METHODS: This is a prospective, randomised, crossover, single-blinded study conducted from February 2018 to February 2019 among adult subjects attending respiratory clinic Universiti Kebangsaan Malaysia Medical Centre (UKMMC).
RESULTS: Forty-six subjects were recruited with 27 males (58.7%). The mean age was 54 (+11) year old. The baseline median Body Mass Index (BMI) was 34.2 kg/m2 (Interquartile Range IQR: 30.8 kg/m2 -41.7 kg/m2); baseline median AHI 28.8 /hour (IQR 21.2/hour-54.0/hour); andbaseline median ESS 15 (IQR 13-16). After intervention, the median AHI was 5.0 / hour (IQR 4.2/hour-6.0/hour) at fixed CPAP arm; APAP arm was 5.5/ hour (IQR 4.2/hour-6.3/hour); p<0.01. The median ESS at fixed CPAP arm was 2 (IQR 0-3); APAP arm was 2 (IQR 1-3); p < 0.01. Those who preferred APAP were 22 subjects (47.8%) and had median optimal CPAP pressure 13.0 cmH2O (IQR 12.0 cmH2O -13.5 cmH2O); 24 subjects (52.2%) who preferred Fixed CPAP had median optimal CPAP pressure 8.0 cmH2O (IQR 6.3 cmH2O -8.7 cmH2O); p<0.01. Median baseline BMI was 37.6 kg/m2 (IQR 30.8 kg/m2 -43.0 kg/m2) for those who preferred APAP and 32.3 kg/m2 (IQR 30.8 kg/m2 - 38.4 kg/m2) for subjects preferred Fixed CPAP; p=0.03.
DISCUSSION: Fixed CPAP maybe considered as first line therapy for symptomatic moderate and severe OSA with titrated optimal CPAP pressure less than 8 cmH2O and BMI less than 32.3 kg/m2; based on subjects' preference. Baseline AHI and average daily CPAP usage was not statisticallysignificant in affecting patient preference between fixed and auto adjusting CPAP. This is the first study of its kind conducted in Malaysia.
METHODS: This study belongs to a part of an ongoing Singapore/Malaysia cross-sectional genetics and epidemiological study (SMCSGES). Genotype-phenotype associations were assessed by performing a genotyping assay on n = 4,348 ethnic Chinese individuals from the SMCSGES cohort. The phosphorylation levels of receptors and signaling proteins in the MAPK signaling cascades, including ErbB2, EGFR, and ERK1/2, were compared across the genotypes of asthma-associated SNPs through in vitro and ex vivo approaches.
RESULTS: The ERBB2 tag-SNP rs1058808 was significantly associated with allergic asthma, with the allele "G" identified as protective against the disease (adjusted logistic p = 6.56 × 10-9, OR = 0.625, 95% CI: 0.544-0.718). The allele "G" of rs1058808 resulted in a Pro1170Ala mutation that results in lower phosphorylation levels of ErbB2 in HaCat cells (p < 0.001), whereas the overall ERBB2 mRNA expression and the phosphorylation levels of EGFR remained unaffected. In the SMCSGES cohort, individuals carrying the genotype "GG" of rs1058808 had lower phosphorylated ERK1/2 proteins in the MAPK signaling cascade. A lower phosphorylation level of ERK1/2 was also associated with reduced asthma risk.
CONCLUSIONS: The present findings highlighted the involvement of a functional exonic variant of ERBB2 in asthma development via modulating the MAPK signaling cascade.