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BMJ Open Respiratory Research

BMJ

Preprints posted in the last 30 days, ranked by how well they match BMJ Open Respiratory Research's content profile, based on 32 papers previously published here. The average preprint has a 0.03% match score for this journal, so anything above that is already an above-average fit.

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Primary Care Providers Journey with OSA Care, Challenges and Strategies: A Qualitative Study

Cho, W.; Cheng, M.; Blades, K.; David, O.; Tsai, W.; Povitz, M.; McBrien, K.; Donald, M.; Pendharkar, S.

2026-05-20 respiratory medicine 10.64898/2026.05.15.26353339 medRxiv
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Purpose: Obstructive sleep apnea (OSA) is a treatable chronic condition associated with significant health and societal consequences. Primary care providers (PCPs) often manage OSA with support from sleep specialists but face challenges navigating a complex system of care. By developing a Journey Map, we sought to identify factors influencing primary care OSA management and the associated PCPs' perspectives and emotions. Methods: Twenty-one Calgary-based PCPs were interviewed as part of a study evaluating a primary care management pathway for OSA. We used conventional content analysis, utilizing inductive coding to define journey phases and deductive coding via the Theoretical Domains Framework (TDF) to identify barriers and enablers. These were then mapped onto journey phases for OSA management to create a Journey Map. Results: The Journey Map included five phases of OSA care. PCPs described feeling neutral during the Learning phase and expressed neutral to positive emotions during the Patient Encounter and Diagnosing OSA phases. In contrast, the Initial Treatment and Ongoing Management phases were associated with neutral to negative emotional experiences. Barriers included limited OSA-related training and education, unclear roles among provider groups, and low patient engagement. Enablers included accessible knowledge resources, a shared key role in OSA screening, and availability of sleep testing. Opportunities to enhance primary care OSA management were identified at each step. Conclusion: This study identified several behavioural factors influencing PCP decision-making across the OSA care continuum. The Journey Map illustrates how high diagnostic confidence of PCPs shifts to escalating challenges and negative sentiment during treatment and long-term management of OSA. Keywords: obstructive sleep apnea; primary health care; health service delivery; process assessments; attitude of health personnel

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A Pilot Study of the EMPOWER Music-based Intervention to Reduce Pulmonary Air Trapping in COPD

Taylor, J.; Choi, J.; Abdolijomoor, A.; Brunkan, M. C.; Wilson, A. L.; Castro, M.; Stewart, N.; Hanson-Abromeit, D.; Lepping, R. J.

2026-06-02 respiratory medicine 10.64898/2026.05.26.26350616 medRxiv
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Rationale: Air trapping in functional areas of the lung is common in chronic obstructive pulmonary disease (COPD). We developed a novel music-based intervention, Engagement of Music for Pulmonary Obstruction With Expiratory Restoration (EMPOWER) aimed at reducing air trapping and functional small airways disease (fSAD) in patients with COPD. Objectives: We conducted a pilot study to assess if air trapping and fSAD in COPD patients are reduced by our targeted EMPOWER music-based singing intervention. Methods: Participants completed four weeks of singing and vocalizing with a board-certified music therapist. Pre- and post-intervention assessments of standard pulmonary function tests (PFTs), and quantitative computed tomography (qCT) lung imaging documented changes in air trapping. Pre- and post-intervention change in psychological and patient-reported outcomes of hope, emotional wellbeing, agency and COPD symptom burden were also obtained. Main Results: All five adult participants with COPD who enrolled completed the study and reported strong interest in continuing with a similar program. Additionally, we observed trends toward improvement in qCT-measured fSAD, six-minute walk distance, and patient-reported symptoms on the COPD Assessment Test. Conclusion: Results of this preliminary study showed improvements in both patient-reported and imaging-indicated respiratory outcomes, suggesting that targeted singing components in music-based interventions such as the EMPOWER intervention may support physiological lung function changes in COPD patients.

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Mapping the common and rare variant genetic risk landscape for pulmonary fibrosis with and without family history

Lucas, S.; Raspin, K.; Nelson, N.; Graham, P.; Chear, S.; Zappala, C.; Keir, G.; Goh, N.; Hopkins, P.; Ellis, S.; Navaratnam, V.; Cooper, W.; Glaspole, I.; Reynolds, P.; Chia, C.; Grainge, C.; Kendall, P.; Troy, L.; Nunez Martinez, N.; Peljto, A.; Fingerlin, T.; Schwartz, D.; Walsh, S.; Moodley, Y.; Walters, H.; Robertson, J.; Bryan, T.; Chambers, D.; Mackintosh, J.; Corte, T.; Dickinson, J. L.

