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Background: This study aimed to assess the feasibility and safety of a problem-solving exercise program based on the items in the short physical performance battery (SPPB) for older patients with chronic respiratory diseases (CRDs) to inform future randomized controlled trials., Methods: This was a multicenter, prospective, non-randomized feasibility study. Participants with CRD received an enhancement program based on the SPPB decline items (balance, walk, and/or chair stand) for 4 weeks. The feasibility, safety, and efficacy of the problem-solving exercise program in improving the SPPB score, physical function, and step count (measured using a pedometer) were assessed., Results: Overall, 36 patients were enrolled in this study, and adherence to the exercise program was high (100%). No exercise program-related adverse events were observed. The implementation of the exercise program ranged from 70 to 100%. The mean daily step count increased from 2152 ± 1498 steps during the first week to 2899 ± 1865 steps in the last week (p<0.01). Additionally, the SPPB total score increased from 8.9 ± 1.8 points to 10.7 ± 1.3 points at the end of the program (p<0.001)., Conclusions: The problem-solving exercise program based on SPPB is feasible and safe for older patients with CRDs. However, the effectiveness of this exercise program should be validated in large-scale, randomized-controlled trials in the future., Trial Registration: University Hospital Medical Information Network Center (UMIN-CTR) UMIN: approval number: UMIN000048761., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: High-frequency chest wall oscillation (HFCWO) devices are used to improve airway clearance in various respiratory conditions. This study comprehensively assesses the evidence on efficacy and safety and identifies trends in scientific publications and patents across geographic regions., Methods: This study utilized an integrated approach, combining bibliographic and bibliometric research with artificial intelligence (AI) tools. Four databases - PubMed, Europe Pubmed Central, Cochrane Database of Systematic Reviews, and CINAHL - were searched for systematic reviews on the effectiveness of treatment options for HFCWO. The AMSTAR-2 tool was used to evaluate the risk of bias in systematic reviews. Bibliographic research synthesized the evidence following PRISMA and Cochrane guidelines. The Dimensions platform was used for bibliometric analysis to provide insights into the global landscape. AI tools with prompt engineering tools Chain-of-Thoughts (CoT) and Tree of Thoughts (ToT) were used to enhance data extraction capabilities., Results: The umbrella review identified 12 systematic reviews supporting the effectiveness of HFCWO in improving pulmonary function parameters, sputum characteristics, dyspnea, health scores, and quality of life in conditions including cystic fibrosis, bronchiectasis, chronic obstructive pulmonary disease (COPD), or neuromuscular diseases, with varying evidence of certainty. Eight of the twelve reviews had a moderate to high AMSTAR-2 confidence level, while several studies lacked sufficient descriptions of methods, treatment regimens, outcome measures, and adverse effects. Despite the absence of adverse events, the overall evidence quality between studies is evaluated as low to very low. Bibliometric analysis found a significant increase in global interest over the past two decades, with 230 research publications, 137 patents, and 56 clinical trials., Conclusions: The study highlights the potential of HFCWO devices in respiratory care but demands more robust evidence. The increasing interest in airway clearance devices highlights the necessity for HFCWO mechanism and safety research, underlining its therapeutic relevance in respiratory medicine. The interdisciplinary integration of AI tools and prompt engineering contributes to a nuanced understanding of the available evidence., Competing Interests: Declaration of competing interest AM is the inventor and developer of Expector®, a high-frequency chest wall oscillation device in Brazil's development phase. The other authors declare no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: Our study aims to clarify the causality between air pollutants and lung function, chronic respiratory diseases, and the potential mediating effects of inflammatory proteins., Method: We employed Mendelian Randomization (MR) analysis with comprehensive instrumental variables screening criteria to investigate the effects of air pollutants on lung function and chronic lung diseases. Our study incorporated genetic instruments for air pollutants, ensuring F -statistics above 20.86. A total of 18 MR analyses were conducted using the inverse-variance weighted approach, along with heterogeneity and pleiotropy tests to validate the results. Mediated MR analysis was utilized to evaluate the inflammatory proteins mediating the effects of air pollutants., Result: MR analysis demonstrated significant causal interactions of particulate matter 2.5 (PM 2.5 ), PM 10 , and Nitrogen dioxide (NO 2 ) with lung function decline. Specifically, PM 10 negatively affected forced expiratory volume in one second (FEV 1 ) (OR: 0.934, 95% CI: 0.904-0.965, p  = 4.27 × 10 -5 ), forced vital capacity (FVC) (OR: 0.941, 95% CI: 0.910-0.972, p  = 2.86 × 10 -4 ), and FEV 1 /FVC (OR: 0.965, 95% CI: 0.934-0.998, p  = 0.036). PM 2.5 and NO 2 were identified as potential risk factors for impairing FEV 1 (OR: 0.936, 95% CI: 0.879-0.998, p  = 0.042) and FEV 1 /FVC (OR: 0.943, 95% CI: 0.896-0.992, p  = 0.024), respectively. For chronic respiratory diseases, PM 2.5 and NO 2 were associated with increased COPD incidence (OR: 1.273, 95% CI: 1.053-1.541, p  = 0.013 for PM 2.5 ; OR: 1.357, 95% CI: 1.165-1.581, p  = 8.74 × 10 -5 for NO 2 ). Sensitivity analyses confirmed the robustness of these findings, with no significant heterogeneity or horizontal pleiotropy detected., Conclusion: Our study ascertained the causal correlations of air pollutants with lung function and COPD, emphasizing the importance of reducing air pollution. Interleukin-17A mediates the reduction of FEV 1 and FVC by PM 10 , revealing potential therapeutic targets., 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 © 2024 Li, Liu, Jiang, Xu, Liu and Jia.)

Major histocompatibility complex class I (MHC I) molecules present peptides to CD8+ T-cells for immunosurveillance of infection and cancer. Recent studies indicate lineage-specific heterogeneity in MHC I expression. While respiratory diseases rank among the leading causes of mortality, studies in mice have shown that lung epithelial cells (LECs) express the lowest levels of MHC I in the lung. This study aims to answer three questions: (i) Do human LECs express low levels of MHC I? (ii) Is LEC MHC I expression modulated in chronic respiratory diseases? (iii) Which factors regulate MHC I levels in human LECs? We analyzed human LECs from parenchymal explants using single-cell RNA sequencing and immunostaining. We confirmed low constitutive MHC I expression in human LECs, with significant upregulation in chronic respiratory diseases. We observed a sexual dimorphism, with males having higher MHC I levels under steady-state conditions, likely due to differential redox balance. Our study unveils the complex interplay between MHC I expression, sex, and respiratory disease. Since MHC I upregulation contributes to the development of immunopathologies in other models, we propose that it may have a similar impact on chronic lung disease., (© 2024 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Chronic respiratory diseases (CRD) are responsible for more than four million deaths worldwide and have become especially prevalent in developed countries. Although the current therapies help manage daily symptoms and improve patients' quality of life, there is a major need to prevent exacerbations triggered mainly by respiratory infections. Therefore, CRD patients are a prime target for vaccination against infectious agents. In the present manuscript we review the state of the art of available vaccines specifically indicated in patients with CRDs. In addition to pneumococcus, influenza, pertussis, and SARS-CoV-2 vaccines, recently added immunization options like vaccines and monoclonal antibodies against respiratory syncytial virus, are particularly interesting in CRD patients. As new products reach the market, health authorities must be agile in updating immunization recommendations and in the programming of the vaccination of vulnerable populations such as patients with CRDs. Organizational and educational strategies might prove useful to increase vaccine uptake by CRD patients., (Copyright © 2024 The Authors. Published by Elsevier España, S.L.U. All rights reserved.)

Background: The associations between specific types of sugary beverages and major chronic respiratory diseases remain relatively unexplored., Objectives: This study aimed to investigate the associations of sugar-sweetened beverages (SSBs), artificially sweetened beverages (ASBs), and natural juices (NJs) with chronic obstructive pulmonary disease (COPD), asthma, and asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS)., Methods: This prospective cohort study included 210,339 participants from the UK Biobank. Sugary beverage intake was measured in units (glasses/cans/cartons/250 mL) through 24-h dietary questionnaires. Logistic regression and Cox proportional hazards models were used to analyze the prevalence and incidence, respectively. Quantile G-computation was used to estimate the joint associations and relative contributions of the 3 types of sugary beverages., Results: Over a median follow-up of 11.6 y, 3491 participants developed COPD, 4645 asthma, and 523 ACOS. In prevalence analysis, certain categories of SSB and NJ consumption were associated with increased asthma prevalence, while high ASB consumption (>2 units/d) was linked to higher risks of all 3 outcomes. In incidence analysis, high SSB consumption (>2 units/d) was associated with incident COPD (hazard ratio [HR]: 1.53; 95% confidence interval [CI]: 1.19, 1.98) and asthma (HR: 1.22; 95% CI: 0.98, 1.52). Dose‒response relationships were observed for ASB consumption with all 3 outcomes (continuous HR: 1.98; 95% CI: 1.36, 2.87, for COPD; continuous HR: 1.65; 95% CI: 1.24, 2.20, for asthma; and continuous HR: 2.84; 95% CI: 1.20, 6.72, for ACOS). Moderate NJ consumption (>0-1 unit/d) was inversely associated with COPD (HR: 0.89; 95% CI: 0.82, 0.97), particularly grapefruit and orange juice. Joint exposure to these beverages (per unit increase) was associated with COPD (HR: 1.15; 95% CI: 1.02, 1.29) and asthma (HR: 1.16; 95% CI: 1.06, 1.27), with ASBs having greater positive weights than SSBs., Conclusions: Consumption of SSBs and ASBs was associated with increased risks of COPD, asthma, and potentially ACOS, whereas moderate NJ consumption was associated with reduced risk of COPD, depending on the juice type., Competing Interests: Conflict of interest The authors report no conflicts of interest., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Purpose: This study aimed to elucidate the causal relationship between Obstructive Sleep Apnea (OSA) and Chronic Respiratory Diseases (CRDs), employing Mendelian Randomization (MR) to overcome limitations inherent in observational studies., Methods: Utilizing a two-sample MR approach, this study analyzed genetic variants as instrumental variables to investigate the causal link between OSA and various CRDs, including chronic obstructive pulmonary disease (COPD), asthma, bronchiectasis, and idiopathic pulmonary fibrosis (IPF). Data were sourced from the FinnGen Consortium (OSA, n = 375,657) and UK Biobank, focusing on genome-wide associations between single-nucleotide polymorphisms (SNPs) and the diseases. Instrumental variables were selected based on strict criteria, and analyses included a random-effects inverse-variance weighted method supplemented by several sensitivity analyses., Results: The study suggests a protective effect of OSA against COPD (OR = 0.819, 95% CI 0.722-0.929, P-value = 0.002), which becomes non-significant after adjusting for BMI, indicating a potential mediating role of BMI in the OSA-COPD nexus. No significant causal links were found between OSA and other CRDs (asthma, IPF, bronchiectasis) or between COPD, asthma, and OSA., Conclusions: Our findings reveal a BMI-mediated protective effect of OSA on COPD, with no causal connections identified between OSA and other CRDs. These results emphasize the complex relationship between OSA, BMI, and COPD, guiding future clinical strategies and research directions, particularly in light of the study's genetic analysis limitations., (© 2024. The Author(s).)

