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In lung transplant recipients, long-term graft survival relies on the control of inflammation and tissue remodeling to maintain graft functionality and avoid chronic lung allograft dysfunction. Although advances in clinical practice have improved transplant success, the mechanisms by which the balance between inflammation and remodeling is maintained are largely unknown. To assess whether host-microbe interactions in the transplanted lung determine the immunologic tone of the airways, and consequently could impact graft survival. Microbiota DNA and host total RNA were isolated from 203 bronchoalveolar lavages obtained from 112 patients post-lung transplantation. Microbiota composition was determined using 16S ribosomal RNA analysis, and expression of a set of genes involved in prototypic macrophage functions was quantified using real-time quantitative polymerase chain reaction. We show that the characteristics of the pulmonary microbiota aligned with distinct innate cell gene expression profiles. Although a nonpolarized activation was associated with bacterial communities consisting of a balance between proinflammatory (e.g., Staphylococcus and Pseudomonas) and low stimulatory (e.g., Prevotella and Streptococcus) bacteria, \"inflammatory\" and \"remodeling\" profiles were linked to bacterial dysbiosis. Mechanistic assays provided direct evidence that bacterial dysbiosis could lead to inflammatory or remodeling profiles in macrophages, whereas a balanced microbial community maintained homeostasis. The crosstalk between bacterial communities and innate immune cells potentially determines the function of the transplanted lung offering novel pathways for intervention strategies.

Background Physical inactivity and sedentary behaviours (PiA/SED) are among the major modifiable risk factors for chronic diseases. Behaviour change models for PA can shape personalised interventions leading to sustainable lifestyle changes. We hypothesise that screening for PiA/SED by a general practitioner, followed by a personalised intervention by a physiotherapist, could reduce PiA/SED in inactive adults. Methods We designed a prospective, multicentre, cluster-randomised, controlled, step-wedge study. Adult patients without chronic illnesses will be recruited in 8 multi-professional health centres. They will receive educational content on PiA/SED. During the intervention periods, patients will see a physiotherapist for a functional assessment, and an intervention aimed at improving PiA/SED using a serious game. Two follow-up appointments at months 2 and 4 (M2-4) are planned to maintain patient motivation. At M6, a 7-day actimetry will be performed, and at M6-12, questionnaires and semi-structured interviews will close the study. Two primary endpoints will be analysed using a pre-specified hierarchical sequential analysis: the proportion of patients changing PiA/SED at M6. Secondary objectives include: 1-describing changes in PiA/SED at M6 and M12, 2-exploring the link between patient characteristics and changes in PiA/SED, 3-describing participants’ quality of motivation, satisfaction of basic psychological needs, feelings of self-efficacy, perceived levels of vitality and energy, and self-esteem, 4-describing the strategies, barriers and facilitators of behavioural changes, 5-studying the correlation between questionnaires measuring physical activity and actimetry, 6-identifying the perceived barriers and facilitators to implement this care pathway. Assuming that 10% of patients in the control period will improve their PA and that the intervention will increase it by 20%, 160 patients provides 82% power to observe a significant difference. Discussion This design will harmonise the skills of all professionals in the field of motivational support for PiA/SED and providing information about the risks associated with PiA/SED. Patients in the intervention group will also receive individual support for behaviour changes related to PiA/SED. Considering public health, this study will contribute to increase primary prevention by healthcare professionals. Finally, this study will assess the effectiveness, adherence, satisfaction of the stakeholders involved in this pathway allowing to consider its implementation in routine primary care. SPIRIT 2025 checklist of items see supplement files. Trial registration ClinicalTrials n° NCT06678906, https://clinconnect.io/trials/NCT06678906#about-company-tab , first registration October 14, 2024, Trial updated February 05, 2025.

The ageing population in Europe, particularly in rural areas, creates new health challenges, including patients with multiple comorbidities and difficult access to care. Advanced Practice Nurses (APNs) could play a key role in improving access and care for frail older patients in France's rural areas, although how to achieve this remains unclear. This study aimed to identify the healthcare needs of frail patients living at home in rural areas and those of their healthcare providers to assess the potential role of APNs in addressing these needs. This interpretive descriptive qualitative study was conducted from June to September 2023, using focus groups (FGs). Three FGs with 20 participants, including healthcare providers and frail older people, were conducted in two French rural areas. Data were analysed using thematic analyse to identify key needs and potential APN contributions. The healthcare needs identified were: improving access to care, maintaining human interactions, and providing coordinated, preventive care. Participants emphasised the importance of interprofessional collaboration and the central role of APNs, whose expanded skillset enables them to coordinate care with caregivers and professionals. However, challenges remain, including a lack of understanding of the APN's skills and concerns about their integration within the care team. APNs could support access to person-centred, coordinated home care in rural areas by acting as key references for patients, caregivers, and teams. However, limited awareness of their role and concerns from other professionals remain barriers to their integration.