2026-05-21 respiratory medicine 10.64898/2026.05.15.26351995 medRxiv
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Background Genetic studies to date are yet to define the major portion of the genetic risk for adult-onset pulmonary fibrosis (PF). Further the dearth of knowledge of clinically actionable variants for PF is hampering efforts to implement genetic testing to aid early diagnosis and improve disease management. Here we evaluated the contribution of rare and common variants to PF in cohorts with and without a family history of PF. Method Whole genome sequencing (WGS) was performed in a familial cohort comprising PF cases and their family members (85 individuals representing 55 families); and 122 cases from the Australian IPF Registry (AIPFR) with and without a self-reported family history of PF. WGS data were interrogated for rare potentially PF-causing variants in 33 genes previously associated with PF. Variants that were rare and predicted to be likely causative were formally curated using the American College of Medical Genetics and Association for Molecular Pathology (ACMG-AMP) guidelines. Additionally, to examine the common risk variant contribution, a weighted polygenic risk score (PRS) was generated using 16 previously IPF-associated common SNPs. PRS were generated from WGS for the 85 clinically confirmed familial cases and 122 AIPFR cases. In the remaining 202 AIPFR cases, PRS were generated from TaqMan genotyping data. Results Interrogation of WGS generated from 207 individuals with PF revealed multiple rare putative pathogenic variants in both familial and AIPFR cohorts. Formal curation revealed pathogenic (P) or likely pathogenic (LP) variants confirmed in TERT or RTEL1 in four families (7.3%) with the majority of remaining variants classified as variants of uncertain significance (VUS; 12.7%) in seven additional families. Amongst AIPFR participants, four variants met the threshold for classification as P/LP variants (3.3%), with a further six individuals found to harbour VUS following curation (4.9%). Overall weighted PRS did not differ significantly between individuals with familial PF or with no reported family history. However, PRS in all patient groups were significantly elevated compared with population controls. Conclusion VUS remain the major portion of rare variants identified in known PF -related genes. For ~80% individuals with a confirmed family history no potentially causative variants were identified in known PF related genes nor was there evidence that a high burden of common variants contributed to risk in these families. Similarly, we found no evidence that a high burden of common variants contributes to a significant proportion of risk PF in those individuals with no reported family history.

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Determinants of total and inhaled allergen-specific immunoglobulin E in the middle-aged and elderly population

Al Fatly, M.; Leonard, S.; van Daele, P.; Helleman, G.; Tobari-azandeh, E.; Lahousse, L.; Veenbergen, S.; Chaker, L.

2026-05-15 allergy and immunology 10.64898/2026.05.12.26352742 medRxiv
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Background: The determinants of immunoglobulin E (IgE) remain poorly understood in older adults, a population with an increasing burden of chronic diseases. Identifying IgE's determinants may improve its clinical interpretation in the evaluation of allergic and IgE-related conditions. Objective: To investigate age, sex, smoking, alcohol, body mass index (BMI), corticosteroid use, and season as potential determinants of total IgE (tIgE) and inhaled allergen-specific IgE (sIgE). Methods: Using Rotterdam Study data, we investigated the determinants of tIgE and sIgE using multivariable linear regression. Longitudinal changes and the effects of corticosteroids were assessed with linear mixed models. Results: We included 8769 participants, of which 478 had repeated IgE measurements. Age showed a U-shaped relationship with tIgE and L-shaped relationship with sIgE (both p<0.001). Women had lower tIgE (OR [95%CI]: 0.69 [0.65-0.74]), whereas current smokers (1.34 [1.23-1.46]), higher BMI (1.01 [1.01-1.02]), topical corticosteroid users (1.27 [1.07-1.50]) and inhaled corticosteroid users (1.93 [1.64-2.26]) showed higher tIgE. Women (0.96 [0.92-1.00]), former smokers (0.87 [0.83-0.91]) and current smokers (0.72 [0.68-0.76]) had lower sIgE, whereas topical corticosteroid users (1.20 [1.07-1.35]) and inhaled corticosteroid users (1.20 [1.07-1.35]) showed higher sIgE. Over time, tIgE and sIgE decreased (p<0.001) but did not significantly change after corticosteroid use. Conclusion: We identified age, sex, smoking, BMI, season and topical and inhaled corticosteroids as determinants of tIgE and sIgE. Incorporating these determinants may improve IgE's clinical interpretation for the diagnosis and management of allergic and IgE-related conditions. Future research should investigate how these determinants shape IgE's relationship with chronic diseases in aging populations.

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Influenza vaccine effectiveness against pneumonia and COPD exacerbations among patients with chronic obstructive pulmonary disease in Thailand: A national test-negative design study, 2013-2024

Chawalchitiporn, S.; Tantiyavarong, P.; Kittiwatanachod, J.; Naosri, S.; Prasert, K.; Praphasiri, P.

2026-05-27 epidemiology 10.64898/2026.05.26.26354178 medRxiv
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Background/Objectives: Influenza infection is a major trigger of pneumonia and acute exacerbations among patients with chronic obstructive pulmonary disease (COPD). However, national laboratory-confirmed evidence on influenza vaccine effectiveness (VE) in this high-risk population remains limited. This study aimed to estimate the effectiveness of seasonal influenza vaccination against influenza-associated pneumonia and COPD exacerbations among patients with COPD in Thailand.Methods: We conducted a nationwide retrospective test-negative design study using administrative healthcare data from the National Health Security Office linked with laboratory-confirmed influenza surveillance data between June 1, 2013, and May 31, 2025, covering twelve influenza seasons (2013-2024). COPD-related clinical episodes among patients aged [&ge;]40 years who presented with pneumonia or acute exacerbation of COPD and underwent RT-PCR testing for influenza were included. Multilevel Poisson regression models were used to estimate adjusted risk ratios (RRs), and VE was calculated as (1 - adjusted RR) x 100.Results: A total of 606,072 COPD-related clinical episodes were included, of which 192,224 (31.7%) were influenza-positive. The overall adjusted VE against influenza-associated pneumonia was 63.2% (95% CI: 62.5-64.0), while VE against influenza-associated COPD exacerbations was 67.0% (95% CI: 48.8-78.8). VE estimates were broadly similar across age groups and remained substantial across COPD severity strata. Although point estimates were numerically higher in severe and very severe COPD, subgroup differences should be interpreted cautiously.Conclusions: Seasonal influenza vaccination was associated with substantial protection against influenza-associated pneumonia and COPD exacerbations among patients with COPD in Thailand.