Background: The current literature inadequately addresses the extent to which remote monitoring should be integrated into care models for chronic respiratory diseases (CRDs)., Objective: This study examined a remote monitoring program (RMP) in cystic fibrosis (CF) by exploring experiences, future perspectives, and use behavior over 3 years, with the aim of developing future directions for remote monitoring in CRDs., Methods: This was a mixed methods, multicenter, observational study in 5 Dutch CF centers following a sequential explanatory design. Self-designed questionnaires using the technology acceptance model were sent out to people with CF who had a minimum of 12 months of experience with the RMP and local health care professionals (HCPs). Questionnaire outcomes were used to inform semistructured interviews with HCPs and people with CF. Qualitative findings were reported following the COREQ (Consolidated Criteria for Reporting Qualitative Research) checklist. Anonymous data on use frequency of all people with CF were analyzed., Results: Between the second quarter of 2020 and the end of 2022, a total of 608 people with CF were enrolled in the program, and a total of 9418 lung function tests and 2631 symptom surveys were conducted. In total, 65% (24/37) of HCPs and 89% (72/81) of people with CF responded to the questionnaire, and 7 HCPs and 12 people with CF participated in semistructured interviews. Both people with CF and HCPs were positive about remote monitoring in CF care and found the RMP a good addition to daily care (people with CF: 44/72, 61%; HCPs: 21/24, 88%). Benefits ranged from supporting individual patients to reducing health care consumption. The most valued monitoring tool was home spirometry by both people with CF (66/72, 92%) and HCPs (22/24, 92%). Downsides included the potential to lose sight of patients and negative psychosocial effects, as 17% (12/72) of people with CF experienced some form of stress due to the RMP. A large majority of people with CF (59/72, 82%) and HCPs (22/24, 92%) wanted to keep using the RMP in future, with 79% (19/24) of HCPs and 75% (54/72) of people with CF looking forward to more replacement of in-person care with digital care during periods of well-being. Future perspectives for the RMP were centered on creating hybrid care models, personalizing remote care, and balancing individual benefits with monitoring burden., Conclusions: Remote monitoring has considerable potential in supporting people with CF and HCPs within the CF care model. We identified 4 practice-based future directions for remote monitoring in CF and CRD care. The strategies, ranging from patient driven to prediction driven, can help clinicians, researchers, and policy makers navigate the rapidly changing digital health field, integrate remote monitoring into local care models, and align remote care with patient and clinician needs., (©Martinus C Oppelaar, Yvette Emond, Michiel A G E Bannier, Monique H E Reijers, Hester van der Vaart, Renske van der Meer, Josje Altenburg, Lennart Conemans, Bart L Rottier, Marianne Nuijsink, Lara S van den Wijngaart, Peter J F M Merkus, Maud Heinen, Jolt Roukema. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 06.08.2024.)

Background: The interleukin-2 (IL-2) family of cytokines, including IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21, are pivotal regulators of the immune response, impacting both innate and adaptive immunity. Understanding their molecular characteristics, receptor interactions, and signalling pathways is essential for elucidating their roles in health and disease., Objectives: This review provides a comprehensive overview of the IL-2 family of cytokines, highlighting their molecular biology, receptor interactions, and signalling mechanisms. Furthermore, it explores the involvement of IL-2 family cytokines in the pathogenesis of chronic respiratory diseases, with a specific focus on chronic obstructive pulmonary disease (COPD) and asthma., Methods: A thorough literature review was conducted to gather insights into the molecular biology, receptor interactions, and signalling pathways of IL-2 family cytokines. Additionally, studies investigating the roles of these cytokines in chronic respiratory diseases, particularly COPD and asthma, were analysed to discern their implications in wider pathophysiology of disease., Results: IL-2 family cytokines exert pleiotropic effects on immune cells, modulating cellular proliferation, differentiation, and survival. Dysregulation of IL-2 family cytokines has been implicated in the pathogenesis of chronic respiratory illnesses, including COPD and asthma. Elevated levels of IL-2 and IL-9 have been associated with disease severity in COPD, while IL-4 and IL-9 play crucial roles in asthma pathogenesis by promoting airway inflammation and remodelling., Conclusion: Understanding the intricate roles of IL-2 family cytokines in chronic respiratory diseases provides valuable insights into potential therapeutic targets for these conditions. Targeting specific cytokines or their receptors may offer novel treatment modalities to attenuate disease progression and improve clinical outcomes in patients with COPD and asthma., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Lung cancer (LC) is the leading cause of cancer-related mortality, and it is caused by many factors including cigarette smoking. Despite numerous treatment strategies for LC, its five-year survival is still poor (<20 %), attributable to treatment resistance and lack of early diagnosis and intervention. Importantly, LC incidence is higher in patients affected by chronic respiratory diseases (CRDs) such as asthma and chronic obstructive pulmonary disorder (COPD), and LC shares with other CRDs common pathophysiological features including chronic inflammation, oxidative stress, cellular senescence, and airway remodelling. Remodelling is a complex process resulting from the aberrant activation of tissue repair secondary to chronic inflammation, oxidative stress, and tissue damage observed in the airways of CRD patients, and it is characterized by irreversible airway structural and functional alterations, concomitantly with tissue fibrosis, epithelial-to-mesenchymal transition (EMT), excessive collagen deposition, and thickening of the basement membrane. Many processes involved in remodelling, particularly EMT, are also fundamental for LC pathogenesis, highlighting a potential connection between CRDs and LC. This provides rationale for the development of novel treatment strategies aimed at targeting components of the remodelling pathways. In this study, we tested the in vitro therapeutic activity of rat fecal microbiome extract (FME) on A549 human lung adenocarcinoma cells. We show that treatment with FME significantly downregulates the expression of six proteins whose function is at the forefront between airway remodelling and LC development: Snail, SPARC, MUC-1, Osteopontin, MMP-2, and HIF-1α. The results of this study, if confirmed by further investigations, provide proof-of-concept for a novel approach in the treatment of LC, focused on tackling the airway remodelling mechanisms underlying the increased susceptibility to develop LC observed in CRD patients., Competing Interests: Declaration of Competing Interest The authors of the manuscript submitted to the journal “Pathology - Research and Practice”, have no conflict of interest to declare., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Poland is a country with a high burden of COPD and its risk factors. This population-wide and geospatial study on COPD in Poland, aimed to analyze changes in hospitalizations of patients with a diagnosis of COPD between 2006 and 2019 as well as to identify changes in the demographic characteristics of patients hospitalized with COPD. This is a retrospective analysis of hospital discharge records of patients with a diagnosis of COPD (ICD-10 code J44 and age 40 and over), hospitalized in Poland between 2006 and 2019. Data were analyzed separately for all patients hospitalized with COPD (primary and secondary diagnosis), for patients admitted due to COPD (primary diagnosis) and patients hospitalized with COPD as a comorbidity (secondary diagnosis). Between 2006 and 2019, a total of 1,663,420 hospital admissions of patients with COPD were reported. Between 2006 and 2019, the annual number of patients hospitalized due to COPD decreased by 53.8%, including 57.3% among men and 46.6% among women. The number of patients hospitalized with COPD as comorbidity increased by 35.8%. The lowest hospital admissions rate was in north-western Poland and the highest in north-eastern Poland. Among patients admitted due to COPD, the percentage of women increased from 32.6% to 37.7%. The percentage of patients admitted due to COPD and living in rural areas decreased from 51.2% in 2006 to 40.8%in 2019. This study provided data on changes in sociodemographic characteristics of hospitalizations of patients with a diagnosis of COPD, including overall reduction in COPD admissions but an increase in COPD burden among women.

Background: Although evidence has documented the associations of ambient air pollution with chronic respiratory diseases (CRDs) and lung function, the underlying metabolic mechanisms remain largely unclear., Research Question: How does the metabolomic signature for air pollution relate to CRD risk, respiratory symptoms, and lung function?, Study Design and Methods: We retrieved 171,132 participants free of COPD and asthma at baseline from the UK Biobank, who had data on air pollution and metabolomics. Exposures to air pollutants (particulate matter with diameter ≤ 2.5 μm [PM 2.5 ], particulate matter with a diameter ≤ 10 μm, nitrogen oxide [NO X ], and NO 2 ) were assessed for 4 years before baseline considering residential address histories. We used 10-fold cross-validation elastic net regression to identify air pollution-associated metabolites. Multivariable Cox models were used to assess the associations between metabolomic signatures and CRD risk. Mediation and pathway analysis were conducted to explore the metabolic mechanism underlying the associations., Results: During a median follow-up of 12.51 years, 8,951 and 5,980 incident COPD and asthma cases were recorded. In multivariable Cox regressions, air pollution was positively associated with CRD risk (eg, hazard ratio per interquartile range increment in PM 2.5 , 1.09; 95% CI, 1.06-1.13). We identified 103, 86, 85, and 90 metabolites in response to PM 2.5 , particulate matter with a diameter ≤ 10 μm, NO X , and NO 2 exposure, respectively. The metabolomic signatures showed significant associations with CRD risk (hazard ratio per SD increment in PM 2.5 metabolomic signature, 1.11; 95% CI, 1.09-1.14). Mediation analysis showed that peripheral inflammatory and erythrocyte-related markers mediated the effects of metabolomic signatures on CRD risk. We identified 14 and 12 perturbed metabolic pathways (energy metabolism and amino acid metabolism pathways, etc) for PM 2.5 and NO X metabolomic signatures., Interpretation: Our study identifies metabolomic signatures for air pollution exposure. The metabolomic signatures showed significant associations with CRD risk, and inflammatory- and erythrocyte-related markers partly mediated the metabolomic signatures-CRD links., Competing Interests: Financial/Nonfinancial Disclosures None declared., (Copyright © 2024 American College of Chest Physicians. All rights reserved.)

