Featured
-
-
Article
| Open AccessImpacts of human mobility on the citywide transmission dynamics of 18 respiratory viruses in pre- and post-COVID-19 pandemic years
Population mobility is associated with SARS-CoV-2 transmission but its impacts on other respiratory viruses are not well understood. Here, the authors investigate associations between mobile phone-derived mobility metrics and the dynamics of 18 respiratory viruses in Seattle, Washington from 2018 to 2022.
- Amanda C. Perofsky
- , Chelsea L. Hansen
- & Cécile Viboud
-
Article
| Open AccessA common polymorphism in the Intelectin-1 gene influences mucus plugging in severe asthma
Type 2 inflammation drives the formation of pathologic mucus in patients with asthma. Here, authors reveal a role for intelectin-1 in IL-13-induced mucus properties, and that an ITLN1 eQTL is associated with protection from the formation of mucus plugs in T2-high asthma.
- Jamie L. Everman
- , Satria P. Sajuthi
- & Max A. Seibold
-
Article
| Open AccessGenetic association of inflammatory marker GlycA with lung function and respiratory diseases
Here, the authors observed significant genetic correlation of GlycA with lung function, asthma and COPD and identified ten shared loci revealing potential shared biological mechanisms involving ubiquitination and Wnt/β-catenin signaling.
- Yanjun Guo
- , Quanhong Liu
- & Weihong Chen
-
Article
| Open AccessSingle-cell division tracing and transcriptomics reveal cell types and differentiation paths in the regenerating lung
This study uses single-cell transcriptomics to examine how lung cells respond to targeted damage. The authors employ genetically modified mouse models and cell sorting to enrich for rare, actively dividing cells, revealing cell types/states and alternative differentiation paths.
- Leila R. Martins
- , Lina Sieverling
- & Claudia Scholl
-
Article
| Open AccessFrequency, kinetics and determinants of viable SARS-CoV-2 in bioaerosols from ambulatory COVID-19 patients infected with the Beta, Delta or Omicron variants
SARS-CoV-2 can be spread by aerosols. Here the authors show that between 50-60% of ambulatory COVID-19 patients exhale culturable virus and that this is associated with lower neutralizing antibody titers and suppression of immune related transcriptomic pathways.
- S. Jaumdally
- , M. Tomasicchio
- & K. Dheda
-
Article
| Open AccessLong-term exposure to ambient PM2.5, particulate constituents and hospital admissions from non-respiratory infection
The study evaluated the impact of PM2.5 and its constituents on hospital admissions from non-respiratory infection. Here, the authors showed that nonrespiratory infections are an under-appreciated health effect of PM2.5 while Sulfates contributed the largest weights in the observed associations
- Yijing Feng
- , Edgar Castro
- & Joel Schwartz
-
Article
| Open AccessComparative effectiveness of alternative intervals between first and second doses of the mRNA COVID-19 vaccines
The optimal timing between first and second mRNA COVID-19 vaccine doses has not been established. Here, the authors use electronic health record data from Georgia, USA in a target trial emulation study to estimate vaccine effectiveness against infection for different dose intervals.
- Kayoko Shioda
- , Alexander Breskin
- & Elizabeth T. Rogawski McQuade
-
Article
| Open AccessHHV-6B detection and host gene expression implicate HHV-6B as pulmonary pathogen after hematopoietic cell transplant
Lower respiratory tract disease is a common complication after allogeneic hematopoietic cell transplant (HCT), but underlying reasons remain unclear. Here the authors show that HHV-6B detection in the lungs of allogeneic HCT recipients is associated with increased risk for death and distinct host gene expression profiles, implicating HHV-6B as a pulmonary pathogen in these patients.
- Joshua A. Hill
- , Yeon Joo Lee
- & Michael Boeckh
-
Article
| Open AccessCullin5 drives experimental asthma exacerbations by modulating alveolar macrophage antiviral immunity
Asthma may be exacerbated by respiratory viral infection, but the cellular and molecular mechanisms are still unclear. Here the authors show, using mouse models of asthma with influenza infection, that asthma-induced cullin5 in alveolar macrophages suppresses IFN-β production to promote neutrophilic inflammation but dampens antiviral immunity.