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Key stakeholder perspectives on implementation of mHealth and NCD- related interventions in Kenyan Emergency Departments.

Soma, G.; Mercado, L.; Rayo, J.; Armstrong-Hough, M.; Bernstein, S. L.; Abroms, L.; Ngaruiya, C.

2026-06-03 emergency medicine 10.64898/2026.06.01.26354650 medRxiv
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Abstract Background: Emergency Department (ED) populations are a high-risk group that are opportune for interventions targeting NCDs and NCD risk factors, like tobacco use. Mobile health (mHealth)interventions such as Text2Quit, a novel text message-based mHealth tool addressing tobacco cessation in the US, have demonstrated effectiveness for tobacco cessation and for ED-based mHealth interventions in High Income Countries (HIC). To successfully adapt and implement such mHealth interventions in limited resource settings like African EDs, it is essential to examine the implementation climate and engage key stakeholders. These implementers provide invaluable insight to understand healthcare system level factors that affect adoption, implementation and maintenance of the interventions. Methods: We conducted 12 semi-structured key informant interviews (KIIs) with ED administrators and staff including 2 departmental heads, 5 medical doctors, 3 nurses, and 2 clinical officers at a national referral hospital in Kenya. This was guided by RE-AIM framework indicators of Adoption, Implementation, and Maintenance (eg feasibility of intervention integration, and suggestions to improve implementation). Interviews were conducted in English, recorded, professionally transcribed and translated, and analyzed using a constant comparative analysis approach, according to grounded theory principles. Findings: Key informants were positive about the adoption of them Health intervention in Kenyan EDs and across different health facility levels in Kenya due to the perceived need for the program, facility and staff receptiveness and existing healthcare infrastructure to leverage. Recommended implementation strategies included follow-up mechanisms for program participants, inclusion of all healthcare cadres in implementation and increased sensitization and the use of champions. Barriers to Implementation in the ED included competing clinical priorities with emergency cases, limited staffing and shame associated with smoking. Conclusion: Implementing a mobile health tobacco cessation program like Text2Quit is feasible and acceptable in Kenyan EDs when supported by targeted strategies.

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Rental housing may contribute to racial and ethnic disparities in upper respiratory infections

Bhavnani, D.; Dunphy, P.; Wilkinson, M.; Haber, A. L.; Matsui, E. C.

2026-05-17 epidemiology 10.64898/2026.05.13.26351511 medRxiv
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Objective: Upper respiratory infections (URI) are the major trigger of asthma exacerbations in children with asthma and are more likely to be reported by Black and Mexican American children compared to White children in the US. We aimed to evaluate the extent to which obesity, nicotine exposure, household size, and socioeconomic status (SES) explained this excess URI risk among all children and among children with asthma. Study Design: Data collected on children aged 6-17 years from the National Health and Nutritional Examination Survey (2007-2012) were analyzed using survey weights and a mediation approach. Household SES was analyzed as a cumulative score reflecting income poverty ratio, education, and rental housing. URI was defined as cough, cold, phlegm, runny nose, or other respiratory illness (excluding hay fever and allergies) in the past 7 days. Results: Obesity and serum cotinine, a marker of nicotine exposure, explained little to none of the excess risk of URI while SES explained 36.4% (95% CI=34.1, 38.6) in Black and 28.5% (95% CI=26.7, 30.5) in Mexican American children. Living in rental housing and income poverty ratio<2, explained half (49.6%, 95% CI=46.9-52.3) and 20% (19.7%, 95% CI=18.9-20.5) of the excess URI risk among Black children, respectively. In Mexican American children, rental housing and low educational attainment each explained approximately 15-17% of the excess URI risk. Results were comparable among children with asthma. Conclusions: Markers of poverty, such as rental housing, contributed substantially to the excess risk of URI among Black and Mexican American children, including among those with asthma.

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Oxygen-based endotypes of Obstructive Sleep Apnea

Wellman, A.; Messineo, L.; Azarbarzin, A.; Esmaeili, N.; Aishah, A.; Vena, D.; Sumner, J.; White, D.; Sands, S.

2026-06-04 respiratory medicine 10.64898/2026.06.03.26354835 medRxiv
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Objective: Several endotypes contribute to the development of Obstructive Sleep Apnea (OSA). However, efforts to measure these endotypes have been challenging. In this paper, we propose a new method that overcomes some of these challenges. Methods: To test the feasibility of this new method, data from the Sleep Heart Health Study (SHHS) were analyzed and two oxygen-based endotypes were identified and plotted on a graphical model: the steady-state SpO2 and the SpO2 arousal threshold. The first is the oxygen saturation that would occur during sleep if there were no arousals, and it is a measure of upper airway collapsibility (a more collapsible airway produces a lower SpO2). The latter is the oxygen saturation that triggers arousals. These endotypes were validated by assessing their ability to detect positional and state-related changes in airway collapsibility and arousal threshold. Results: The study showed that it was feasible to measure oxygen-based endotypes in 95% of SHHS participants. As expected, steady-state SpO2 was lower during supine vs. non-supine sleep, as well as during REM vs. NREM sleep. Also, the SpO2 arousal threshold was similar between supine and non-supine sleep. However, SpO2 arousal threshold was not lower in REM sleep vs. NREM sleep. Therefore, in 3 of the 4 conditions, the oxygen-based endotypes moved in the expected direction due to positional or sleep state changes. Conclusion: Although further validation experiments are required, this study indicates that OSA endotyping using the pulse oximetry signal is feasible. The oxygen-based endotypes could be used to aid therapeutic decision making.