Background Targeted lung denervation (TLD) is a novel bronchoscopic therapy that disrupts parasympathetic pulmonary nerve input to the lung reducing clinical consequences of cholinergic hyperactivity. The AIRFLOW-1 study assessed safety and TLD dose in patients with moderate-to-severe, symptomatic COPD. This analysis evaluated the long-term impact of TLD on COPD exacerbations, pulmonary function, and quality of life over 3 years of follow up. Methods TLD was performed in a prospective, energy-level randomized (29 W vs 32 W power), multicenter study (NCT02058459). Additional patients were enrolled in an open label confirmation phase to confirm improved gastrointestinal safety after procedural modifications. Durability of TLD was evaluated at 1, 2, and 3 years post-treatment and assessed through analysis of COPD exacerbations, pulmonary lung function, and quality of life. Results Three-year follow-up data were available for 73.9% of patients (n = 34). The annualized rate of moderate to severe COPD exacerbations remained stable over the duration of the study. Lung function (FEV 1 , FVC, RV, and TLC) and quality of life (SGRQ-C and CAT) remained stable over 3 years of follow-up. No new gastrointestinal adverse events and no unexpected serious adverse events were observed. Conclusion TLD in COPD patients demonstrated a positive safety profile out to 3 years, with no late-onset serious adverse events related to denervation therapy. Clinical stability in lung function, quality of life, and exacerbations were observed in TLD treated patients over 3 years of follow up.

The prevalence of asthma has nearly doubled over the last decades. Twentieth century changes in environmental and lifestyle factors, including changes in dietary habits, physical activity and the obesity epidemic, have been suggested to play a role in the increase of asthma prevalence and uncontrolled asthma worldwide. A large body of evidence has suggested that obesity is a likely risk factor for asthma, but mechanisms are still unclear. Regarding diet and physical activity, the literature remains inconclusive. Although the investigation of nutritional factors as a whole (i.e., the “diet, physical activity and body composition” triad) is highly relevant in terms of understanding underlying mechanisms, as well as designing effective public health interventions, their combined effects across the life course has not received a lot of attention. In this review, we discuss the state of the art regarding the role of nutritional factors in asthma, for each window of exposure. We focus on the methodological and conceptual challenges encountered in the investigation of the complex time-dependent interrelations between nutritional factors and asthma and its control, and their interaction with other determinants of asthma. Lastly, we provide guidance on how to address these challenges, as well as suggestions for future research.

Rationale: Targeted lung denervation (TLD) is a novel bronchoscopic treatment for the disruption of parasympathetic innervation of the lungs. Objectives: To assess safety, feasibility, and dosing of TLD in patients with moderate to severe COPD using a novel device design. Methods: Thirty patients with COPD (forced expiratory volume in 1 s 30–60%) were 1:1 randomized in a double-blinded fashion to receive TLD with either 29 or 32 W. Primary endpoint was the rate of TLD-associated adverse airway effects that required treatment through 3 months. Assessments of lung function, quality of life, dyspnea, and exercise capacity were performed at baseline and 1-year follow-up. An additional 16 patients were enrolled in an open-label confirmation phase study to confirm safety improvements after procedural enhancements following gastrointestinal adverse events during the randomized part of the trial. Results: Procedural success, defined as device success without an in-hospital serious adverse event, was 96.7% (29/30). The rate of TLD-associated adverse airway effects requiring intervention was 3/15 in the 32 W versus 1/15 in the 29 W group, p = 0.6. Five patients early in the randomized phase experienced serious gastric events. The study was stopped and procedural changes made that reduced both gastrointestinal and airway events in the subsequent phase of the randomized trial and follow-up confirmation study. Improvements in lung function and quality of life were observed compared to baseline values for both doses but were not statistically different. Conclusions: The results demonstrate acceptable safety and feasibility of TLD in patients with COPD, with improvements in adverse event rates after procedural enhancements.

IntroductionObstructive sleep apnoea syndrome (OSAS) is one of the most common chronic diseases. It may be associated with symptoms of excessive daytime sleepiness and neurocognitive and cardiovascular complications. First line therapy for OSAS involves home continuous positive airway pressure (CPAP), however, nearly half of patients do not adhere with this treatment over the long term. Cognitive-behavioural interventions that include health professionals and patient and public involvement are increasingly advocated in the fields of education and research. We hypothesise that a peer-driven intervention could help patients with OSAS to resume CPAP use after discontinuation.Methods and analysisWe have designed a prospective, multicentre randomised, controlled trial that will be coconducted by health professionals, a home provider of CPAP and patients as experts or peers or participants. The primary aim is to evaluate the impact of a 6-month, peer-driven intervention to promote the resumption of CPAP after discontinuation. We anticipate that 20% of patients in the intervention group will reuse CPAP as compared with 6% in control group, thus, 104 patients must be included in each group. The secondary aims are (1) to evaluate the impact of the peer-driven intervention on adherence to CPAP compared with the control group (mean adherence and percentage of nights with at least 4 hours’ use/night for 70% of nights); (2) to determine factors associated with resumption of CPAP; (3) to assess patient satisfaction with the peer-driven intervention at 6 months; (4) to evaluate the feasibility and the execution of the peer-driven intervention and peer satisfaction. Adult outpatients with an established diagnosis of severe OSA (Apnoea-Hypopnoea Index >30 events/hour) that have stopped using CPAP within 4–12 months after initiation will be recruited. The peers who will perform the intervention will be patients with OSAS treated with CPAP with good adherence (at least 4 hours/night, 70% of nights) and trained in motivational enhancement and cognitive-behavioural therapies. Trained peers will conduct three interviews within 6 months with participants.Ethics and disseminationEthical approval has been obtained from the French Regional Ethics Committee CPP Ouest II-Angers, (IRB 21.02.25.68606 (2021/2025)). All participants will sign written informed consent. The results will be presented at conferences and published in peer-reviewed journals as well as public media.Trial registration number NCT04538274

