ERS International Congress 2023: highlights from the Respiratory Clinical Care and Physiology Assembly.

It is a challenge to keep abreast of all the clinical and scientific advances in the field of respiratory medicine. This article contains an overview of laboratory-based science, clinical trials and qualitative research that were presented during the 2023 European Respiratory Society International Congress within the sessions from the five groups of Assembly 1 (Respiratory Clinical Care and Physiology). Selected presentations are summarised from a wide range of topics: clinical problems, rehabilitation and chronic care, general practice and primary care, electronic/mobile health (e-health/m-health), clinical respiratory physiology, exercise and functional imaging.

Association of Muscle Quality and Pain in Adults With Symptomatic Knee Osteoarthritis, Independent of Muscle Strength: Findings From a Cross-Sectional Study.

OBJECTIVE: Knee osteoarthritis (OA) is a leading cause of chronic pain in adults and shows wide interindividual variability, with peripheral and central factors contributing to the pain experience. Periarticular factors, such as muscle quality (eg, echo intensity [EI] and shear wave velocity [SWV]), may contribute to knee OA pain; however, the role of muscle quality in OA symptoms has yet to be fully established. METHODS: Twenty-six adults (age >50 years) meeting clinical criteria for knee OA were included in this cross-sectional study. Quantitative ultrasound imaging was used to quantify EI and SWV in the rectus femoris of the index leg. Pearson correlations followed by multiple linear regression was used to determine associations between muscle quality and pain, controlling for strength, age, sex, and body mass index. RESULTS: EI and SWV were significantly associated with movement-evoked pain (b = 0.452-0.839, P = 0.024-0.029). Clinical pain intensity was significantly associated with SWV (b = 0.45, P = 0.034), as were pressure pain thresholds at the medial (b = -0.41, P = 0.025) and lateral (b = -0.54, P = 0.009) index knee joint line, adjusting for all covariates. Pain interference was significantly associated with knee extension strength (b = -0.51, P = 0.041). CONCLUSION: These preliminary findings suggest that EI and SWV may impact knee OA pain and could serve as malleable treatment targets. Findings also demonstrate that muscle quality is a unique construct, distinct from muscle strength, which may impact pain and treatment outcomes. More research is needed to fully understand the role of muscle quality in knee OA.

Enhancing massed prolonged exposure with cannabidiol to improve posttraumatic stress disorder: Design and methodology of a pilot randomized clinical trial.

Background: The impact of posttraumatic stress disorder (PTSD) is substantial and often results in pervasive functional impairments. Although evidence-based treatments for PTSD are established, there remains room for improvement as many individuals continue to meet diagnostic criteria even after successful treatment completion. Cannabidiol (CBD) has attracted considerable attention based on its potential to treat a myriad of health conditions. CBD may decrease anxiety and facilitate extinction learning processes, two critical targets of trauma-focused psychotherapies. We present the design and methods for a pilot randomized clinical trial to examine the combination of CBD and prolonged exposure for PTSD. Methods: Participants (n = 24) will be randomized to CBD or placebo for 18 days delivered in combination with ten daily prolonged exposure sessions over two weeks. The study medication will be Epidiolex® (250 mg BID). The PTSD Checklist for DSM-5 will be the primary outcome to assess PTSD severity at baseline, during treatment, and at 1-month follow-up. Blood, saliva, and heart rate will be collected during treatment to assess intervention effects on biological outcomes related to PTSD and the endocannabinoid system. Results: Consistent with the purpose of a pilot, our goals are to evaluate the feasibility of study procedures, safety of the intervention, and the preliminary effect of CBD to inform a larger trial. Descriptive and inferential statistics will be used to address study aims. Conclusion: Findings will inform decision making on combining CBD with behavioral interventions for PTSD to enhance outcomes and mitigate the morbidity of this debilitating condition.

Modelling bronchial epithelial-fibroblast cross-talk in idiopathic pulmonary fibrosis (IPF) using a human-derived in vitro air liquid interface (ALI) culture.