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Preferences for treatment for latent tuberculosis infection in primary care among people in the United States at increased risk of tuberculosis: a pilot survey

Aschmann, H. E.; Tang, A. S.; Lee, M.; Salcedo, K. L.; Murrill, M. T.; Chen, G.; Ouyang, Y.; Lui, K.; Rahman, M.; Flood, J.; Kerkhoff, A. D.; Lin, T. K.; Shete, P. B.; for the Tuberculosis Epidemiologic Studies Consortium,

2026-05-22 primary care research 10.64898/2026.05.20.26352199 medRxiv
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Objectives Tuberculosis (TB) in the United States disproportionately affects non-U.S.-born individuals. While testing this population for TB infection is recommended, little is known about individuals' willingness to take treatment for latent TB infection (LTBI). To address this gap, we conducted a pilot preference survey among individuals from countries with high TB incidence. Design Cross-sectional survey supported by language concordant community health workers. Setting Federally qualified health center, serving a primarily Asian immigrant community, in San Francisco. Participants Adults eligible for risk-based LTBI testing based on place of birth seeking primary care. Outcome measures Perspectives on TB disease, risk of reinfection, and willingness to accept treatment if diagnosed with LTBI conditional on different factors, such as side effects, costs, and other treatment burden. Results Among 60 participants, the median age was 48 years (interquartile range 35-63 years), 52% were women, and 100% spoke Chinese. Infecting others (n=35, 58%), risk of death (n=30, 50%), and potential isolation (n=25, 42%) were the most worrisome consequences of TB disease. Reinfection risk, risk of liver damage, cost, TB progression risk, clinic visits, and blood draws were most often considered moderately or very important when deciding whether to take LTBI treatment (n=53 to 57, 88-95%). While most participants (n=56, 93%) were willing to take treatment if diagnosed with LTBI even at a 10-year TB progression risk below 1% and willing to accept a risk of liver damage (n=41, 68%), less than half would accept LTBI treatment if there were any associated cost (n=28, 47%). Finally, many participants had concerns about their reinfection risk after completing LTBI treatment (n=34, 57%). Conclusions Amongst surveyed participants, TB disease and its consequences such as hospitalization, death and infecting others were worrisome, and participants had a high level of willingness to take treatment if diagnosed with LTBI. Future assessments of how people weigh tradeoffs regarding LTBI diagnosis and treatment could inform interventions to increase LTBI treatment acceptance and completion.

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Digital assessment of real-world physical activity in Pulmonary Hypertension: A Systematic Review and Meta-Analysis

Brehm, S.; Fiengo Tanaka, L.; Majeed, Y.; Barnikel, M.; Le Roux, C.; Ghiani, A.; Jansen, C.-P.; Jaeger, S. U.

2026-05-12 respiratory medicine 10.64898/2026.05.08.26351469 medRxiv
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BackgroundThe assessment of daily-life physical activity (DLPA) using wearables in patients with pulmonary hypertension (PH) can provide information on real-world function, potentially enhancing the evaluation of disease progression. Research QuestionWhat is the existing evidence on sensor-based DLPA assessment in patients with PH and its quality? Study Design and MethodsWe searched MEDLINE and Embase from inception to January 13, 2026, extracting data on devices, DLPA outcomes, and associations with clinical outcomes. We obtained pooled estimates through random-effects models and assessed evidence quality using a customized tool. ResultsWe identified 33 studies (29 adult, 4 pediatric) including 1,257 patients mainly with pulmonary arterial hypertension (PAH), followed by chronic thromboembolic PH (CTEPH), and only rarely with PH due to lung diseases and/or hypoxia. Participants were predominantly female, WHO functional class II-III. Most studies investigated step count and time spent in different physical activity levels, but showed substantial heterogeneity in devices and their utilization. The meta-estimate was 4,811 daily steps. A moderate positive correlation was found between daily step count and six-minute walking distance (6MWD) (r=0.59, 95%CI 0.47-0.69); a weak positive correlation was found between time spent in moderate-to-vigorous physical activity and 6MWD (r=0.38; 95% CI 0.26-0.49). Inconsistent wear-time definition, non-wear reporting and temporal misalignment of DLPA may compromise validity and comparability. InterpretationWearable-based DLPA assessment in PH is feasible, though high-quality evidence remains scarce. Future research should standardize procedures, terminology, and reporting of DLPA outcomes. Concordance with established measures such as the 6MWD, and their ability to predict clinical outcomes and disease progression need to be demonstrated.

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Neurodiversity in the Paediatric Chronic Pain Clinic: An Audit

Buechner, H.; Themistokleous, G.; Orr, M.; Lawson, E.; Smart, E.; Donaghy, A.; Wallace, E.

