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Real-world impact of Elexacaftor-Tezacaftor-Ivacaftor treatment in young people with Cystic Fibrosis: A longitudinal study medRxiv. Respir. Med. Pub Date : 2024-03-16 Gary J Connett, Scott Maguire, Tom C Larcombe, Naomi Scanlan, Supriya S Shinde, Thilini Muthukumarana, Amanda Bevan, Ruth H Keogh, Julian P Legg
Introduction: Elexacaftor, Tezacaftor, Ivacaftor (ETI) became available in the UK in August 2020 to treat people with Cystic Fibrosis (CF) aged > 12 years. We report a real-world study of clinical outcomes in young people treated with ETI at our CF centre within the first two years of its availability. Methods: Participants aged 12 to 17 were identified within our clinic, with demographic data supplemented
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Quantifying Oxygen Demand by Patients Hospitalized with COVID-19 at a Large Safety-Net Hospital Using Multiple Methodologies medRxiv. Respir. Med. Pub Date : 2024-03-15 Sky Vanderburg, Tyler Law, Priya B. Shete, Elisabeth D. Riviello, Carolyn M. Hendrickson, Gregory D. Burns, Vivek Jain, Michael S. Lipnick
Background: During the COVID-19 pandemic, many facilities worldwide struggled to forecast oxygen demand, which often exceeded oxygen supply to the detriment of patient care. Accurate estimates of oxygen demand by patients with COVID-19 are scarce, and proposed estimation methods have not been fully evaluated or implemented. To address this knowledge gap, oxygen demand by COVID-19 patients was calculated
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Long-Term Clinical and Sustained REMIssion in Severe Eosinophilic Asthma treated with Mepolizumab: The REMI-M study medRxiv. Respir. Med. Pub Date : 2024-03-15 Claudia Crimi, Santi Nolasco, Alberto Noto, Angelantonio Maglio, Vitaliano Nicola Quaranta, Danilo Di Bona, Giulia Scioscia, Francesco Papia, Maria Filomena Caiaffa, Cecilia Calabrese, Maria D'Amato, Corrado Pelaia, Raffaele Campisi, Carolina Vitale, Luigi Ciampo, Silvano Dragonieri, Elena Minenna, Federica Massaro, Lorena Gallotti, Luigi Macchia, Massimo Triggiani, Nicola Scichilone, Giuseppe Valenti
Background: Biological therapies, such as mepolizumab, have transformed the treatment of severe eosinophilic asthma. While mepolizumab's short-term effectiveness is established, there is limited evidence on its ability to achieve long-term clinical remission. Objective: To evaluate the long-term effectiveness and safety of mepolizumab, explore its potential to induce clinical and sustained remission
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Proteogenomic analysis of air-pollution-associated lung cancer reveals prevention and therapeutic opportunities medRxiv. Respir. Med. Pub Date : 2024-03-13 Honglei Zhang, Chao Liu, Shuting Wang, Qing Wang, Xu Feng, Huawei Jiang, Yong Zhang, Xiaosan Su, Gaofeng Li
Air pollution significantly impact lung cancer progression, but there is a lack of a comprehensive molecular characterization of clinical samples associated with air pollution. Here, we performed a proteogenomic analysis of lung adenocarcinoma (LUAD) in 169 female never-smokers from the Xuanwei area (XWLC cohort), where coal smoke is the primary contributor to the high lung cancer incidence. Genomic
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Development and Validation of an Asthma Policy Model for Canada:Lifetime Exposures and Asthma outcomes Projection (LEAP) medRxiv. Respir. Med. Pub Date : 2024-03-13 Tae Yoon Lee, John Petkau, Kate M Johnson, Stuart Turvey, Amin Adibi, Padmaja Subbarao, Mohsen Sadatsafavi
Purpose: To develop Lifetime Exposures and Asthma outcomes Projection (LEAP), a reference policy model for evaluating health outcomes and costs of asthma interventions and policies for the Canadian population. Methods: Following the best practice guidelines for development, we first created a conceptual map with a steering committee of clinician experts and economic modelers through a modified Delphi-process
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Influence of frailty on cardiovascular events and mortality in patients with Chronic Obstructive Pulmonary Disease (COPD): Study Protocol for a multicentre European observational study. medRxiv. Respir. Med. Pub Date : 2024-03-13 Alessia Verduri, Enrico Clini, Ben Carter, Jonathan Hewitt
Background Frailty is a clinical state that increases susceptibility to minor stressor events. The risk of frailty is higher in chronic conditions, such as Chronic Obstructive Pulmonary Disease (COPD). Recent studies on COPD have shown that patients living with frailty have an increased risk of mortality. The presence of cardiovascular diseases or conditions are common in COPD and may increase the
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COPD with elevated sputum group 2 innate lymphoid cells is characterized by severe disease medRxiv. Respir. Med. Pub Date : 2024-03-07 Cameron Flayer, Angela Linderholm, Moyar Ge, Maya Juarez, Lisa Franzi, Tina Tham, Melissa Teuber, Shu-Yi Liao, Michael Schivo, Brooks Kuhn, Amir Zeki, Angela Haczku
Rationale: Pulmonary innate immune cells play a central role in the initiation and perpetuation of chronic obstructive pulmonary disease (COPD), however the precise mechanisms that orchestrate the development and severity of COPD are poorly understood. Objectives: We hypothesized that the recently described family of innate lymphoid cells (ILCs) play an important role in COPD. Methods: Subjects with