Idiopathic Pulmonary Fibrosis (IPF) is a devastating form of respiratory disease with a life expectancy of 3-4 years. Inflammation, epithelial injury and myofibroblast proliferation have been implicated in disease initiation and, recently, epithelial-fibroblastic crosstalk has been identified as a central driver. However, the ability to interrogate this crosstalk is limited due to the absence of in vitro models that mimic physiological conditions. To investigate IPF dysregulated cross-talk, primary normal human bronchial epithelial (NHBE) cells and primary normal human lung fibroblasts (NHLF) or diseased human lung fibroblasts (DHLF) from IPF patients, were co-cultured in direct contact at the air-liquid interface (ALI). Intercellular crosstalk was assessed by comparing cellular phenotypes of co-cultures to respective monocultures, through optical, biomolecular and electrical methods. A co-culture-dependent decrease in epithelium thickness, basal cell mRNA (P63, KRT5) and an increase in transepithelial electrical resistance (TEER) was observed. This effect was significantly enhanced in DHLF co-cultures and lead to the induction of epithelial to mesenchymal transition (EMT) and increased mRNA expression of TGFß-2, ZO-1 and DN12. When stimulated with exogenous TGFß, NHBE and NHLF monocultures showed a significant upregulation of EMT (COL1A1, FN1, VIM, ASMA) and senescence (P21) markers, respectively. In contrast, direct NHLF/NHBE co-culture indicated a protective role of epithelial-fibroblastic cross-talk against TGFß-induced EMT, fibroblast-to-myofibroblast transition (FMT) and inflammatory cytokine release (IL-6, IL-8, IL-13, IL-1ß, TNF-α). DHLF co-cultures showed no significant phenotypic transition upon stimulation, likely due to the constitutively high expression of TGFß isoforms prior to any exogenous stimulation. The model developed provides an alternative method to generate IPF-related bronchial epithelial phenotypes in vitro, through the direct co-culture of human lung fibroblasts with NHBEs. These findings highlight the importance of fibroblast TGFß signaling in EMT but that monocultures give rise to differential responses compared to co-cultures, when exposed to this pro-inflammatory stimulus. This holds implications for any translation conclusions drawn from monoculture studies and is an important step in development of more biomimetic models of IPF. In summary, we believe this in vitro system to study fibroblast-epithelial crosstalk, within the context of IPF, provides a platform which will aid in the identification and validation of novel targets.

A Conformable Organic Electronic Device for Monitoring Epithelial Integrity at the Air Liquid Interface.

Air liquid interfaced (ALI) epithelial barriers are essential for homeostatic functions such as nutrient transport and immunological protection. Dysfunction of such barriers are implicated in a variety of autoimmune and inflammatory disorders and, as such, sensors capable of monitoring barrier health are integral for disease modelling, diagnostics and drug screening applications. To date, gold-standard electrical methods for detecting barrier resistance require rigid electrodes bathed in an electrolyte, which limits compatibility with biological architectures and is non-physiological for ALI. This work presents a flexible all-planar electronic device capable of monitoring barrier formation and perturbations in human respiratory and intestinal cells at ALI. By interrogating patient samples with electrochemical impedance spectroscopy and simple equivalent circuit models, disease-specific and patient-specific signatures are uncovered. Device readouts are validated against commercially available chopstick electrodes and show greater conformability, sensitivity and biocompatibility. The effect of electrode size on sensing efficiency is investigated and a cut-off sensing area is established, which is one order of magnitude smaller than previously reported. This work provides the first steps in creating a physiologically relevant sensor capable of mapping local and real-time changes of epithelial barrier function at ALI, which will have broad applications in toxicology and drug screening applications.

Digesting Digestion: An Educational Laboratory to Teach Students about Enzymes and the Gastrointestinal Tract.

