lso present.

The impact of treatment for obstructive sleep apnoea (OSA) on reduction of cardiovascular risk is unclear. This study aimed to examine the effect of continuous positive airway pressure (CPAP) on ambulatory blood pressure (BP) and subclinical myocardial injury in subjects with OSA and hypertension.

Subjects with hypertension requiring at least three anti-hypertensive medications and moderate-severe OSA were enrolled. Eligible subjects were randomized (11) to receive either CPAP treatment or control (no CPAP) for eight weeks. Changes in ambulatory BP and serum biomarkers were compared. Stratified analysis according to circadian BP pattern was performed.

Ninety two subjects (75% men; age, 51±8 years; apnoea-hypopnoea index 40±8 events·h

, taking average of 3.4 anti-hypertensive drugs [range 3-6]) were randomised. The group on CPAP treatment, compared to the control group, demonstrated significant reduction in 24-h systolic BP (-4.4 mmHg, 95% CI -8.7 to -0.1, p=0.046), 24-h diastolic BP (-2.9 mmHg, 95% CI -5.5 to -0.2, p=0.032), daytime systolic BP (-5.4 mmHg, -9.7 to -1.0, p=0.016) and daytime diastolic BP (-3.4 mmHg, 95% CI -6.1 to -0.8, p=0.012). CPAP treatment was associated with significant BP lowering only in non-dippers, but not in dippers. AF-353 Serum troponin I (mean difference -1.74 pg·mL

, 95% CI -2.97 to -0.5, p=0.006) and brain natriuretic peptide (-9.1 pg·mL

, 95% CI -17.6 to -0.6, p=0.036) were significantly reduced in CPAP compared to control group.

In a cohort with OSA and multiple cardiovascular risk factors including difficult-to-control hypertension, short-term CPAP treatment improved ambulatory BP and alleviated subclinical myocardial injury and strain.

In a cohort with OSA and multiple cardiovascular risk factors including difficult-to-control hypertension, short-term CPAP treatment improved ambulatory BP and alleviated subclinical myocardial injury and strain.Development of therapeutic approaches for rare respiratory diseases is hampered by the lack of systems that allow medium-to-high-throughput screening of fully differentiated respiratory epithelium from affected patients. This is a particular problem for primary ciliary dyskinesia (PCD), a rare genetic disease caused by mutations in genes that adversely affect ciliary movement and consequently mucociliary transport. Primary cell culture of basal epithelial cells from nasal brush biopsies, followed by ciliated differentiation at air-liquid interface (ALI) has proven to be a useful tool in PCD diagnostics but the technique’s broader utility, including in pre-clinical PCD research, has been restricted by the limited number of basal cells that it is possible to expand from such biopsies. Here, we describe an immunofluorescence screening method, enabled by extensive expansion of PCD patient basal cells and their culture into differentiated respiratory epithelium in miniaturised 96-well transwell format ALI cultures. Analyses of ciliary ultrastructure, beat pattern and beat frequency indicate that a range of different PCD defects can be retained in these cultures. As proof-of-principle, we performed a personalised investigation in a patient with a rare and severe form of PCD (reduced generation of motile cilia, RGMC), in this case caused by a homozygous nonsense mutation in the MCIDAS gene. The screening system allowed drugs that induce translational readthrough to be evaluated alone or in combination with nonsense-mediated decay inhibitors. Restoration of basal body formation in the patient’s nasal epithelial cells was seen in vitro, suggesting a novel avenue for drug evaluation and development in PCD.

Despite increased interest in MSC-based cell therapies for the acute respiratory distress syndrome (ARDS), clinical investigations have not yet been successful and understanding of the potential

mechanisms of MSC actions in ARDS remain limited. ARDS is driven by an acute severe innate immune dysregulation, often characterised by inflammation, coagulation, and cell injury. How this inflammatory microenvironment influences MSC functions remains to be determined.

To comparatively assess how the inflammatory environment present in ARDS lungs

the lung environment present in healthy volunteers alters MSC behaviors.

Clinical grade human bone marrow-derived MSCs (hMSCs) were exposed to bronchoalveolar lavage fluid (BALF) samples obtained from ARDS patients or from healthy volunteers. Following exposure, hMSCs and their conditioned media were evaluated for a broad panel of relevant properties including viability, levels of expression of inflammatory cytokines, gene expression, cell surface HLA expression, functions.Longitudinal epidemiological data are scarce on the relation between dietary intake of vitamin A and respiratory outcomes in childhood. We investigated whether a higher intake of preformed vitamin A or provitamin β-carotene in mid-childhood is associated with higher lung function and with asthma risk in adolescence.In the Avon Longitudinal Study of Parents and Children, dietary intakes of preformed vitamin A and β-carotene equivalents were estimated by food frequency questionnaire at 7 years of age. Post- bronchodilator forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and forced expiratory flow at 25-75% of FVC (FEF25-75) were measured at 15.5 years and transformed to z scores. Incident asthma was defined by new cases of doctor-diagnosed asthma at age 11 or 14 years.In multivariable adjusted models, a higher intake of preformed vitamin A was associated with higher lung function and a lower risk of incident asthma comparing top versus bottom quartiles of intake, regression coefficients (95% confidence intervals) for FEV1 and FEF25-75 were, respectively, 0.21 (0.05-0.38; P-trend 0.008) and 0.18 (0.03-0.32; P-trend 0.02); odds ratios (95% confidence intervals) for FEV1/FVC ratio below the lower limit of normal and incident asthma were, respectively, 0.49 (0.27-0.90, P-trend 0.04) and 0.68 (0.47, 0.99; P-trend 0.07). In contrast, there was no evidence for association with β-carotene. We also found some evidence for modification of the associations between preformed vitamin A intake and lung function by BCMO1, NCOR2 and CC16 gene polymorphisms.A higher intake of preformed vitamin A, but not β-carotene, in mid-childhood is associated with higher subsequent lung function and lower risk of fixed airflow limitation and incident asthma.