ABSTRACT
Purpose@#Cysteinyl leukotrienes (CysLTs) have been recognized as key mediators associated with type 2 inflammation in the airways of asthmatic patients. CysLTs are associated with airway constriction, eosinophil recruitment/activation, and airway remodeling. The study aimed to understand the role of CysLTs in adult asthmatics in a real-world clinical setting. @*Methods@#One hundred five adult asthmatics who had maintained antiasthmatic medications were enrolled. Asthmatic subjects were classified into 2 groups according to urinary leukotriene E4 (uLTE4) levels, and their clinical parameters and inflammatory mediators, including forced expiratory volume in 1 second (FEV1) %, fractional exhaled nitric oxide (FeNO), blood eosinophil count, serum periostin (sPON), and urinary eosinophil derived neurotoxin (uEDN) were compared between the high-uLTE4 and low-uLTE4 groups. @*Results@#The prevalence of chronic rhinosinusitis (CRS), severe asthma, and aspirin-exacerbated respiratory disease (AERD) were significantly higher in the high-uLTE4 group than in the low-uLTE4 group. The high-uLTE4 group had lower FEV1% and maximal midexpiratory flow %, but higher FeNO levels than the low-uLTE4 group. In addition, blood eosinophil count, sPON, and uEDN levels were significantly higher in the high-uLTE4 group than in the low-uLTE4 group. The presence of AERD and levels of FeNO, sPON, and uEDN were significantly associated with higher uLTE4 levels in asthmatics. @*Conclusion@#CysLTs are associated with type 2 inflammation in the airways of asthmatic patients, contributing to the development of AERD, CRS, and asthma severity. The stratification of clinical phenotypes according to the uLTE4 level could support optimizing anti-inflammatory therapy for better control of asthma.
ABSTRACT
A novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019 in China. The mutated coronavirus spread worldwide, and some patients infected with SARS-CoV-2 developed coronavirus disease 2019 (COVID-19) manifested with upper respiratory infection, pneumonia, or respiratory distress. Since the SARS-CoV-2 pandemic was declared with surging confirmed cases and mortality of COVID-19 worldwide, it has reshaped our way of living and how to manage patients with allergic diseases. The medical staff, including allergy specialists, has been at the forefront of fighting against the SARSCoV-2 pandemic and is struggling to guarantee safety to themselves and their patients. Thanks to vigorous research into the relationship between SARS-CoV-2 and allergic diseases, we have become able to treat allergic patients with the best of evidence to date. The clinician should make a careful decision on each clinical situation with regard to patient characteristics, local and national circumstances as well as the knowledge we have, since it is still limited. We hope further efforts to identify the nature of SARS-CoV-2 and COVID-19 clearer and effective SARS-CoV-2 vaccination will soon remove the grim picture of the worldwide pandemic and bring us back to normal.
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Background/Aims@#Omalizumab is the first biologic known to be effective in patients with severe allergic asthma. @*Methods@#This study was conducted as a multicenter, single-group, open trial to evaluate the improvement in the quality of life with the additional administration of omalizumab for 24 weeks in Korean patients with severe persistent allergic asthma. @*Results@#Of the 44 patients, 31.8% were men and the mean age was 49.8 ± 11.8 years. A score improvement of 0.5 points or more in the Quality of Life Questionnaire for Korean Asthmatics (KAQLQ) was noted in 50.0% (22/44) of the patinets. In the improved group, the baseline total immunoglobulin E (IgE) level and the amount of omalizumab used were higher, and the day and night asthma symptoms were more severe, compared to those in the non-improved group. According to the Global Evaluation of Treatment Effectiveness, favorable outcomes were found in 78.6% of patients. The Korean asthma control test (p < 0.005) and forced expiratory volume in 1 second % predicted (FEV1%; p < 0.01) improved significantly in patients who received omalizumab treatment, compared to that at week 0, and the total dose of rescue systemic corticosteroids significantly decreased (p < 0.05). The improved group on KAQLQ showed a significant improvement in FEV1% (p < 0.001). @*Conclusions@#Omalizumab can be considered a biological treatment for Korean patients with severe allergic asthma. It is recommended to consider omalizumab as add-on therapy in patients with high baseline total IgE levels and severe asthma symptoms.