- Haibo Zhang
- , Keke Xue
- & Lei Sun
-
Article
| Open AccessIncidence and transmission of respiratory syncytial virus in urban and rural South Africa, 2017-2018
Respiratory syncytial virus (RSV) causes a high burden of disease in children, particularly in lower- and middle-income countries. In this prospective household-based observational cohort study in South Africa, the authors estimate the incidence of RSV and identify risk factors for transmission.
- Cheryl Cohen
- , Jackie Kleynhans
- & Stefano Tempia
-
Article
| Open AccessEpithelial SIRT6 governs IL-17A pathogenicity and drives allergic airway inflammation and remodeling
IL-17 mediated inflammation in the lung is mediated by different effector molecules. Here the authors show that the epigenetic regulator epithelial sirtuin 6 (Sirt6) is associated with lung inflammation in asthma patients and that Sirt6 contributes to promotion of inflammation in mouse asthma models.
- Jingyun Quan
- , Xiaoxia Wen
- & Tianwen Lai
-
Article
| Open AccessActivation of ILC2s through constitutive IFNγ signaling reduction leads to spontaneous pulmonary fibrosis
Idiopathic Pulmonary Fibrosis (IPF) consists of lung inflammation and collagen deposition leading to reduced lung function and non-inducible mouse models are needed. Here the authors show a spontaneous mouse IPF model where Ifngr1-/-Rag2-/- mice show enhanced ILC2 activation and function along with pathology similar to IPF.
- Natsuko Otaki
- , Yasutaka Motomura
- & Kazuyo Moro
-
Article
| Open AccessMaternal antibiotic exposure enhances ILC2 activation in neonates via downregulation of IFN1 signaling
Treatment of pregnant animals with antibiotics can have unexpected effects on offspring. Here the authors use mouse models to show that antibiotic treatment of mothers leads to changes in ILC2 phenotype in neonatal lungs accompanied by changes in the microbiota and microbiota derived butyrate.
- Haixu Xu
- , Xianfu Yi
- & Jie Zhou
-
Article
| Open AccessEstimating the potential impact and diagnostic requirements for SARS-CoV-2 test-and-treat programs
Antivirals are now available for treating COVID-19 but must be used early in the course of infection to be effective. Here, the authors use mathematical modelling to assess the potential public health impacts of antiviral use considering different levels of testing and country sociodemographic characteristics.
- Alvin X. Han
- , Emma Hannay
- & Colin A. Russell
-
Article
| Open AccessAssessing the value of integrating national longitudinal shopping data into respiratory disease forecasting models
Novel indicators of infectious disease prevalence could improve real-time surveillance and support healthcare planning. Here, the authors show that sales data for non-prescription medications from a UK high street retailer can improve the accuracy of models forecasting mortality from respiratory infections.
- Elizabeth Dolan
- , James Goulding
- & Laila J. Tata
-
Article
| Open AccessEvaluation of pragmatic oxygenation measurement as a proxy for Covid-19 severity
There is a need for an accurate measure of pulmonary oxygenation function that can be used as an intermediate endpoint in pragmatic clinical trials, to increase statistical power and efficiency. Here, the authors show that the S/F94, a modification of the S/F ratio, is a simple, meaningful and effective intermediate outcome measure.
- Maaike C. Swets
- , Steven Kerr
- & J. Kenneth Baillie
-
Article
| Open AccessTLR7 promotes smoke-induced experimental lung damage through the activity of mast cell tryptase
Toll-like receptor 7 (TLR7) normally recognizes exogenous single-stranded RNA for the activation of innate immunity. Here the authors show that TLR7 may also contribute, via the modulation of mast cell functions, to experimental, cigarette smoke-induced mouse models of emphysema, thereby hinting TLR7 as a potential therapeutic target for human lung inflammation.
