enrolled in this study. The WT and fSAD% were significantly positively associated with cough and dyspnea, respectively. For QOL, WT and Emph% showed significant negative associations with the SAQ. However, there was no significant association between lung function and symptom perception or between lung function and QOL. CONCLUSION: Overall, WT, fSAD%, and Emph% measured using chest CT were associated with subjective symptom perception and QOL in patients with severe asthma. This study provides a basis for clarifying the clinical correlates of imaging-derived metrics and for understanding the mechanisms of respiratory symptom perception.

Nation-Wide Retrospective Analysis of Allogeneic Stem Cell Transplantation in Patients with Multiple Myeloma: A Study from Korean Multiple Myeloma Working Party (KMM1913).

Purpose: The role of allogeneic stem cell transplantation (alloSCT) in multiple myeloma (MM) treatment remains controversial. We conducted a retrospective, multicenter, nationwide study in Korea to evaluate the outcomes of alloSCT in Asian patients with MM. Materials and Methods: Overall, 109 patients with MM who underwent alloSCT between 2003 and 2020 were included in this study. Data were collected from the Korean Multiple Myeloma Working Party Registry. Results: The overall response rate and stringent complete response (sCR) plus CR rates were 67.0 and 46.8%, respectively, after alloSCT. At a median follow-up of 32.5 months, the 3-year probability of progression-free survival (PFS) and overall survival (OS) rates were 69.3 and 71.8%, respectively. The 3-year probabilities of OS rates in the upfront alloSCT, tandem auto-alloSCT, and later alloSCT groups were 75.0, 88.9, and 61.1%, respectively. Patients who achieved CR before or after alloSCT had significantly longer OS (89.8 vs. 18 months and 89.8 vs. 15.2 months, respectively). Even though patients who did not achieve CR prior to alloSCT, those who achieve CR after alloSCT had improved PFS and OS compared to those who had no achievement of CR both prior and after alloSCT. Patients who underwent alloSCT with 1-2 prior treatment lines had improved PFS (22.4 vs. 4.5 months) and OS (45.6 vs. 15.3 months) compared to those with three or more prior treatment lines. Conclusion: AlloSCT may be a promising therapeutic option especially for younger, chemosensitive patients with earlier implementation from relapse.

Work-related asthma in adults with severe asthma from the Korean Severe Asthma Registry (KoSAR).

Background: Exposure to allergens or irritants in the workplace may affect asthma control and the quality of life (QoL) of patients with asthma. Objective: To examine the prevalence and characteristics of work-related asthma (WRA) in adult patients with severe asthma. Methods: We analyzed data from the Korean Severe Asthma Registry (KoSAR), which is a nationwide multicenter observational study on severe asthma in Korea. Severe asthma was defined according to the American Thoracic Society (ATS) and the European Respiratory Society (ERS) guidelines. WRA was identified on the basis of asthma symptom aggravation at the workplace, as indicated by responses to a structured questionnaire. We compared the demographic and clinical characteristics and QoL between adult patients with severe asthma and WRA and those without WRA. Results: Among 364 patients with severe asthma who were employed at the time of enrollment, 65 (17.9%) had WRA. There were no significant differences in age, sex, obesity, or smoking history between the WRA and non-WRA groups. However, individuals with WRA exhibited a higher prevalence of anxiety (7.7% vs 2.4%, P = 0.046) and depression (12.3% vs 3.7%, P = 0.010) than those without. The levels of asthma control, lung function, and frequency of asthma exacerbations were similar between the two groups, but patients with WRA reported lower QoL, as determined by the Quality of Life Questionnaire for Adult Korean Asthmatics (56.6 ± 14.6 vs. 63.5 ± 13.9, P < 0.001). Conclusion: Patients with severe asthma and WRA are more likely to experience anxiety and depression and have lower QoL than those without WRA.

The KAAACI Guidelines for Sublingual Immunotherapy.