Objective: To assess validity and responsiveness of the Extended Rehabilitation Complexity Scale (RCS-E v13) to in-hospital pulmonary rehabilitation (PR) in individuals with chronic respiratory diseases (CRD)., Design: Cross-sectional, multicentric study. Assessments in individuals attending units on 2 nonconsecutive days., Setting: Fourteen in-hospital PR units., Participants: Five hundred forty-seven individuals (59.2% male, age 72y [range, 65-78y]): 317 with chronic respiratory failure because of various causes (CRF); 96 with chronic obstructive pulmonary disease without CRF (COPD), 39 tracheostomized and ventilated (TX/V), and 95 with other diseases (Miscellaneous)., Intervention: Assessment of RCS-E v13 before and after the PR program., Main Outcome Measures: RCS-E v13 and outcome measures: Barthel Index (BI), Barthel Index Dyspnea (BiD), Medical Research Council scale for dyspnea (MRC), COPD Assessment Test (CAT), Short Physical Performance Battery (SPPB), and 6-minute walk test (6MWT)., Results: The highest RCS-E v13 admission values (median [interquartile range]) were found in TX/V (17 [15-18]) as compared with other groups (8 [7-10], 10 [9-12], and 8 [8-10] in COPD, CRF, and Miscellaneous, respectively, P<.001). At admission and discharge, RCS-E v13 correlated strongly with BI, 6MWT, and SPPB and moderately with MRC and BiD (r=.43-.60). After the program, RCS-E v13 as well as all outcome measures improved significantly in all groups (P<.001 for all). The size of improvement was different among groups according to the different variables. In the overall group, the effect size was high for changes in RCS-E v13 (Cohen's d=-2.0984), CAT (d=-1.1937), MRC (d=-1.0505), BiD (d=-.9364), and SPPB (d=.9231) whereas it was moderate for 6MWT (d=.7670) and BI (d=.6574)., Conclusions: RCS-E v13 varies according to different CRD, is responsive to PR, has good construct and concurrent validity, and correlates with most of the accepted outcome measures of PR. Its scoring may provide useful information on the care burden of individuals undergoing PR., (Copyright © 2024 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: Even though dynamic multidisciplinary team discussions are crucial for end-of-life care management and decisions concerning chronic obstructive pulmonary disease (COPD), the details of the discussion contents remain poorly understood. This study aimed to identify essential considerations in decision-making for patients with chronic respiratory diseases to enhance a consensus-based approach. Materials and Methods: A qualitative content analysis of focus group conversations on published clinical case reports in the Japanese community about end-of-life care for patients with chronic respiratory disorders was conducted. The cases were searched through Igaku Chuo Zasshi (ICHUSHI) and Google in February 2021, using the keywords: "COPD", "chronic respiratory diseases", and "end-of-life care". A total of 41 healthcare professionals participated in the focus group discussions. Results: Four major themes evolved from the qualitative content analysis: unpredictable disease prognosis and stages, low awareness of patients on disease severity, acute exacerbations, and home oxygen therapy (HOT). The participants perceived that assessment of severity and prognosis in chronic respiratory diseases such as COPD was a core discussion point to enhance patients' decision-making. The study's findings also indicated that healthcare providers evaluate the influence of acute aggravation of the condition on patients' perceived health status and decision-making. Conclusion: The study reaffirms the significance of informed consent in patients with chronic respiratory disease. It details how, after a thorough assessment of disease severity, patients are given personalized explanations of standardized HOT. This approach ensures they fully understand the unpredictable nature and various stages of their condition resulting from acute exacerbations., Competing Interests: None declared., (©2024 The Japanese Association of Rural Medicine.)

Objective: To quantify the impact of different air pollutants on respiratory health based on robust estimates based on international data and to summarise the evidence of associations between indoor exposure to those pollutants and respiratory morbidity in the Portuguese population., Results: Several systematic reviews and meta-analyses (MA) at the world level demonstrate the impact of indoor air quality on respiratory health, with indoor particulate matter and gasses exerting a significant effect on the airways. Volatile organic compounds (VOC) have been related to asthma and lung cancer. However, only meta-analyses on biomass use allowed documentation of long-term respiratory effects. While early publications concerning Portuguese-based populations mainly focused on indoor exposure to environmental tobacco smoke, later studies relocated the attention to relevant exposure environments, such as day care buildings, schools, residences and nursing homes. Looking at the pooled effects from the reviewed studies, high levels of carbon dioxide and particulate matter in Portuguese buildings were significantly associated with asthma and wheezing, with VOC and fungi showing a similar effect in some instances., Conclusions: Despite the significant reduction of indoor air pollution effects after the 2008 indoor smoking prohibition in public buildings, studies show that several indoor air parameters are still significantly associated with respiratory health in Portugal. The country shares the worldwide necessity of standardisation of methods and contextual data to increase the reach of epidemiological studies on household air pollution, allowing a weighted evaluation of interventions and policies focused on reducing the associated respiratory morbidity., Competing Interests: Conflicts of interest None., (Copyright © 2023 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.)

Objective: To compare the impact of telerehabilitation versus conventional rehabilitation on the recovery outcomes of patients with chronic respiratory disease (CRD)., Methods: The Cochrane Library, MEDLINE, Web of Science and Embase were searched to collect randomized controlled trials (RCTs) on telerehabilitation for the rehabilitation of patients with chronic respiratory system diseases since the establishment of the database to November 14, 2023. Two researchers independently screened the literature and extracted valid data according to the inclusion criteria. The quality assessment of included studies was conducted individually by using the RoB 2(Risk of Bias 2) tool, followed by meta-analysis using RevMan5.3 software., Results: Based on inclusion and exclusion criteria, 21 RCTs were included, comprising 3030 participants, with 1509 in the telerehabilitation group and 1521 in the conventional rehabilitation group. Meta-analysis results indicated that compared to conventional rehabilitation, video conference-based telerehabilitation demonstrated significant improvements in short-term (≤ 6 months) outcomes, including 6-min walk distance (6MWD) (MD = 7.52, 95% CI: 2.09, 12.94), modified Medical Research Council Dyspnea Scale (mMRC) (MD = -0.29, 95% CI: -0.41, -0.18), COPD assessment test (CAT) (MD = -1.77, 95% CI: -3.52, -0.02), HADS (MD = -0.44, 95% CI: -0.86, -0.03), and St. George's Respiratory Questionnaire (SGRQ's) activity, impact, and symptom scores. In the long term (> 6 months), although improvements persisted in 6WMD [MD = 12.89, 95% CI (-0.37, 26.14)], mMRC [MD = -0.38, 95% CI (-0.56, -0.21)], CAT [MD = -1.39, 95% CI (-3.83, 1.05)], Hospital anxiety and depression scale (HADS) [MD = -0.34, 95% CI (-0.66, -0.03)], and SGRQ's Activity, Impact, and Symptom scores between intervention and control groups, statistically significant differences were observed only for mMRC and HADS. Without considering time factors, the intervention group exhibited some improvement in FEV1% predicted and the forced expiratory volume in the first one second (FEV1)/ forced vital capacity (FVC) (%) without statistical significance compared to the control group., Conclusion: Telerehabilitation therapy demonstrates short-term benefits in enhancing patients' daily activity capacity, improving respiratory function, and enhancing mental health status, thereby improving patients' quality of life. However, further high-quality, large-sample RCTs are required to ascertain its long-term effectiveness conclusively., Trial Registration: This study protocol was approved and registered in PROSPERO: CRD 42024509154., (© 2024. The Author(s).)

Introduction In patients with severe chronic pulmonary diseases, there is often a need for oxygen therapy to continue after discharge from hospitalization. Long-term oxygen therapy (LTOT) has been shown to significantly reduce mortality in such patients and improve longevity by helping to correct oxygen deficiency in the bloodstream and prevent organ failure and the development of cor pulmonale (right-sided heart failure). Therefore, considering the sociocultural background of India, the objective of the present study was to evaluate patients' perceptions of LTOT using semi-structured interviews, to evaluate patients' perceptions of activities and participation, and to evaluate the quality of life (QOL) of patients with LTOT. Methodology A mixed-method study was performed at a tertiary care hospital for six months. Twenty-four chronic respiratory patients were included in the present study. The patients' perception was evaluated about LTOT using semi-structured interviews, activities, and participation using a validated activity and participation checklist and the QOL of patients with LTOT using the World Health Organization Quality of Life Brief Version (WHOQOL-BREF) questionnaire. Results Twenty-four patients were interviewed and transcripts were analyzed through thematic analysis. Descriptive statistical analysis was performed for activity and participation along with QOL. The mean age of the patients involved was 58.5 ± 9.54 years, which involved a maximum of male patients consisting of 13 (54.2%) in comparison to female patients. The duration of oxygen use in months was 31.4 ± 29.4, the daily oxygen usage in hours was 17.3 ± 6.6, and the oxygen flow rate (L/min) was found to be 2.3 ± 0.97 at rest and 3.6 ± 1.4 on activity. In addition, the oxygen use by the patients was preferable as prescribed by 15 (62.5%) patients. Patients' perspectives on LTOT demonstrated that 10 (41.7%) patients perceived oxygen as relieving symptoms while most patients used oxygen during walking indoors activity involving 22 patients (91.7%), with 17 (77.3%) reporting improved ability and five (22.7%) facing obstacles. Instrumental activities involving walking shorter distances (less than 1 km) involved a high usage of oxygen with 20 patients (83.3%) using it, where 15 (75%) found it beneficial, three (15%) encountered obstacles, and two (10%) noted no effect from its use. Social interaction found that only one patient (4.20%) used oxygen at work, finding it helpful, but the majority, 20 (83.4%), did not go to work at all. Moreover, oxygen usage during transportation reported that travel using private vehicles involved a maximum of patients (16, 66.7%). Furthermore, for inquiries related to QOL, the results demonstrated that for the four domains of WHOQOL-BREF, consisting of physical health, psychological, social relationships, and environment, the mean values were found to be 48.33 ±10.66, 54.79 ± 13.7, 55.75 ±11.1, and 60.25 ± 12.6, respectively. Conclusion LTOT has been perceived to be a life-saving intervention by majority of the chronic respiratory disease patients of increased severity. Patients experienced various issues in daily activities and participation, which have affected their QOL. Overall, a lack of awareness and knowledge regarding the purpose, dosage, benefit, and usage of oxygen therapy was found to be evident and needs to be focused., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Ethical Committee of Seth Gordhandas Sunderdas Medical College and King Edward Memorial Hospital issued approval EC/193/2019. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Jiandani et al.)