Digestion is a fundamentally important process for an individual's life. However, the physical process of digestion is hidden inside the body, making it challenging to understand and a particularly difficult topic for students to learn in the classroom. Traditional approaches to teaching body processes include a mixture of textbook teaching and visual learning. However, digestion is not particularly visual. This activity is designed to engage students using a combination of visual, inquiry-based, and experiential learning approaches and introduces the scientific method to students in secondary school. The laboratory simulates digestion, creating a "stomach" inside of a clear vial. Students fill the vials with a protease solution and visually observe the digestion of food. By making predictions about the types of biomolecules that will be digested, students begin to learn and understand basic biochemistry in a relatable context, while simultaneously understanding anatomical and physiological concepts. We trialled this activity at two schools, where we received positive feedback from teachers and students, indicating that the practical enhanced student understanding of the digestion process. We see this lab as a valuable learning activity that can be extended broadly across multiple classrooms around the world.

Measuring fascicle lengths of extrinsic and intrinsic thumb muscles using extended field-of-view ultrasound.

Complex motion of the human thumb is enabled by the balanced architectural design of the extrinsic and intrinsic thumb muscles. Given that recent imaging advances have not yet been applied to enhance our understanding of the in vivo properties of thumb muscles, the objective of this study was to test the reliability and validity of measuring thumb muscle fascicle lengths using extended field of view ultrasound (EFOV-US). Three muscles (FPL: flexor pollicis longus, APB: abductor pollicis brevis, and ECU: extensor carpi ulnaris) were imaged in eight healthy adults (4 female; age, 21.6 ± 1.3 years; height, 175.9 ± 8.3 cm)[mean ± SD]. Measured fascicle lengths were compared to cadaveric data (all muscles) and ultrasound data (ECU only). Additionally, to evaluate how fascicle lengths scale with anthropometric measurements, height, forearm length, hand length, and hand width were recorded. The EFOV-US method obtained precise fascicle length measurements [mean ± SD] for the FPL (6.2 ± 0.5 cm), APB (5.1 ± 0.3 cm), and ECU (4.0 ± 0.4 cm). However, our EFOV-US measurements were consistently different (p < 0.05) than prior cadaveric data, highlighting the need to better understand differences between in vivo and ex vivo fascicle length measurements. Fascicle length was significantly related to only hand length (r2 = 0.56, p = 0.03) for APB, highlighting that anthropometric scaling may not accurately estimate thumb muscle length. As the first study to apply EFOV-US to measure thumb muscle fascicle lengths, this study expands the utility of this imaging technology within the upper limb.

Transfer-Tattoo-Like Cell-Sheet Delivery Induced by Interfacial Cell Migration.

A direct transfer of a cell sheet from a culture surface to a target tissue is introduced. Commercially available, flexible parylene is used as the culture surface, and it is proposed that the UV-treated parylene offers adequate and intermediate levels of cell adhesiveness for both the stable cell attachment during culture and for the efficient cell transfer to a target surface. The versatility of this cell-transfer process is demonstrated with various cell types, including MRC-5, HDFn, HULEC-5a, MC3T3-E1, A549, C2C12 cells, and MDCK-II cells. The novel cell-sheet engineering is based on a mechanism of interfacial cell migration between two surfaces with different adhesion preferences. Monitoring of cytoskeletal dynamics and drug treatments during the cell-transfer process reveals that the interfacial cell migration occurs by utilizing the existing transmembrane proteins on the cell surface to bind to the targeted surface. The re-establishment and reversal of cell polarity after the transfer process are also identified. Its unique capabilities of 3D multilayer stacking, freeform design, and curved surface application are demonstrated. Finally, the therapeutic potential of the cell-sheet delivery system is demonstrated by applying it to cutaneous wound healing and skin-tissue regeneration in mice models.

Linear relationship between electromyography and shear wave elastography measurements persists in deep muscles of the upper extremity.