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Increased luminal area of large conducting airways in patients with COVID-19 and post-acute sequelae of COVID-19 A retrospective case-control study medRxiv. Respir. Med. Pub Date : 2024-03-02 Solomiia Zaremba, Alex J Miller, Erik A Ovrom, Jonathon W Senefeld, Chad C Wiggins, Paolo B Dominelli, Ravindra Ganesh, Ryan T Hurt, Brian J Bartholmai, Brian T Welch, Juan G Ripoll, Michael J Joyner, Andrew H Ramsook
Background Coronavirus disease 2019 (COVID–19) is associated with enlarged luminal areas of large conducting airways. In 10—30% of patients with acute COVID–19 infection, symptoms persist for more than 4 weeks (referred to as post–acute sequelae of COVID–19, or PASC), and it is unknown if airway changes are associated with this persistence. Thus, we aim to investigate if luminal area of large conducting
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Single cell sequencing reveals cellular landscape alterations in the airway mucosa of patients with pulmonary long COVID medRxiv. Respir. Med. Pub Date : 2024-02-28 Firoozeh V.Gerayeli, Hye Yun Park, Stephen Milne, Xuan Li, Chen Xi Yang, Josie Tuong, Rachel Eddy, Elizabeth Guinto, Chung Y Cheung, Julia Shun-Wei Yang, Cassie Gilchrist, Dina Yehia, Tara Stach, Tawimas Shaipanich, Jonathon Leipsic, Graeme Koelwyn, Janice Leung, Don D Sin
To elucidate the important cellular and molecular drivers of pulmonary long COVID, we generated a single-cell transcriptomic map of the airway mucosa using bronchial brushings from patients with long COVID who reported persistent pulmonary symptoms. Adults with and without long COVID were recruited from the general community in greater Vancouver, Canada. The cohort was divided into those with pulmonary
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Post Tuberculosis (TB) Bronchiectasis versus Non-TB Bronchiectasis in Northern Pakistan: A single centre retrospective cohort study on frequency, demographics, microbiology, and complications medRxiv. Respir. Med. Pub Date : 2024-02-20 Anbesan Hoole, Ahsan Ilyas, Matthew Cant, Sunaina Munawar, Rizwan Hameed, Shahzad Gill, Joel Riaz, Issac Siddiq
Introduction While Post Tuberculous (TB) Bronchiectasis is the most common cause of Bronchiectasis in South Asia, there has been little research into its microbiology and clinical characteristics in Pakistan. This single centre retrospective cohort study at Bach Christian Hospital (BCH) in rural Northern Pakistan seeks to address this issue. Methods Demographic, Imaging, Aetiological and Microbiological
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STUDY ABOUT THE EFFECTS OF SMOKING ON SLEEP APNEA IN A SAMPLE OF SYRIAN SOCIETY medRxiv. Respir. Med. Pub Date : 2024-02-18 Deena Osama Al Chaar, mudar Al Chaar, hussam Al bardan, Adele Al Chaar
Background To explore whether the use of cigarettes affects the prevalence of obstructive sleep apnea (OSA) in adults. Methods A questionnaire-based cross- sectional study was conducted among 233 participants. The questionnaire link was published on November 13, 2023 on social media sites and the Internet.The adults were divided into four groups: noncurrent smokers, current electronic cigarettes (e-cigarette)
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Anti-inflammatory effects of oral prednisolone at stable state in people treated with mepolizumab: a proteomic and bulk transcriptomics analysis medRxiv. Respir. Med. Pub Date : 2024-02-15 Imran Howell, Freda Yang, Vanessa Brown, Jennifer Cane, Emanuele Marchi, Adnan Azim, John Busby, Pamela Jane McDowell, Sarah Diver, Catherine Borg, Liam Heaney, Ian Pavord, Chris Brightling, Rekha Chaudhuri, Timothy SC Hinks
Mepolizumab is an anti-interleukin-5 monoclonal antibody treatment for severe eosinophilic asthma (SEA) that reduces asthma exacerbations. Residual airway inflammation on mepolizumab may lead to persistent exacerbations. Oral corticosteroids have broad anti-inflammatory effects and remain the main treatment for these residual exacerbations. Our study aimed to explore the nature and corticosteroid-responsiveness
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Clinical and economic burden of lower respiratory tract infection due to respiratory syncytial virus in young children in Germany medRxiv. Respir. Med. Pub Date : 2024-02-13 Caroline Beese, Lea Bayer, Bennet Huebbe, Jennifer Riedel, Sima Melnik, Gordon Brestrich, Christof Von Eiff, Tobias Tenenbaum
Background: Clinical and economic burden of infections due to respiratory syntactical virus (RSV) in children <2 years of age in Germany is still underestimated. Methods: In a retrospective health claims analysis, we identified RSV inpatient and outpatient episodes based on year-round specific RSV ICD-10 diagnoses or unspecified lower respiratory tract infection diagnoses during the RSV-season. High-risk
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Harnessing Deep Learning to Detect Bronchiolitis Obliterans Syndrome from Chest CT medRxiv. Respir. Med. Pub Date : 2024-02-08 Mateusz Kozinski, Doruk Oner, Jakub Gwizdala, Catherine Beigelman, Pascal Fua, Angela Koutsokera, Alessio Casutt, Michele De Palma, john-david Aubert, Horst Bischof, Christophe von Garnier, Sahand Rahi, Martin Urschler, Nahal Mansouri
Bronchiolitis Obliterans Syndrome (BOS), a fibrotic airway disease following lung transplantation, conventionally relies on pulmonary function tests (PFTs) for diagnosis due to limitations of CT images. Thus far, deep neural networks (DNNs) have not been used for BOS detection. We optimized a DNN for detection of BOS solely using CT scans by integrating an innovative co-training method for enhanced