- Gang Liu
- , Tatt Jhong Haw
- & Philip M. Hansbro
-
Article
| Open AccessRNA m6A methylation modulates airway inflammation in allergic asthma via PTX3-dependent macrophage homeostasis
The function of METTL3 and RNA methylation is important in various biological processes. Here the authors show that METTL3 is reduced in childhood asthma patients and that conditional knockout of Mettl3 in mouse myeloid cells enhances Th2 response and allergic asthma associated with changes in macrophage function.
- Xiao Han
- , Lijuan Liu
- & Yufeng Zhou
-
Article
| Open AccessThe airway microbiota of neonates colonized with asthma-associated pathogenic bacteria
Here, Thorsen et al. bridge new and previous results from the COPSAC2000 prospective birth cohort and the later COPSAC2010 cohort, by constructing a combined bacterial pathogen score with implications for the early-life airway microbiota and the risk of asthma later in childhood
- Jonathan Thorsen
- , Xuan Ji Li
- & Jakob Stokholm
-
Article
| Open AccessLung extracellular matrix modulates KRT5+ basal cell activity in pulmonary fibrosis
Idiopathic pulmonary fibrosis has been associated with aberrant expansion of KRT5-expressing basal cells. Here the authors show how changes in the ECM glycoprotein SPARC restrict the movement of KRT5+ cells, affecting their retention within fibrotic tissue.
- Richard J. Hewitt
- , Franz Puttur
- & Clare M. Lloyd
-
Article
| Open AccessBridging of host-microbiota tryptophan partitioning by the serotonin pathway in fungal pneumonia
Serotonin regulates mood as well as intestinal homeostasis, but its role in lung immune homeostasis is less clear. Here, Renga et al. show that serotonin regulates immune and microbial metabolic functions in respiratory pneumonia, beyond its mood regulatory function, by modulating tryptophan metabolism in the cystic fibrosis lung.
- Giorgia Renga
- , Fiorella D’Onofrio
- & Luigina Romani
-
Article
| Open AccessEpigenome-wide association analysis of infant bronchiolitis severity: a multicenter prospective cohort study
DNA methylation patterns that are associated with disease can reveal genes involved in disease etiology. Here, the authors identify blood DNA methylation signatures that are associated with bronchiolitis severity and play important roles in tissues, cells, and pathways.
- Zhaozhong Zhu
- , Yijun Li
- & Kohei Hasegawa
-
Article
| Open AccessAutocrine TGF-β-positive feedback in profibrotic AT2-lineage cells plays a crucial role in non-inflammatory lung fibrogenesis
IPF is a progressive disease with few inflammatory pathology. Here, using alveolar organoid technology, the authors identified autocrine TGF-β-positive feedback in AT2-lineage cells as a core mechanism of inflammation-independent lung fibrogenesis.
- Yasunori Enomoto
- , Hiroaki Katsura
- & Mitsuru Morimoto
-
Article
| Open AccessDelayed gut microbiota maturation in the first year of life is a hallmark of pediatric allergic disease
Here, using participants in the CHILD birth cohort, the authors reveal that impaired 1-year microbiota maturation may be universal to 5-year pediatric allergies, mediated by functional and metabolic imbalances of compromised mucous integrity, elevated oxidative activity, decreased fermentation, and elevated trace amines.
- Courtney Hoskinson
- , Darlene L. Y. Dai
- & Stuart E. Turvey
-
Article
| Open AccessTrimannose-coupled antimiR-21 for macrophage-targeted inhalation treatment of acute inflammatory lung damage
Macrophages are increasingly recognized as key drivers of lung damage in acute pneumonia including COVID-19. Here, the authors report on a first-in-class, inhalable, carbohydrate-coupled microRNA-inhibitor for selective targeting of macrophages and that prevents pulmonary hyperinflammation.