Background: Prior observational research has indicated a potential link between pediatric asthma and united airways disease (UAD). However, these findings could be subject to confounding factors and reverse causation. Therefore, our study utilizes Mendelian randomization (MR) method to further investigate the causal relationship between pediatric asthma and UAD., Methods: We conducted a comprehensive two-sample Mendelian randomization (MR) analysis to investigate the association between pediatric asthma and seven groups of UAD, including chronic sinusitis, chronic rhinitis, nasopharyngitis and pharyngitis, chronic diseases of tonsils and adenoids, chronic laryngitis and laryngotracheitis, chronic bronchitis, bronchiectasis, chronic obstructive pulmonary disease (COPD). The present study employed a range of methods for two-sample MR analysis, including inverse variance weighted (IVW), MR-Egger regression, Simple mode, weighted median, and weighted models. The conclusion of the MR analysis primarily relies on the IVW results, while other analytical methods are utilized as supplementary evidence to ensure result robustness in this MR analysis. And sensitivity analyses were conducted, including heterogeneity test, horizontal pleiotropy test, MR-PRESSO test, and leave-one-out analysis to validate the results., Results: The results of the MR analysis indicate significant causal effects of pediatric asthma on chronic rhinitis, nasopharyngitis and pharyngitis (IVW: OR = 1.15, 95%CI: 1.05-1.26, p -value = 0.003), chronic diseases of tonsils and adenoids (IVW: OR = 1.07, 95%CI: 1.00-1.15, p -value = 0.038), chronic bronchitis (IVW: OR = 1.51, 95%CI: 1.42-1.62, p -value <0.001), bronchiectasis (IVW: OR = 1.51, 95%CI: (1.30-1.75), p -value <0.001), and COPD (IVW: OR = 1.43, 95%CI: 1.34-1.51, p -value <0.001). However, no significant causal association was observed between pediatric asthma and chronic sinusitis (IVW: OR = 1.00, 95%CI: 1.00-1.00, p -value = 0.085), chronic laryngitis and laryngotracheitis (IVW: OR = 1.05, 95%CI: 0.90-1.21, p -value = 0.558)., Conclusion: Our findings support a potential causal relationship between pediatric asthma and UAD, suggesting that pediatric asthma may be a potential risk factor for various UAD., 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 © 2024 Gao, Cai, Hu, Zhu and Wang.)

Oxidation processes in mitochondria and different environmental insults contribute to unwarranted accumulation of reactive oxygen species (ROS). These, in turn, rapidly damage intracellular lipids, proteins, and DNA, ultimately causing aging and several human diseases. Cells have developed different and very effective systems to control ROS levels. Among these, removal of excessive amounts is guaranteed by upregulated expression of various antioxidant enzymes, through activation of the NF-E2-Related Factor 2 (NRF2) protein. Here, we show that Mitogen Activated Protein Kinase 15 (MAPK15) controls the transactivating potential of NRF2 and, in turn, the expression of its downstream target genes. Specifically, upon oxidative stress, MAPK15 is necessary to increase NRF2 expression and nuclear translocation, by inducing its activating phosphorylation, ultimately supporting transactivation of cytoprotective antioxidant genes. Lungs are continuously exposed to oxidative damages induced by environmental insults such as air pollutants and cigarette smoke. Interestingly, we demonstrate that MAPK15 is very effective in supporting NRF2-dependent antioxidant transcriptional response to cigarette smoke of epithelial lung cells. Oxidative damage induced by cigarette smoke indeed represents a leading cause of disability and death worldwide by contributing to the pathogenesis of different chronic respiratory diseases and lung cancer. Therefore, the development of novel therapeutic strategies able to modulate cellular responses to oxidative stress would be highly beneficial. Our data contribute to the necessary understanding of the molecular mechanisms behind such responses and identify new potentially actionable targets., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Pulmonary rehabilitation (PR) is one of the most effective therapies for chronic respiratory diseases, yet it is significantly underutilized. There are several patient-related, geographic, societal, and health system-related barriers to PR. People with chronic respiratory disease face a collectively high burden of treatments including health care provider visits, medications, oxygen and other durable medical equipment, and providers' recommendation to undertake PR may be considered an added burden more than a likely benefit. Transportation difficulties, lack of insurance coverage, competing time priorities, low knowledge of PR, lack of perceived likely benefit, comorbidities, and other factors also pose obstacles to participation in PR for patients. Geographic availability of PR is heterogenous; in the United States, out-patient center-based PR programs are often not available within close proximity to patients' residence, posing barriers to patients' access to it. PR programs are lacking altogether in many areas; rural areas are particularly affected. Existing PR programs are often poorly funded and underresourced. Socioeconomic and racial disparities also influence patients' likelihood of receiving PR. Also, health care professionals (HCPs) often do not refer their patients with chronic respiratory disease to PR, owing to a lack of knowledge and awareness of its content and benefits, patient candidacy, or of the referral process. A limited number of multidisciplinary HCPs trained in PR likely also contributes to limited access to PR for patients. Collectively, these multifaceted barriers to PR create unacceptable health care disparities. Strategies to address barriers to PR are urgently needed in order to enable individuals who need to receive it., Competing Interests: Dr Rochester discloses relationships with Boehringer Ingelheim, GSK, and AstraZeneca., (Copyright © 2024 by Daedalus Enterprises.)

Background: Exposure to pesticides is a global public health problem, especially for children. Its association with chronic respiratory disease among children has attracted considerable attention, but the existing evidence remains inconclusive and cannot be certain. Therefore, this systematic review and meta-analysis aim to determine the global pooled effect size of association with pesticide exposure and asthma, wheezing, and respiratory tract infections among children., Methods: A comprehensive search was conducted for relevant literature from electronic databases, including PubMed, Google Scholar, Hinari, Semantic Scholar, and Science Direct. Studies that provided effect size on the association between pesticide exposure and childhood asthma, wheezing, and respiratory tract infections in children were included. The articles were screened, data was extracted, and the quality of each study was assessed with four independent reviewers. Random effects models for significant heterogeneity and fixed effect models for homogeneous studies were conducted to estimate pooled effect sizes with 95% confidence intervals using Comprehensive Meta-Analysis version 3.3.070 and MetaXL version 2. Funnel plot and Higgins I 2 statistics were used to determine the heterogeneity of the included studies. Subgroup analyses were computed based on the types of pesticide exposure, study design, sample size category, and outcome assessment technique., Result: A total of 38 articles with 118,303 children less than 18 years of age were included in this meta-analysis. Pesticide exposure among children increased the risk of asthma by 24%; (OR = 1.24, 95% CI: 1.14-1.35) with extreme heterogeneity ( I 2  = 81%, p  < 0.001). Exposure to pesticides increased the odds of developing wheezing among children by 34% (OR = 1.34, 95% CI: 1.14-1.57), with high heterogeneity ( I 2  = 79%, p  < 0.001) and also increased the risk of developing lower respiratory tract infection by 79% (OR = 1.79, 95% CI: 1.45-2.21) with nonsignificant low heterogeneity ( I 2  = 30%, p -value = 0.18)., Conclusion: This meta-analysis provided valuable evidence supporting the association between childhood asthma, wheezing, and lower respiratory tract infection with pesticide exposure. The findings would contribute to a better understanding of the estimate of the effect of pesticide exposure on respiratory health in children and inform evidence-based preventive strategies and public health interventions., 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 © 2024 Keleb, Daba, Asmare, Bayou, Arefaynie, Mohammed, Tareke, Kebede, Tsega, Endawkie, Kebede, Abera, Abeje and Enyew.)

Background: Dyspnea, a common symptom of chronic respiratory diseases (CRDs), is closely linked to higher levels of functional impairment and death, leading to significant societal and financial challenges. Despite numerous clinical trials and systematic reviews suggested the potential benefits of acupuncture for chronic obstructive pulmonary disease (COPD) and lung cancer, there is currently insufficient evidence to conclusively prove its effectiveness in alleviating dyspnea in patients with CRDs., Methods: To compile and evaluate the existing data on the effectiveness and safety of acupuncture for managing dyspnea in CRDs. Randomized controlled trials investigating acupuncture for the treatment of dyspnea in patients with CRDs, such as COPD, lung cancer, asthma, bronchiectasis, interstitial lung disease, chronic pulmonary heart disease and bronchitis, were searched and retrieved from five electronic databases in English or Chinese., Results: A total of 23 studies meeting the inclusion criteria were found in databases, covering various CRDs such as COPD, lung cancer, and asthma. A meta-analysis that compared acupuncture to a control group (which included no acupuncture and sham acupuncture) found significant advantages for acupuncture in reducing dyspnea severity ( P  = 0.0003), increasing 6MWD ( P  < 0.00001), improving quality of life measured by St. George's Respiratory Questionnaire ( P  = 0.03) and karnofsky performance status score ( P  < 0.00001). No significance was found in breathing physiology represented by FEV 1 ( P  = 0.34) and FVC ( P  = 0.15). There was a comparable incidence of negative outcomes in both groups ( P  = 0.07). Results were consistent when compared to sham acupuncture. In addition, subgroup analyses were also consistent when different diseases or types of acupuncture were analyzed., Conclusions: Acupuncture may be an effective and safe non-pharmacological complementary intervention to relief dyspnea for patients with CRDs. Nevertheless, research with high quality and large sample sizes is needed for further investigation., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: The aim of the present study was to investigate the possible connection between occupational status and chronic respiratory diseases (CRDs) among the Iranian population., Methods: The present cross-sectional study was conducted on 9934 individuals aged 35-70 years enrolled in the Rafsanjan Cohort Study (RCS), a component of the Prospective Epidemiological Research Studies in Iran (PERSIAN). Detailed questionnaires were used to collect information on various factors, such as occupation, sociodemographic characteristics, medical history, anthropometric measurements, physical activity, cigarette and hookah smoking, opium use, and alcohol consumption. The association between occupational class and CRD was evaluated using logistic regression models for rare events., Results: In the present study, 4624 (46.55%) participants were male, and 5310 (53.45%) were female. The prevalence of CRD among all participants was 2.61%. Occupational activities were classified into two categories: In class I, the largest group was the homemaker and unemployment category (41.73%), followed by self-employment (34.39%), employment (13.03%), and retired individuals (10.84%). In class II, there were pistachio farmers (12.61%), copper miners (3.62%), and others in various occupations (83.76%). Subjects with CRD were significantly more likely to be homemakers, unemployed, elderly, female, less educated, and obese. There was no significant relationship between CRD and job type/occupational status after adjusting for some potential confounding variables., Conclusions: There was no significant relationship between CRD and job type/occupational status. However, longitudinal studies are needed to assess the impact of job type/occupational status on the risk of CRD., (© 2024. The Author(s).)