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Racial and ethnic associations with interstitial lung disease and healthcare utilization in patients with systemic sclerosis medRxiv. Respir. Med. Pub Date : 2024-02-03 Ann-Marcia Comfort Tukpah, Jonathan Rose, Diane Seger, Gary Matt Hunninghake, David W Bates
Rationale: Racial and ethnic differences in presentation and outcomes have been reported in systemic sclerosis (SSc) and SSc-interstitial lung disease (ILD). However, diverse cohorts and additional modeling can improve understanding of risk features and outcomes, which is important for reducing associated disparities. Objective(s): To determine if there are racial/ethnic differences associated with
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Neighborhood Disadvantage Association with Sleep Apnea and Longitudinal Cardiovascular Events in a Large Clinical Cohort medRxiv. Respir. Med. Pub Date : 2024-02-03 Cinthya Pena-Orbea, David Bruckman, Jarrod E. Dalton, J Darryl Thornton, Jay L Alberts, Catherine M Heinzinger, Nancy Foldvary-Schaefer, Reena Mehra
Background The association between neighborhood socioeconomic disadvantage and poor cardiovascular outcomes is well established; however, less is known about its interplay with obstructive sleep apnea. Methods Adult cardiovascular disease-naïve patients who underwent sleep testing at Cleveland Clinic in Ohio from August of 1998 to August of 2021 were included in this cohort. The primary exposure was
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CARDIORESPIRATORY DYNAMICS DURING PRONE POSITIONING FOR SEVERE ARDS: A RETROSPECTIVE COHORT STUDY medRxiv. Respir. Med. Pub Date : 2024-02-02 Andrew Barros, Seung Wook Lee, J Randall Moorman
Objectives To elucidate the changes in cardiorespiratory dynamics during neuromuscular blockade and prone positioning and determine the associations between changes in cardiorespiratory dynamics following prone positioning and mortality. Design Single center retrospective cohort study of patients admitted to the medical ICU between June 1, 2020 and September 1, 2022 who received prone positioning while
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Disentangling Predictors of COPD Mortality with Probabilistic Graphical Models medRxiv. Respir. Med. Pub Date : 2024-02-01 Tyler C. Lovelace, Min Hyung Ryu, Minxue Jia, Peter Castaldi, Frank C Sciurba, Craig P. Hersh, Panayiotis Benos
Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of mortality. Predicting mortality risk in COPD patients can be important for disease management strategies. Although scores for all-cause mortality have been developed previously, there is limited research on factors that may directly affect COPD-specific mortality. We used probabilistic (causal) graphs to analyze clinical baseline COPDGene
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A systematic review of multi-variate time series approaches to extract predictive asthma biomarkers from routinely collected diary data medRxiv. Respir. Med. Pub Date : 2024-01-31 Franz Aaron Clemeno, Matthew Richardson, Salman Siddiqui
Objectives: Longitudinal data is commonly acquired in asthma studies, to help assess asthma progression in patients, and to determine predictors of future outcomes, including asthma exacerbations and asthma control. Different methods exist for quantifying temporal behaviour in routinely collected diary variables to obtain meaningful predictive biomarkers of asthma outcomes. The aims of this systematic
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Labored breathing pattern: an unmeasured dimension of respiratory pathophysiology medRxiv. Respir. Med. Pub Date : 2024-01-28 Valerie E Cyphers, Swet M Patel, Brendan D McNamara, William B Ashe, Sarah J Ratcliffe, Joseph Randall Moorman, Jessica Keim-Malpass, Shrirang Mukund Gadrey, Sherry L Kausch
Introduction: Respiratory failure is a common organ failure syndrome in hospitalized patients1. Vital sign monitoring (like respiratory rate & oximetry) is a necessary aspect of risk stratification, but it is not sufficient. In one study of hospitalized patients, 46% of the patients had no significant vital sign change in the 24 hours before an unplanned intubation2. Therefore, clinicians must also
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October 2018 – December 2023 time-series analysis of pediatric RSV immunizations and RSV-associated hospitalizations medRxiv. Respir. Med. Pub Date : 2024-01-25 Brianna M. Goodwin Cartwright, Samuel Gratzl, Patricia J Rodriguez, Charlotte Baker, Nick Stucky
This study describes two population under age two 1) who received an RSV immunization and 2) experienced RSV-associated hospitalizations since 2018. Results show low uptake of the RSV immunization. RSV-associated hospitalizations exhibited earlier and higher peaks in the 2021/22 and 2022/23 seasons compared to previous years.
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Neutrophil extracellular trap formation linked to idiopathic pulmonary fibrosis severity and survival medRxiv. Respir. Med. Pub Date : 2024-01-25 Scott M. Matson, Linh T. Ngo, Yui Sugawara, Veani Fernando, Claudia Lugo, Imaan Azeem, Alexis Harrison, Alex Alsup, Emily Nissen, Devin Koestler, Michael P. Washburn, Michaella J. Rekowski, Paul J. Wolters, Joyce S. Lee, Joshua J. Solomon, M. Kristen Demoruelle
Rationale Neutrophil counts in bronchoalveolar lavage fluid in idiopathic pulmonary fibrosis are associated with worse outcomes; however, the underlying mechanisms are unknown. Neutrophil extracellular trap formation is associated with worse outcomes in several chronic lung diseases however, there is an unknown role in idiopathic pulmonary fibrosis.