ABSTRACT
Anaphylaxis is a life-threatening systemic allergic reaction presenting various clinical manifestations. Its prevalence has increased in almost all age groups and both sexes. Food, venom, and drugs are major causes in both children and adults; a higher prevalence of food-induced anaphylaxis is noted in children, while a higher prevalence of drug-induced anaphylaxis is noted in adults. The pathogenic mechanism is mediated by immunologic and nonimmunologic mechanisms, where mast cells and basophils are key cells that release mediators. A diagnosis of anaphylaxis is mainly based on clinical symptoms and physical findings; however, an increased serum tryptase level is a useful biomarker. Epinephrine is the first-line drug to treat acute symptoms, and an epinephrine auto-injector should be prescribed for each patient. Antihistamines and systemic corticosteroids are used to relieve symptoms. This review updates current issues in the management of anaphylaxis as well as the new guidelines for proper diagnosis and treatment.
ABSTRACT
Background/Aims@#Omalizumab is the first biologic known to be effective in patients with severe allergic asthma. @*Methods@#This study was conducted as a multicenter, single-group, open trial to evaluate the improvement in the quality of life with the additional administration of omalizumab for 24 weeks in Korean patients with severe persistent allergic asthma. @*Results@#Of the 44 patients, 31.8% were men and the mean age was 49.8 ± 11.8 years. A score improvement of 0.5 points or more in the Quality of Life Questionnaire for Korean Asthmatics (KAQLQ) was noted in 50.0% (22/44) of the patinets. In the improved group, the baseline total immunoglobulin E (IgE) level and the amount of omalizumab used were higher, and the day and night asthma symptoms were more severe, compared to those in the non-improved group. According to the Global Evaluation of Treatment Effectiveness, favorable outcomes were found in 78.6% of patients. The Korean asthma control test (p < 0.005) and forced expiratory volume in 1 second % predicted (FEV1%; p < 0.01) improved significantly in patients who received omalizumab treatment, compared to that at week 0, and the total dose of rescue systemic corticosteroids significantly decreased (p < 0.05). The improved group on KAQLQ showed a significant improvement in FEV1% (p < 0.001). @*Conclusions@#Omalizumab can be considered a biological treatment for Korean patients with severe allergic asthma. It is recommended to consider omalizumab as add-on therapy in patients with high baseline total IgE levels and severe asthma symptoms.
ABSTRACT
Background/Aims@#The efficacy and safety of mepolizumab in patients with severe eosinophilic asthma has been evaluated in a global clinical trial programme. This post hoc analysis assesses the efficacy and safety of mepolizumab in Korean patients. @*Methods@#Data from Korean patients in the Phase III, placebo-controlled, randomised DREAM (MEA112997/NCT01000506) and MENSA (MEA115588/ NCT01691521) studies were included. Patients ≥ 12 years old with severe eosinophilic asthma received mepolizumab (DREAM: 75, 250 or 750 mg intravenously [IV]; MENSA: 75 mg IV or 100 mg subcutaneously [SC]), or placebo every 4 weeks for 52 weeks (DREAM) or 32 weeks (MENSA). The primary outcome was the rate of clinically significant asthma exacerbations. Secondary outcomes included forced expiratory volume in 1 second (FEV1), Asthma Control Questionnaire (ACQ) and St George’s Respiratory Questionnaire (SGRQ) scores (MENSA only). Blood eosinophil counts (BEC) and safety were assessed throughout. @*Results@#Reductions in the rate of clinically significant asthma exacerbations were observed with the approved (100 mg SC) and bioequivalent (75 mg IV) doses of mepolizumab in Korean patients who participated in DREAM and MENSA. In MENSA, trends for improvements from baseline at week 32 in pre-bronchodilator FEV1 (75 mg IV group), ACQ-5 and SGRQ scores (in both treatment groups) were seen versus placebo in Korean patients. Incidence of on-treatment adverse events was similar in Korean patients versus non-Korean patients as were observed reductions from baseline in BEC. @*Conclusions@#Mepolizumab treatment provided clinical benefits for Korean patients with severe eosinophilic asthma; the safety profile is consistent with the overall population.
ABSTRACT
Anaphylaxis is a life-threatening systemic allergic reaction presenting various clinical manifestations. Its prevalence has increased in almost all age groups and both sexes. Food, venom, and drugs are major causes in both children and adults; a higher prevalence of food-induced anaphylaxis is noted in children, while a higher prevalence of drug-induced anaphylaxis is noted in adults. The pathogenic mechanism is mediated by immunologic and nonimmunologic mechanisms, where mast cells and basophils are key cells that release mediators. A diagnosis of anaphylaxis is mainly based on clinical symptoms and physical findings; however, an increased serum tryptase level is a useful biomarker. Epinephrine is the first-line drug to treat acute symptoms, and an epinephrine auto-injector should be prescribed for each patient. Antihistamines and systemic corticosteroids are used to relieve symptoms. This review updates current issues in the management of anaphylaxis as well as the new guidelines for proper diagnosis and treatment.
