Background Asthma in obese individuals is poorly understood, these patients are often refractory to standard therapy. Objectives To gain insights into the pathogenesis and treatment of asthma in obese individuals by determining how obesity and bariatric surgery affect asthma control, airway hyperresponsiveness and markers of asthmatic inflammation. Methods A prospective study of (i) asthmatic and non-asthmatic bariatric surgery patients compared at baseline, and (ii) asthmatic patients followed for 12 months after bariatric surgery. Results We studied 23 asthmatic and 21 non-asthmatic patients undergoing bariatric surgery. At baseline, asthmatics had lower FEV1 and FVC, and lower levels of lymphocytes in bronchoalveolar lavage. Following surgery, asthmatic participants experienced significant improvements in asthma control (asthma control score 1.55 to 0.74, p < 0.0001) and asthma quality of life (4.87 to 5.87, p < 0.0001). Airways responsiveness to methacholine improved significantly (PC20 3.9 to 7.28, p = 0.03). There was a statistically significant interaction between IgE status and change in airways responsiveness (p for interaction term = 0.01), improvement in AHR was significantly related to change in BMI in those with normal IgE (p = 0.02, R2 = 0.46). The proportion of lymphocytes in bronchoalveolar lavage and production of cytokines from activated peripheral blood CD4+ T cells increased significantly. Conclusions Bariatric surgery improves airway hyperresponsiveness in obese asthmatics with normal serum IgE. Weight loss has dichotomous effects on airway physiology and T cell function typically involved in the pathogenesis of asthma, suggesting that obesity produces a unique phenotype of asthma that will require a distinct therapeutic approach.

Self-assembled peptide nanostructures have been increasingly exploited as functional materials for applications in biomedicine and energy. The emergent properties of these nanomaterials determine the applications for which they can be exploited. It has recently been appreciated that nanomaterials composed of multicomponent coassembled peptides often display unique emergent properties that have the potential to dramatically expand the functional utility of peptide-based materials. This review presents recent efforts in the development of multicomponent peptide assemblies. The discussion includes multicomponent assemblies derived from short low molecular weight peptides, peptide amphiphiles, coiled coil peptides, collagen, and β-sheet peptides. The design, structure, emergent properties, and applications for these multicomponent assemblies are presented in order to illustrate the potential of these formulations as sophisticated next-generation bio-inspired materials.

BackgroundAsthma is a chronic inflammatory disease of the airway that is characterized by a Th2-type of immune response with increasing evidence for involvement of Th17 cells. The role of IL-6 in promoting effector T cell subsets suggest that IL-6 may play a functional role in asthma. Classically IL-6 has been viewed as an inflammatory marker, along with TNFα and IL-1β, rather than as regulatory cytokine.ObjectiveTo investigate the potential relationship between IL-6 and other proinflammatory cytokines, Th2/Th17 cytokines and lung function in allergic asthma, and thus evaluate the potential role of IL-6 in this disease.MethodsCytokine levels in induced sputum and lung function were measured in 16 healthy control and 18 mild-moderate allergic asthmatic subjects.ResultsThe levels of the proinflammatory biomarkers TNFα and IL-1β were not different between the control and asthmatic group. In contrast, IL-6 levels were specifically elevated in asthmatic subjects compared with healthy controls (p < 0.01). Hierarchical regression analysis in the total study cohort indicates that the relationship between asthma and lung function could be mediated by IL-6. Among Th2 cytokines only IL-13 (p < 0.05) was also elevated in the asthmatic group, and positively correlated with IL-6 levels (rS = 0.53, p < 0.05).ConclusionsIn mild-moderate asthma, IL-6 dissociates from other proinflammatory biomarkers, but correlates with IL-13 levels. Furthermore, IL-6 may contribute to impaired lung function in allergic asthma.

Supramolecular hydrogels are emerging as next-generation alternatives to synthetic polymers for drug delivery applications. Self-assembling peptides are a promising class of supramolecular gelators for in vivo drug delivery that have been slow to be adopted despite advantages in biocompatibility due to the relatively high cost of producing synthetic peptide hydrogels compared to synthetic polymer gels. Herein, we describe the development and use of inexpensive low-molecular-weight cationic derivatives of phenylalanine (Phe) as injectable hydrogels for in vivo delivery of an anti-inflammatory drug, diclofenac, for pain mitigation in a mouse model. N-Fluorenylmethoxycarbonyl phenylalanine (Fmoc-Phe) derivatives were modified at the carboxylic acid with diaminopropane (DAP) to provide Fmoc-Phe-DAP molecules that spontaneously and rapidly self-assemble in aqueous solutions upon addition of physiologically relevant sodium chloride concentrations to give hydrogels. When self-assembly occurs in the presence of diclofenac, the drug molecule is efficiently encapsulated within the hydrogel network. These hydrogels exhibit robust shear-thinning behavior, mechanical stability, and drug release profiles to enable application as injectable hydrogels for in vivo drug delivery. Delivery of diclofenac in vivo was demonstrated by a localized injection of an Fmoc-F 5 -Phe-DAP/diclofenac hydrogel into the ankle joint of mice with induced ankle injury and associated inflammation-induced pain. Remediation of pain in the ankle joint was observed immediately after the initial injection and was sustained for a period of nearly 2 weeks, while diclofenac controls remediated pain for less than 1 day. These data demonstrate the promise of these supramolecular hydrogels as inexpensive next-generation materials for sustained and localized drug delivery in vivo.