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Blood Cholesterol and Triglycerides Associate with Right Ventricular Function in Pulmonary Hypertension medRxiv. Respir. Med. Pub Date : 2024-01-22 Battoul Fakhry, Laura Peterson, Suzy A.A. Comhair, Jacqueline Sharp, Margaret Park, W. H. Wilson Tang, Donald R. Neumann, Frank P. DiFilippo, Samar Farha, Serpil C. Erzurum, Anny Mulya
Background: Blood lipids are dysregulated in pulmonary hypertension (PH). Lower high-density lipoproteins cholesterol (HDL-C) and low-density lipoproteins cholesterol (LDL-C) are associated with disease severity and death in PH. Right ventricle (RV) dysfunction and failure are the major determinants of morbidity and mortality in PH. This study aims to test the hypothesis that dyslipidemia is associated
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Diagnosis in children with prolonged or recurrent cough: findings from the Swiss Paediatric Airway Cohort medRxiv. Respir. Med. Pub Date : 2024-01-22 Maria Christina Mallet, Annina Elmiger, Sarah Glick, Tayisiya Krasnova, Carmen CM de Jong, Barbara Kern, Alexander Moeller, Nicolas Regamey, Oliver Sutter, Jakob Usemann, SPAC Study Team, Eva SL Pedersen, Claudia E. Kuehni
Introduction: Prolonged or recurrent cough is a common reason for referral to pediatric pulmonologists, yet few studies have assessed its causes. We examined records of children visiting respiratory outpatient clinics in Switzerland and assessed how diagnoses vary by age. Methods: We analyzed data from the multicenter Swiss Paediatric Airway Cohort study. We included 363 children (median age 6 years
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Diagnostic utility of in vivo expressed mycobacterial RNA transcripts in pleural fluid for the differential diagnosis of tuberculous pleuritis medRxiv. Respir. Med. Pub Date : 2024-01-11 Prabhdeep Kaur, Sumedha Sharma, Sudhanshu Abhishek Sinha, Ashutosh N. Aggarwal, Khushpreet Kaur, Rakesh Yadav, Sunil Sethi, Amanjit Bal, Indu Verma
Background Tuberculous pleuritis (TBP), the extra-pulmonary manifestation of tuberculosis, is the second most common after TB lymphadenitis. Histopathology using biopsy samples is the most sensitive diagnostic procedure for TBP, however the biopsy acquisition is invasive. Therefore, better screening markers for diagnosis using pleural fluid are required. The pathogen biomarkers expressed at the site
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JOINT CLINICAL AND MOLECULAR SUBTYPING OF COPD WITH VARIATIONAL AUTOENCODERS medRxiv. Respir. Med. Pub Date : 2024-01-10 Enrico Maiorino, Margherita De Marzio, Zhonghui Xu, Jeong Yun, Rob Chase, Craig P Hersh, Scott Weiss, Edwin Silverman, Peter Castaldi, Kimberly Glass
Chronic Obstructive Pulmonary Disease (COPD) is a complex, heterogeneous disease. Traditional subtyping methods generally focus on either the clinical manifestations or the molecular endotypes of the disease, resulting in domain-specific classifications that may not capture its full complexity. Here, we introduce an integrative approach based on variational autoencoders to integrate clinical and blood
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Priorities and barriers for research related to primary ciliary dyskinesia medRxiv. Respir. Med. Pub Date : 2024-01-09 Myrofora Goutaki, Yin Ting Lam, Bruna Rubbo, James D Chalmers, Panayiotis Kouis, Gemma Marsh, Jean-Francois Papon, Johanna Raidt, Phil Robinson, Laura Behan, Jane S Lucas
Background: Despite advances in primary ciliary dyskinesia (PCD) research, many questions remain; diagnosis is complex and no disease specific therapies exist. Using a mixed-methods approach, we aimed to identify priorities for clinical and epidemiological research and explore barriers to research. Methods: To obtain rich, relevant, diverse data, we performed in-depth semi-structured interviews with
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Assessing Causal Relationships Between Diabetes Mellitus and Idiopathic Pulmonary Fibrosis medRxiv. Respir. Med. Pub Date : 2024-01-04 Samuel Moss, Cosetta Minelli, Olivia Leavy, Richard Allen, Nick Oliver, Louise Wain, Gisli Jenkins, Iain Stewart
Rationale Idiopathic Pulmonary Fibrosis (IPF) is a disease of progressive lung scarring. There is a known association between IPF and diabetes mellitus (DM), but it is unclear whether this association is due to causal relationships between these traits.
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Diagnosis and Severity Assessment of COPD using a Novel Fast-Response Capnometer And Interpretable Machine Learning medRxiv. Respir. Med. Pub Date : 2023-12-21 Leeran Talker, Cihan Dogan, Daniel Neville, Rui Hen Lim, Henry Broomfield, Gabriel Lambert, Ahmed B Selim, Thomas Brown, Laura Wiffen, Julian C Carter, Helen F Ashdown, Gail Hayward, Elango Vijaykumar, Scott T Weiss, Anoop Chauhan, Ameera X Patel
Introduction Spirometry is the gold standard for COPD diagnosis and severity determination, but is technique-dependent, non-specific, and requires administration by a trained healthcare professional. There is a need for a fast, reliable, and precise alternative diagnostic test. This study's aim was to use interpretable machine learning to diagnose COPD and assess severity using 75-second carbon dioxide
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Age- and disease severity-associated changes in the nasopharyngeal microbiota of COVID-19 patients medRxiv. Respir. Med. Pub Date : 2023-12-22 Fernando Pérez-Sanz, Sylwia D. Tyrkalska, Carmen Álvarez-Santacruz, Antonio Moreno-Docón, Victoriano Mulero, María L. Cayuela, Sergio Candel
Dysbiosis has been linked to the pathogenesis of multiple diseases. Although dozens of publications have associated changes in the nasopharyngeal microbiota to patient’s susceptibility to COVID-19, results from these studies are highly variable and contradictory in many cases. Addressing the limitations in previous research responsible for that variability, this study uses 16S rRNA gene sequencing