ABSTRACT
Purpose@#Recent studies of food allergy (FA) at all ages are scanty in Korea. We performed this study to better understand severity-related and age-stratified causes of FA from infants to older adults in a single tertiary hospital in Korea. @*Methods@#A retrospective medical record review was performed on patients of all ages diagnosed with immediate-type FA between March 2008 and February 2018 in Ajou University Hospital. @*Results@#A total of 4,680 cases of FA among 2,733 patients were reported. The distribution of onset ages of the first FA symptom was as follows: 45.3% below 2 years, 16.2% at 2–6 years, 5.5% at 7–12 years, 4.0% at 13–18 years, 16.9% at 19–40 years, 10.4% at 41–65 years, and 1.8% above 65 years of age. The major 10 causative foods were hen’s eggs (17.2%), cow’s milk (16.7%), wheat (8.6%), crustaceans (8.5%), fish (4.6%), walnuts (4.4%), pork (3.2%), peanuts (3.2%), shellfish (3.0%), and peach (2.2%). The culprits ranked from the 11th to the 20th were as follows: soybean, apple, chicken, buckwheat, beef, kiwi, almonds, perilla seeds, tomato, and squid. The top 3 causative foods in children were hen’s eggs, cow’s milk, and wheat, while those in adults were crustaceans, wheat, and fish. Food-induced anaphylaxis was reported in 29.2% of all cases, with cow’s milk, hen’s eggs, wheat, crustaceans, fish, walnuts, pork, shellfish, buckwheat, and peanuts being the major 10 causes. @*Conclusion@#This study could provide a better understanding of the detailed ranks of the causes of FA according to severity and age in Korea.
ABSTRACT
Background/Aims@#Primary immunodef iciency (PID) is a serious comorbid condition in adult asthmatics that have frequent exacerbations, which requires monthly replacement of intravenous immunoglobulin (IVIG). However, the prevalence and clinical significance of PID in adult asthmatics in Korea have not yet been reported. The aim of this study is to assess the prevalence of PID and its association with asthma exacerbation in Korean adult asthmatics. @*Methods@#A total of 2,866 adult asthmatics were enrolled in this study. The PID group was defined as subjects who had lower levels of immunoglobulin G (IgG)/ A/M and/or IgG subclass presenting with recurrent respiratory infections. Serum samples were assayed for total IgG/A/M by immunoturbidimetry, and IgG subclasses by nephelometry. @*Results@#Of the 2,866 asthmatic patients enrolled, 157 (5.49%) had PID (classified as the PID group), while those without PID was classified as the non-PID group. IgG subclass deficiency (58%) is most prevalent, among which IgG3 subclass deficiency was most common (58%). The relative risk of asthma exacerbation was 1.70 times higher in the PID group compared to the non-PID group (1.696; 95% confidence interval, 1.284 to 2.239; p < 0.001); the prevalence of severe asthma was significantly higher in the PID group than in the non-PID group (32.48% vs. 13.00%, p < 0.001). Thirty-five among 157 patients in the PID group d maintained IVIG to prevent asthma exacerbation. @*Conclusions@#It is suggested that PID, especially IgG3 subclass deficiency, is a significant risk factor for asthma exacerbation. Screening of IgG subclass levels and IVIG replacement should be considered in the management in adult asthmatics.
