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Background: Psychosocial factors have been informally associated with Chronic Spontaneous Urticaria (CSU); however, the relationship between psychosocial factors and CSU remains relatively unexplored in the scientific literature., Objective: This review aims to provide an evaluation of peer reviewed studies exploring psychosocial factors and CSU., Methods: A systematic search was performed over four databases identifying studies exploring psychosocial factors in relation to CSU published between the years 1995 and 2022., Results: Eighteen studies were included for narrative analysis, and 33 psychosocial factors were identified. These were split into two subgroups: psychosocial factors that were associated with CSU symptoms aggravation/onset (n = 20), and psychosocial factors expected to be impacted by CSU symptoms (n = 13)., Conclusion: This review has highlighted a need for more research and interventions to support individuals with psychosocial factors involved in CSU., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Positive Psychology Interventions (PPI) are widely applied to improving wellbeing and helping individuals flourish. At the same time, Lifestyle Medicine (LM) offers an opportunity to boost PPI and psychological research, by expanding its capacity beyond psychology, to include the body and social environment. However, little is known about the relationship between LM and positive psychology flourishing models. Flourishing is as a stage of optimal human functioning that goes beyond moderate wellbeing. The objective of this cross-sectional study was to, (1) identify which of the six LM pillars (sleep, physical exercise, eating well, alcohol intake, social engagement, stress management) best-predicted flourishing; (2) examine the relationship between the number of LM pillars used by individuals and flourishing; and (3) determine the odds of using LM pillars by flourishers. A total of 1,112 participants, mostly female professionals (73%), aged 40-59 (77%), based in Ireland, completed an online survey. Regression analysis showed that all six LM pillars predicted flourishing as measured by the PERMA Profiler (including the Physical Health component) and the Mental Health Continuum (MHC). Moreover, the chi-square and odds ratio analysis showed that those who flourished were three times more likely to use 3-6 LM pillars than those who were moderately well; and nine times more likely than languishers. The results are discussed in the context of their contribution to enhancing the population's health and wellbeing., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Burke and Dunne.)

Background: Chronic spontaneous urticaria is a common disorder that is poorly understood and frequently misdiagnosed. Psychological difficulties are a significant factor in dermatological diseases and may also aggravate symptom burden. Mind-body interventions are used as a complementary approach to alleviate symptoms in chronic diseases and may represent a valuable non-pharmacological approach in CSU., Methods: We sought to develop and evaluate the feasibility of an 8-week attention-based training (ABT) programme, coupled to biofeedback technology for CSU. Through convergent interviews, we gathered information from individuals with urticaria about possible links between stress, mood and skin symptoms. Using these data, we recruited 12 participants to engage in an amended ABT programme for patients with CSU, comprising eight 90-min sessions held weekly. Participants completed psychometric measures and measures of urticaria symptomatology as assessed by the urticaria control test, prior to and after the intervention. Adherence to ABT practice was measured using individual inner balance devices which tracked heart rate variability. We completed qualitative interviews after the intervention to obtain feedback on participant experience of the programme., Results: Participants with CSU described how their psychological wellbeing can be linked to skin symptoms, poor sleep and difficulty concentrating. An amended ABT programme was found to be an acceptable component of care in the management of CSU. Retention of participants in the programme was challenging with 33% participants dropping out of the programme. For those who did complete the programme, three participants exceeded weekly practice at week 8. A decrease in severity of urticaria symptomatology as measured by the urticaria control test was observed upon completion of the intervention. The most commonly cited barrier to implementation of the programme was the time commitment required., Conclusions: Integrating an ABT programme into routine clinical care for CSU patients is feasible and was deemed acceptable and valuable by individuals who took part. Further formal evaluation of ABT for CSU including the analysis of biochemical parameters is required to determine its role in the management of this distressing condition., Trial Registration: This trial is registered with ISRCTN with study ID ISRCTN13672947 . Registration took place on 22/09/2020 (retrospectively registered).

