Association of genetic variations in neurokinin-2 receptor with enhanced cough sensitivity to capsaicin in chronic cough.

BACKGROUND: Chronic cough is associated with increased sensitivity to inhaled capsaicin, and both tachykinins and their receptors play important roles in the cough reflex. However, associations between polymorphisms of the tachykinin receptor genes and cough sensitivity in patients with non-productive chronic cough have not been reported. METHODS: Direct sequencing was used to identify single nucleotide polymorphisms (SNPs) in the genes for the neurokinin-1 and neurokinin-2 receptors (NK-1R and NK-2R, respectively). Informative non-synonymous SNPs were scored using the single base extension method for 312 patients with chronic cough and for 100 age matched healthy controls. The cough response to capsaicin was recorded for 312 patients with chronic cough, and the potential genetic association between cough sensitivity to capsaicin and the NK-1R and NK-2R genotypes was evaluated. RESULTS: Two informative SNPs were identified in NK-2R (Gly231Glu and Arg375His), whereas no informative SNP was found in NK-1R. After adjusting for atopy, sex, age, and smoking, the prevalence of enhanced cough sensitivity to capsaicin was higher in the chronic cough patients with the 231Glu allele (p = 0.004; OR 1.69 (95% CI 1.18 to 2.42)) and the 231Glu_375Arg haplotype (p = 0.003; OR 1.71 (95% CI 1.20 to 2.24)). Moreover, the lowest capsaicin concentration to cause five consecutive coughs (C5) was significantly lower in patients with 231Glu (mean (SD) 44.1 (53.2) v 60.9 (55.8) microM/l, p = 0.04) and those with 231Glu_375Arg (43.2 (52.7) v 69.6 (52.0) microM/l, p = 0.03). CONCLUSIONS: The results of this study suggest that NK-2R gene polymorphisms are involved in the enhanced cough sensitivity to capsaicin of patients with chronic cough.

Sensitization to Empynase(pronase B) in exposed hospital personnel and identification of the Empynase allergen.

BACKGROUND: Empynase is a proteolytic enzyme that is widely used as an anti-inflammatory drug in Korea. We evaluated the prevalence of sensitization to Empynase in association with respiratory allergy symptoms in exposed hospital personnel, and identified the IgE-binding components in the Empynase extract, using sera with high levels of specific IgE antibodies. METHODS: A total of 154 hospital personnel (135 nurses and 19 pharmacists) who worked in a university hospital and 123 unexposed healthy control subjects were enrolled. A questionnaire was administered that addressed demographics, job category, history of atopic diseases, diverse symptoms including nasal and lower respiratory symptoms, and the association of symptoms with work. Skin prick tests (SPTs) to common aeroallergens and Empynase extract were performed. Empynase-specific IgE antibody was detected by ELISA, and ELISA inhibition tests were conducted. IgE-binding components were identified by SDS-PAGE and IgE immunoblotting. RESULTS: Forty-two subjects (27.3%) complained of work-related respiratory symptoms (WRRS). Five nurses (3.7%) and one pharmacist (5.3%) had work-related asthma symptoms, and 34 nurses (25.2%) and six pharmacists (31.6%) had work-related rhinitis symptoms. The prevalence of sensitization to Empynase on SPTs was 20.1%, and tended to be higher in pharmacists (31.6%) than in nurses (18.5%). It was estimated that 3.9-8.4% of hospital personnel had WRRS attributable to Empynase. The duration of exposure was longer in positive SPT responders than in negative responders (51.9+/-27.5 vs. 39.2+/-27.3 months, respectively; P<0.05), and the prevalence of Empynase-positive SPTs was significantly higher in subjects with asthma than in those without asthma (57.1% vs. 18.4%, respectively; P<0.05). The levels of Empynase-specific IgE antibodies were significantly higher in pharmacists (76.1+/-83.4 OD units) and nurses (56.3+/-103.0 OD units) than in normal controls (39.8+/-12.7 OD units; P<0.05). Seven subjects (two pharmacists and five nurses) had high serum levels of Empynase-specific IgE antibodies; six of these subjects had WRRS. ELISA inhibition tests were performed with the sera of these six subjects, revealing significant inhibition only with the addition of Empynase. Four strongly staining protein bands (sizes: 36, 33, 16, and 10 kDa) from Empynase extract were observed to bind to the IgE antibodies of sensitized subjects. Conclusion Exposure to Empynase powder may cause rhinitis and asthma in hospital personnel, and the pathogenic mechanism appears to be IgE mediated.

Association between bronchodilating response to short-acting beta-agonist and non-synonymous single-nucleotide polymorphisms of beta-adrenoceptor gene.

BACKGROUND: With beta-agonists being the most widely used agents in the treatment of asthma, in vitro studies reported that beta(2)-adrenergic receptor (ADRB2) polymorphisms are associated with agonist-promoted down-regulation. OBJECTIVE: The present population-based study aimed to evaluate the association between bronchodilating response to inhaled short-acting beta-agonist and two non-synonymous single-nucleotide polymorphisms (SNPs) of ADRB2 (ADRB2-16 and ADRB2-27). METHODS: Two hundred and nine children with reduction in forced expiratory volume in 1 s of more than 20% on methacholine bronchial challenge underwent bronchodilating response testing 5 min after the inhalation of 200 mug of albuterol. Of these 209, 195 gave peripheral blood for genotyping of ADRB2 polymorphisms. RESULTS: The bronchodilating response was significantly higher in subjects with the homozygous Arg16 than in those with the homozygous Gly16. It was further demonstrated that haplotype pairs of the homozygous Arg16Gln27 and of the heterozygous Arg16Gln27/Gly16Glu27 showed the highest bronchodilating responses, and the haplotype pairs of the homozygous Gly16Gln27 the lowest response. As a whole, the bronchodilating response was more positively associated with the combined quantity of Arg16 and Glu27 polymorphisms than with that of Arg16 alone. CONCLUSION: Non-synonymous SNPs of ADRB2 at codons 16 and 27 is significantly associated with bronchodilating response to inhaled short acting beta-agonists.

