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Despite the devastating impact of many lung diseases on human health, there is still a significant unmet medical need in respiratory diseases, for which inhaled delivery represents a crucial strategy. More guidance on how to design and carry out multidisciplinary inhaled projects is needed. When designing inhaled drugs, the medicinal chemist must carefully balance the physicochemical properties of the molecule to achieve optimal target engagement in the lung. Although the medicinal chemistry strategy is unique for each project, and will change depending on multiple factors, such as the disease, target, systemic risk, delivery device, and formulation, general guidelines aiding inhaled drug design can be applied and are summarised in this review., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background and Aims: (1) To demonstrate that a 13-year-old male can be successfully fitted with a C-Leg® microprocessor-controlled knee. (2) To use validated outcome measurement tools to assess change in mobility, physical function, fatigue and quality of life after fitting., Case Description and Methods: A 13-year-old unilateral traumatic trans-femoral amputee was studied pre-C-Leg fitting and 2 weeks and 10 months post C-Leg fitting., Findings and Outcomes: The 6-Minute Walk Test improved by 33% from 360 to 480 m. PedsQL™ Multidimensional Fatigue Scale improved by 32% from 68 to 90, and PedsQL™ Quality of Life Scale improved 14 points, with minimal clinically important difference of 4.36 points., Conclusion: In this case, the provision of a microprocessor-controlled knee in the context of a new prosthesis with new socket system produced improvements for the patient in walking speed, fatigue and quality of life., Clinical Relevance: This case report shows that n = 1 methodology can be used to demonstrate clinical improvement in an adolescent subject when using an intervention (C-Leg) which is not supported in this age group by published evidence., (© The International Society for Prosthetics and Orthotics 2013.)

Asthma and chronic obstructive pulmonary disease (COPD) are characterized in their pathogenesis by chronic inflammation in the airways. Phosphoinositide 3-kinase δ (PI3Kδ), a lipid kinase expressed predominantly in leukocytes, is thought to hold much promise as a therapeutic target for such inflammatory conditions. Of particular interest for the treatment of severe respiratory disease is the observation that inhibition of PI3Kδ may restore steroid effectiveness under conditions of oxidative stress. PI3Kδ inhibition may also prevent recruitment of inflammatory cells, including T lymphocytes and neutrophils, as well as the release of proinflammatory mediators, such as cytokines, chemokines, reactive oxygen species, and proteolytic enzymes. In addition, targeting the PI3Kδ pathway could reduce the incidence of pathogen-induced exacerbations by improving macrophage-mediated bacterial clearance. In this review, we discuss the potential and highlight the unknowns of targeting PI3Kδ for the treatment of respiratory disease, focusing on recent developments in the role of the PI3Kδ pathway in inflammatory cell types believed to be critical to the pathogenesis of COPD., (© 2013 New York Academy of Sciences.)