Do we really target the receptors? Deposition and co-deposition of ICS-LABA fixed combination drugs.

Fixed dose combinations of aerosolized bronchodilators and steroids are routinely used in current asthma and COPD management. As spatial distribution of their receptors within the human airways is different, it is a challenging task to deliver the right drug component to the right receptor. The aim of this work was to apply numerical methods to analyse the airway deposition distribution of two inhalation corticosteroid (ICS) - long-acting beta-agonist (LABA) combination drugs in comparison with the distribution of the corresponding receptors. Our results revealed that different combination drugs exhibit different co-deposition patterns depending on the aerodynamic properties of their components. While ICS and LABA components of Symbicort® Turbuhaler® had similar deposition efficiencies in the same airway generation throughout the whole respiratory tract, the steroid component of Relvar® Ellipta® had up to 25% higher deposition than its bronchodilator component in the large bronchi and up to 40% lower deposition in the deeper airways. Present results highlight the need for extensive research to elucidate whether each drug component should deposit according to its receptor distribution or similar deposition distribution patterns of the components should be attained to benefit from the synergistic effects documented in the open literature. Once this aspect clarified, the next step will be to tailor the aerodynamic properties of each component of combination drugs to yield the desired deposition distribution in the lungs.

Circulating Soluble Urokinase-Type Plasminogen Activator Receptor in Obstructive Sleep Apnoea.

Background and Objectives: Obstructive sleep apnoea (OSA) is associated with heightened systemic inflammation and a hypercoagulation state. Soluble urokinase-type plasminogen activator receptor (suPAR) plays a role in fibrinolysis and systemic inflammation. However, suPAR has not been investigated in OSA. Materials and Methods: A total of 53 patients with OSA and 15 control volunteers participated in the study. Medical history was taken and in-hospital sleep studies were performed. Plasma suPAR levels were determined by ELISA. Results: There was no difference in plasma suPAR values between patients with OSA (2.198 ± 0.675 ng/mL) and control subjects (2.088 ± 0.976 ng/mL, p = 0.62). Neither was there any difference when patients with OSA were divided into mild (2.134 ± 0.799 ng/mL), moderate (2.274 ± 0.597 ng/mL) and severe groups (2.128 ± 0.744 ng/mL, p = 0.84). There was no significant correlation between plasma suPAR and indices of OSA severity, blood results or comorbidities, such as hypertension, diabetes, dyslipidaemia or cardiovascular disease. Plasma suPAR levels were higher in women when all subjects were analysed together (2.487 ± 0.683 vs. 1.895 ± 0.692 ng/mL, p < 0.01), and also separately in controls (2.539 ± 0.956 vs. 1.411 ± 0.534 ng/mL, p = 0.02) and patients (2.467 ± 0.568 vs. 1.991 ± 0.686 ng/mL, p < 0.01). Conclusions: Our results suggest that suPAR does not play a significant role in the pathophysiology of OSA. The significant gender difference needs to be considered when conducting studies on circulating suPAR.

Oscillometrically Measured Aortic Pulse Wave Velocity Reveals Asymptomatic Carotid Atherosclerosis in a Middle-Aged, Apparently Healthy Population.

BACKGROUND: Asymptomatic atherosclerosis is a common entity even at young age. Studies have suggested a strong relationship between increased arterial stiffness and asymptomatic carotid atherosclerosis (ACA) in general population, particularly in those with high cardiovascular risk, but no data exist from a younger population free from recognized cardiovascular disease. Hypothesis. We hypothesized there is an association between ACA and aortic pulse wave velocity (PWVao) in middle-aged, apparently healthy, normotensive population to reveal increased cardiovascular risk. METHODS: We examined the relationship between ACA and PWVao in 236 apparently healthy, asymptomatic, normotensive, middle-aged subjects (age 47 ± 8 years; 52% women). PWVao was measured with the oscillometric method (Arteriograph). ACA was assessed by carotid artery ultrasonography. RESULTS: ACA was present in 51 subjects. Subjects with ACA were older (p < 0.009), more likely to be smokers (p < 0.009), more likely to be smokers (p < 0.009), more likely to be smokers (p < 0.009), more likely to be smokers (p < 0.009), more likely to be smokers (p < 0.009), more likely to be smokers (p < 0.009), more likely to be smokers (p < 0.009), more likely to be smokers (. CONCLUSIONS: PWVao measured by the Arteriograph proved to be an independent marker of ACA. Our study may reveal high CV risk, detected as increased PWVao, which according to our study is related in a very high probability to asymptomatic carotid atherosclerosis in apparently healthy, young, and middle-aged subjects.