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Deep immune profiling of chronic rhinosinusitis in allergic and non-allergic cohorts using mass cytometry medRxiv. Respir. Med. Pub Date : 2023-12-22 Fana Alem Kidane, Lena Müller, Marianne Rocha-Hasler, Aldine Tu, Victoria Stanek, Nicholas Campion, Tina Bartosik, Mohammed Zghaebi, Slagjana Stoshikj, Daniela Gompelmann, Andreas Spittler, Marco Idzko, Sven Schneider, Julia Eckl-Dorna
Background Chronic rhinosinusitis (CRS) is characterized by persistent nasal and paranasal sinus mucosa inflammation. It comprises two phenotypes, namely CRS with nasal polyps (CRSwNP) and without (CRSsNP). CRSwNP can be associated with asthma and hypersensitivity to non-steroidal anti-inflammatory drugs (NSAIDs) in a syndrome known as NSAID-exacerbated respiratory disease (N-ERD). Furthermore, CRS
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Single-cell analysis of bronchoalveolar cells in inflammatory and fibrotic post-COVID lung disease medRxiv. Respir. Med. Pub Date : 2023-12-19 Puja Mehta, Blanca Sanz-Magallon Duque de Estrada, Emma K Denneny, Kane Foster, Carolin T Turner, Andreas Mayer, Martina Milighetti, Manuela Plate, Kaylee B Worlock, Masahiro Yoshida, Jeremy S Brown, Marko Z Nikolic, Benjamin M Chain, Mahdad Noursadeghi, Rachel C Chambers, Joanna C Porter, Gillian S Tomlinson
Background: Persistent radiological lung abnormalities are evident in many survivors of acute coronavirus disease 2019 (COVID-19). Consolidation and ground glass opacities are interpreted to indicate subacute inflammation whereas reticulation is thought to reflect fibrosis. We sought to identify differences at molecular and cellular level, in the local immunopathology of post-COVID inflammation and
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Comparative transcriptomic analyses of peripheral blood mononuclear cells of patients with non-pneumonia and severe pneumonia at 1 year-Long-COVID-19 medRxiv. Respir. Med. Pub Date : 2023-12-14 Ozgecan Kayalar, Pelin Duru Cetinkaya, Vahap Eldem, Serap Argun Baris, Nurdan Koktürk, Selim Can Kuralay, Hadi Rajabi, Nur Konyalilar, Deniz Mortazavi, Seval Kubra Korkunc, Sinem Erkan, Gizem Tuşe Aksoy, Gul Eyikudamaci, Pelin Pinar Deniz, Oya Baydar Toprak, Pinar Yildiz Gulhan, Gulseren Sagcan, Neslihan Kose, Aysegul Tomruk Erdem, Fusun Fakili, Onder Ozturk, Ilknur Basyigit, Hasim Boyaci, Emel Azak
Long-COVID-19 manifests as a multisystemic condition with varied symptoms lingering beyond three weeks of acute SARS-CoV-2 infection, though its underlying mechanisms remain elusive. Aiming to decipher the long-term molecular impacts of COVID-19, we conducted a transcriptomic analysis on PBMCs from 1-year post-covid patients, including individuals without pneumonia (NP, n=10), those with severe pneumonia
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Identifying low-dimensional trajectories of mechanically-ventilated patient systems: Empirical phenotypes of joint patient+care processes to enhance temporal analysis in ARDS research medRxiv. Respir. Med. Pub Date : 2023-12-15 J.N. Stroh, Peter D. Sottile, Yanran Wang, Bradford J. Smith, Tellen D. Bennett, Marc Moss, David J. Albers
Mechanically ventilated patients generate waveform data that corresponds to patient interaction with unnatural forcing. This breath information includes both patient and apparatus sources, imbuing data with broad heterogeneity resulting from ventilator settings, patient efforts, patient-ventilator dyssynchronies, injuries, and other clinical therapies. Lung-protective ventilator settings outlined in
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Non-generalizability of biomarkers for mortality in SARS-CoV-2: a meta-analyses series medRxiv. Respir. Med. Pub Date : 2023-12-12 ME Rahman Shuvo, Max Schwiening, Felipe Soares, Oliver Feng, Susana Abreu, Niki Veale, Q Gao, William Thomas, AA Roger Thompson, Richard J Samworth, Nicholas W Morrell, Stefan J Marciniak, Elaine Soon
Rationale Sophisticated prognostic scores have been proposed for SARS-CoV-2 but do not always perform consistently. We conducted these meta-analyses to uncover why and to investigate the impact of vaccination and variants.
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Clinical risk factors and blood protein biomarkers of 10-year pneumonia risk medRxiv. Respir. Med. Pub Date : 2023-12-09 Ming-Ming Lee, Yi Zuo, Katrina Steiling, Joseph P. Mizgerd, Bindu Kalesan, Allan J. Walkey
Background Chronic inflammation may increase susceptibility to pneumonia.
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Respiratory rates among rural Gambian children: a community-based cohort study medRxiv. Respir. Med. Pub Date : 2023-12-06 Polycarp Mogeni, Sharon Amima, Jennifer Gunther, Margaret Pinder, Lucy S. Tusting, Umberto D’Alessandro, Simon Cousens, Steve W. Lindsay, John Bradley
Abstract Background: Although ranges of normal respiratory rates (RR) have been described for children under five years old living in the tropics, there are few datasets recording rates in older children. The present study was designed to capture the changes in RR with age and to examine its association with nutritional status and environmental factors. Methods: A cohort of rural Gambian children aged
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Age-related Muscle Fat Infiltration in Lung Screening Participants: Impact of Smoking Cessation medRxiv. Respir. Med. Pub Date : 2023-12-05 Kaiwen Xu, Thomas Z Li, James G Terry, Aravind R Krishnan, Stephen A Deppen, Yuankai Huo, Fabien Maldonado, John Jeffrey Carr, Bennett A Landman, Kim L Sandler
