MUC5B rs35705950 minor allele associates with older age and better survival in idiopathic pulmonary fibrosis.

BACKGROUND AND OBJECTIVE: The minor T-allele of the MUC5B promoter polymorphism rs35705950 is strongly associated with idiopathic pulmonary fibrosis (IPF). However, conflicting results have been reported on the relationship between the MUC5B minor allele and survival and it is unknown whether a specific subgroup of IPF patients might benefit from MUC5B minor allele carriage. We investigated the association between MUC5B rs35705950, survival and patient characteristics in a real-world population of European IPF patients. METHODS: In this retrospective study, 1751 patients with IPF from 8 European centres were included. MUC5B rs35705950 genotype, demographics, clinical characteristics at diagnosis and survival data were analysed. RESULTS: In a multi-variate Cox proportional hazard model the MUC5B minor allele was a significant independent predictor of survival when adjusted for age, sex, high resolution computed tomography pattern, smoking behaviour and pulmonary function tests in IPF. MUC5B minor allele carriers were significantly older at diagnosis (p = 0.001). The percentage of MUC5B minor allele carriers increased significantly with age from 44% in patients aged <56 year, to 63% in patients aged >75. In IPF patients aged <56, the MUC5B minor allele was not associated with survival. In IPF patients aged ≥56, survival was significantly better for MUC5B minor allele carriers (45 months [CI: 42-49]) compared to non-carriers (29 months [CI: 26-33]; p = 4 × 10-12 ). CONCLUSION: MUC5B minor allele carriage associates with a better median transplant-free survival of 16 months in the European IPF population aged over 56 years. MUC5B genotype status might aid disease prognostication in clinical management of IPF patients.

Prognostication of progressive pulmonary fibrosis in connective tissue disease-associated interstitial lung diseases: A cohort study.

Background: Connective tissue diseases-associated interstitial lung disease (CTD-ILD) is a heterogeneous condition that impairs quality of life and is associated with premature death. Progressive pulmonary fibrosis (PPF) has been identified as an important risk factor for poor prognosis. However, different criteria for PPF are used in clinical studies, which may complicate comparison between trials and translation of study findings into clinical practice. Methods: This is a retrospective single center study in patients with CTD-ILD. The prognostic relevance of PPF definitions, including INBUILD, ATS/ERS/JRS/ALAT 2022, and simplified progressive fibrosing (simplified PF) criteria, were examined in this cohort and validated in the other reported Dutch CTD-ILD cohort. Results: A total of 230 patients with CTD-ILD were included and the median follow-up period was six (3-9) years. Mortality risk was independently associated with age (adjusted HR 1.07, p < 0.001), smoking history (adjusted HR 1.90, p = 0.045), extent of fibrosis on high-resolution computed tomography (HRCT) at baseline (adjusted HR 1.05, p = 0.018) and baseline DLCO (adjusted HR 0.97, p = 0.013). Patients with regular pulmonary function tests in the first 2 years (adjusted HR 0.42, p = 0.002) had a better survival. The prognostic relevance for survival was similar between the three PPF criteria in the two cohorts. Conclusion: Higher age, smoking, increased extent of fibrosis and low baseline DLCO were associated with poor prognosis, while regular pulmonary function evaluation was associated with better survival. The INBUILD, ATS/ERS/JRS/ALAT 2022, and simplified PF criteria revealed similar prognostication.

Is grip strength a predictor for total muscle strength in healthy children, adolescents, and young adults?

The primary purpose of this study was to examine whether grip strength is related to total muscle strength in children, adolescents, and young adults. The second purpose was to provide reference charts for grip strength, which could be used in the clinical and research setting. This cross-sectional study was performed at primary and secondary schools and the University of Applied Sciences. Three hundred and eighty-four healthy Dutch children, adolescents, and young adults at the age of 8 to 20 years participated. Isometric muscle strength was measured with a handheld dynamometer of four muscle groups (shoulder abductors, grip strength, hip flexors, and ankle dorsiflexors). Total muscle strength was a summing up of shoulder abductors, hip flexors, and ankle dorsiflexors. All physical therapists participated in a reliability study. The study was started when intratester and intertester reliability was high (Pearson correlation coefficient >0.8). Grip strength was strongly correlated with total muscle strength, with correlation coefficients between 0.736 and 0.890 (p < 0.01). However, the correlation was weaker when controlled for weight (0.485-0.564, p < 0.01). Grip strength is related to total muscle strength. This indicates, in the clinical setting, that grip strength can be used as a tool to have a rapid indication of someone's general muscle strength. The developed reference charts are suitable for evaluating muscle strength in children, adolescents, and young adults in clinical and research settings.

Impact of UKPDS risk estimation added to a first subjective risk estimation on management of coronary disease risk in type 2 diabetes - An observational study.

AIMS: To investigate the impact of the UKPDS risk engine on management of CHD risk in T2DM patients. METHODS: Observational study among 139 GPs. Data from 933 consecutive patients treated with a maximum of two oral glucose lowering drugs, collected at baseline and after twelve months. GPs estimated the CHD risk themselves and afterwards they calculated this with the UKPDS risk engine. Under- and overestimation were defined as a difference >5 percentage points difference between both calculations. The impact of the UKPDS risk engine was assessed by measuring differences in medication adjustments between the over-, under- and accurately estimated group. RESULTS: In 42.0% the GP accurately estimated the CHD risk, in 32.4% the risk was underestimated and in 25.6% overestimated. Mean difference between the estimated (18.7%) and calculated (19.1%) 10 years CHD risk was -0.36% (95% CI -1.24 to 0.52). Male gender, current smoking and total cholesterol level were associated with underestimation. Patients with an subjectively underestimated CHD risk received significantly more medication adjustments. Their UKPDS 10 year CHD risk did not increase during the follow-up period, contrary to the other two groups of patients. CONCLUSIONS: The UKPDS risk engine may be of added value for risk management in T2DM.