2026-06-03 pediatrics 10.64898/2026.06.02.26354725 medRxiv
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Objective: To compare the characteristics, management and outcomes of neurodivergent (ND) children with neurotypical (NT) children attending a chronic pain clinic. Design: An audit of all patients attending the clinic from 2010-2025 using electronic patient records. Setting: A tertiary pain centre in Scotland. Patients: 724 patients were included in the analysis, 193 (26%) were neurodivergent. Patients were included if they had a documented referral to the pain clinic and attendance to at least one clinic appointment. Patients were excluded if no pain clinic letter could be found on their records. Results: There was a significant increase in the percentage of children with neurodiversity attending the chronic pain clinic compared to neurotypical children (p = 0.004) accounting for over a third of children last seen in the period of 2023-2025. ND children were most likely to present with musculoskeletal pain compared with NT children (p = 0.033) representing over half of all ND children's presentations with pain. ND children were more likely to report being bedbound (18% ND, 13% NT, p = 0.0352) or needing a walking aid (40% ND, 25% NT, p = 0.000) due to chronic pain and had a higher number of referrals (ND median = 18.4, 1QR, NT median = 12.44, IQR10.28 p = 0.000). ND children were more likely to live in areas of deprivation (Cochran-Armitage test, Z -2.15, p = 0.0315). Conclusions: Children with neurodiversity are overrepresented in the chronic pain clinic, and more often present to tertiary services with musculoskeletal pain. They are more likely to have multiple referrals, spend longer with the pain service and less likely to be discharged due to pain improvement. These findings highlight the need for focused strategies to address chronic pain in neurodivergent children. Services should consider how best to identify and support children with neurodiversity and chronic pain. Key Messages {middle dot} What is already known on this topic: While there has been research regarding the role of neurodiversity in pain perception, there are gaps in knowledge regarding the influence of neurodiversity on the development and persistence of chronic pain in children. {middle dot} What this study adds: A growing proportion of neurodiverse children attended the pain clinic. Neurodiverse children presented with more severely impactful pain, they spent a longer duration of time within the pain clinic and were less likely to be discharged due to pain improvement. {middle dot} How this study might affect research, practice or policy: Identifying neurodiverse children as a patient group with distinct requirements may prompt adaptations in chronic pain management practices. This audit provides an initial framework for subsequent research.

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Neutrophil-primed immunopathology in poorly-controlled diabetes worsens matrix destruction in pulmonary tuberculosis

Thong, P. M.; Hu, T. H.; Ooi, J. S. G.; Loh, F. K.; Lee, H.; Bai, C.; Chong, H. T.; Chang, A. J. W.; Choong, C. V.; Galamay, L.; Beh, D. L. L.; Ang, A. X. Y.; Lum, L. H. W.; Yang, S. P.; Lim, A. Y. L.; Mok, S. F.; Vallejo, A. F.; Kao, S. L.; Chan, K. R.; Ong, C. W. M.

2026-05-26 respiratory medicine 10.64898/2026.05.24.26353970 medRxiv
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Background: Diabetes mellitus (DM) worsens pulmonary tuberculosis (TB) and drives systemic hyper-inflammation, but the underlying mechanisms remain unknown. Neutrophils have key roles in TB immunopathology and lung cavitation. Here, we determine the role of neutrophils in DMTB patients and in driving TB immunopathology. Methods: Sputum and plasma from 30 TB and 30 DMTB patients were analysed for proteases and cytokines using Luminex bead array. Whole blood transcriptomics identified transcriptional differences. Single-cell RNA sequencing characterised neutrophil subsets and dysregulated pathways. Neutrophil function of poorly-controlled DM patients (HbA1c>8%) and healthy controls (HC) were examined following Mycobacterium tuberculosis stimulation, including reactive oxygen species (ROS), neutrophil extracellular traps (NETs), and phagocytosis. Pathways were interrogated using chemical inhibitors, protein array and western blot. Results: Compared to non-diabetic TB patients, poorly-controlled DMTB patients showed up-regulated sputum MMP-8 and MMP-9, associated with increased collagen-destruction and lung cavity formation. Circulating neutrophil count and neutrophil-derived plasma MMP-8 were up-regulated, alongside transcriptional enrichment of extracellular matrix degradation and inflammatory pathways including TNF and RAGE. Single-cell profiling identified reduced cycling neutrophil subset and myelocytes in DMTB, with overall reduced antibacterial and cell-killing signatures. Ex vivo mycobacterial stimulation of DM neutrophils increased ROS and MMP-9 with impaired NETs and delayed phagocytosis. TNFR1, TNFR2, and RAGE were up-regulated. RAGE inhibition with rosiglitazone mitigated Mtb-induced ROS and MMP-8 release. Conclusion: DM worsens neutrophil-driven tissue destruction and inflammation in TB via dysregulated TNF and RAGE-signalling, priming neutrophils towards immunopathology. Targeting RAGE alongside tight glycaemic control may dampen neutrophil hyper-inflammatory responses to limit tissue destruction.

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Risk of apnoea-related cardiorespiratory instability in preterm infants is modulated by clinical, demographic and dynamic indicators

Chen, Y.; Ketheeswaranathan, V.; Fordington, S.; Baxter, L.; Stevens, F.; Zandvoort, C. S.; Gawthorpe, R.; Villarroel, M.; Berthouze, L.; Hartley, C.

