Respiratory tract diseases

  • Article
    | Open Access

    China operates a national surveillance program for acute respiratory infections and sampled over 200,000 patients between 2009–2019. Here, the authors present results from this program and describe patterns by age, pathogen type, presence of pneumonia, and season.

    • Zhong-Jie Li
    • , Hai-Yang Zhang
    •  & Jun Wang
  • Article
    | Open Access

    Environmental and genetic risk factors affect the distal airway epithelium in idiopatic pulmonary fibrosis (IPF) but the role of the epithelium in IPF remains unclear. Here the authors show that pathologic activation of the ERBB-YAP axis induces dynamic and structural dysfunction in the distal airway epithelium eliciting a pro-fibrotic phenotype in mesenchymal cells.

    • Ian T. Stancil
    • , Jacob E. Michalski
    •  & David A. Schwartz
  • Article
    | Open Access

    Matthew M. Hernandez and Ana S. Gonzalez-Reiche and colleagues report evidence of SARSCoV-2 infections in respiratory pathogen-negative nasopharyngeal specimens collected in New York, which date back to over one month before the first officially documented case in the state. The findings provide insights in to the origins of the virus in New York.

    • Matthew M. Hernandez
    • , Ana S. Gonzalez-Reiche
    •  & Emilia Mia Sordillo
  • Article
    | Open Access

    Idiopathic pulmonary fibrosis (IPF) is a fatal adult lung disease. Here the authors investigate the functional significance of PDCD5 in club cells as a mediator of lung fibrosis and potential therapeutic target for IPF.

    • Soo-Yeon Park
    • , Jung Yeon Hong
    •  & Ho-Geun Yoon
  • Article
    | Open Access

    The role of the CD200–CD200R axis in regulating pulmonary inflammation is not completely understood. Here the authors show CD200R is expressed on type 2 innate lymphoid cells (ILC2s), and its engagement by CD200 ameliorates airway hyperreactivity and allergic asthma via inhibition of NF-κB signaling.

    • Pedram Shafiei-Jahani
    • , Doumet Georges Helou
    •  & Omid Akbari
  • Article
    | Open Access

    T cells compose a critical component of the immune response to coronavirus infection with SARS-CoV-2. Here the authors characterise the T cell response to SARS CoV-2 in patients and their close contacts, and show the presence of SARS-CoV-2 specific T cells in the absence of detectable virus infection.

    • Zhongfang Wang
    • , Xiaoyun Yang
    •  & Pixin Ran
  • Article
    | Open Access

    Autoimmune pulmonary alveolar proteinosis (aPAP) is a complex lung disease caused by abnormal surfactant homeostasis. Here, the authors carry out a genome-wide association study of aPAP in a Japanese cohort, finding variants in the MHC and suggesting predisposition to abnormal antibody production.

    • Saori Sakaue
    • , Etsuro Yamaguchi
    •  & Yukinori Okada
  • Article
    | Open Access

    There are no targeted pharmacologic therapies to treat lung injury during mechanical ventilation (MV). Here the authors identify a mechanosensitive microRNA (miR-146a) in alveolar macrophages during MV and increase miR-146a to supraphysiological levels in these cells to mitigate ventilator induced lung injury.

    • Christopher M. Bobba
    • , Qinqin Fei
    •  & Joshua A. Englert
  • Article
    | Open Access

    In asthma, mucus plugging is an important cause of airflow obstruction, but it is not targeted by widely used bronchodilator and anti-inflammatory drugs. Here the authors show that reduction of disulfide bonds that hold mucin polymers together reverses asthma-like obstruction in mice.

    • Leslie E. Morgan
    • , Ana M. Jaramillo
    •  & Christopher M. Evans
  • Article
    | Open Access

    Genetic variants discovered through genome-wide association studies for asthma together account for a small portion of the heritability. Here, the authors identify a possible epistatic relationship between coding variants in FUT2 and ABO, especially pronounced in severe and early onset asthma.

    • Tarunveer S. Ahluwalia
    • , Anders U. Eliasen
    •  & Klaus Bønnelykke
  • Article
    | Open Access

    Preclinical studies have shown that negative pressure ventilation ex situ lung perfusion results in less ventilator-induced lung injury compared to positive pressure ventilation of donor lungs during transplantation procedures. Here the authors perform a single-arm clinical trial with 12 participants to study patient survival and primary graft dysfunction with ex situ lung perfusion.

    • Max T. Buchko
    • , Nasim Boroumand
    •  & Jayan Nagendran
  • Article
    | Open Access

    The analysis of metabolites offers promises in biomarker discovery. Here the authors demonstrate the metabolomics analysis of sub-nanoliter samples using triboelectric nanogenerator inductive nanoelectrospray ionization, which they apply to exhaled breath condensate from cystic fibrosis patients and mesenchymal stromal cells.

    • Yafeng Li
    • , Marcos Bouza
    •  & Facundo M. Fernández
  • Article
    | Open Access

    Understanding how SARS-CoV-2 gains initial entry into the human body is a key step towards the development of prophylaxes and therapeutics for COVID-19. Here, the authors show that ACE2, the receptor for SARS-CoV-2, is abundantly expressed in the motile cilia of the human nasal and respiratory tract and is not affected by the use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers.