Tuberculosis (TB) is the leading infectious killer in the world. Mycobacterium tuberculosis (Mtb), the bacteria that causes the disease, is phagocytosed by alveolar macrophages (AM) and infiltrating monocyte-derived macrophages (MDM) in the lung. Infected macrophages then upregulate effector functions through epigenetic modifications to make DNA accessible for transcription. The metabolic switch to glycolysis and the production of proinflammatory cytokines are key effector functions, governed by epigenetic changes, that are integral to the ability of the macrophage to mount an effective immune response against Mtb. We hypothesised that suberanilohydroxamic acid (SAHA), an FDA-approved histone deacetylase inhibitor (HDACi), can modulate epigenetic changes upstream of the metabolic switch and support immune responses during Mtb infection. The rate of glycolysis in human MDM, infected with Mtb and treated with SAHA, was tracked in real time on the Seahorse XFe24 Analyzer. SAHA promoted glycolysis early in the response to Mtb. This was associated with significantly increased production of IL-1β and significantly reduced IL-10 in human MDM and AM. Since innate immune function directs downstream adaptive immune responses, we used SAHA-treated Mtb-infected AM or MDM in a co-culture system to stimulate T cells. Mtb-infected macrophages that had previously been treated with SAHA promoted IFN-γ, GM-CSF, and TNF co-production in responding T helper cells but did not affect cytotoxic T cells. These results indicate that SAHA promoted the early switch to glycolysis, increased IL-1β, and reduced IL-10 production in human macrophages infected with Mtb. Moreover, the elevated proinflammatory function of SAHA-treated macrophages resulted in enhanced T helper cell cytokine polyfunctionality. These data provide an in vitro proof-of-concept for the use of HDACi to modulate human immunometabolic processes in macrophages to promote innate and subsequent adaptive proinflammatory responses., (Copyright © 2020 Cox, Coleman, Gogan, Phelan, Ó Maoldomhnaigh, Dunne, Basdeo and Keane.)

Vitamin A deficiency strongly predicts the risk of developing tuberculosis (TB) in individuals exposed to Mycobacterium tuberculosis (Mtb). The burden of antibiotic-resistant TB is increasing globally; therefore, there is an urgent need to develop host-directed adjunctive therapies to treat TB. Alveolar macrophages, the niche cell for Mtb, metabolize vitamin A to all-trans retinoic acid (atRA), which influences host immune responses. We sought to determine the mechanistic effects of atRA on the host immune response to intracellular bacterial infection in primary human and murine macrophages. In this study, atRA promoted autophagy resulting in a reduced bacterial burden in human macrophages infected with Mtb and Bordetella pertussis, but not bacillus Calmette-Guérin (BCG). Autophagy is induced by cytosolic sensing of double-stranded DNA via the STING/TBK1/IRF3 axis; however, BCG is known to evade cytosolic DNA sensors. atRA enhanced colocalization of Mtb, but not BCG, with autophagic vesicles and acidified lysosomes. This enhancement was inhibited by blocking TBK1. Our data indicate that atRA augments the autophagy of intracellular bacteria that trigger cytosolic DNA-sensing pathways but does not affect bacteria that evade these sensors. The finding that BCG evades the beneficial effects of atRA has implications for vaccine design and global health nutritional supplementation strategies. The ability of atRA to promote autophagy and aid bacterial clearance of Mtb and B. pertussis highlights a potential role for atRA as a host-directed adjunctive therapy.