2026-05-17 pediatrics 10.64898/2026.05.13.26353101 medRxiv
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Background: Apnoea of prematurity is common and may cause desaturation and/or bradycardia. There is marked variability in infants cardiorespiratory responses to apnoea, despite standardised clinical thresholds. Factors influencing apnoea-related cardiorespiratory instability and whether instability can be predicted warrant investigation. Methods: 181,511 apnoeas >5 seconds were identified from continuous physiological recordings from 146 preterm infants <37 weeks postmenstrual age. Cardiorespiratory instability was defined as bradycardia (>30% heart rate reduction) and/or oxygen desaturation (<85%). Mixed-effects models assessed clinical, demographic and dynamic modulators of the relationship between apnoea duration and cardiorespiratory instability. Machine learning (XGBoost) was used to train models to predict apnoea-related cardiorespiratory instability. Results: Longer duration apnoeas were associated with increased instability, although variability was substantial and 3.6% of apnoeas <10 seconds were associated with cardiorespiratory instability, while 61.2% of apnoeas [&ge;]20 seconds were not. Multiple clinical/demographic (postmenstrual and gestational age, sex, weight z-score, and ventilation mode) and dynamic (baseline heart rate, oxygen saturation, and recent apnoea clustering) factors were associated with increased instability risk. Apnoea-related cardiorespiratory instability could be predicted with a balanced test accuracy of 75.8% when incorporating all features, while a model using only clinical/demographic features achieved 66.0%. Conclusions: Multiple factors influence cardiorespiratory responses to apnoea. Predictive modelling may enable personalised apnoea definitions, improving individualised care.

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Distinct fibrotic, epithelial and immune transcriptomic programs in phenotypes of chronic lung allograft dysfunction

Ishiwata, T.; Berra, G.; Allen, J.; Burman, A.; Wilson, G.; Carter, Z.; Watanabe, T.; Solomon, M.; Keshavjee, S.; Yeung, J.; Juvet, S. C.; Martinu, T.

2026-05-28 bioinformatics 10.64898/2026.05.24.727536 medRxiv
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BackgroundChronic lung allograft dysfunction (CLAD) is the major cause of late mortality after lung transplantation and includes two principal phenotypes, bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS). RAS and other phenotypes with RAS-like opacities (RLO) on chest imaging have a poorer prognosis. Despite clear clinical and pathological differences, molecular distinctions between phenotypes remain poorly defined. We aimed to explore gene transcriptional profiles across CLAD phenotypes and relevant controls. MethodsWe performed bulk RNA sequencing on explanted lung tissue from 45 lung transplant recipients with end-stage CLAD (20 with RLO and 25 without RLO). Samples from twenty-seven control donor and lobectomy lungs and sixteen idiopathic pulmonary fibrosis (IPF) lungs served as comparators. Non-negative matrix factorization (NMF) was used to identify latent transcriptomic signatures, which were correlated with clinical, radiologic, and histopathologic features. ResultsNMF identified seven distinct gene signatures that segregated CLAD phenotypes. RLO-CLAD lungs were enriched for extracellular matrix remodeling and B-cell/plasma cell-associated signatures, overlapping partly with IPF, whereas non-RLO-CLAD showed relative enrichment of epithelial injury and surfactant-response pathways. Signatures related to epithelial homeostasis and ciliary/microtubule function were progressively reduced from control lungs to non-RLO-CLAD and were most suppressed in RLO-CLAD. ConclusionsRLO-CLAD and non-RLO-CLAD, aligning with RAS and BOS phenotypes, show distinct transcriptomic signatures. RLO-CLAD is characterized by profibrotic and humoral immune signatures with profound epithelial dysfunction, whereas non-RLO-CLAD shows relative enrichment of epithelial injury responses. These data provide molecular stratification of CLAD and support the development of phenotype-specific biomarkers and targeted therapies.

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Collagen crosslinking and organizational patterns reflect common disease processes in idiopathic pulmonary fibrosis and non-resolving acute respiratory distress syndrome

Nizamoglu, M.; Carpaij, O. A.; Borghuis, T.; Vonk, J. M.; Morrison, M. C.; Hanemaaijer, R.; Wolters, P. J.; Pillay, J.; Burgess, J. K.

2026-05-13 pathology 10.64898/2026.05.09.723675 medRxiv
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RationaleFibrotic lung diseases, such as idiopathic pulmonary fibrosis (IPF) and fibroproliferative remodeling in acute respiratory distress syndrome (ARDS), are characterized by increased extracellular matrix (ECM) deposition. However, measuring collagen accumulation alone does not capture differences in ECM organization or biochemical maturation that may distinguish persistent fibrosis from potentially reversible remodeling. ObjectivesTo examine collagen organization characteristics and mature (pyridinoline) collagen crosslinking amount in established end stage fibrotic lung disease (IPF) and fibroproliferation following an acutely damaged lung (non-resolving (NR) ARDS) and to investigate any relationships in these parameters and temporal tissue remodeling. MethodsHuman lung tissue samples from control subjects, patients with IPF, and NR-ARDS were analyzed. Collagen amount and fiber organization were digitally quantified using picrosirius red staining. Mature collagen crosslinking was assessed by quantification of pyridinoline crosslinks. Measurements and Main ResultsLung tissue from both IPF and NR-ARDS lungs had higher collagen content compared with controls. Collagen fiber organization differed between groups. IPF lungs exhibited collagen architectures consistent with established fibrosis, whereas NR-ARDS lungs showed altered but less stabilized collagen organization despite similarly elevated collagen levels. Mature collagen crosslinks were significantly higher in IPF lungs but not in NR-ARDS lungs compared to controls. Integrated analyses identified distinct disease-associated ECM phenotypes, indicating that higher collagen abundance in NR-ARDS, unlike IPF, is not accompanied by more mature and persistent collagen crosslinking. ConclusionsDespite shared increases in collagen content, IPF and NR-ARDS lungs differ fundamentally in collagen organization and crosslinking maturity, suggesting differences in the reversibility of these conditions.