High prevalence of current asthma and active smoking effect among the elderly.

BACKGROUND: Although asthma is a common cause of morbidity in adults, relatively few objectively measured population studies of asthma prevalence in adult populations have been conducted. OBJECTIVE: To evaluate the prevalence of asthma, based on both a questionnaire and methacholine bronchial provocation test, and to determine the risk factors of asthma prevalence in an adult population. METHODS: A total of 2,467 adults, who were randomly selected from metropolitan urban, non-metropolitan urban and rural areas, responded to the modified ISAAC questionnaire, and underwent methacholine bronchial provocation tests and skin prick tests to locally common aeroallergens. RESULTS: The prevalence of current asthma based on the questionnaire and the methacholine challenge was 2.0% in adults younger than 40, 3.8% in 40- to 54-year-olds, 7.7% in 55- to 64-year-olds and 12.7% in those aged 65 or higher. For subjects of 55-64 years, active smoking was found to be significantly related with the prevalence of current asthma and bronchial hyper-responsiveness, although smoking was positively associated with percentage predictive value of forced expiratory volume of 1 s (FEV1). CONCLUSION: The prevalence of current asthma is common among the elderly, and active smoking may play an important role in the development of asthma and bronchial hyper-responsiveness among the elderly.

Differences in sensitization rates to outdoor aeroallergens, especially citrus red mite (Panonychus citri), between urban and rural children.

BACKGROUND: A recent investigation has suggested that citrus red mite (Panonychus citri, CRM) is the most important allergen in citrus-cultivating farmers with asthma and allergic rhinitis. OBJECTIVE: A cross-sectional survey was performed to evaluate the prevalence of asthma and chronic rhinitis symptoms and sensitization to common indoor and outdoor aeroallergens, including CRM and Japanese cedar pollen, in rural and urban Korean children. METHODS: A total of 2,055 children (1,055 subjects living in rural areas with citrus farms and 1,000 controls in urban areas without citrus farms) were enrolled. They were evaluated by a questionnaire, and by skin prick tests with 13 common indoor and outdoor aeroallergens, including CRM and Japanese cedar pollen. RESULTS: The prevalence of wheezing and chronic rhinitis symptoms during the last 12 months was 8.3% and 35.7% in the rural children and 10.5% and 22.4% in the control group. The most common sensitizing allergens in order of decreasing frequency were Dermatophagoides pteronyssinus (26.6%), Dermatoplagoides farinae (22.7%), CRM (14.2%), cockroach (11.3%), and Japanese cedar pollen (9.7%) among the rural children, but the sensitization rates to CRM and Japanese cedar pollen were 1.3% and 0.2% among the control children, respectively. The prevalence of wheeze during the last 12 months was not different between rural children with sensitization to CRM or Japanese cedar pollen and those without sensitization (5.4% vs 6.1%; 6.9% vs 5.9%). However, the prevalence of chronic rhinitis during the last 12 months was higher among those with sensitization to CRM or to Japanese cedar pollen than among those without sensitization (40.8% vs 34.4%; 51.5% vs 33.5%). CONCLUSIONS: CRM is a common sensitizing allergen in rural children, and the sensitization rates to outdoor aeroallergens, especially CRM and Japanese cedar pollen, are very different between children from rural and urban areas in Korea.

Citrus red mite (Panonychus citri) is a common sensitizing allergen among children living around citrus orchards.

BACKGROUND: A recent investigation has suggested that Panonychus citri (citrus red mite) is the most common causative allergen in citrus-cultivating farmers with asthma or allergic rhinitis. OBJECTIVE: A cross-sectional survey was performed to evaluate the prevalence of asthma and sensitization to P. citri among children living around citrus orchards. METHODS: A total of 1,055 children living around citrus orchards were enrolled. There were 544 boys and 511 girls with a mean age of 12.3 (range 7 to 16) years. They were evaluated by the ISAAC questionnaire, and a skin prick test with 13 common aeroallergens including P. citri and Japanese cedar pollen. Children who recorded ever having experienced wheezing on the questionnaire were evaluated by methacholine bronchial provocation test and determined to have asthma if they showed bronchial hyperresponsiveness to methacholine simultaneously. RESULTS: The positive skin test response to one or more inhalant allergens except P. citri was 35.5%, but when including P. citri, the positive response increased to 37.7%. The most common sensitizing allergens in the order of decreasing frequency were Dermatophagoides pteronyssinus (26.6%), D. farinae (22.7%), P. citri (14.2%), cockroach (11.3%), and Japanese cedar pollen (9.7%). Among the children without sensitization to house dust mites, the sensitization rate to P. citri was significantly higher in those 13 and over than in those under 12 (5.8% versus 2.5%, P < .05). The prevalence of asthma was not different between the children with sensitization to P. citri and those without it (5.4% versus 4.0%, P > .05), although the prevalence was higher in those with sensitization to D. pteronyssinus or D. farinae than in those without sensitization to these allergens (7.9% versus 2.9%, P < .05; 9.7% versus 2.6%, P < .05). CONCLUSION: Citrus red mite is a common sensitizing allergen among children living around citrus orchards. The features of sensitization and development of asthma are different between citrus red mite and house dust mites.