Allergen immunotherapy is regarded as the only disease-modifying treatment option for various allergic conditions, including allergic rhinitis and asthma. Among the routes of administration of allergens, sublingual immunotherapy (SLIT) has gained clinical interest recently, and the prescription of SLIT is increasing among patients with allergies. After 30 years of SLIT use, numerous pieces of evidence supporting its efficacy, safety, and mechanism allows SLIT to be considered as an alternative option to subcutaneous immunotherapy. Based on the progressive development of SLIT, the current guideline from the Korean Academy of Asthma, Allergy, and Clinical Immunology aims to provide an expert opinion by allergy, pediatrics, and otorhinolaryngology specialists with an extensive literature review. This guideline addresses the use of SLIT, including 1) mechanisms of action, 2) appropriate patient selection for SLIT, 3) the currently available SLIT products in Korea, and 4) updated information on its efficacy and safety. This guideline will facilitate a better understanding of practical considerations for SLIT.

Real-World Effectiveness of Biologics in Patients With Severe Asthma: Analysis of the KoSAR.

PURPOSE: Severe asthma is associated with high morbidity and healthcare utilization; however, treatment options for these patients are limited. This study aimed to determine the therapeutic effects of biologics in clinical practice. METHODS: This multicenter, retrospective cohort study included 136 patients who received biologics for at least 4 months between September 2017 and July 2022 at 25 medical centers affiliated with the Korean Severe Asthma Registry (KoSAR). The study evaluated the treatment effects, including acute exacerbation rates, maintenance of oral corticosteroid dosages, lung function, quality of life, blood eosinophil count, and fractional exhaled nitric oxide (FeNO) levels, by comparing measurements before and after 4 months of biologic treatment. Responses for each medication was evaluated based on the Global Evaluation of Treatment Effectiveness score, and any adverse reactions were summarized. RESULTS: With the administration of biologics over the course of 4 months, there was a reduction in asthma acute exacerbations, a significant improvement in lung function, and a significant decrease in daily maintenance dose of oral steroid. Blood eosinophil counts decreased in the mepolizumab and reslizumab groups, while FeNO levels decreased only in the dupilumab group. The Asthma Control Test, Quality of Life Questionnaire for Adult Korean Asthmatics, and the EuroQol-visual analogue scale scores showed a significant improvement. Most patients (80.15%) responded to the biologic treatment. Meanwhile, non-responders often had chronic rhinosinusitis as a comorbidity, exhibited lower lung function, and required higher doses of oral steroids. No severe adverse events were reported. CONCLUSIONS: Biologics are highly effective in Korean patients with Type 2 severe asthma, significantly reducing acute exacerbation rates and doses of oral corticosteroids, while also improving lung function. Therefore, it seems beneficial to administer biologics without any restrictions to patients exhibiting Type 2 severe asthma.

Characteristics of Severe Asthma in the Elderly: Observations From the Korean Severe Asthma Registry (KoSAR).

PURPOSE: Few studies have compared the clinical characteristics of severe asthma (SA) in elderly patients compared to that in nonelderly patients. METHODS: We analyzed data from the Korean SA Registry, a nationwide, real-world observational study of SA in Korea. The baseline clinical characteristics, disease control status, and medication use of the patients were compared between elderly (≥ 65 years) and nonelderly groups. RESULTS: Of the 864 patients with SA, 260 (30.1%) were in the elderly group. The elderly group had lower atopy rate, but had higher prevalence of chronic obstructive pulmonary disease (COPD), hypertension, and osteoporosis than did the nonelderly group. The elderly group had a lower rate of type 2 inflammation and lower levels of forced expiratory volume in 1 second (FEV1) (% predicted) and FEV1/forced vital capacity ratio than did the nonelderly group (P < 0.05 for all). However, asthma symptom scores and the frequency of asthma exacerbation were not significantly different between the 2 groups. Of controller medications, biologics were less frequently used in the elderly group (P < 0.05 for all). CONCLUSIONS: SA in the elderly is characterized by lower lung function, less type 2-low airway inflammation, and comorbidity with COPD. These findings are being taken into consideration in the management of elderly patients with SA in real-world clinical practice.

Interplay between chronic inflammation and clonal haematopoiesis of indeterminate potential in Behçet's disease.