Rationale: Skeletal muscle fat infiltration progresses with aging and is worsened among individuals with a history of cigarette smoking. Many negative impacts of smoking on muscles are likely reversible with smoking cessation. Objectives: To determine if the progression of skeletal muscle fat infiltration with aging is altered by smoking cessation among lung cancer screening participants. Methods:
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Mitochondrial DNA Copy Number Variation in Asthma Risk, Severity, and Exacerbations medRxiv. Respir. Med. Pub Date : 2023-12-05 Weiling Xu, Yun Soo Hong, Bo Hu, Suzy A. A. Comhair, Allison J. Janocha, Joe G. Zein, Ruoying Chen, Deborah A. Meyers, David T. Mauger, Victor E. Ortega, Eugene R. Bleecker, Mario Castro, Loren C. Denlinger, John V. Fahy, Elliot Israel, Bruce D. Levy, Nizar N. Jarjour, Wendy C. Moore, Sally E. Wenzel, Benjamin Gaston, Chunyu Liu, Dan E. Arking, Serpil C. Erzurum
Rationale: Although airway oxidative stress and inflammation are central to asthma pathogenesis, there is limited knowledge of the relationship of asthma risk, severity, or exacerbations to mitochondrial dysfunction, which is pivotal to oxidant generation and inflammation. Objectives: We investigated whether mitochondrial DNA copy number (mtDNA-CN) as a measure of mitochondrial function is associated
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Connecting the Dots: Systematic Exploration of COVID-19 and Acute Kidney Injury through Meta-Analysis medRxiv. Respir. Med. Pub Date : 2023-12-02 Md. Safiullah Sarker, Rubiyat Jahan
Objective COVID-19 pandemic is a danger for the whole world. Also, our knowledge about acute kidney injury (AKI) in COVID-19 patients is incomplete. Few studies informed that the problem of AKI is a common complication, but other studies concluded that AKI is only an unusual event during COVID-19 infection. This study using meta-analysis tools aimed to find disease progression and mortality risk in
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Effect of mRNA vaccination on pulmonary sequelae after mild COVID-19 medRxiv. Respir. Med. Pub Date : 2023-12-04 Daniel Gagiannis, Carsten Hackenbroch, Fabian Zech, Frank Kirchhoff, Wilhelm Bloch, Katharina Junghans, Konrad Steinestel
Background: Previous studies indicate a protective role for SARS-CoV-2 vaccination against development of pulmonary post-acute sequelae of COVID (PASC). We compared clinical, imaging, histopathology and ultrastructural features of pulmonary PASC with and without prior vaccination in a consecutive cohort of 54 unvaccinated, 17 partially vaccinated and 28 fully vaccinated patients who presented with
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Impact of Treatment Adherence and Inhalation Technique on asthma outcomes of Pediatric Patients: A Longitudinal Study medRxiv. Respir. Med. Pub Date : 2023-11-30 Catalina Lizano-Barrantes, Olatz Garin, Karina Mayoral, Alexandra L. Dima, Angels Pont, M. Araceli Caballero-Rabasco, Manuel Praena-Crespo, Laura Valdesoiro-Navarrete, María Teresa Guerra, Alberto Bercedo-Sanz, Montse Ferrer, the ARCA Group
Introduction We aimed to evaluate the longitudinal relationships, both at between- and within-person levels, that adherence to inhaled corticosteroids-based maintenance treatment and inhalation technique present with symptom control, exacerbations, and health-related quality of life (HRQoL) in children and adolescents with asthma.
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Pulmonary microbiome and transcriptome signatures reveal distinct pathobiologic states associated with mortality in two cohorts of pediatric stem cell transplant patients medRxiv. Respir. Med. Pub Date : 2023-11-30 Matt S. Zinter, Christopher C. Dvorak, Madeline Y. Mayday, Gustavo Reyes, Miriam R. Simon, Emma M. Pearce, Hanna Kim, Peter J. Shaw, Courtney M. Rowan, Jeffrey J. Auletta, Paul L. Martin, Kamar Godder, Christine N. Duncan, Nahal R. Lalefar, Erin M. Kreml, Janet R. Hume, Hisham Abdel-Azim, Caitlin Hurley, Geoffrey D.E. Cuvelier, Amy K. Keating, Muna Qayed, James S. Killinger, Julie C. Fitzgerald, Rabi
Lung injury is a major determinant of survival after pediatric hematopoietic cell transplantation (HCT). A deeper understanding of the relationship between pulmonary microbes, immunity, and the lung epithelium is needed to improve outcomes. In this multicenter study, we collected 278 bronchoalveolar lavage (BAL) samples from 229 patients treated at 32 children’s hospitals between 2014-2022. Using paired
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The Development, Optimization, and Validation of Four Different Machine Learning Algorithms to Identify Ventilator Dyssynchrony medRxiv. Respir. Med. Pub Date : 2023-11-29 Peter D Sottile, Bradford Smith, Marc Moss, David J Albers
Objective Invasive mechanical ventilation can worsen lung injury. Ventilator dyssynchrony (VD) may propagate ventilator-induced lung injury (VILI) and is challenging to detect and systematically monitor because each patient takes approximately 25,000 breaths a day yet some types of VD are rare, accounting for less than 1% of all breaths. Therefore, we sought to develop and validate accurate machine
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Lipidomics for diagnosis and prognosis of pulmonary hypertension medRxiv. Respir. Med. Pub Date : 2023-11-29 Natalie Bordag, Bence Miklos Nagy, Elmar Zügner, Helga Ludwig, Vasile Foris, Chandran Nagaraj, Valentina Biasin, Ulrich Bodenhofer, Christoph Magnes, Bradley A. Maron, Silvia Ulrich, Tobias J. Lange, Konrad Hötzenecker, Thomas Pieber, Horst Olschewski, Andrea Olschewski
Background Pulmonary hypertension (PH) poses a significant health threat with high morbidity and mortality, necessitating improved diagnostic tools for enhanced management. Current biomarkers for PH lack functionality and comprehensive diagnostic and prognostic capabilities. Therefore, there is a critical need to develop biomarkers that address these gaps in PH diagnostics and prognosis.