- Christina Beck
- , Deepak Ramanujam
- & Stefan Engelhardt
-
Article
| Open AccessSafety and immunogenicity of a phase 1/2 randomized clinical trial of a quadrivalent, mRNA-based seasonal influenza vaccine (mRNA-1010) in healthy adults: interim analysis
Here the authors report initial findings of a phase 1 clinical trial, showing that an investigational, mRNA-based vaccine for seasonal influenza (mRNA-1010) has no safety concerns and produces immune responses in adults that are similar or higher than a licensed comparator vaccine.
- Ivan T. Lee
- , Raffael Nachbagauer
- & Robert Paris
-
Article
| Open AccessDeep learning to estimate lung disease mortality from chest radiographs
Risk assessment of lung disease mortality is currently limited. Here, authors show that deep learning can estimate lung disease mortality from a chest x-ray beyond risk factors, which may help to identify individuals at risk in screening and cancer populations.
- Jakob Weiss
- , Vineet K. Raghu
- & Hugo J.W.L. Aerts
-
Article
| Open AccessLung endothelial cells regulate pulmonary fibrosis through FOXF1/R-Ras signaling
Pulmonary fibrosis results from dysregulated lung repair, but the role of endothelial cells (EC) in fibrosis is unclear. Here, the authors show that FOXF1/R-Ras signalling in EC inhibits profibrotic mediators and that ECspecific nanoparticle FOXF1 gene therapy decreases lung fibrosis in mice.
- Fenghua Bian
- , Ying-Wei Lan
- & Tanya V. Kalin
-
Article
| Open AccessAn interactive murine single-cell atlas of the lung responses to radiation injury
Radiation damages the healthy lung and triggers severe side effects. Here the authors provide a single cell atlas of the lung responses to radiation injury to explore the spatio-temporal dynamics of the mechanisms leading to radio-induced pulmonary fibrosis.
- Sandra Curras-Alonso
- , Juliette Soulier
- & Charles Fouillade
-
Article
| Open AccessRhinovirus-induced epithelial RIG-I inflammasome suppresses antiviral immunity and promotes inflammation in asthma and COVID-19
Viral infections and exposure to inhaled allergens are linked to asthma onset, exacerbations and progression. Here, the authors used controlled experimental rhinovirus infection in patients with and without asthma, and further assessed in vitro the role of house dust mite allergen combined with rhinovirus and SARS-CoV-2 infection. They discovered that rhinovirus-induced activation of epithelial RIG-I inflammasome supresses antiviral immunity, promotes inflammation during asthma exacerbations and aggravates subsequent infection with SARS-CoV-2, particularly upon house dust mite exposure.
- Urszula Radzikowska
- , Andrzej Eljaszewicz
- & Milena Sokolowska
-
Article
| Open AccessInterstitial lung disease diagnosis and prognosis using an AI system integrating longitudinal data
Accurate diagnosis of interstitial lung disease subtypes and prediction of patient survival rates remains challenging. Here, the authors develop AI algorithms to combine patient’s clinical history and longitudinal CT images to help clinicians diagnose and classify subtypes and dynamically predict disease progression and prognosis.
- Xueyan Mei
- , Zelong Liu
- & Yang Yang
-
Article
| Open AccessTelomere length associates with chronological age and mortality across racially diverse pulmonary fibrosis cohorts
The association of telomere length with age and mortality across racially diverse pulmonary fibrosis populations is unknown. Here, the authors show that leukocyte telomere length associates with chronologic age and is predictive of mortality in pulmonary fibrosis across racial groups.
- Ayodeji Adegunsoye
- , Chad A. Newton
- & Imre Noth
-
Article
| Open AccessCircadian clock molecule REV-ERBα regulates lung fibrotic progression through collagen stabilization
The molecular clock REV-ERBα regulates lung injury during fibrosis, but the role of REV-ERBα in fibrogenesis remains unknown. Here, the authors show that REV-ERBα interacts with the lysyl oxidase-collagen axis during fibrogenesis and demonstrate the therapeutic potential of Rev-erbα agonist against lung fibrosis.