The respiratory barrier, a thin epithelial barrier that separates the interior of the human body from the environment, is easily damaged by toxicants, and chronic respiratory diseases are common. It also allows the permeation of drugs for topical treatment. Animal experimentation is used to train medical technicians, evaluate toxicants, and develop inhaled formulations. Species differences in the architecture of the respiratory tract explain why some species are better at predicting human toxicity than others. Some species are useful as disease models. This review describes the anatomical differences between the human and mammalian lungs and lists the characteristics of currently used mammalian models for the most relevant chronic respiratory diseases (asthma, chronic obstructive pulmonary disease, cystic fibrosis, pulmonary hypertension, pulmonary fibrosis, and tuberculosis). The generation of animal models is not easy because they do not develop these diseases spontaneously. Mouse models are common, but other species are more appropriate for some diseases. Zebrafish and fruit flies can help study immunological aspects. It is expected that combinations of in silico, in vitro, and in vivo (mammalian and invertebrate) models will be used in the future for drug development.

Background and Aims: Flavonoids are a class of secondary plant metabolites that have been shown to have multiple health benefits, including antioxidant and anti-inflammatory. This study was to explore the association between dietary flavonoid consumption and the prevalence of chronic respiratory diseases (CRDs) in adults., Methods and Results: The six main types of flavonoids, including isoflavones, anthocyanidins, flavan-3-ols, flavanones, flavones, and flavonols, were obtained from the National Health and Nutrition Examination Survey (NHANES) 2007-2010 and 2017-2018 by the two 24-h recall interviews. The prevalence of CRDs, including asthma, emphysema, and chronic bronchitis, was determined through a self-administered questionnaire. The analysis included 15,753 participants aged 18 years or older who had completed a diet history interview. After adjustment for potential confounders, the inverse link was found with total flavonoids, anthocyanidins, flavanones, and flavones, with an OR (95%CI) of 0.86 (0.75-0.98), 0.84 (0.72-0.97), 0.80(0.69-0.92), and 0.85(0.73-0.98) for the highest group compared to the lowest group. WQS regression revealed that the mixture of flavonoids was negatively linked with the prevalence of CRDs (OR = 0.88 [0.82-0.95], P < 0.01), and the largest effect was mainly from flavanones (weight = 0.41). In addition, we found that flavonoid intake was negatively linked with inflammatory markers, and systemic inflammation significantly mediated the associations of flavonoids with CRDs, with a mediation rate of 12.64% for CRP (P < 0.01)., Conclusion: Higher flavonoid intake was related with a lower prevalence of CRDs in adults, and this relationship may be mediated through systemic inflammation., (© 2024. The Author(s).)

Background: Non-communicable diseases (NCDs) are the leading cause of mortality worldwide, and increasingly so in low- and middle-income countries. Afghanistan is dealing with a double burden of diseases, yet there has been no evidence synthesis on the prevalence of major NCDs and their risk factors., Objective: This study aims to provide a comprehensive synthesis of the existing data on the prevalence of major NCDs and the common related risk factors in Afghanistan., Method: We systematically reviewed scientific articles from 2000 to 2022 that reported the prevalence of diabetes, chronic respiratory diseases (CRDs), cardiovascular diseases (CVDs) or cancer, and their risk factors in Afghanistan. Four online databases (PubMed, Web of Science, Cochrane and Google Scholar) and two local journals in Afghanistan (not indexed online) were systematically searched and screened. Two reviewers independently screened and appraised the quality of the articles. Data extraction and synthesis were performed using tabulated sheets., Results: Among 51 eligible articles, 10 (19.6%) focused on cancer, 10 (19.6%) on diabetes, 4 (7.8%) on CVDs, 4 (7.8%) on CRDs and 23 (45.1%) on risk factors as the primary outcome. Few articles addressed major NCD prevalence; no evidence of CVDs, cancer was 0.15%, asthma ranged between 0.3% and 17.3%, and diabetes was 12%. Pooled prevalence of hypertension and overweight were 31% and 35%, respectively. Central obesity was twice as prevalent in females (76% versus 40%). Similarly, gender differences were observed in smoking and snuff use with prevalence rates of 14% and 25% among males and 2% and 3% among females, respectively. A total of 14% of the population engaged in vigorous activity. Pooled prevalence for physical inactivity, general obesity, fruit and vegetable consumption, dyslipidaemia and alcohol consumption couldn't be calculated due to the heterogeneity of articles., Conclusion: Only little evidence is available on the prevalence of major NCDs in Afghanistan; however, the NCD risk factors are prevalent across the country. The quality of the available data, especially those of the local resources, is poor; therefore, further research should generate reliable evidence in order to inform policymakers on prioritizing interventions for controlling and managing NCDs., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2024.)

Introduction: Accumulative evidence suggests the associations between systemic inflammatory regulators and chronic respiratory diseases (CRDs). However, the intrinsic causation remains implicit. Therefore, this study aimed to examine causative associations by mendelian randomization (MR) and to identify valuable active factors., Methods: Based on data from the GWAS database, we performed MR analyses of 41 serum cytokines from 8,293 Finnish and European descent cohorts from GBMI and UKBB for five major CRDs. We mainly applied inverse variance weighted regression, supplemented by MR-Egger regression, weighted median, maximum likelihood, weighted mode, and simple mode algorithms. Moreover, sensitivity analyses were conducted using Cochrane's Q test, MR-Egger intercept, MR-PRESSO Global test and MR-Steiger filtering. Eventually, the consistency of MR results was assessed by leave-one-out., Results: Our results suggest that 12 genetically predicted systemic inflammatory regulators probably participate in the progression of CRDs, including four risk factors (IL-1RA, IL-4, MIP-1A, PDGF-BB) and one protective factor (IL-6) in IPF, two protective factors (SCF, SDF-1A) in COPD, and two protective factors (SCF, SDF-1A) in asthma, two protective factors (GROA, IL-2RA) were also included in asthma, whereas only one factor (HGF) was protective against bronchiectasis. Additionally, two protective factors (FGF-BASIC, G-CSF) were identified in sarcoidosis. Sensitivity analyses showed no horizontal pleiotropy and significant heterogeneity. Finally, based on the findings of inverse MR analysis, no inverse causal association was uncovered, confirming the robustness of results., Conclusion: Our study unearths potential associations between systemic inflammatory modulators and common CRDs, providing new insights for inflammation-mediated CRD prevention and therapeutic approaches., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Klotho is an anti-aging protein that has multiple functions and may play a key role in the pathogenesis and progression of chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD). Fractional Exhaled Nitric Oxide (FeNO) is a non-invasive and novel biomarker that has the advantages of being simple, fast and reproducible. It can effectively assess the degree of airway inflammation in diseases such as asthma and COPD. Despite these insights, the relationship between serum Klotho levels and FeNO has not been explored yet., Methods: Leveraging data from the National Health and Nutrition Examination Survey (NHANES) spanning 2007 to 2012, we investigated the correlation between FeNO and serum Klotho levels. This association was scrutinized both as continuous variables and within quartile distributions, utilizing the Kruskal-Wallis H test. The correlation between the two variables was assessed through Spearman rank analysis. Employing survey weight-adjusted linear regression models, we gauged the strength of these associations., Results: This study included 6,527 participants with a median FeNO level of 14.5 parts per billion (ppb). We found that FeNO levels varied significantly across different quartiles of Klotho protein (H = 7.985, P = 0.046). We also found a significant positive correlation between serum Klotho levels and FeNO levels in the whole population (Spearman's rho = 0.029, P = 0.019). This correlation remained significant after adjusting for covariates such as age, gender, lung function, smoking status, alcohol use, BMI, cardiovascular disease (including hypertension, heart failure, coronary heart disease, and myocardial infarction), diabetes, inflammatory markers, serum vitamin D level and BUN (P < 0.05 for all). Furthermore, this correlation was stronger at the high (K3) and super high (K4) levels of Klotho than at the low (K1) and medium (K2) levels (β = 1.979 ppb and β = 1.993 ppb for K3 and K4 vs. K1, respectively; 95% CI: 0.497 ~ 2.953 and 95% CI: 0.129 ~ 2.827, respectively; P = 0.007 and P = 0.032, respectively). The β coefficient for serum Klotho was 0.002 ppb/pg/ml., Conclusions: Our study illuminates a positive correlation between serum Klotho levels and FeNO. Further study is needed to verify the causality of this association and elucidate the underlying mechanisms., (© 2024. The Author(s).)

Background: Chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD) and bronchiectasis, present significant threats to global health. Recent studies have revealed the crucial role of the lung microbiome in the development of these diseases. Pathogens have evolved complex strategies to evade the immune response, with the manipulation of host cellular epigenetic mechanisms playing a pivotal role. There is existing evidence regarding the effects of Pseudomonas on epigenetic modifications and their association with pulmonary diseases. Therefore, this study aims to directly assess the connection between Pseudomonas abundance and chronic respiratory diseases. We hope that our findings will shed light on the molecular mechanisms behind lung pathogen infections., Methods: We analyzed data from 366 participants, including individuals with COPD, acute exacerbations of COPD (AECOPD), bronchiectasis, and healthy individuals. Previous studies have given limited attention to the impact of Pseudomonas on these groups and their comparison with healthy individuals. Two independent datasets from different ethnic backgrounds were used for external validation. Each dataset separately analyzed bacteria at the genus level., Results: The study reveals that Pseudomonas, a bacterium, was consistently found in high concentrations in all chronic lung disease datasets but it was present in very low abundance in the healthy datasets. This suggests that Pseudomonas may influence cellular mechanisms through epigenetics, contributing to the development and progression of chronic respiratory diseases., Conclusions: This study emphasizes the importance of understanding the relationship between the lung microbiome, epigenetics, and the onset of chronic pulmonary disease. Enhanced recognition of molecular mechanisms and the impact of the microbiome on cellular functions, along with a better understanding of these concepts, can lead to improved diagnosis and treatment., (© 2023. The Author(s).)