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The Dermatology Life Quality Index is a useful patient reported outcome measure in individuals with severe erythema nodosum leprosum: a post-hoc analysis of the Methotrexate and Prednisolone study - MaPs in ENL

de Barros, B.; Maximus, N.; Sultana, F.; Acharya, B.; Pai, V. V.; Wakade, A.; Bhame, B.; Hamza, A.; Getachew, A.; Alinda, M. D.; Listiawan, M. Y.; Nigusse, S. D.; Deanna, D. A.; Napit, I.; Mahesh, M.; Darlong, J.; Nicholls, P.; Genser, B.; Lambert, S.; Lockwood, D. N. J.; Walker, S. L.

2026-05-24 dermatology 10.64898/2026.05.21.26353785 medRxiv
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BACKGROUND Erythema nodosum leprosum (ENL) is a severe inflammatory complication of leprosy associated with disability, morbidity and mortality. Impairment of health-related quality of life (HRQoL) in ENL has been reported using the Dermatology Life Quality Index (DLQI) and the 36-Item Short Form Health Survey (SF-36), the latter validated in people affected by leprosy. Understanding the correlation between these measures is important to determine whether the shorter dermatology-specific DLQI provides a valid and practical measure of HRQoL in ENL. OBJECTIVES To examine the relationship between DLQI and SF-36 scores in individuals with ENL using data from the Methotrexate and Prednisolone study in ENL (MaPs in ENL). METHODS A post-hoc analysis of prospectively collected HRQoL data from the trial sites in India, Indonesia, and Nepal of the MaPs in ENL multicentre randomised clinical trial was performed. HRQoL was assessed using the DLQI and SF-36 at enrolment and at weeks 24, 48 and 60. Associations between DLQI and SF-36 physical (PCS) and mental (MCS) component summary scores were evaluated using correlation analyses and multivariable linear regression at enrolment, and linear mixed-effects models during follow-up adjusted for age, sex, recruiting centre and enrolment SF-36 scores. RESULTS A total of 383 paired HRQoL assessments from 129 participants were analysed. At enrolment, HRQoL impairment was substantial (median DLQI 19, IQR 15-21; mean PCS 30.3 + - 7.3; mean MCS 33.3 + - 8.4). DLQI scores improved markedly during follow-up. Across all timepoints, DLQI was strongly inversely correlated with PCS and MCS (both p<0.001). In adjusted analyses, higher DLQI scores were consistently associated with lower PCS and MCS. At enrolment, each 1-point increase in DLQI was associated with a 0.66-point reduction in PCS and a 0.51-point reduction in MCS (both p<0.001). These associations remained strong during follow-up, with no evidence that they varied over time. CONCLUSIONS DLQI scores were strongly and consistently associated with SF-36 physical and mental health scores. These findings support the use of the DLQI as a practical patient reported outcome measure to assess the HRQoL associated with ENL and its change following treatment.

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Understanding problems and solutions related to accessing cervical screening for people with a physical disability, condition, impairment or difference

Kemp, E.; Sim, J.; Wright-Bevans, K.; Renke, S.; Chew-Graham, C. A.; Finney, A.; Harper, C.; Marlow, L. A.; Sherman, S. M.

2026-06-03 primary care research 10.64898/2026.05.27.26354052 medRxiv
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Background Physically Disabled women are less likely to access cervical screening than non-disabled women, yet little research has been conducted to understand the problems that Disabled women face or potential solutions. Methods A cross-sectional online survey was conducted with 1493 UK-based participants who identified as having a physical disability, impairment, condition, or difference that makes cervical screening difficult or impossible. Participants were presented with statements about cervical screening problems and potential solutions and asked to indicate agreement using a 5-point scale. They also provided open-ended comments. Data were analysed using descriptive statistics, multinomial logistic regression and thematic analysis. Results More than half of participants reported delaying/missing (46.8%) or never attending (8.8%) screening, with most of those (71.0% and 81.4% respectively) indicating that the main reason was disability-related factors. The highest levels of agreement for problems were for concerns about pain, embarrassment, and fear of what the test might find and for potential solutions were for having a doctor or nurse who is willing to try different solutions, discusses specific needs, and understands physical disability. Never-attendance (OR = 0.022, 95% CI 0.014, 0.035) and delaying or missing appointments, (OR = 0.057, 95% CI 0.043, 0.076) negatively predicted future screening attendance. Six themes were identified from open-ended comments, supporting and extending the quantitative findings. Conclusion Disabled women face the same problems related to cervical screening as non-disabled women and additionally face disability-specific problems. Cervical sample taker training should incorporate ways to support physically Disabled women to have equitable access to screening.

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Segmental Lung Sound Analysis in Obstructive Lung Diseases Using Electronic Stethoscope; a protocol to establish an acoustic repository

Anuradha, H.; Yasaratne, D.; GMRI, G.; Parakrama, E.; Severin, R.