Objectives: Rates of burnout and stress in healthcare practitioners are steadily increasing. Emergency department (ED) staff are particularly susceptible to such poor outcomes. Mantra meditation (MM) may contribute to increased well-being. The primary aim of this study was to obtain indepth qualitative feedback on ED staff's experience of a MM programme. A secondary objective was to harness staff's perception of the ED working environment., Design: Qualitative study., Setting: ED in St James' Hospital, Dublin, Ireland., Participants: Doctors, nurses, allied health professionals and administrative staff (n=10, eight women, mean age 35.6 years) working in the ED who attended a MM programme., Methods: Semistructured interviews were conducted by a trained independent researcher. Interviews were transcribed and thematically analysed., Results: Five main themes and six subthemes were identified: work pressure and perceived stress; perceived benefits of meditation (with subthemes of increased attention/awareness, improved emotion regulation and new coping mechanisms, relaxation and sleep quality); conflicting attitudes to practice; barriers to meditation practice (with subthemes of schedule, length of practice and individual differences); and facilitators to practice., Conclusion: ED staff in this study described the demands of their work and voiced a need for a workplace well-being programme. Our findings suggest that MM might represent a viable tool to develop attention and awareness, improve emotion regulation and improve their capacity to cope with stress, which may impact their workplace well-being, wider health service, patient safety and quality of care. Support from the organisation is considered to be integral to embedding of a workplace well-being programme, such as the practice of meditation into their daily lives., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Human γδ T cells expressing the Vδ1 T cell receptor (TCR) recognize self and microbial antigens and stress-inducible molecules in a major histocompatibility complex-unrestricted manner and are an important source of innate interleukin (IL)-17. Vδ1 T cells are expanded in the circulation and intestines of patients with human immunodeficiency virus (HIV) infection. In this study, we show that patients with HIV have elevated frequencies, but not absolute numbers, of circulating Vδ1 T cells compared to control subjects. This increase was most striking in the patients with Candida albicans co-infection. Using flow cytometry and confocal microscopy, we identify two populations of Vδ1 T cells, based on low and high expression of the ε chain of the CD3 protein complex responsible for transducing TCR-mediated signals (denoted CD3ε lo and CD3ε hi Vδ1 T cells). Both Vδ1 T cell populations expressed the CD3 ζ-chain, also used for TCR signaling. Using lines of Vδ1 T cells generated from healthy donors, we show that CD3ε can be transiently downregulated by activation but that its expression is restored over time in culture in the presence of exogenous IL-2. Compared to CD3ε hi Vδ1 T cells, CD3ε lo Vδ1 T cells more frequently expressed terminally differentiated phenotypes and the negative regulator of T cell activation, programmed death-1 (PD-1), but not lymphocyte-activation gene 3, and upon stimulation in vitro , only the CD3ε hi subset of Vδ1 T cells, produced IL-17. Thus, while HIV can infect and kill IL-17-producing CD4 + T cells, Vδ1 T cells are another source of IL-17, but many of them exist in a state of exhaustion, mediated either by the induction of PD-1 or by downregulation of CD3ε expression.

A considerable proportion of patients with chronic obstructive pulmonary disease (COPD) entering pulmonary rehabilitation (PR) report psychological distress, which is often accompanied by poor physical health status. Mindfulness-based cognitive therapy (MBCT) has been shown to improve psychological and physical outcomes in other chronic diseases. We therefore evaluated the efficacy of MBCT as an add-on to a standard PR programme in COPD.COPD patients eligible for PR were cluster randomised to receive either an 8-week, group-based MBCT programme as an add-on to an 8-week PR programme (n=39), or PR alone (n=45). The primary outcomes of psychological distress and physical health status impairment were measured with the Hospital Anxiety and Depression Scale (HADS) and the COPD Assessment Test (CAT) before randomisation (T1), mid- (T2) and post-intervention (T3), and at 3 (T4) and 6 (T5) months' follow-up .A statistically significant time×arm effect was found for the HADS (Cohen's d =0.62, 95% CIs ( d )=0.18-1.06, p=0.010). The treatment effect on the CAT failed to reach statistical significance ( d =0.42, 95% CIs ( d )=-0.06-0.90, p=0.061).MBCT showed a statistically significant and durable effect on psychological distress, indicating that MBCT may be an efficacious add-on to standard PR programmes in COPD., Competing Interests: Conflict of interest: Disclosures can be found alongside this article at erj.ersjournals.com, (Copyright ©ERS 2018.)