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Correlation between Galanin and its receptor with the serum electrolytes in Long-COVID patients medRxiv. Respir. Med. Pub Date : 2023-11-27 Wasim Talib Mahdi Al Masoodi, Sami Waheed Radhi, Habiba Khdair Abdalsada, Hussein Kadhem Al-Hakeim
Background: Long-COVID is a complicated condition with prolonged SARS-CoV-2 symptoms. Several variables have been studied in this illness. Among the less studied variables are galanin and its receptor (GalR1). The Galanin system is involved in the pathophysiology of several age-related chronic disorders, including alcoholism, chronic pain, and bowel and skin inflammation. The aim of the study is to
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Navigational Bronchoscopy versus Computed Tomography-guided Transthoracic Needle Biopsy for the Diagnosis of Indeterminate Lung Nodules: protocol and rationale for the VERITAS multicenter randomized trial medRxiv. Respir. Med. Pub Date : 2023-11-23 Robert J. Lentz, Katherine Frederick-Dyer, Virginia B. Planz, Tatsuki Koyama, Matthew C. Aboudara, Briana Swanner, Lance Roller, See-Wei Low, Cristina Salmon, Sameer K. Avasarala, Todd C. Hoopman, Momen M. Wahidi, Kamran Mahmood, George Z. Cheng, James M. Katsis, Jonathan S. Kurman, Pierre-François D’Haese, Joyce Johnson, Eric L. Grogan, Charla Walston, Lonny Yarmus, Gerard A. Silvestri, Otis B. Rickman
Background Lung nodule incidence is increasing. Many nodules require biopsy to discriminate between benign and malignant etiologies. The gold-standard for minimally invasive biopsy, computed tomography-guided transthoracic needle biopsy (CT-TTNB), has never been directly compared to navigational bronchoscopy, a modality which has recently seen rapid technological innovation and is associated with improving
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CD206 upregulation in monocytes within whole blood cultures correlates with lung function in Cystic Fibrosis: a pilot study medRxiv. Respir. Med. Pub Date : 2023-11-17 Sonali Singh, Jessica Longmate, David Onion, Paul Williams, Miguel Camara, Alan R Smyth, Helen Barr, Luisa Martinez-Pomares
Chronic inflammation dominates disease pathogenesis in Cystic Fibrosis (CF) and there is a need to characterise CF immunity. Whole blood cultures offer a cost-effective and non-invasive approach to investigate immune responses within the host environment. Here we used whole blood cultures to investigate the differentiation potential of monocytes (CD45+CD14+ cells) in CF (N=10) and controls (N=8) in
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The effects of inhaled corticosteroids on healthy airways medRxiv. Respir. Med. Pub Date : 2023-11-16 Emanuele Marchi, Timothy Stopford Christopher Hinks, Matthew Richardson, Latifa Khalfaoui, Fiona Symon, Poojitha Rajasekar, Rachel Clifford, Beverley Hagardon, Cary D Austin, Julia MacIsaac, Michael S Kobor, Salman Siddiqui, Jordan S Mar, Joseph R Arron, David Choy, Peter H Bradding
Rationale: The effects of inhaled corticosteroids (ICS) on healthy airways are poorly defined. Objectives: To delineate the effects of ICS on gene expression in healthy airways, without confounding caused by changes in disease-related genes and disease-related alterations in ICS-responsiveness. Methods: Randomised open-label bronchoscopy study of high dose ICS therapy in 30 healthy adult volunteers
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Mapping the common barriers to optimal COPD care in high and middle-income countries: qualitative perspectives from clinicians medRxiv. Respir. Med. Pub Date : 2023-11-13 Orjola Shahaj, Anne Meiwald, Krishnan Puri Sudhir, Rupert Gara-Adams, Peter Wark, Alexis Cazaux, Abelardo Elizondo Rios, Sergey Avdeev, Elisabeth Jane Adams
Background: Although predominantly preventable and treatable, chronic obstructive pulmonary disease (COPD) is a leading cause of death globally. Guidelines for managing the condition are widely available, yet COPD care remains suboptimal in many settings, including high and middle-income countries (HICs and MICs). Several approaches are used to diagnose and manage COPD, resulting in substantial variation
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Impact of non-invasive ventilation on exacerbation frequency in COPD patients medRxiv. Respir. Med. Pub Date : 2023-11-13 Maximilian Zimmermann, Georgi Margalitadze, Doreen Kroppen, Wolfram Windisch, Daniel Sebastian Majorski, Melanie Berger, Sarah Bettina Stanzel, Maximilian Wollsching-Strobel
BACKGROUND: Acute exacerbations of COPD are key events in the natural course of the patients illness, as they significantly impair the health condition, accelerate the deterioration of lung function, worsen the prognosis for the patient and account for the majority of the COPD-related healthcare costs. Particularly in patients with a pre-existing non-invasive ventilation (NIV) therapy, a reduction
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The Association of Alpha Globin Gene Copy Number with Exhaled Nitric Oxide in a Cross-sectional Study of Healthy Black Adults medRxiv. Respir. Med. Pub Date : 2023-11-10 A. Parker Ruhl, Jarrett M. Jackson, Carlos J. Carhuas, Jessica G. Nino de Rivera, Michael P. Fay, Loretta G. Que, J. Brice Weinberg, Hans C. Ackerman
Introduction: The genetic determinants of fractional exhalation of nitric oxide (FeNO), a marker of lung inflammation, are understudied in Black individuals. Alpha globin (HBA) restricts nitric oxide signaling in arterial endothelial cells via interactions with nitric oxide synthase (NOS); however, its role in regulating the release of NO from respiratory epithelium is less well understood. We hypothesized
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Comparative sensitivity of Early Cystic Fibrosis Lung Disease detection tools in school aged children medRxiv. Respir. Med. Pub Date : 2023-11-07 Katie J Bayfield, Oliver Weinheimer, Anna Middleton, Christie Boyton, Rachel Fitzpatrick, Brendan Kennedy, Anneliese Blaxland, Geshani Jayasuriya, Neil Caplain, Mark O Wielpuetz, Lifeng Yu, Craig J Galban, Terry E Robinson, Brian Bartholmai, Per M Gustafsson, Dominic A Fitzgerald, Hiran Selvadurai, Paul D Robinson