BACKGROUND: Clonal haematopoiesis of indeterminate potential (CHIP) is a predisposition to haematological malignancy whose relationship with chronic inflammatory diseases, such as cardiovascular diseases, has been highlighted. Here, we aimed to investigate the CHIP emergence rate and its association with inflammatory markers in Behçet's disease (BD). METHODS: We performed targeted next-generation sequencing to detect the presence of CHIP using peripheral blood cells from 117 BD patients and 5004 healthy controls between March 2009 and September 2021 and analysed the association between CHIP and inflammatory markers. RESULTS: CHIP was detected in 13.9% of patients in the control group and 11.1% of patients in the BD group, indicating no significant intergroup difference. Among the BD patients of our cohort, five variants (DNMT3A, TET2, ASXL1, STAG2, and IDH2) were detected. DNMT3A mutations were the most common, followed by TET2 mutations. CHIP carriers with BD had a higher serum platelet count, erythrocyte sedimentation rate, and C-reactive protein level; older age; and lower serum albumin level at diagnosis than non-CHIP carriers with BD. However, the significant association between inflammatory markers and CHIP disappeared after the adjustment for various variables, including age. Moreover, CHIP was not an independent risk factor for poor clinical outcomes in patients with BD. CONCLUSIONS: Although BD patients did not have higher CHIP emergence rates than the general population, older age and degree of inflammation in BD were associated with CHIP emergence.

Clinical aspects of severe cutaneous adverse reactions caused by beta-lactam antibiotics: A study from the Korea SCAR registry.

Background: Although beta-lactams are 1 of the major causative agents of severe cutaneous adverse reactions (SCAR), their epidemiology and clinical aspects have been poorly studied. This study aimed to investigate the characteristics of SCAR caused by beta-lactams in the Korean SCAR registry. Methods: We retrospectively analyzed beta-lactam-induced SCAR cases collected from 28 tertiary university hospitals in Korea between 2010 and 2015. The SCAR phenotypes included Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), SJS-TEN overlap, and drug reaction with eosinophilia and systemic symptoms (DRESS). Beta-lactams were classified according to their chemical structures: penicillins, cephalosporins, and carbapenems. The causative beta-lactams, clinical and laboratory features, treatments, and outcomes were evaluated. Results: Among the 275 antibiotic-induced SCAR cases, 170 patients developed SCAR induced by beta-lactams. Beta-lactam antibiotic-induced SCAR showed more frequent SJS/TEN compared to SCAR induced by non-beta-lactam antibiotics (SJS/TEN/SJS-TEN overlap/DRESS: 36.5/11.2/5.9/46.5% vs. 23.8/10.5/2.9/62.9%, P = 0.049). Cephalosporin was the most common culprit drug. Particularly, 91 and 79 patients presented with SJS/TEN and DRESS, respectively. The odds ratio (OR) for poor prognosis, such as sequelae and death, was significantly increased in subjects with SJS-TEN overlap and TEN and carbapenem as culprit drug in the multivariate analysis (OR, 35.61; P = 0.016, OR, 28.07; P = 0.006, OR 30.46; P = 0.027). Conclusion: Among antibiotic-induced SCAR, clinical features were different depending on whether the culprit drug was a beta-lactam antibiotic or SCAR type. The poor prognosis was related to SJS-TEN overlap, TEN type, and carbapenem as the culprit drug.

Skin Test-Guided Strategy to Select Alternative Iodinated Contrast Media in Patients With Immediate Hypersensitivity Reaction: A Prospective Confirmative Study.