Recent works have demonstrated a linear relationship between muscle activation and shear modulus in various superficial muscles. As such, it may be possible to overcome limitations of traditional electromyography (EMG) methods by assessing activation using shear wave elastography. However, the relationship has not been wholly validated in deep muscles. This study measured the association between squared shear wave velocity, which is related to shear modulus, and activation within superficial and deep muscles. This relationship was also compared between surface and intramuscular EMG electrodes. We simultaneously recorded EMG and shear wave velocity in one deep (brachialis) and one superficial (brachioradialis) muscle in ten healthy individuals during isometric elbow flexion across a wide range of contraction intensities. Muscle activation and squared shear wave velocity demonstrated good reliability (ICC > 0.75) and showed a linear relationship (P < 0.05) for all muscle/EMG electrode type combinations (study conditions) after down-sampling. Study condition was not a significant within-subject factor to the slope or intercept of the relationship (P > 0.05). This work demonstrates that activation of both superficial and deep muscles can be assessed noninvasively using ultrasound shear wave elastography and is a critical step toward demonstrating elastography's utility as an alternative to EMG.

In Vitro Models for Studying Respiratory Host-Pathogen Interactions.

Respiratory diseases and lower respiratory tract infections are among the leading cause of death worldwide and, especially given the recent severe acute respiratory syndrome coronavirus-2 pandemic, are of high and prevalent socio-economic importance. In vitro models, which accurately represent the lung microenvironment, are of increasing significance given the ethical concerns around animal work and the lack of translation to human disease, as well as the lengthy time to market and the attrition rates associated with clinical trials. This review gives an overview of the biological and immunological components involved in regulating the respiratory epithelium system in health, disease, and infection. The evolution from 2D to 3D cell biology and to more advanced technological integrated models for studying respiratory host-pathogen interactions are reviewed and provide a reference point for understanding the in vitro modeling requirements. Finally, the current limitations and future perspectives for advancing this field are presented.

Can single-use bronchoscopes help prevent nosocomial COVID-19 infections?

Introduction: The reduction of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission has been achieved through numerous public health initiatives worldwide. In the hospital environment, certain high-risk procedures have the potential to cause transmission of the virus to health-care workers and nosocomial transmission to patients through different mechanisms including the generation of aerosols and fomite formation via contamination of medical devices.Areas covered: Aerosol-generating procedures such as bronchoscopy are considered high risk for SARS-CoV-2 transmission. As a result, single-use devices should be used where possible and changing to single-use flexible bronchoscopes has been advised by respiratory societies internationally. In this paper, we outline the rationale for this advice and have analyzed the evidence relating to the reduction in SARS-CoV-2 transmission arising from a switch to these single-use devices and the potential impact that this switch may have on the quality of pulmonology services.Expert opinion: In this paper, we outline the rationale for this advice and have analyzed the evidence relating to the reduction in SARS-CoV-2 transmission arising from a switch to these single-use devices and the potential impact that this switch may have on the quality of pulmonology services.

Building Scaffolds for Tubular Tissue Engineering.

Hollow organs and tissue systems drive various functions in the body. Many of these hollow or tubular systems, such as vasculature, the intestines, and the trachea, are common targets for tissue engineering, given their relevance to numerous diseases and body functions. As the field of tissue engineering has developed, numerous benchtop models have been produced as platforms for basic science and drug testing. Production of tubular scaffolds for different tissue engineering applications possesses many commonalities, such as the necessity for producing an intact tubular opening and for formation of semi-permeable epithelia or endothelia. As such, the field has converged on a series of manufacturing techniques for producing these structures. In this review, we discuss some of the most common tissue engineered applications within the context of tubular tissues and the methods by which these structures can be produced. We provide an overview of the general structure and anatomy for these tissue systems along with a series of general design criteria for tubular tissue engineering. We categorize methods for manufacturing tubular scaffolds as follows: casting, electrospinning, rolling, 3D printing, and decellularization. We discuss state-of-the-art models within the context of vascular, intestinal, and tracheal tissue engineering. Finally, we conclude with a discussion of the future for these fields.

Single-Use (Disposable) Flexible Bronchoscopes: The Future of Bronchoscopy?