Background: Effective detection of early lung disease in cystic fibrosis (CF) is critical to understanding early pathogenesis and evaluating early intervention strategies. We aimed to compare ability of several proposed sensitive functional tools to detect early CF lung disease as defined by CT structural disease in school aged children. Methods: 50 CF subjects (mean+/-SD 11.2+/-3.5y, range 5-18y)
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The effect of D-cycloserine on brain connectivity over a course of pulmonary rehabilitation medRxiv. Respir. Med. Pub Date : 2023-11-06 Sarah Louise Finnegan, Olivia Harrison, Martyn Ezra, Catherine J Harmer, Thomas E. Nichols, Najib M Rahman, Andrea Reinecke, Kyle T.S Pattinson
Rationale: Combining traditional therapies such as pulmonary rehabilitation with brain-targeted drugs may offer new therapeutic opportunities for the treatment of chronic breathlessness. Recent work has shown that D-cycloserine, a partial NMDA-receptor agonist which has been shown to enhance cognitive behavioural therapies, modifies the relationship between breathlessness related brain activity and
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Day-to-day Variability Indices improve utility of Oscillometry in Paediatric Asthma medRxiv. Respir. Med. Pub Date : 2023-11-06 Jane Hoang, Alexander Wong, Kate Hardaker, Sashritha Peiris, Ediane de Queiroz Andrade, Anneliese Blaxland, Penelope Field, Dominic A Fitzgerald, Geshani Jayasuriya, Chetan Pandit, Hiran Selvadurai, Greg G King, Cindy Thamrin, Paul D Robinson
Background Oscillometry may provide paediatric asthma with a feasible sensitive tools for objective remote monitoring. Methods School-aged cohorts of healthy, well controlled and poorly controlled asthma (defined as ≥2 exacerbations within preceding 12m) performed daily home-based oscillometry for 3-4 months (C-100 tremoflo, Thorasys Ltd), alongside objective measures of asthma control (ACQ weekly
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MDA5-autoimmunity and Interstitial Pneumonitis Contemporaneous with the COVID-19 Pandemic (MIP-C) medRxiv. Respir. Med. Pub Date : 2023-11-05 Khizer Iqbal, Saptarshi Sinha, Paula David, Gabriele De Marco, Sahar Taheri, Ella McLaren, Sheetal MAISURIA, Gururaj ARUMUGAKANI, Zoe Ash, Catrin BUCKLEY, Lauren COLES, Chamila HETTIARACHCHI, Gayle SMITHSON, Maria SLADE, Rahul Shah, Helena MARZO-ORTEGA, Mansoor Keen, Catherine Lawson, Joanna McLorinan, Sharmin NIZAM, Hanu Reddy, Omer Sharif, Shabina Sultan, Gui Tran, Mark WOOD, Samuel WOOD, Pradipta
Background: Anti-MDA5 (Melanoma differentiation-associated protein-5) positive dermatomyositis (MDA5+-DM) is characterised by rapidly progressive interstitial lung disease (ILD) and high mortality. MDA5 senses single-stranded RNA and is a key pattern recognition receptor for the SARS-CoV-2 virus. Methods: This is a retrospective observational study of a surge in MDA5 autoimmunity, as determined using
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Intra-breath oscillometry detects ventilation inhomogeneity in Cystic Fibrosis children medRxiv. Respir. Med. Pub Date : 2023-11-04 Tamara L Blake, Paul Robinson, Maddison Deery, Claire Wainwright, Zoltan Hantos, Peter D Sly
Background: Ventilation inhomogeneity (VI) is measured in patients with Cystic Fibrosis (CF) by lung clearance index (LCI) using the Multiple Breath Washout (MBW). In young children, feasibility is often low within busy clinical settings. Intra-breath oscillometry (IB-OSC) measures respiratory system reactance (Xrs), which is determined by the same physiological principles. Given the high feasibility
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Early Progressive Peripheral Airway Dysfunction after Allogeneic Haematopoietic Stem Cell Transplantation is associated with chronic Graft vs Host disease not BOS-0p medRxiv. Respir. Med. Pub Date : 2023-11-04 Christopher Htun, Robin Schoeffel, Sandra Rutting, Jacqueline Huvanandana, Cindy Thamrin, Alun Pope, Craig Phillips, Matthew Greenwood, Victoria Pechey, Gregory G King, Paul D Robinson
Background: Current spirometric-based criteria for diagnosis of bronchiolitis obliterans syndrome (BOS) may miss early peripheral airway disease associate with disease onset. Multiple breath washout (MBW) and oscillometry offer improved sensitivity, but longitudinal changes occurring in allogeneic haematopoietic stem cell transplantation (HSCT) are unknown. Objective: In this longitudinal study of
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Impaired lung function and lung cancer risk in 461,183 healthy individuals: a cohort study medRxiv. Respir. Med. Pub Date : 2023-10-31 Thu Win Kyaw, Min-Kuang Tsai Tsai, Chi-Pang Wen, Chin-Chung Shu, Ta-Chen Su, Xifeng Wu, Wayne Gao
Background It has been known that smoking and various lung diseases including lung cancer can cause lung function impairment. However, the impact of different types of lung function impairments, such as preserved ratio impaired spirometry (PRISm) and airflow obstruction (AO), on the incidence and mortality of lung cancer in both general and never-smoker populations remains unclear. We wished to examine
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Comparison of nasopharyngeal swab vs. lower respiratory tract specimen PCR for the diagnosis of Pneumocystis jirovecii pneumonia medRxiv. Respir. Med. Pub Date : 2023-10-30 Rusheng Chew, Sarah Tozer, Kimberly Ulett, David Paterson, David Whiley, Theo Sloots, David Fielding, Christopher Zappala, Farzad Bashirzadeh, Justin Hundloe, Cheryl Bletchley, Marion Woods
Background and objective. Diagnosis of P. jirovecii pneumonia (PJP) is by PCR on lower respiratory tract specimens, the collection of which is not always well-tolerated and requires trained staff and costly equipment not usually available in low-resource settings. We aimed to evaluate P. jirovecii PCR performed on nasopharyngeal swabs (NPS) as a diagnostic test for PJP, as well as the impact of specimen