Alveolar macrophages (AMs) from mice and humans have long been known to contribute to maintaining tolerance in the lung. Studies have shown that AMs can induce anergy in CD4(+) T cells. Nitric oxide, prostaglandins, and leukotrienes have been implicated in AM-mediated tolerance. However, it remains unclear what effect, if any, AMs exert on FoxP3 induction in CD4(+) T cells from mice and humans, and whether or not other immunomodulators might play a role. AMs were isolated from bronchoalveolar lavage (BAL) fluid from either mice or humans, and cocultured with enriched naive CD4(+)FoxP3(-) T cells. We show here for the first time that AMs and AM-conditioned media (AM-CM) from mice and humans induced FoxP3 expression in naive CD4(+) T cells in vitro, an outcome that was reversed in part either by inhibiting retinoic acid (RA) binding to its receptor (RAR), or by blocking transforming growth factor (TGF)-β₁ signaling. A nasal administration of the RAR antagonist reduced the frequencies of CD4(+)FoxP3(+) T cells in the lungs of mice after aerosol challenge with Bordetella pertussis. In addition, we found that the intranasal vaccination of mice with ovalbumin (OVA) protein in conjunction with an RAR inhibitor led to a significant increase in OVA-specific serum IgE. Our findings suggest that AMs can mediate tolerance in the lungs of mice and humans via RA and TGF-β₁. These data may have implications in the development of nasal vaccines in the future.

For the busy clinician, educator, or manager, it is becoming an increasing challenge to filter the literature to what is relevant to one's practice and then update one's practice based on the current evidence. The purpose of this paper is to review the recent literature related to long-term oxygen therapy, pulmonary rehabilitation, airway management, acute lung injury and acute respiratory distress syndrome, respiratory care education, and respiratory care management. These topics were chosen and reviewed in a manner that is most likely to have interest to the readers of Respiratory Care.

Naturally occurring CD4(+)CD25(hi)Foxp3(+) Tregs (nTregs) are highly proliferative in blood. However, the kinetics of their accumulation and proliferation during a localized antigen-specific T cell response is currently unknown. To explore this, we used a human experimental system whereby tuberculin purified protein derivative (PPD) was injected into the skin and the local T cell response analyzed over time. The numbers of both CD4(+)Foxp3(-) (memory) and CD4(+)Foxp3(+) (putative nTreg) T cells increased in parallel, with the 2 populations proliferating at the same relative rate. In contrast to CD4(+)Foxp3(-) T cell populations, skin CD4(+)Foxp3(+) T cells expressed typical Treg markers (i.e., they were CD25(hi), CD127(lo), CD27(+), and CD39(+)) and did not synthesize IL-2 or IFN-gamma after restimulation in vitro, indicating that they were not recently activated effector cells. To determine whether CD4(+)Foxp3(+) T cells in skin could be induced from memory CD4(+) T cells, we expanded skin-derived memory CD4(+) T cells in vitro and anergized them. These cells expressed high levels of CD25 and Foxp3 and suppressed the proliferation of skin-derived responder T cells to PPD challenge. Our data therefore demonstrate that memory and CD4(+) Treg populations are regulated in tandem during a secondary antigenic response. Furthermore, it is possible to isolate effector CD4(+) T cell populations from inflamed tissues and manipulate them to generate Tregs with the potential to suppress inflammatory responses.