    • Ivan T. Lee
    • , Tsuguhisa Nakayama
    •  & Peter K. Jackson
  • Article
    | Open Access

    The αvβ6 integrin is key in activating the pro-fibrotic cytokine TGFβ in idiopathic pulmonary fibrosis. Here, the authors show an inhaled small molecule αvβ6 inhibitor GSK3008348 induces prolonged inhibition of TGFβ signaling pathways in human and murine models of lung fibrosis via αvβ6 degradation.

    • Alison E. John
    • , Rebecca H. Graves
    •  & Robert J. Slack
  • Article
    | Open Access

    Pulmonary fibrosis is a major public health problem with unclear mechanism and limited therapeutic options. Here the authors show that a fibroblast-enriched endoplasmic reticulum protein, TXNDC5, promotes pulmonary fibrosis by stabilizing TGFBR1 and show the potential of TXNDC5 as a therapeutic target against pulmonary fibrosis.

    • Tzu-Han Lee
    • , Chih-Fan Yeh
    •  & Kai-Chien Yang
  • Article
    | Open Access

    Surfactant protein B (SP-B) deficiency is a genetic lung disease that results in lethal respiratory distress within months of birth. Here, the authors describe a gene therapy strategy using a rationally designed AAV6 capsid that restores surfactant homeostasis, prevents lung injury, and improves survival in a mouse model of SP-B deficiency.

    • Martin H. Kang
    • , Laura P. van Lieshout
    •  & Bernard Thébaud
  • Article
    | Open Access

    Injury repair is characterized by the generation of transient cell states important for tissue recovery. Here, the authors present a single cell RNA-seq map of recovery from bleomycin lung injury in mice and uncover a Krt8+ transitional stem cell state that precedes the regeneration of AT1 cells and persists in human lung fibrosis.

    • Maximilian Strunz
    • , Lukas M. Simon
    •  & Herbert B. Schiller
  • Article
    | Open Access

    Pulmonary hypertension is a devastating disease with elevation of pulmonary artery pressure and related to abnormal calcium signalling. Here, the authors show that suppression or stabilization of the calcium channel ryanodine receptor 2 may be a potential treatment approach for this disease.

    • Lin Mei
    • , Yun-Min Zheng
    •  & Yong-Xiao Wang
  • Article
    | Open Access

    Collagen production by lung cells is critical to maintain organ architecture but can also drive pathological scarring. Here the authors perform single cell RNA sequencing of collagen-producing lung cells identifying a subset of pathologic fibroblasts characterized by Cthrc1 expression which are concentrated within fibroblastic foci in fibrotic lungs and show a pro-fibrotic phenotype.

    • Tatsuya Tsukui
    • , Kai-Hui Sun
    •  & Dean Sheppard
  • Article
    | Open Access

    Asthma is a common disease of the airways for which numerous genetic loci have been identified. Here, Han et al. carry out a genome-wide analysis for asthma to identify additional loci, report sex-stratified and genetic risk score analyses, and functionally follow-up one locus using a murine model of airway hyperreactivity.

    • Yi Han
    • , Qiong Jia
    •  & Hooman Allayee
  • Article
    | Open Access

    Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease and adult lung spheroid cells have been shown to promote regeneration in animal models of IPF. Here the authors show that the secretome and exosomes of lung spheroid cells is effective as inhalation treatment in rodent models of lung injury and fibrosis and superior to the counterparts derived from mesenchymal stem cells.

    • Phuong-Uyen C. Dinh
    • , Dipti Paudel
    •  & Ke Cheng
  • Article
    | Open Access

    Complex diseases often share genetic determinants and symptoms, but the mechanistic basis of disease interactions remains elusive. Here, the authors propose a network topological measure to identify proteins linking complex diseases in the interactome, and identify mediators between COPD and asthma.

    • Enrico Maiorino
    • , Seung Han Baek
    •  & Amitabh Sharma
  • Article
    | Open Access

    Here, the authors present the results of a mother–child cohort randomized clinical trial of n-3 LCPUFA and vitamin D maternal supplementation, finding an association between supplement-induced microbiota changes in infant airways at age 1-month but not the infant fecal or maternal vaginal microbiome.

    • Mathis H. Hjelmsø
    • , Shiraz A. Shah
    •  & Hans Bisgaard
  • Article
    | Open Access

    Asthma is a common allergic airway disease with significant inter-individual heterogeneity. Here, Olafsdottir et al. report a genome-wide meta-analysis of two large population-based cohorts to identify sequence variants that associate with asthma risk and perform follow-up functional analyses on a protective loss-of-function variant in TNFRSF8.

    • Thorunn A. Olafsdottir
    • , Fannar Theodors
    •  & Kari Stefansson
  • Article
    | Open Access

    Here, Thorsen et al. examine the microbiota during the first three months of life in a cohort of 700 children and find that microbial diversity and the relative abundances of Veillonella and Prevotella in the airways at one month of age are associated with topical immune mediators and asthma by age 6 years.

    • Jonathan Thorsen
    • , Morten A. Rasmussen
    •  & Hans Bisgaard
  • Article
    | Open Access

    The Chlamydia pneumoniae adhesin LIPP plays a role in host cell entry and infection. Here, the authors find that LIPP binds to the host plasma membrane and mediates phosphatidylserine translocation, enhancing pathogen internalization without induction of apoptosis.

    • Jan N. Galle
    • , Tim Fechtner
    •  & Johannes H. