Differences in asthma genetics between Chinese and other populations

Asthma is caused by complex gene-gene and gene-environment interactions. Most asthma genes are not replicable across populations, which is possibly because of differences in the epidemiology of these genes. Our case-control association and next-generation sequencing studies revealed substantial discrepancies in the frequencies of single nucleotide polymorphisms (SNPs) and haplotype blocks for asthma genes between Chinese and other populations. The minor allele frequencies for nearly half of our studied SNPs differed by 0.2 or greater between southern Chinese subjects in Hong Kong and European white populations, African populations, or both. Because genome-wide association studies for asthma have not been performed in Chinese subjects, we cannot tell whether the genomic findings of recent consortium-based genome-wide association studies are applicable to our population. In addition, our group performed Roche 454 pyrosequencing on a 100-kb area spanning each of 10 asthma loci in 24 healthy Hong Kong children. For the 17q21 locus, there was substantial variation in the haplotype structures that were constructed from 224 common SNPs among Hong Kong subjects and 6 ethnic groups under the 1000 Genomes Project. Sixteen mostly small haplotype blocks were formed in Hong Kong, whereas 6 haplotype blocks were identified in Han Chinese in Beijing and central European subjects and 11 and 19 blocks were identified in Puerto Rican and Yoruba African subjects. In conclusion, differences in allele frequencies of asthma genes and haplotype structures of asthma loci are found between Chinese subjects and other ethnic groups. These sequence variations must be considered during the selection of tagging SNPs for replicating genetic associations between populations

Determinants of, and reference equation for, exhaled nitric oxide in the Chinese population

Measurement of fractional exhaled nitric oxide concentration (FeNO) has been proposed as a useful biomarker for monitoring and management of airway diseases. Limited information is available regarding reference levels of FeNO levels in Chinese adults. This study aimed to investigate the reference equation and determinants of FeNO in Chinese adults. 1093 (577 males) healthy nonsmoking subjects aged 18-90 years were recruited. FeNO was measured online using a chemiluminescence analyser. Other assessments included spirometry, skin prick tests, total serum IgE levels and eosinophil count in peripheral blood. The geometric mean FeNO was 32.6 (95% reference interval (RI) 31.4-33.7) ppb for all subjects. FeNO values were higher in males than females (geometric mean (95% RI) 38.3 (36.5-40.2) ppb versus 27.1 (25.8-28.5) ppb, p\u3c0.0001), and in atopic than nonatopic subjects (34.6 (33.0-36.3) ppb versus 29.8 (28.3-31.4) ppb, p\u3c0.0001). FeNO correlated with age (r(2) = 0.23), height (r(2) = 0.20), IgE level (r(2) = 0.18) and percentage eosinophil count (r(2) = 0.18) (all p\u3c0.0001), but not with spirometric parameters. Based on multiple regression modelling, the reference equation of FeNO value was: log(FeNO) = 0.781 + 0.104(sex) + 0.004(age) + 0.084(atopy) + 0.003(height in cm), where for sex 1 = male and 0 = female, age is measured in years, for atopy 1 = atopic and 0 = nonatopic, and height is measured in cm. The FeNO of Chinese adults is higher than that of the Caucasian population, and is affected by age, sex, height and atopic status. This study provides useful references for the interpretation of FeNO

Asthma and bronchodilator responsiveness are associated with polymorphic markers of ARG1, CRHR2 and chromosome 17q21

Objective: Asthma is caused by complex interactions between multiple genes. β2-Agonist is the standard rescue treatment to relieve asthma symptoms and bronchoconstriction. A genetic study for spirometric parameters helps to predict the responses to this antiasthma treatment. This study investigated the relationship between asthma and bronchodilator responsiveness (BDR) and eight asthma genes. Methods: Fifteen single-nucleotide polymorphisms in these genes were genotyped in 345 Chinese asthmatics and 464 controls. Gene–gene interactions were analysed by generalized multifactor dimensionality reduction (GMDR). Results: The diagnosis of asthma was associated with rs7216389 in ORMDL3 [odds ratio (OR) 0.74 and 95% confidence interval (95% CI) 0.56–0.99] and rs3756780 in ARG1 (OR 0.67, 95% CI 0.51–0.89) and BDR with rs2749935 in ARG1. However, none of these associations remained significant at 5% when adjusted for multiple testing by the Bonferroni correction or a false discovery rate. GMDR analyses revealed that rs7216389 in ORMDL3 and rs3756780 in ARG1 might interact for a risk of asthma. Individuals with high-risk genotypes had OR 1.66 (95% CI 1.24–2.23) for asthma when compared with those with low-risk genotypes. GMDR suggested a two-locus model with rs2749935 in ARG1 and rs2190242 in CRHR2 to be associated with BDR. Specifically, reversibility of forced expiratory volume in 1 s was higher in high-risk than that in low-risk patients [mean (95% CI): 10.7 (8.6–12.9) vs. 6.8 (5.9–7.6)%] ; with the latter group showing higher forced expiratory volume in 1 s reversibility compared with high-risk controls [2.8 (1.4–4.3)%]. Conclusion: ARG1 and ORMDL3 may interact to determine the risk of asthma and ARG1 and CRHR2 to alter BDR in asthmatics. Nonetheless, this study is only hypothesis-generating as none of the single marker comparisons is significant when adjusted for multiple testing. These findings need to be confirmed in independent populations