BACKGROUND: Iodinated contrast media (ICM) are a common cause of drug-induced immediate hypersensitivity reaction (IHR). Repeated use of ICM is often necessary; therefore, a standardized protocol to prevent recurrence of IHR is required. OBJECTIVE: We aimed to propose an intradermal skin test (IDT)-guided strategy for previous reactors to prevent recurrence of IHR. METHODS: We conducted a prospective multicenter study from May 2018 to December 2020 and recruited patients who had experienced IHR to ICM. Once enrolled, the participants underwent IDT with a causative ICM. The alternatives for reexposure were selected using the following protocol: (1) if the IDT with the culprit ICM was positive, further skin tests with other available ICM were conducted to choose IDT-negative agents as alternatives, and (2) if the IDT with the culprit ICM was negative, a randomly changed ICM was used without additional skin tests. The recurrence and severity of hypersensitivity were assessed in subsequent computed tomography examinations. Premedication was administered according to the severity of the index event in all cases. RESULTS: A total of 496 participants were enrolled, and 299 were reexposed to ICM. Among 269 participants who followed the protocol, 228 (84.8%) completed computed tomography examinations without adverse reactions, and IHR recurred in 16 of 30 participants (53.3%) who did not follow the protocol (P < .001). In addition, application of the protocol reduced the severity of IHR in recurred cases (P = 0.003). CONCLUSIONS: Our IDT-guided strategy not only reduced recurrence of IHR to ICM but also mitigated the severity in recurred cases. This provides evidence for recommending an IDT to diagnose ICM allergy and find safe alternatives.

KAAACI Guidelines for Allergen Immunotherapy.

Allergen immunotherapy (AIT) is a causative treatment for various allergic diseases such as allergic rhinitis, allergic asthma, and bee venom allergy that induces tolerance to offending allergens. The need for uniform practice guidelines in AIT is continuously growing because of the increasing discovery of potential candidates for AIT and evolving interest in new therapeutic approaches. This guideline is an updated version of the Korean Academy of Asthma Allergy and Clinical Immunology recommendations for AIT published in 2010. This updated guideline proposes an expert opinion by allergy, pediatrics, and otorhinolaryngology specialists with an extensive literature review. The guideline deals with basic knowledge and methodological aspects of AIT, including mechanisms, clinical efficacy, patient selection, allergens extract selection, schedule and doses, management of adverse reactions, efficacy measurements, and special consideration in pediatrics. The guidelines for sublingual immunotherapy will be covered in detail in a separate article.

The role of natural killer T cells in the pathogenesis of acute exacerbation of human asthma.

BACKGROUND: Natural killer T (NKT) cells have been reported to play a crucial role in the pathogenesis of asthma in a mouse model of acute asthma. The present study aimed to investigate the role of NKT cells in the immune pathogenesis of acute exacerbation of human asthma. METHODS: Blood and sputum were obtained at baseline and 8 h after a challenge in 20 asthmatics who underwent allergen bronchial provocation testing and during exacerbation and convalescence in 9 asthmatics who were admitted to hospital with an acute exacerbation after an upper respiratory tract infection. 6B11+ or Vα24+ NKT cells were measured with flow cytometry. Inflammatory cells, cytokines and chemokines were determined in sputum. RESULTS: The number of blood NKT cells did not change after a positive allergen challenge compared to the baseline. However, blood CD4+Vα24+ NKT cells decreased during infection-associated asthma exacerbations compared to the convalescence measurements of the same patients (p < 0.05) or the baseline measurements of asthmatics who underwent allergen challenges (p < 0.01). The number of sputum NKT cells did not change after a positive allergen challenge or during infection-associated asthma exacerbations. Eosinophils and various cytokines and chemokines increased in sputum during infection-associated asthma exacerbations. Blood CD4+Vα24+ NKT cells were inversely related to sputum eosinophils (Spearman's correlation coefficient = -0.62; p < 0.01). CONCLUSION: Blood NKT cells decreased during infection-associated asthma exacerbation and were inversely associated with eosinophilic airway inflammation, suggesting that blood NKT cells might be mobilized to the airways and lungs during asthma exacerbation in humans.

Allergic contact stomatitis caused by a titanium nitride-coated implant abutment: a clinical report.

A patient developed contact mucositis after being treated with a titanium nitride implant abutment. Patch testing disclosed a positive reaction to titanium nitride. After removal of the titanium nitride-coated abutment and placement of an uncoated abutment, all signs and symptoms disappeared. This clinical report suggests that titanium nitride-coated abutments may be a potential allergen in some patients.