2026-05-28 respiratory medicine 10.64898/2026.05.27.26354263 medRxiv
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Introduction Obstructive lung diseases (OLDs) are responsible for high rates of illness and death worldwide. Inflammation, chronic airflow limitation, and bronchial remodeling occur in OLD and eventually result in the unique respiratory sounds. Despite its subjective and having low reproducibility, still traditional auscultation using a manual stethoscope is the main method used to identify the lung sounds. Nevertheless, the combination of recent advancements in digital stethoscopes and AI (Artificial Intelligence) has permitted the objective measurement of lung sounds. Nevertheless, there is a lack of standardized, region-specific databases for AI training and validation. Even though lung sound classification is an emerging aspect in research and telerehabilitation the lobar wise acoustic pattern is still novel due to lack of prevailing database to train AI models. Identifying this gap this study aims to develop an acoustic repository and analyze the data using segmental lung sounds from patients with OLDs and healthy controls through an electronic stethoscope. Methods and analysis This is a cross sectional observational study involving 120 participants (60 OLD patients and 60 healthy controls). Lobar wise acoustic signals will be captured using an electronic stethoscope in healthy and diseases population. The data will be analyzed using Audacity software for annotations and then it will be used for feature extraction and statistical analysis. The acoustic features extracted through Audacity, will include frequency, intensity, pitch, and root mean square (RMS) energy. Repeated measures ANOVA will be applied to compare mean sound intensities across lung segments while Pearson correlation will be used to assess associations with body composition parameters. The data will then be standardized for AI-based diagnostic applications. Ethics and dissemination The study is being reviewed from the Ethics Review Committee, Faculty of Medicine, University of Peradeniya (2025/EC/87) will be sought. Informed consent will be obtained in writing. The dissemination of results will take place through peer-reviewed publications and the creation of a public database containing lung sounds from the region.

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Cross-Ancestry Remapping of the Chromosome 1q31 Th2 pathway-associated interval Refines an Asthma Association Signal in Patients with Steroid-Dependent Disease

Qu, H.-Q.; Qiu, H.; Mentch, F. D.; Cardinale, C. J.; Hakonarson, H.

2026-05-15 respiratory medicine 10.64898/2026.05.06.26352550 medRxiv
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Background: The chromosome 1q31 Th2 pathway-associated interval has been linked to asthma, but its phenotype specificity and cross-ancestry architecture remain unclear. Methods: We analyzed African (AFR) and European (EU) ancestry datasets, including 9,965 asthma cases and 37,391 controls of AFR, and 6,074 cases and 116,255 controls of EU ancestry. Imputed dosage-based association analyses were performed for asthma, steroid-dependent asthma (SDA), and non-steroid-dependent asthma, followed by QC-filtered SDA remapping, leave-one-batch-out analysis, cross-ancestry comparison, and functional enrichment. Results: Strong regional association was observed only for SDA. After quality-control (QC) filtering, the SDA signal remained significant in both ancestries, with 2,280 genome-wide significant variants in AFR and 859 in EU. Cross-ancestry comparison identified 3,129 significant variants: 10 shared, 2,270 AFR-specific, and 849 EU-specific. Shared variants showed concordant effects, whereas 237 variants showed nominal heterogeneity. AFR-specific signals included PTPRC variants with larger effects in AFR. Functional enrichment suggested different biological emphases within the same interval: immune and contractile airway-wall biology in AFR, and additional neuroaxonal components in EU. Conclusions: The 1q31 interval is strongly associated with SDA in both AFR and EU populations, and its fine-scale architecture differs by ancestry. These findings highlight population-specific effects within a shared SDA susceptibility interval, with potential implications for population-informed precision medicine in steroid responsiveness and asthma management.

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Association between remnant cholesterol-to-HDL-C ratio and obstructive sleep apnea risk in U.S. adults: a cross-sectional analysis of NHANES 2015-2018

Zhu, Z.; Shan, S.

2026-05-13 epidemiology 10.64898/2026.05.09.26352793 medRxiv
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BackgroundSeveral lipid ratios have been linked to obstructive sleep apnea (OSA) risk in NHANES, yet two questions central to clinical translation remain unanswered: how much of the association is carried by central adiposity, and whether the dose-response curve contains an actionable threshold. We addressed both for the remnant cholesterol-to-HDL-C ratio (RC/HDL-C). MethodsWe analysed 3,635 adults aged [&ge;]20 years from NHANES 2015-2018. OSA risk was ascertained from the Sleep Disorders Questionnaire. Multivariable logistic regression estimated odds ratios across three nested models. Restricted cubic splines and segmented regression characterised the dose-response and located the inflection point. Mediation by body roundness index (BRI) was quantified by nonparametric percentile bootstrap (1,000 resamples). Discrimination was compared by ROC analysis, with stratified and trimmed-sample sensitivity analyses. ResultsOSA risk was identified in 1,361 participants (37.4%). Each one-unit rise in RC/HDL-C carried 23% higher adjusted odds of OSA (OR 1.23, 95% CI 1.03-1.47); the highest quartile carried 49% higher odds than the lowest (P-trend < 0.001). The dose-response was nonlinear, with an inflection at RC/HDL-C = 0.232: below this point each 0.1-unit increase raised odds by 54% (OR 1.54, 95% CI 1.16-2.05); above it the curve plateaued. BRI mediated 82.7% of the total effect (ACME 0.039, P < 0.001), with the indirect pathway 2.8 times stronger in women. AUCs were 0.599 (BRI) and 0.564 (RC/HDL-C). ConclusionsRC/HDL-C showed a modest, threshold-shaped association with OSA risk in U.S. adults, with central adiposity (BRI) as the predominant mediating factor. These exploratory findings, based on questionnaire-defined OSA, warrant prospective validation in cohorts with polysomnography.