Background: Filamentous haemagglutinin (FHA) of Bordetella pertussis subverts host immune responses by inhibiting interleukin (IL)12 and enhancing IL10 production by macrophages and dendritic cells, and promoting the induction of regulatory T cells., Hypothesis: Injection of FHA would ameliorate disease in a T cell-dependent model of colitis via the induction of anti-inflammatory cytokines and regulatory T cells., Methods: Colitis was induced by injection of CD4CD45RB(high) naive T cells into severe combined immunodeficient (SCID) mice. Mice were treated with four subcutaneous injections of FHA or buffer alone., Results: Parenteral injection of FHA stimulated IL10 and/or transforming growth factor beta production in local and mesenteric lymph nodes and Peyer's patches of mice 2-6 h after administration. Compared with phosphate-buffered saline-treated mice, FHA-treated SCID mice had significantly (p<0.01) less weight loss, lower colon weight, less colon shrinkage and reduced inflammatory lesions. The therapeutic effect of FHA was associated with enhanced IL10 and reduced type 1 and type 2 T helper cytokine production by spleen cells. Finally, FHA also attenuated the symptoms of colitis in SCID mice transferred with CD4CD45RB(high) T cells from IL10-deficient mice., Conclusions: Our finding shows that FHA suppresses type 1 T helper and pro-inflammatory cytokines, and ameliorates disease activity in a chronic T cell-dependent model of colitis, an effect that was not dependent on IL10 production by T cells, but was associated with induction of anti-inflammatory cytokines in vivo. Having already been used as a pertussis vaccine component in children, FHA is a promising candidate for clinical testing in patients with Crohn's disease.

After acute infection Epstein-Barr virus (EBV)-specific memory CD8+ T cells exit cell cycle, and a proportion of these antigen-experienced cells re-express CD45RA (CD45 which predominantly express exon A). However, the signals involved are not known. We investigated the roles of interleukin 15 (IL-15) and interferon-alpha/beta (IFN-I) in these processes, since these mediators have a crucial but undefined role in the maintenance of CD8+ T-cell memory. We show that IFN-I (but not IL-15) allows activated EBV-specific CD8+ T cells to leave cell cycle without entering apoptosis. This was associated with up-regulation of the cyclin inhibitor p27, but not of CD45RA. In contrast, IL-15 (but not IFN-I) induced "homeostatic" proliferation and CD45RA re-expression by these cells in vitro. Different signals, therefore, induce quiescence and CD45RA re-expression in activated EBV-specific CD8+ T cells. After T-cell receptor (TCR) activation freshly isolated CD45RA+ antigen-experienced CD8+ T cells show poor proliferative activity but are highly cytotoxic and secrete IFN-gamma efficiently. This suggests functional reprogramming toward effector function but away from proliferation. The induction of quiescence and the generation of proliferation-independent effector CD8+ T cells that re-express CD45RA may minimize the impact of replicative senescence in virus-specific populations that would otherwise occur during decades of persistent infection.

During acute infection, latent and lytic Epstein-Barr virus (EBV) epitope-specific CD8(+) T cells have a CD45RO(+) CD45RA(-) phenotype. However, after resolution of the infection, a large proportion of these cells, particularly those specific for lytic viral epitopes, re-express the CD45RA molecule. The role of CD8(+) CD45RA(+) T cells in ongoing immunity to EBV and other viruses is unknown. We now demonstrate that, relative to their CD45RO(+) counterparts, the EBV-specific CD8(+) T cells that revert to CD45RA expression after acute infectious mononucleosis are not in cell cycle, have longer telomeres, and are more resistant to apoptosis partly because of increased Bcl-2 expression. However, the EBV-specific CD8(+) CD45RA(+) T cells have shorter telomeres than the total CD8(+) CD45RA(+) T-cell pool and predominantly express low levels of the CCR7 chemokine receptor, indicating that they are not naive cells. In addition, EBV-specific CD8(+) CD45RA(+) T cells can be induced to proliferate and exhibit potent cytotoxic activity against target cells loaded with specific peptide. Our results strongly suggest, therefore, that EBV-specific CD8(+) CD45RA(+) T cells represent a stabilized virus-specific memory pool and not terminally differentiated effector cells. The identification of mechanisms that enable stable virus-specific CD8(+) T cells to persist after acute infection may lead to the enhancement of antiviral immunity in immunocompromised and elderly persons.