ABSTRACT
Background/Aims@#Asthma is not a single disease but, rather, a heterogeneous inf lammatory disorder with various pathogenic mechanisms. We analyzed the associations between the cellular profile of sputum and the serum levels of inflammatory mediators/cytokines in a cohort of adult asthmatics. @*Methods@#We recruited 421 adult asthmatic patients. All subjects were classified into four groups according to their sputum cellular profiles: G1, eosinophilic; G2, mixed granulocytic; G3, neutrophilic; and G4, paucigranulocytic. Serum levels of cytokines and mediators including periostin, eosinophil-derived neurotoxin (EDN), S100A9, and folliculin were quantified. @*Results@#Among 421 patients, G1 accounted for 149 (35.4%), G2 for 71 (16.9%), G3 for 155 (36.8%), and G4 for 46 (10.9%). Serum periostin and EDN levels were significantly higher in G1 (p = 0.004, and p = 0.031) than in the others. Serum S100A9 levels were elevated in G2 and G3 (p = 0.008). Serum folliculin levels differed significantly among the four groups, with the highest level in G4 (p = 0.042). To identify G1 from G1 plus G2 groups, the optimal serum cut-off levels were 1.71 ng/mL for periostin, and 1.61 ng/mL for EDN. When these two parameters were combined, the sensitivity was 76.0% and the specificity was 64.3% (area under the curve, 0.701; p = 0.004). @*Conclusions@#The serum periostin and EDN levels may be used as predictors to discriminate the eosinophilic asthma group from patients having eosinophilic or mixed granulocytic asthma, and the serum folliculin level is significantly elevated in patients with paucigranulocytic asthma compared to those with different inflammatory cell profile.
ABSTRACT
Asthma is commonly recognized as a heterogeneous condition with a complex pathophysiology. With advances in the development of multiple medications for patients with asthma, most asthma symptoms are well managed. Nevertheless, 5% to 10% of adult asthmatic patients (called severe asthma) are in uncontrolled or partially controlled status despite intensive treatment. Especially, severe eosinophilic asthma is one of the severe asthma phenotypes characterized by eosinophilia in sputum/blood driven by type 2 immune responses. Eosinophils have been widely accepted as a central effector cell in the lungs. Some evidence has demonstrated that persistent eosinophilia in upper and lower airway mucosa contributes to asthma severity by producing various mediators including cytokines, chemokines and granule proteins. Moreover, extracellular traps released from eosinophils have been revealed to enhance type 2 inflammation in patients with severe asthma. These novel molecules have the ability to induce airway inf lammation and hyperresponsiveness through enhancing innate and type 2 immune responses. In this review, we highlight recent insight into the function of eosinophil extracellular traps in patients with severe asthma. In addition, the role of eosinophil extracellular vesicles in severe asthma is also proposed. Finally, current biologics are suggested as a potential strategy for effective management of severe eosinophilic asthma.
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PURPOSE: Asthma control in older asthmatics is often less effective, which may be attributed to small airway dysfunction and poor inhalation technique. We compared the efficacy of 2 inhalers (fluticasone propionate/formoterol treatment using a pressurized metered-dose inhaler [p-MDI group] vs. fluticasone propionate/salmeterol treatment using a dry powder inhaler [DPI group]) in older asthmatics.METHODS: We conducted a 12-week, randomized, open-label, parallel-designed trial in older patients (over 55 years old) with moderate-to-severe asthma, and compared the efficacy and safety for asthma control between the 2 groups. Subgroup analyses on disease duration and air trapping were performed. Clinical parameters, including changes in lung function parameters, inhaler technique and adherence, were compared with monitoring adverse reactions between the 2 groups.RESULTS: A total of 68 patients underwent randomization, and 63 (30 in the p-MDI group and 33 in the DPI group) completed this study. The p-MDI group was non-inferior to the DPI group with regard to the rate of well-controlled asthma (53.3% vs. 45.5%, P < 0.001; a predefined non-inferiority limit of 17%). In subgroup analyses, the proportion of patients who did not reach well-controlled asthma in the p-MDI group was non-inferior to that in the DPI group; the difference was 12.7% among those with a longer disease duration (≥ 15 years) and 17.5% among those with higher air-trapping (RV/TLC ≥ 45%), respectively (a predefined non-inferiority limit of 17%, P < 0.001). No significant differences were observed in lung function parameters, inhalation techniques, adherence and adverse reactions between the 2 groups.CONCLUSION: These results suggest that the p-MDI group may be comparable to the DPI group in the management of older asthmatics in aspects of efficacy and safety.