COPD care programme can reduce readmissions and in-patient bed days

SummaryBackgroundChronic obstructive pulmonary disease (COPD) is a common disease worldwide with significant morbidity and mortality.AimTo investigate the effect of a comprehensive COPD management programme in decreasing COPD readmissions 1 year before and 1 year after the programme.Method185 (166 males) patients admitted for acute exacerbation of COPD (AECOPD) were recruited between September 2010 and December 2012. COPD care team provided crisis support and maintenance therapy for the COPD patients for a total of 16 weeks. The protocol included COPD clinic run by respiratory physicians, COPD education and nurse clinics by respiratory nurses, out-patient pulmonary rehabilitation programme by physiotherapists, fast track doctor's clinic, telephone hotline for patients and nurse telephone calls to patients. Readmissions over a period of 1 year were assessed.ResultsThe mean (SD) age of the subjects and FEV1 % predicted normal were 76.9 ± 7.37 yrs and 44.4  ±  20.7% respectively. 40 (21.6%) patients required non-invasive positive pressure ventilation during the recruitment admission. Admissions for AECOPD decreased from 2.39 ± 2.05 one year before programme to 1.65 ± 2.1 one year after programme (mean difference 0.75 ± 2.11 episodes, p < 0.001). The length of hospital stay was reduced from 12.17 ± 9.14 days one year before programme to 9.09 ± 12.1 days one year after the programme (mean difference 3.09 ± 12.1 days, p < 0.001). The FEV1 percentage predicted and quality of life measured by St George's Respiratory Questionnaire showed no significant improvement at 16 weeks after recruitment into the programme as compared to at 6 weeks.ConclusionCOPD care programme is effective in decreasing readmissions and length of hospital day for COPD patients

An Adjunct Intervention for Management of Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD)

Objectives: Application of transcutaneous electrical nerve stimulation over acupuncture points (Acu-TENS) is a noninvasive intervention that has recently been shown to alleviate dyspnea in patients with stable chronic obstructive pulmonary disease (COPD). This case report aims to explore the role of Acu-TENS in patients diagnosed with COPD during the acute exacerbation. Study design: The study design was a case report. Setting: The study was conducted in an inpatient setting. Subject: The subject was a 74-year-old man admitted to the hospital due to acute exacerbation of COPD (AECOPD). Intervention: Treatment consisted of application of TENS on EX-B1 (Dingchuan) for 45 minutes. Outcome measures: Oxygen saturation, heart rate, and dyspnea score were measured before, immediately after, and 45 minutes after Acu-TENS intervention. Other than the physiologic measures, 10 mL of venous blood was taken from the cubital vein for assessment of b-endorphin level, white blood cell count, tumor necrosis factor–a (TNF-a), and C-reactive protein (CRP) level before and immediately postintervention. Results: Postintervention, improved oxygen saturation, and reduction in heart rate and dyspneic sensation were observed accompanied by a raised blood b-endorphin level but the level of white blood cell count, TNF-a, and CRP remain unchanged. Conclusions: Application of 45 minutes Acu-TENS appeared to alleviate symptoms in a patient with AECOPD. The role of adjunctive Acu-TENS therapy during acute exacerbation warrants further investigationGriffith Health FacultyNo Full Tex

Key recommendations for primary care from the 2022 Global Initiative for Asthma (GINA) update

The Global Initiative for Asthma (GINA) was established in 1993 by the World Health Organization and the US National Heart Lung and Blood Institute to improve asthma awareness, prevention and management worldwide. GINA develops and publishes evidence-based, annually updated resources for clinicians. GINA guidance is adopted by national asthma guidelines in many countries, adapted to fit local healthcare systems, practices, and resource availability. GINA is independent of industry, funded by the sale and licensing of its materials. This review summarizes key practical guidance for primary care from the 2022 GINA strategy report. It provides guidance on confirming the diagnosis of asthma using spirometry or peak expiratory flow. GINA recommends that all adults, adolescents and most children with asthma should receive inhaled corticosteroid (ICS)-containing therapy to reduce the risk of severe exacerbations, either taken regularly, or (for adults and adolescents with “mild” asthma) as combination ICS–formoterol taken as needed for symptom relief. For patients with moderate–severe asthma, the preferred regimen is maintenance-and-reliever therapy (MART) with ICS–formoterol. Asthma treatment is not “one size fits all”; GINA recommends individualized assessment, adjustment, and review of treatment. As many patients with difficult-to-treat or severe asthma are not referred early for specialist review, we provide updated guidance for primary care on diagnosis, further investigation, optimization and treatment of severe asthma across secondary and tertiary care. While the GINA strategy has global relevance, we recognize that there are special considerations for its adoption in low- and middle-income countries, particularly the current poor access to inhaled medications