Considering a huge burden of chronic respiratory diseases (CRDs) in India, there is a need for locally relevant Pulmonary rehabilitation (PR) services. This cross-sectional survey was aimed to explore the interest, needs and challenges among various stakeholders for PR in Pune city, India. At the outpatient respiratory medicine department of a multi-speciality hospital in Pune, India, 403 eligible people with CRDs were invited to participate in the survey, of which 370 (92%) responded and agreed to participate. (220 males, mean ± SD age 56 ± 15 years). Out of the 370, 323 (87%) people with CRDs were keen to attend PR. In a multiple selection question, there was inclination towards paper-based manuals home-based (70%) and web-based (84%) programs. 207 healthcare providers (HCPs), including physicians, pulmonologists and physiotherapists involved in the care of people living with CRDs across Pune city were invited to participate in the survey. Out of the 207, (80%) of the HCPs believed that PR was an effective management strategy and highlighted the lack of information on PR and need for better understanding of PR (48%) and its referral process. The surveyed stakeholders are ready to take up PR, identifying specific needs around further knowledge of PR, modes of delivery, and referral processes, that could potentially feed the development of relevant PR programs in the Indian healthcare settings., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

It has become increasingly common to utilize RNA treatment to treat respiratory illnesses. Experimental research on both people and animals has advanced quickly since the turn of the twenty-first century in an effort to discover a treatment for respiratory ailments that could not be accomplished with earlier techniques, specifically in treating prevalent respiratory diseases such as lung cancer, chronic obstructive pulmonary disease (COPD), respiratory infections caused by viruses, and asthma. This chapter has provided a comprehensive overview of the scientific evidence in applying RNA therapy to treat respiratory diseases. The chapter describes the development of this therapy for respiratory diseases. At the same time, the types of RNA therapy for respiratory diseases have been highlighted. In addition, the mechanism of this therapy for respiratory diseases has also been covered. These insights are indispensable if this therapy is to be developed widely., (Copyright © 2024. Published by Elsevier Inc.)

Objectives: Pulmonary Rehabilitation (PR) is a high-impact intervention for individuals with idiopathic pulmonary fibrosis (IPF) but access is limited in India. PR barriers include distance to travel, lack of service provision and lack of healthcare professionals to deliver PR, thus it is disproportionate to the immense burden of IPF in India. We explored the lived experiences of people living with IPF, family caregivers (CGs) and healthcare workers (HCWs) as well as their views towards home-based PR (HBPR) in Delhi, India., Methods: A qualitative study using semi-structured interviews with individuals with IPF (n = 20), CGs (n = 10) and HCWs (n = 10) was conducted. Data were analysed using codebook thematic analysis., Results: Three major themes were generated: (i) Health impact, which included pathophysiological changes, range of symptoms experienced, disease consequences and impact of comorbidities; (ii) Disease management, which described strategies to control the progression and overall management of IPF, such as medications and exercises; (iii) Mode of Pulmonary Rehabilitation, which described perceptions regarding HBPR, comparisons with centre-based programmes, and how HBPR may fit as part of a menu of PR delivery options., Conclusion: People living with IPF, family caregivers and healthcare workers were positive about the potential implementation of HBPR and suggested the development of a paper-based manual to facilitate HBPR over digital/online approaches. The content of HBPR should be sensitive to the additional impact of non-IPF health issues and challenges of reduced interactions with healthcare professionals., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: Task shifting, an approach to address physician shortage through redistribution of clinical tasks, may help address the high burden of chronic respiratory diseases like asthma and COPD. We aimed to measure its utility and impact in the Obstructive Lung Disease program (OLD)., Methods: A retrospective, cross-sectional study was conducted at five integrated outpatient departments of Primary Care Program within Indus Hospital & Health Network, Pakistan, from January 2018 to March 2023. After a formative evaluation, registered nurses were trained as Lung Health Nurses (LHNs) to perform spirometry, collect Patient Reported Outcome Measures (PROMs) including Asthma Control Test (ACT), modified Medical Research Council (mMRC) dyspnea score and COPD Assessment Test (CAT), counsel on inhaler use and tobacco cessation, and refer to pulmonary rehabilitation (PR). Data was collected online contemporaneously on REDCap and later analyzed using Excel and STATA 14., Results: Pre-implementation, a monthly average of 126 asthmatics and 33 COPD patients visited primary care centers. Medical records of 147 OLD patients showed 8% received inhaler education, 3% completed ACT and 2% had mMRC documented. Implementation included capacity building of nine LHNs. Of 7427 referrals to the program, 86% underwent nurse-led assessments. LHNs performed spirometry (92%), PROMs assessments [ACT (89%), CAT (91%), mMRC (85%)], inhaler education (97%), tobacco cessation advice (85%) and made PR referrals (94%)., Conclusion: Trained nurses can play a role in providing holistic and timely care for patients with CRDs and strengthen existing healthcare systems. Future directions may include expanding nurse clinical counselling roles through telehealth monitoring and home management., Competing Interests: Conflicts of interest: None., (Copyright: © Pakistan Journal of Medical Sciences.)

Background: Access to healthcare is part of every individual's human rights; however, many studies have illustrated that ethnic minority patients seem to be confronted with barriers when using healthcare services. Understanding how healthcare utilities are accessed from the perspective of patients and why healthcare disparities occur with patients from a minority background has the potential to improve health equality and care quality. This qualitative systematic review aims to gain insights into the experiences of people with chronic respiratory diseases (CRDs) from a minority background and explore factors contributing to their experiences in accessing healthcare to inform related health policy makers and healthcare providers., Methods: This systematic review complied with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, where the Joanna Briggs Institute meta-aggregative instrument facilitated the qualitative synthesis. The study protocol was registered with PROSPERO (CRD42022346055). PubMed, Scopus, Web of Science, and CINAHL were the databases explored., Results: From the papers selected, 47 findings were derived from 10 included studies, and four synthesised findings were generated: (1) the relationship between patients and healthcare professionals affects the usage of healthcare services; (2) patients' perceptions and cultural beliefs affect their compliance with disease management; (3) personal behaviours affect the usage of healthcare services; and (4) health resource inequalities have an impact on accessing healthcare services., Conclusions: This systematic review demonstrates that ethnic minorities with CRDs face inequalities when engaging in healthcare. The relationship between patients and clinicians impacting the use of healthcare is the most pivotal discovery, where not speaking the same language and being of a different race alongside the accompanying criticism and faith in facilities are key contributors to this effect. In addition, the thinking patterns of these marginalised groups may reflect their cultural upbringing and diminish their engagement with therapies. This paper has uncovered ways to attenuate inequalities amongst ethnic minorities in engaging with healthcare providers and provides insight into building effective equity-promoting interventions in healthcare systems. To overcome these disparities, coaching doctors to communicate better with minority cohorts could help such patients to be more comfortable in connecting with medical facilities.

Background: The use of case-based reimbursement for medical rehabilitation is greatly discussed. The investigators explored the relationship between disability and reimbursement opportunities in individuals with respiratory diseases undergoing in-hospital pulmonary rehabilitation (PR), considering the correlation (if any) between the Rehabilitation Complexity Scale (RCS-E v13) scores used at admission and the actual reimbursement., Methods: This study is part of a larger prospective multicenter study conducted by eight Pulmonary Rehabilitation Units in Italy. Here, investigators considered only data from the Lombardy Region. On January 30 th or February 28 th , 2023, participants were allocated according to the main DRG into 4 groups [tracheostomized/ventilated (TX/V), chronic respiratory failure (CRF), COPD, and miscellaneous group]. We recorded anthropometrics, diagnosis, international outcome measures, and calculated admission and discharge RCS-E v13 scores and hospital stay reimbursement according to the healthcare system (HS)., Results: Three hundred and sixteen participants were evaluated. Patients were elderly, in the majority of cases with CRF, presenting comorbidities, disability, dyspnea, and reduced effort tolerance. At admission, RCS-E v13 showed an average moderate value of complexity. The median (IQR) HS reimbursement/stay was different among groups. RCSE v13 evaluated at admission was weakly (r=0.3471), but significantly related to the HS reimbursement/stay (p<0.0001) mainly due to TX/V and miscellaneous subgroups, while no relationship was found for COPD and CRF patients. After PR, all outcome measures improved significantly in all groups (p<0.001 for all). Higher RCS-E v13 scores at admission did not correspond to a proper amount of reimbursement, being this latter under- or over-estimated if compared to needs assessed by RCS-E v13. RCS-E v13 at discharge decreased for all subgroups (range from -6 to -11) reaching a low value of complexity., Conclusions: The RCS-E v13 disability score does not fully mirror the HS reimbursement for patients undergoing inhospital PR., (Copyright © 2023, the Author(s).)

Background: Chronic respiratory diseases (CRDs) contribute significantly to morbidity and mortality worldwide and in India. Access to nonpharmacological options, such as pulmonary rehabilitation (PR), are, however, limited. Given the difference between need and availability, exploring PR, specifically remotely delivered PR, in a resource-poor setting, will help inform future work., Objective: This study explored the perceptions, experiences, needs, and challenges of patients with CRDs and the potential of and the need for PR from the perspective of patients as well as medical professionals involved in the referral (doctors) and delivery (physiotherapists) of PR., Methods: In-depth qualitative semistructured interviews were conducted among 20 individuals diagnosed with CRDs and 9 medical professionals. An inductive thematic analysis approach was used as we sought to identify the meanings shared both within and across the 2 participant groups., Results: The 20 patients considered lifestyle choices (smoking and drinking), a lack of physical activity, mental stress, and heredity as the triggering factors for their CRDs. All of them equated the disease with breathlessness and a lack of physical strength, consulting multiple doctors about their physical symptoms. The most commonly cited treatment choice was an inhaler. Most of them believed that yoga and exercise are good self-management strategies, and some were performing yoga postures and breathing exercises, as advised by friends or family members or learned from a televised program or YouTube videos. None of them identified with the term "pulmonary rehabilitation," but many were aware of the exercise component and its benefits. Despite being naive to smartphone technology or having difficulty in reading, most of them were enthusiastic about enrolling in an application-based remotely delivered digital PR program. The 9 medical professionals were, however, reluctant to depend on a PR program delivered entirely online. They recommended that patients with CRDs be supported by their family to use technology, with some time spent with a medical professional during the program., Conclusions: Patients with CRDs in India currently manage their disease with nonguided strategies but are eager to improve and would benefit from a guided PR program to feel better. A home-based PR program, with delivery facilitated by digital solutions, would be welcomed by patients and health care professionals involved in their care, as it would reduce the need for travel, specialist equipment, and setup. However, low digital literacy, low resource availability, and a lack of expertise are of concern to health care professionals. For India, including yoga could be a way of making PR "culturally congruent" and more successful. The digital PR intervention should be flexible to individual patient needs and should be complemented with physical sessions and a feedback mechanism for both practitioners as well as patients for better uptake and adherence., (©Rashmi Padhye, Shruti D Sahasrabudhe, Mark W Orme, Ilaria Pina, Dipali Dhamdhere, Suryakant Borade, Meenakshi Bhakare, Zahira Ahmed, Andy Barton, Mahavir Modi, Dominic Malcolm, Sundeep Salvi, Sally J Singh. Originally published in JMIR Formative Research (https://formative.jmir.org), 07.11.2023.)