Subject(s)
Humans , Airway Management , Asthma , Dry Powder Inhalers , Fluticasone , Inhalation , Lung , Medication Adherence , Metered Dose Inhalers , Nebulizers and Vaporizers , Random AllocationABSTRACT
PURPOSE: The prevalence of asthma is increasing globally as the world population increases; however, and the prevalence and mortality of asthma have not been extensively investigated. Also, the effects of severity and aging on asthma prevalence and mortality are unknown. We aimed to investigate trends of the prevalence and mortality of asthma as well as health care uses and costs over 14 years according to disease severity by using real-world data in Korea.METHODS: Using the National Health Insurance Sharing Service database, we extracted asthmatic patients having diagnosis codes of asthma and prescription records of antiasthmatic medications from 2002 to 2015 and categorized them according to asthma exacerbation and regular treatment. We defined asthma-associated death in terms of patients' prescription records within 3 months before all-cause death, then linked with the Cause of Death Statistics. The annual asthma-related health care uses and costs were analyzed.RESULTS: The prevalence rates of asthma (1.6% to 2.2%) and severe asthma (SA; 3.5% to 6.1% among total asthmatics) have increased steadily over the decade in Korea, where the proportion of elderly asthmatics having increased. The asthma-related health care uses and costs had increased during the study period with the highest uses/costs in SA. The asthma mortality had a steady rising trend from 16.2 to 28.0 deaths per 100,000 with the highest mortality in SA.CONCLUSIONS: The prevalence and mortality of asthma as well as SA increases along with the burden of health care uses/costs. More active interventions, including changes in health care policies, are needed to reduce the prevalence and mortality of asthma, especially SA.
Subject(s)
Aged , Humans , Aging , Asthma , Cause of Death , Delivery of Health Care , Diagnosis , Health Care Costs , Korea , Mortality , National Health Programs , Prescriptions , PrevalenceABSTRACT
Subject(s)
Humans , Angioedema , Asthma , Classification , Diagnosis , Drug Hypersensitivity , Hypersensitivity , Phenotype , Rhinitis , UrticariaABSTRACT
Purpose@#A need for useful measures reflective of the socio-economic burden of chronic urticaria (CU) has arisen. To obtain utility estimates for CU, we investigated EuroQol-5-Dimension (EQ-5D) indices according to urticaria control status and urticaria severity. @*Methods@#In this prospective observational study, we administered patient-oriented questionnaires on EQ-5D and urticaria outcomes, including Urticaria Activity Score over 7 days (UAS7), Urticaria Control Test (UCT), and CU-specific quality of life (CU-QOL). EQ-5D utility index scores were compared according to urticaria control status and disease severity. Conditional process analysis (CPA) was used to map EQ-5D utility scores from UAS7 and UCT. @*Results@#Greater EQ-5D utility values were obtained in patients with better urticaria control (0.91 ± 0.10 for well controlled CU, 0.84 ± 0.12 for partly controlled, 0.77 ± 0.14 for uncontrolled, P < 0.001). According to CU severity, mean utility values were ranged from 0.746 (severe, UAS7 ≥ 28) to 0.860 (moderate), 0.878 (mild), and 0.953 (urticaria free). CPA suggested that UAS7 was directly correlated with UCT (regression coefficient, −0.251; 95% confidence interval [CI], −0.278, −0.223; P < 0.001) and EQ-5D utility (−0.002; 95% CI, −0.003, −0.001; P = 0.007) after controlling for age, sex, urticaria duration, and combined allergic diseases. @*Conclusions@#EQ-5D values increased with improvement in urticaria control and decreased with urticaria severity. A predictive model mapping EQ-5D utility from UAS7 and UCT scores suggested that EQ-5D can be useful for the pharmacoeconomic evaluation of individualized treatments for CU patients.
ABSTRACT
Purpose@#Cold air is a major environmental factor that exacerbates asthma. Transient receptor potential melastatin family member 8 (TRPM8) is a cold-sensing channel expressed in the airway epithelium. However, its role in airway inflammation remains unknown. We investigated the role of TRPM8 in innate immune responses in bronchial epithelial cells and asthmatic subjects. @*Methods@#The TRPM8 mRNA and protein expression on BEAS2B human bronchial epithelial cells was examined by real-time polymerase chain reaction (PCR), immunofluorescence staining and western blotting. Additionally, interleukin (IL)-4, IL-6, IL-8, IL-13, IL-25 and thymic stromal lymphopoietin (TSLP) levels before and after menthol, dexamethasone and N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl) piperazine-1-carboxamide (BCTC) treatments were measured via real-time PCR. TRPM8 protein levels in the supernatants of induced sputum from asthmatic subjects and normal control subjects were measured using enzyme-linked immunosorbent assay, and mRNA levels in sputum cell lysates were measured using real-time PCR. @*Results@#Treatment with up to 2 mM menthol dose-dependently increased TRPM8 mRNA and protein in BEAS2B cells compared to untreated cells (P < 0.001) and concomitantly increased IL-25 and TSLP mRNA (P < 0.05), but not IL-33 mRNA. BCTC (10 μM) significantly abolished menthol-induced up-regulation of TRPM8 mRNA and protein and IL-25 and TSLP mRNA (P < 0.01). TRPM8 protein levels were higher in the supernatants of induced sputum from asthmatic subjects (n = 107) than in those from healthy controls (n = 19) (P < 0.001), and IL-25, TSLP and IL-33 mRNA levels were concomitantly increased (P < 0.001). Additionally, TRPM8 mRNA levels correlated strongly with those of IL-25 and TSLP (P < 0.001), and TRPM8 protein levels were significantly higher in bronchodilator-responsive asthmatic subjects than in nonresponders. @*Conclusions@#TRPM8 may be involved in the airway epithelial cell innate immune response and a molecular target for the treatment of asthma.