- Qixin Wang
- , Isaac Kirubakaran Sundar
- & Irfan Rahman
-
Article
| Open AccessInsights into pulmonary phosphate homeostasis and osteoclastogenesis emerge from the study of pulmonary alveolar microlithiasis
Osteoclasts are derived from circulating myeloid cells to mediate bone repair, maintenance and remodeling. Here, the authors show that the lung also recruits and reprograms monocytes and alveolar macrophages into osteoclast-like cells to clear pathogenic particles from the airspace.
- Yasuaki Uehara
- , Yusuke Tanaka
- & Francis X. McCormack
-
Article
| Open AccessRetinoids stored locally in the lung are required to attenuate the severity of acute lung injury in male mice
Retinoids can act as transcriptional regulators to regulate cell proliferation, differentiation, and other processes. Here, the authors show that uncompromised vitamin A (retinoid) metabolism and signaling in alveolar lipofibroblasts, endothelial and epithelial cells are required to lessen the severity of an acute inflammatory challenge in adult mouse lungs.
- Igor O. Shmarakov
- , Galina A. Gusarova
- & William S. Blaner
-
Perspective
| Open AccessFuture therapies for cystic fibrosis
The cystic fibrosis landscape has changed dramatically over the last few decades, with improvements in patient quality of life, prognosis and predicted survival. In part, this is related to the availability of novel CFTR modulator drugs, although prior advances in symptom-directed therapies and diagnosis had already led to substantial improvements. However, the authors, part of a national CF focused group, recognize that more needs to be done and outline their considerations on research priorities in this perspective.
- Lucy Allen
- , Lorna Allen
- & Jane C. Davies
-
Article
| Open AccessInflammatory and infectious upper respiratory diseases associate with 41 genomic loci and type 2 inflammation
The shared genetics between upper respiratory diseases have not been well studied. Here, the authors find shared and distinct genetic loci for pharyngeal and sinonasal inflammatory conditions, which show shared heritability with autoimmune conditions and immune deficiency, highlighting the TNFR2 pathway.
- Elmo C. Saarentaus
- , Juha Karjalainen
- & Aarno Palotie
-
Article
| Open AccessTiming and cell specificity of senescence drives postnatal lung development and injury
Senescence causes age-related diseases and stress-related injury, but it is also physiologically essential during development. Here, Yao et al. show that programmed senescence in mesenchymal cells orchestrates postnatal lung development and that neonatal hyperoxia can induce senescence, particularly in type II, Pdgfra+ mesenchymal and immune cells, during the alveolar stage, resulting in lung injury.
- Hongwei Yao
- , Joselynn Wallace
- & Phyllis A. Dennery
-
Article
| Open AccessSARS-CoV-2 viral entry and replication is impaired in Cystic Fibrosis airways due to ACE2 downregulation
Patients with cystic fibrosis are not reporting particularly sever outcomes upon SARS-CoV-2 infection. Here, the authors demonstrate decreased ACE2 levels is cystic fibrosis airway epithelia associated with impaired viral entry and replication.
- Valentino Bezzerri
- , Valentina Gentili
- & Marco Cipolli
-
Article
| Open AccessA population-based matched cohort study of major congenital anomalies following COVID-19 vaccination and SARS-CoV-2 infection
The risks of major congenital anomalies associated with SARS-CoV-2 vaccination in early pregnancy are not well understood. Here, the authors conduct a population-based cohort study using electronic health records from Scotland and find no evidence of an association, supporting vaccine safety in pregnancy.
- Clara Calvert
- , Jade Carruthers
- & Rachael Wood
-
Article
| Open AccessBA.2 and BA.5 omicron differ immunologically from both BA.1 omicron and pre-omicron variants
SARS-CoV-2 omicron variant BA.1 has shown increased transmissibility and immune escape, relative to previous SARS-CoV-2 variants. In this study, authors utilise antigenic cartography to characterise the neutralisation profiles of omicron sub-lineages, BA.2 and BA.5, in comparison to BA.1 and pre-omicron variants.