Background: Sub-Saharan Africa (SSA) has experienced a surge of non-communicable diseases (NCDs) including chronic obstructive pulmonary disease (COPD) over the past two decades. Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD), in this study we have estimated the burden and attributable risk factors of COPD across SSA countries between 1990 and 2019., Methods: COPD burden and its attributable risk factors were estimated using data from the 2019 GBD. Percentage change was estimated to show the trend of COPD estimates from 1990 to 2019. COPD estimates attributable by risk factors were also reported to ascertain the risk factor that brings the greatest burden by sex and locations (at country and regions level)., Findings: In 2019, all-age prevalent cases of COPD in SSA were estimated to be 10.3 million (95% Uncertainty Intervals (UI) 9.7 million to 10.9 million) showing an increase of 117% compared with the number of all-age COPD cases in 1990. From 1990 to 2019, SSA underwent an increased percentage change in all-age YLDs due to COPD ranging from 41% in Lesotho to 203% in Equatorial Guinea. The largest premature mortality due to COPD was reported from Central SSA accounting for 729 subjects (95% UI, 509-1078). The highest rate of DALYs attributable to COPD was observed in Lesotho. Household air pollution from solid fuel was the primary contributor of the age standardized YLDs, death rate, and DALYs rate per 100,000 population., Interpretation: The prevalence of COPD in SSA has had a steady increase over the past three decades and has progressively become a major public health burden across the region. Household air pollution from solid fuel is the primary contributor to COPD related burden, and its percentage contribution showed a similar trend to the reduction of COPD attributed age-standardized DALY rate. The methodological limitations of surveys and datapoints included in the GBD need to be considered when interpreting these associations., Funding: There are no specific fundings received for this study. The Global Burden of Disease study was supported by funding from the Bill & Melinda Gates Foundation., Competing Interests: All authors in the writing team declare no competing interests., (© 2023 The Authors.)

Introduction: Six-min walk test (6MWT) is easy to use, the least expensive, and a quick measure of physical function and it reflects the capacity to perform our day-to-day activities hence quality of life can be assessed with 6MWT. This study was planned to assess the role of 6MWT in chronic respiratory disease patients and its association with spirometry-based functional grading at a rural tertiary care center of northern India., Materials and Methods: This was a hospital-based cross-sectional study done between December 2019 and July 2021. In this study, 110 patients were included as per inclusion and exclusion criteria. 6MWT and spirometry were conducted as per the American Thoracic Society/European Research Society recommendation using Spiropalm 6MWT and the association between 6MWT and spirometry was assessed., Results: A total of 110 chronic respiratory disease patients were included in the study. There were 69 (63%) males while 41 (37%) were females. Among study participants, chronic obstructive pulmonary disease patients were the most common 48 (43.6%) patients, followed by asthma 28 (25.5%), posttuberculosis sequelae patients 22 (20%), interstitial lung disease 9 (8.2%), and bronchiectasis 3 (2.7%) patients were found. There was a significant positive correlation of 6-min walk distance (6MWD) and % predicted 6MWD with spirometric parameters, forced expiratory volume in 1 s (FEV 1 ), forced vital capacity (FVC) and there was a significant positive correlation of 6MWD with FEV 1 % (predicted) also. 6MWD and % predicted 6MWD negatively correlated with FEV 1 /FVC and association between 6MWD and FEV 1 /FVC was not statistically significant and between % predicted 6MWD and FEV 1 /FVC, it was found statistically significant., Conclusion: The 6MWD traveled by chronic respiratory disease patients was significantly lower than the predicted 6MWD and 6MWD correlated with spirometric variables well. Therefore, it can conclude that 6MWT is a useful alternative of spirometry in the management of chronic respiratory disease patients in resource-limited settings., Competing Interests: None

Purpose: To gain insight into medication satisfaction and factors associated with chronic respiratory disease, particularly chronic obstructive pulmonary disease (COPD) in older adults, focusing on public health issues and improving the health of the older adult population., Methods: This cross-sectional study was conducted from October 2022 to November 2022 in 24 hospitals in different regions of Hunan Province, China. Older adult patient treatment satisfaction was assessed using the Treatment Satisfaction Questionnaire for Medication version II. Multiple regression analysis was used to identify factors independently associated with patient treatment satisfaction., Results: Only 15.9% of all patients scored above 80 in the effectiveness domain, while 11.6 and 16.5% scored above 80 in the convenience and global satisfaction domains, respectively, while 17.3% reported having side effects. Interstitial lung disease was associated with lower drug satisfaction than other disorders ( p  < 0.05). Multifactorial regression analysis showed that age, education background, profession, and smoking status were independently associated with satisfaction among patients with chronic respiratory diseases ( p  < 0.05). Education background, profession, CAT score, number of acute exacerbations, duration of home oxygenation and duration of home ventilator use were independently associated with satisfaction in patients with COPD ( p  < 0.05)., Conclusion: Low satisfaction with chronic respiratory drug therapy was associated with age, education background, profession and smoking status. Satisfaction was lower for patients with interstitial lung disease. For COPD, CAT score, education background, profession, number of acute exacerbations, home oxygen and ventilator use influence satisfaction. Clinicians can identify appropriate patients and communicate effectively with them throughout treatment and follow-up, vigorously promote smoking cessation and home oxygen therapy, increase medication satisfaction, especially among older adults, and in turn improve public health and the quality of life of older adults., 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 © 2023 Wu, Meng, Zeng, Ma and Chen.)

ActiGraph ® is a valid, frequently used, accelerometer to quantify moderate to vigorous physical activities (MVPA) in people with COPD. The impact of ActiGraph processing techniques on this population is unknown. This study aimed to explore the effect of data reduction techniques on MVPA in people with COPD. MVPA/day, through ActiGraph GT3X+, was estimated using: Troiano, Freedson 98 and FreedsonVM3 cutoffs, 15-s and 60-s epochs, and normal and low-frequency extension (LFE) filters. Cutoff, epoch, and filter effects were explored with Aligned Rank Transform-ANOVA. Lin's concordance correlation coefficients and Bland-Altman plots were used to evaluate agreement and bias between different techniques. The analysis included 136 people with COPD (79% male; 68 ± 8 years; FEV1 51 ± 17% predicted). MVPA/day differed according to cutoff, filter, and epoch selection ( p -value < 0.001). FreedsonVM3 cutoff, 15-s epochs, and LFE yielded the highest MVPA (45 min/day, 68% of physically active participants). Troiano cutoff, 60-s epochs, and normal filter yielded the lowest MVPA (8 min/day, 20% of physically active participants). Only comparisons between Troiano and Freedson98 cutoffs presented an almost perfect agreement. ActiGraph data reduction techniques affected MVPA/day estimates and their interpretation at the individual and group level. Studies using different processing criteria should not be compared in people with COPD. Future studies with a gold standard are required to ascertain which processing technique produces the most accurate MVPA estimates in COPD. Meanwhile, future trials employing the ActiGraph GT3X+ may consider estimating MVPA based on Freedson VM3 cutofffs, 60-s epochs, and normal filter.

Bronchi of chronic obstructive pulmonary disease (COPD) are the site of extensive cell infiltration, allowing persistent contact between resident cells and immune cells. Tissue fibrocytes interaction with CD8 + T cells and its consequences were investigated using a combination of in situ , in vitro experiments and mathematical modeling. We show that fibrocytes and CD8 + T cells are found in the vicinity of distal airways and that potential interactions are more frequent in tissues from COPD patients compared to those of control subjects. Increased proximity and clusterization between CD8 + T cells and fibrocytes are associated with altered lung function. Tissular CD8 + T cells from COPD patients promote fibrocyte chemotaxis via the CXCL8-CXCR1/2 axis. Live imaging shows that CD8 + T cells establish short-term interactions with fibrocytes, that trigger CD8 + T cell proliferation in a CD54- and CD86-dependent manner, pro-inflammatory cytokines production, CD8 + T cell cytotoxic activity against bronchial epithelial cells and fibrocyte immunomodulatory properties. We defined a computational model describing these intercellular interactions and calibrated the parameters based on our experimental measurements. We show the model's ability to reproduce histological ex vivo characteristics, and observe an important contribution of fibrocyte-mediated CD8 + T cell proliferation in COPD development. Using the model to test therapeutic scenarios, we predict a recovery time of several years, and the failure of targeting chemotaxis or interacting processes. Altogether, our study reveals that local interactions between fibrocytes and CD8 + T cells could jeopardize the balance between protective immunity and chronic inflammation in the bronchi of COPD patients., Competing Interests: EE, EM, JS, PH, PE, TT, JD, AL, AS, HB, MT, RH, RM, FL, PV, CC No competing interests declared, MZ MZ reports personal fees from AstraZeneca, Boehringer Ingelheim, Novartis, Chiesi, GlaxoSmithKline and non-financial support Lilly outside the submitted work, PG POG has a patent (EP 3050574: Use of plerixafor for treating and/or preventing acute exacerbations of chronic obstructive pulmonary disease) granted. POG reports grants, personal fees and non-financial support from AstraZeneca, personal fees and non-financial support from Chiesi, personal fees and non-financial support from GlaxoSmithKline, personal fees and non-financial support from Novartis, personal fees and non-financial support from Sanofi, outside the submitted work, PB PB has a patent (EP N3050574: Use of plerixafor for treating and/or preventing acute exacerbations of chronic obstructive pulmonary disease) granted. PB reports grants from AstraZeneca, Glaxo-Smith-Kline, Novartis, Chiesi, which support COBRA during the conduct of the study; grants and personal fees from AstraZeneca, BoehringerIngelheim, Novartis, personal fees and non-financial support from Chiesi, Sanofi, Menarini, outside the submitted work, ID ID has a patent (EP 3050574: Use of plerixafor for treating and/or preventing acute exacerbations of chronic obstructive pulmonary disease) granted, (© 2023, Eyraud et al.)