The coronavirus disease (COVID-19) pandemic has highlighted the importance of reducing occupational exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The reprocessing procedure for reusable flexible bronchoscopes (RFBs) involves multiple episodes of handling of equipment that has been used during an aerosol-generating procedure and thus is a potential source of transmission. Single-use flexible bronchoscopes (SUFBs) eliminate this source. Additionally, RFBs pose a risk of nosocomial infection transmission between patients with the identification of human proteins, deoxyribonucleic acid (DNA) and pathogenic organisms on fully reprocessed bronchoscopes despite full adherence to the guidelines. Bronchoscopy units have been hugely impacted by the pandemic with restructuring of pre- and post-operative areas, altered patient protocols and the reassessment of air exchange and cleaning procedures. SUFBs can be incorporated into these protocols as a means of improving occupational safety. Most studies on the efficacy of SUFBs have occurred in an anaesthetic setting so it remains to be seen whether they will perform to an acceptable standard in complex respiratory procedures such as transbronchial biopsies and cryotherapy. Here, we outline their potential uses in a respiratory setting, both during and after the current pandemic.

Evidence for Multiple Classes of Sexually-Violent College Men.

OBJECTIVE: Research on college sexual violence perpetration suggests there are multiple groups of male perpetrators. It is important to understand the distinctions between perpetrator subgroups to determine appropriate prevention strategies, as multiple strategies may be necessary to address multiple types of perpetrators. However, previous studies on subgroups of sexually-violent college men have relied on theoretically based distinctions, and there is currently no consensus on how to best classify perpetrators based on their sexually violent behaviors. The purpose of the current study was to take a data-driven approach to identifying subgroups of sexually-violent college men to help clarify: 1) the number and size of cohesive subgroups of sexually-violent college men, and 2) the types of behaviors that characterize each group. METHODS: 1,982 college men across five universities in the U.S. self-reported their past sexually-violent behaviors, using the Sexual Experiences Survey (SES; Koss et al., 2007). RESULTS: Latent class analysis uncovered evidence for three groups: (1) a group unlikely to perpetrate any SV (88.6%); (2) a group likely to perpetrate SV using coercive tactics (verbal coercion or victim intoxication), but unlikely to use physical force (9.8%); and (3) a group likely to perpetrate the full range of SV (1.5%). Although the coercive tactics group was composed of men unlikely to use forceful tactics, it included the majority who attempted or completed rape based on legal definitions. CONCLUSIONS: Our findings suggest that there are multiple, distinct perpetrator subgroups and signal the need for multiple prevention approaches, including approaches that address campus social norms.

Self-assembled photoactive polyelectrolyte/perylene-diimide composites.

A new class of polyelectrolyte-surfactant (PE-surf) composites having potential applications as thin film organic semiconductors is introduced. These materials are comprised of cationic asymmetrically substituted perylene diimides and oppositely charged poly(acrylate) polyanions. Thin films of the composite materials are prepared by mixing and drop casting aqueous solutions of the two precursors onto appropriate substrates. The resulting materials yield photovoltages of >140 mV for approximately equal to 0.6 W/cm(2) illumination intensities, when incorporated in p-n heterojunction devices. Solution-phase spectra obtained from the PE-surf complexes exhibit excimer-like emission and evidence for formation of weakly coupled aggregates in the ground state. Wide-angle X-ray scattering data show the composite films are locally amorphous, while small-angle X-ray data are consistent with a mixture of polymorphic structures that incorporate planar PE-surf bilayers of 3.9-nm repeat distances. Images obtained by conventional far-field light microscopy and multiphoton-excited fluorescence microscopy (MPEFM) indicate that the films are heterogeneous, incorporating submicrometer sized clusters dispersed among much thinner film regions that also incorporate dye. Polarization-dependent MPEFM studies prove the clusters are semiorganized, yielding order parameters (s and P(4)) of 0.09 and 0.01 for in-plane alignment of the chromophores, consistent with a relatively high degree of disorder.