Pulmonary hypertension is a co-morbidity, which strongly participates in morbi-mortality in patients with chronic obstructive pulmonary disease (COPD). Recent findings showed that bromodomain-containing proteins, in charge of reading histone acetylation, could be involved in pulmonary arterial hypertension. Our aim was to study the effect of I-BET151, an inhibitor of bromodomain and extra-terminal domain (BET), on the right ventricle hypertrophy and pulmonary hypertension, induced by a combination of chronic hypoxia and pulmonary inflammation, as the two main stimuli encountered in COPD. Adult Wistar male rats, exposed to chronic hypoxia plus pulmonary inflammation (CHPI), showed a significant right ventricle hypertrophy (+57%, p < 0.001), an increase in systolic pressure (+46%, p < 0.001) and in contraction speed (+36%, p < 0.001), when compared to control animals. I-BET151 treated animals (CHPI-iB) showed restored hemodynamic parameters to levels similar to control animals, despite chronic hypoxia plus exposure to pulmonary inflammation. They displayed lower right ventricle hypertrophy and hematocrit compared to the CHPI group (respectively −16%, p < 0.001; and −9%, p < 0.05). Our descriptive study shows a valuable effect of the inhibition of bromodomain and extra-terminal domain proteins on hemodynamic parameters, despite the presence of chronic hypoxia and pulmonary inflammation. This suggests that such inhibition could be of potential interest for COPD patients with pulmonary hypertension. Further studies are needed to unravel the underlying mechanisms involved and the net benefits of inhibiting adaptations to chronic hypoxia.

ObjectivesLung transplant (LT) recipients require multidisciplinary care because of the complexity of therapeutic management. Pharmacists are able to detect drug-related problems and provide recommendations to physicians through pharmacists’ interventions (PIs). We aimed at assessing the clinical impact of PIs on therapeutic management in LT outpatients.DesignData were collected prospectively from an LT recipients cohort during 7 years. A multidisciplinary committee assessed retrospectively the clinical impact of accepted PIs.SettingFrench University Hospital.ParticipantsLT outpatients followed from 2009 to 2015.Primary outcome measuresClinical impact of PIs performed by pharmacists using the CLEO tool and the Pareto chart.Results1449 PIs led to a change in patient therapeutic management and were mainly related to wrong dosage (39.6%) and untreated indication (19.6%). The clinical impact of PIs was ‘avoids fatality’, ‘major’ and ‘moderate’, in 0.1%, 7.0% and 57.9%, respectively. Immunosuppressants, antimycotics for systemic use and antithrombotic agents had the greatest clinical impact according to the Pareto chart. PIs related to drug–drug interactions (10%) mainly had a moderate and major clinical impact (82.3%, p<0.0001).ConclusionClinical pharmacists play a key role for detecting drug-related problems mostly leading to a change in therapeutic management among LT outpatients. Our study provides a new insight to analyse the clinical impact of PIs in order to target PIs which have most value and contribute to patient care through interdisciplinary approach.

Some of the Chronic Obstructive Pulmonary Disease (COPD) patients engaged in exercise-based muscle rehabilitation programs are unresponsive. To unravel the respective role of chronic hypoxia and pulmonary inflammation on soleus muscle hypertrophic capacities, we challenged male Wistar rats to repeated lipopolysaccharide instillations, associated or not with a chronic hypoxia exposure. Muscle hypertrophy was initiated by bilateral ablation of soleus agonists 1 week before sacrifice. To understand the role played by the histone acetylation, we also treated our animals with an inhibitor of bromodomains and extra terminal proteins (I-BET) during the week after surgery. Pulmonary inflammation totally inhibited this hypertrophy response under both normoxic and hypoxic conditions (26% lower than control surgery, p < 0.05), consistent with the S6K1 and myogenin measurements. Changes in histone acetylation and class IIa histone deacetylases expression, following pulmonary inflammation, suggested a putative role for histone acetylation signaling in the altered hypertrophy response. The I-BET drug restored the hypertrophy response suggesting that the non-response of muscle to a hypertrophic stimulus could be modulated by epigenetic mechanisms, including histone-acetylation dependant pathways. Drugs targeting such epigenetic mechanisms may open therapeutic perspectives for COPD patients with systemic inflammation who are unresponsive to rehabilitation.