Background: Previous observational studies have found an association between gastroesophageal reflux disease (GERD) and chronic respiratory diseases, but it remains uncertain whether GERD causally influences these diseases. In this study, we aimed to estimate the causal associations between GERD and 5 chronic respiratory diseases., Methods: 88 GERD-associated single nucleotide polymorphisms (SNPs) identified by the latest genome-wide association study were included as instrumental variables. Individual-level genetic summary data of participants were obtained from corresponding studies and the FinnGen consortium. We applied the inverse-variance weighted method to estimate the causality between genetically predicted GERD and 5 chronic respiratory diseases. Furthermore, the associations between GERD and common risk factors were investigated, and mediation analyses were conducted using multivariable MR. Various sensitivity analyses were also performed to verify the robustness of the findings., Results: Our study demonstrated that genetically predicted GERD was causally associated with an increased risk of asthma (OR 1.39, 95%CI 1.25-1.56, P < 0.001), idiopathic pulmonary fibrosis (IPF) (OR 1.43, 95%CI 1.05-1.95, P = 0.022), chronic obstructive disease (COPD) (OR 1.64, 95%CI 1.41-1.93, P < 0.001), chronic bronchitis (OR 1.77, 95%CI 1.15-2.74, P = 0.009), while no correlation was observed for bronchiectasis (OR 0.93, 95%CI 0.68-1.27, P = 0.645). Additionally, GERD was associated with 12 common risk factors for chronic respiratory diseases. Nevertheless, no significant mediators were discovered., Conclusions: Our study suggested that GERD was a causal factor in the development of asthma, IPF, COPD and chronic bronchitis, indicating that GERD-associated micro-aspiration of gastric contents process might play a role in the development of pulmonary fibrosis in these diseases., (© 2023. The Author(s).)

The 77th National Conference of Tuberculosis and Chest Diseases was held on 27th February 2023. The workshop on Pulmonary rehabilitation and smoking cessation was conducted as a part of the various pre-conference workshops being conducted on the occasion. It helped the participants to know regarding the role, efficacy and benefits of pulmonary rehabilitation and smoking cessation for the management of Chronic respiratory diseases., (Copyright © 2023 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.)

Background: Although chronic respiratory diseases are prevalent in Saudi Arabia, there are limited data on the patient burden and associated factors. The aim of this study is to identify the chronic respiratory diseases frequently admitted to pulmonary services and to determine the patient's characteristics, associated comorbidities readmission rate, and reason for a more extended stay in hospital., Methods: A prospective study was conducted over a 5-year period at King Abdulaziz Medical City-Riyadh, Saudi Arabia, in the Pulmonary Division, between March 2015 and December 2019. Data on demographics, comorbidities, and chronic respiratory diseases were collected., Results: Total patients admitted were 1315 patients, female 54.2%, the mean age was 62.4 (SD±17.6), and the ages ranged from 14 to 98 years. Overall, chronic obstructive pulmonary disease was the most common respiratory disease requiring admission (17.9%), followed by interstitial lung disease (15.8%), bronchiectasis (11.9%), and obesity hypoventilation syndrome (10.8%). The most common comorbidities were obesity (42.5%), diabetes 49.1%, and hypertension 54.9%. Only 135 (10.3%) were readmitted within 30 days posthospital discharge. Among the patients who were readmitted, 103 (76.3%) were readmitted due to issues related to previous admission diagnosis, noncompliance 75 (55.5%), social reasons, and premature discharges in 51 (37.8%) and 29 (21.5%) of the cases, respectively. The respiratory disease varied significantly by gender, age, obesity status, comorbidities, length of stay (LOS), and admissions., Conclusion: Chronic respiratory diseases are prevalent in our population and are mainly influenced by gender, age, obesity status, comorbidities, LOS, and admissions. Policymakers and health professionals need to recognize the burden of chronic respiratory diseases on patients and health systems and implement effective prevention programs., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Annals of Thoracic Medicine.)

Summary: Background. Patients and Public Involvement in every stage of the patient-centered health research cycle is the key to the development of innovative solutions with an impact on patients' care. Methods. This protocol describes the development of ConectAR, a network to promote the involvement of patients with asthma and their carers in the health research cycle. Results. This protocol comprehends 4 tasks: 1) define the mission, vision, governance and activities of the network through focus groups; 2) establish the communication strategy and tools; 3) test the feasibility of the network in a Delphi study on the research priorities for asthma in Portugal; 4) coordination and dissemination activities. Conclusions. This network will improve research by ensuring that patients and carers have an active role in the co-creation of impactful solutions for asthma.

Introduction: In response to injury, epithelial cells release alarmins including thymic stromal lymphopoietin (TSLP), high mobility group-box-1 (HMGB1), interleukin (IL)-33 and -25 that can initiate innate immune responses. These alarmins are recognized as activators of T2-immune responses characteristic for asthma, but recent evidence highlighted their role in non-T2 inflammation, airway remodeling, and pulmonary fibrosis making them an attractive therapeutic target for chronic respiratory diseases (CRD)., Areas Covered: In this review, firstly we discuss the role of TSLP, IL-33, IL-25, and HMGB1 in the pathogenesis of asthma, COPD, idiopathic pulmonary fibrosis, and cystic fibrosis according to the published data. In the second part, we summarize the current evidence concerning the efficacy of the antialarmin therapies in CRD. Recent clinical trials showed that anti-TSLP and IL-33/R antibodies can improve severe asthma outcomes. Blocking the IL-33-mediated pathway decreased the exacerbation rate in COPD patients with more important benefit for former-smokers., Expert Opinion: Despite progress in the understanding of the alarmins' role in the pathogenesis of CRD, all their mechanisms of action are not yet identified. Blocking IL-33 and TSLP pathways offers an interesting option to treat severe asthma and COPD, but future investigations are needed to establish their place in the treatment strategies.

PI3Kδ is a lipid kinase which plays a key role in airway inflammatory conditions. Accordingly, the inhibition of PI3Kδ can be considered a valuable strategy for the treatment of chronic respiratory diseases such as Asthma and Chronic obstructive pulmonary disease (COPD). In this work, we describe our efforts to identify new PI3Kδ inhibitors following an "inhalation by design" strategy. Starting from the identification of a purine scaffold, we carried out a preliminary SAR expansion which led to the identification of a new hit characterized by a high enzymatic potency and moderate PI3Kδ selectivity. A subsequent optimization led to novel purine based derivatives with favorable in vitro ADME profiles, which might represent promising starting points for future development of new inhaled drug candidates., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Introduction: Growing evidence indicates that variations in the composition of the gut microbiota are linked to the onset and progression of chronic respiratory diseases (CRDs), albeit the causal relationship between the two remains unclear., Methods: We conducted a comprehensive two-sample Mendelian randomization (MR) analysis to investigate the relationship between gut microbiota and five main CRDs, including chronic obstructive pulmonary disease (COPD), asthma, idiopathic pulmonary fibrosis (IPF), sarcoidosis, and pneumoconiosis. For MR analysis, the inverse variance weighted (IVW) method was utilized as the primary method. The MR-Egger, weighted median, and MR-PRESSO statistical methods were used as a supplement. To detect heterogeneity and pleiotropy, the Cochrane and Rucker Q test, MR-Egger intercept test, and MR-PRESSO global test were then implemented. The leave-one-out strategy was also applied to assess the consistency of the MR results., Results: Based on substantial genetic data obtained from genome-wide association studies (GWAS) comprising 3,504,473 European participants, our study offers evidence that several gut microbial taxa, including 14 probable microbial taxa (specifically, 5, 3, 2, 3 and 1 for COPD, asthma, IPF, sarcoidosis, and pneumoconiosis, respectively) and 33 possible microbial taxa (specifically, 6, 7, 8, 7 and 5 for COPD, asthma, IPF, sarcoidosis, and pneumoconiosis, respectively) play significant roles in the formation of CRDs., Discussion: This work implies causal relationships between the gut microbiota and CRDs, thereby shedding new light on the gut microbiota-mediated prevention of CRDs., 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 © 2023 Shi, Zhao, Geng, Sun and Fan.)

Bronchial asthma (BA) complicated by obesity is a progressive disease phenotype that hardly responds to standard therapy. In this regard, it is important to elucidate cellular and molecular mechanisms of development of this comorbid pathology. In recent years, lipidomics has become an active research tool, opening new opportunities not only for understanding cellular processes in health and disease, but also for providing a personalized approach to medicine. The aim of this study was to characterize the lipidome phenotype based on the study of molecular species of glycerophosphatidylethanolamines (GPEs) in blood plasma of patients with BA complicated by obesity. Molecular species of GPEs were studied in blood samples of 11 patients. Identification and quantification of GPEs was carried out using high resolution tandem mass spectrometry. For the first time in this pathology, a change in the lipidome profile of molecular species of diacyl, alkyl-acyl and alkenyl-acyl HPEs of blood plasma was shown. In BA complicated by obesity, acyl groups 18:2 and 20:4 were dominated in the sn2 position of the molecular composition of diacylphosphoethanolamines. Simultaneously with the increase in the level of GPE diacyls with the fatty acids (FA) 20:4, 22:4, and 18:2, there was a decrease in these FAs in alkyl and alkenyl molecular species of GPEs, thus indicating their redistribution between subclasses. The eicosapentaenoic acid (20:5) deficiency at the sn2 position of alkenyl GPEs in patients with BA complicated by obesity indicates a decrease in the substrate for the synthesis of anti-inflammatory mediators. The resulting imbalance in the distribution of GPE subclasses, due to a pronounced increase in the content of diacyl GPE under conditions of the deficiency of molecular species of ether forms, can probably cause chronic inflammation and the development of oxidative stress. The recognized lipidome profile characterized by the modification of the basic composition and the chemical structure of GPE molecular species in BA complicated by obesity indicates their involvement in the pathogenetic mechanisms underlying BA development. The elucidation of particular roles of individual subclasses of glycerophospholipids and their individual members may contribute to the identification of new therapeutic targets and biomarkers of bronchopulmonary pathology.

Objective: to synthesize the Italian epidemiological contribution to knowledge on indoor pollution respiratory impact, and to analyze the perspective of some GARD countries on the health effects of indoor air pollution., Results: Italian epidemiological analytical studies confirmed a strong relationship between indoor air pollution and health in general population. Environmental tobacco smoke, biomass (wood/coal) fuel for cooking/heating and indoor allergens (house dust mites, cat and dog dander, mold/damp) are the most relevant indoor pollution sources and are related to respiratory and allergic symptoms/diseases in Italy and in other GARD countries such as Mexico, Brazil, Vietnam, India, Nepal and Kyrgyzstan. Community-based global health collaborations are working to improve prevention, diagnosis and care of respiratory diseases around the world, specially in low- and middle-income countries, through research and education., Conclusions: in the last thirty years, the scientific evidence produced on respiratory health effects of indoor air pollution has been extensive, but the necessity to empower the synergies between scientific community and local administrations remains a challenge to address in order to implement effective interventions. Based on abundant evidence of indoor pollution health effect, WHO, scientific societies, patient organizations and other members of the health community should work together to pursue the GARD vision of "a world where all people breathe freely" and encourage policy makers to increase their engagement in advocacy for clean air., (Copyright © 2023 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.)