The phenotype and genotype of adult obstructive sleep apnoea/hypopnoea syndrome

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldObstructive sleep apnoea/hypopnoea syndrome (OSAHS) is a common condition affecting approximately 2-4% of the middle-aged population. A hereditary component to the condition has long been recognised but its genetic basis has been difficult to elucidate. Progress in determining the genotype of OSAHS is hampered by the lack of a consistent definition of phenotype and the large environmental influences on its expression. "Intermediate phenotypes", such as craniofacial structure, obesity and upper airway control, have been utilised. Multiple gene polymorphisms have been explored in association with the latter, as well as with the sequelae of OSAHS, such as hypertension and increased insulin resistance. To date, two genome-wide scans have identified potential regions that may be of interest in further defining the intermediate phenotypes. The present paper focuses on human studies with an update of the most recent work in the area, including a short discussion on methods of genetic studies

The association of spirometric small airways obstruction with respiratory symptoms, cardiometabolic diseases, and quality of life: Results from the Burden of Obstructive Lung Disease (BOLD) study

Background: Spirometric small airways obstruction (SAO) is common in the general population. Whether spirometric SAO is associated with respiratory symptoms, cardiometabolic diseases, and quality of life (QoL) is unknown. Methods: Using data from the Burden of Obstructive Lung Disease study (N = 21,594), we defined spirometric SAO as the mean forced expiratory flow rate between 25 and 75% of the FVC (FEF25-75) less than the lower limit of normal (LLN) or the forced expiratory volume in 3 s to FVC ratio (FEV3/FVC) less than the LLN. We analysed data on respiratory symptoms, cardiometabolic diseases, and QoL collected using standardised questionnaires. We assessed the associations with spirometric SAO using multivariable regression models, and pooled site estimates using random effects meta-analysis. We conducted identical analyses for isolated spirometric SAO (i.e. with FEV1/FVC ≥ LLN). Results: Almost a fifth of the participants had spirometric SAO (19% for FEF25-75; 17% for FEV3/FVC). Using FEF25-75, spirometric SAO was associated with dyspnoea (OR = 2.16, 95% CI 1.77–2.70), chronic cough (OR = 2.56, 95% CI 2.08–3.15), chronic phlegm (OR = 2.29, 95% CI 1.77–4.05), wheeze (OR = 2.87, 95% CI 2.50–3.40) and cardiovascular disease (OR = 1.30, 95% CI 1.11–1.52), but not hypertension or diabetes. Spirometric SAO was associated with worse physical and mental QoL. These associations were similar for FEV3/FVC. Isolated spirometric SAO (10% for FEF25-75; 6% for FEV3/FVC), was also associated with respiratory symptoms and cardiovascular disease. Conclusion: Spirometric SAO is associated with respiratory symptoms, cardiovascular disease, and QoL. Consideration should be given to the measurement of FEF25-75 and FEV3/FVC, in addition to traditional spirometry parameters

Antidepressants and the risk of hyponatremia:a Danish register-based population study

OBJECTIVE: To examine the association between classes of antidepressants and hyponatremia, and between specific antidepressants and hyponatremia. DESIGN: Retrospective register-based cohort study using nationwide registers from 1998 to 2012. SETTING: The North Denmark Region. PARTICIPANTS: In total, 638 352 individuals were included. PRIMARY AND SECONDARY OUTCOME MEASURES: Plasma sodium was obtained from the LABKA database. The primary outcome was hyponatremia defined as plasma sodium (p-sodium) below 135 mmol/L and secondary outcome was severe hyponatremia defined as p-sodium below 130 mmol/L. The association between use of specific antidepressants and hyponatremia was analysed using multivariable Poisson regression models. RESULTS: An event of hyponatremia occurred in 72 509 individuals and 11.36% (n=6476) of these events happened during treatment with antidepressants. Incidence rate ratios and CIs for the association with hyponatremia in the first p-sodium measured after initiation of treatment were for citalopram 7.8 (CI 7.42 to 8.20); clomipramine 4.93 (CI 2.72 to 8.94); duloxetine 2.05 (CI 1.44 to 292); venlafaxine 2.90 (CI 2.43 to 3.46); mirtazapine 2.95 (CI 2.71 to 3.21); and mianserin 0.90 (CI 0.71 to 1.14). CONCLUSIONS: All antidepressants except mianserin are associated with hyponatremia. The association is strongest with citalopram and lowest with duloxetine, venlafaxine and mirtazapine