ABSTRACT
Purpose@#A need for useful measures reflective of the socio-economic burden of chronic urticaria (CU) has arisen. To obtain utility estimates for CU, we investigated EuroQol-5-Dimension (EQ-5D) indices according to urticaria control status and urticaria severity. @*Methods@#In this prospective observational study, we administered patient-oriented questionnaires on EQ-5D and urticaria outcomes, including Urticaria Activity Score over 7 days (UAS7), Urticaria Control Test (UCT), and CU-specific quality of life (CU-QOL). EQ-5D utility index scores were compared according to urticaria control status and disease severity. Conditional process analysis (CPA) was used to map EQ-5D utility scores from UAS7 and UCT. @*Results@#Greater EQ-5D utility values were obtained in patients with better urticaria control (0.91 ± 0.10 for well controlled CU, 0.84 ± 0.12 for partly controlled, 0.77 ± 0.14 for uncontrolled, P < 0.001). According to CU severity, mean utility values were ranged from 0.746 (severe, UAS7 ≥ 28) to 0.860 (moderate), 0.878 (mild), and 0.953 (urticaria free). CPA suggested that UAS7 was directly correlated with UCT (regression coefficient, −0.251; 95% confidence interval [CI], −0.278, −0.223; P < 0.001) and EQ-5D utility (−0.002; 95% CI, −0.003, −0.001; P = 0.007) after controlling for age, sex, urticaria duration, and combined allergic diseases. @*Conclusions@#EQ-5D values increased with improvement in urticaria control and decreased with urticaria severity. A predictive model mapping EQ-5D utility from UAS7 and UCT scores suggested that EQ-5D can be useful for the pharmacoeconomic evaluation of individualized treatments for CU patients.
ABSTRACT
Purpose@#Cold air is a major environmental factor that exacerbates asthma. Transient receptor potential melastatin family member 8 (TRPM8) is a cold-sensing channel expressed in the airway epithelium. However, its role in airway inflammation remains unknown. We investigated the role of TRPM8 in innate immune responses in bronchial epithelial cells and asthmatic subjects. @*Methods@#The TRPM8 mRNA and protein expression on BEAS2B human bronchial epithelial cells was examined by real-time polymerase chain reaction (PCR), immunofluorescence staining and western blotting. Additionally, interleukin (IL)-4, IL-6, IL-8, IL-13, IL-25 and thymic stromal lymphopoietin (TSLP) levels before and after menthol, dexamethasone and N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl) piperazine-1-carboxamide (BCTC) treatments were measured via real-time PCR. TRPM8 protein levels in the supernatants of induced sputum from asthmatic subjects and normal control subjects were measured using enzyme-linked immunosorbent assay, and mRNA levels in sputum cell lysates were measured using real-time PCR. @*Results@#Treatment with up to 2 mM menthol dose-dependently increased TRPM8 mRNA and protein in BEAS2B cells compared to untreated cells (P < 0.001) and concomitantly increased IL-25 and TSLP mRNA (P < 0.05), but not IL-33 mRNA. BCTC (10 μM) significantly abolished menthol-induced up-regulation of TRPM8 mRNA and protein and IL-25 and TSLP mRNA (P < 0.01). TRPM8 protein levels were higher in the supernatants of induced sputum from asthmatic subjects (n = 107) than in those from healthy controls (n = 19) (P < 0.001), and IL-25, TSLP and IL-33 mRNA levels were concomitantly increased (P < 0.001). Additionally, TRPM8 mRNA levels correlated strongly with those of IL-25 and TSLP (P < 0.001), and TRPM8 protein levels were significantly higher in bronchodilator-responsive asthmatic subjects than in nonresponders. @*Conclusions@#TRPM8 may be involved in the airway epithelial cell innate immune response and a molecular target for the treatment of asthma.