- Annika Rössler
- , Antonia Netzl
- & Janine Kimpel
-
Article
| Open AccessLocally organised and activated Fth1hi neutrophils aggravate inflammation of acute lung injury in an IL-10-dependent manner
Acute respiratory distress syndrome (ARDS) is an acute pulmonary disease involving neutrophils. Here the authors characterise lung neutrophil infiltration during ARDS and show that there are neutrophils with different function and transcriptional profile which are regulated by IL-10.
- Kun Wang
- , Muyun Wang
- & Wei Gao
-
Article
| Open AccessThe establishment of COPD organoids to study host-pathogen interaction reveals enhanced viral fitness of SARS-CoV-2 in bronchi
Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory respiratory disease characterized by airflow limitation and infective exacerbations. Here, Chan et al. report the generation of nasopharyngeal and bronchial COPD organoids derived from adult stem cells and employ them in the study of host-pathogen interactions, including SARS-CoV-2 and Pseudomonas aeruginosa.
- Louisa L. Y. Chan
- , Danielle E. Anderson
- & Sanjay H. Chotirmall
-
Article
| Open AccessNasal DNA methylation at three CpG sites predicts childhood allergic disease
Accurate prediction of the onset of childhood allergy is important to clarify the difference between various respiratory diseases. Here the authors propose that the methylation status of three sites in nasal DNA predicts the onset of childhood allergy which may aid diagnosis and monitoring.
- Merlijn van Breugel
- , Cancan Qi
- & Cheng-Jian Xu
-
Article
| Open AccessPEAR1 regulates expansion of activated fibroblasts and deposition of extracellular matrix in pulmonary fibrosis
Currently, there is a lack of effective drugs for the treatment of pulmonary fibrosis. Here, the authors reveal a novel role of PEAR1 in fibroblast activation and demonstrate that activating PEAR1 by monoclonal antibodies might be a promising therapeutic approach for pulmonary fibrosis.
- Yan Geng
- , Lin Li
- & Xuemei Fan
-
Article
| Open AccessThe endocannabinoid anandamide is an airway relaxant in health and disease
Obstructive lung diseases are a frequent cause of morbidity worldwide. Here, the authors identify the endocannabinoid anandamide (AEA) as an airway relaxant under physiological and pathophysiological conditions that can be locally applied to the lung as an aerosol in mice.
- Annika Simon
- , Thomas von Einem
- & Daniela Wenzel
-
Article
| Open AccessDiscerning asthma endotypes through comorbidity mapping
Asthma is a heterogeneous, complex syndrome that arises in individuals with various genetic and exposure variations. Here, the authors show that disease comorbidity patterns can serve as a surrogate for these variations, and identify asthma endotypes distinguished by comorbidity patterns, asthma risk loci, gene expression, and health-related phenotypes.
- Gengjie Jia
- , Xue Zhong
- & Julian Solway
-
Article
| Open AccessConsequences of telomere dysfunction in fibroblasts, club and basal cells for lung fibrosis development
Telomere dysfunction induced by TRF1 depletion in fibroblasts, club and basal cells did not lead to interstitial lung fibrosis, underscoring alveolar type II cells as the relevant cell type in pulmonary fibrosis.
- Sergio Piñeiro-Hermida
- , Paula Martínez
- & Maria A. Blasco
-
Article
| Open AccessStratifin as a novel diagnostic biomarker in serum for diffuse alveolar damage
No reliable serum biomarker for diffuse alveolar damage, a poor prognosis subtype of drug-induced interstitial lung disease, is currently available. Here, the authors show stratifin/14-3-3σ in serum is a promising biomarker for diagnosis of this type of disease.
- Noriaki Arakawa
- , Atsuhito Ushiki
- & Masayuki Hanaoka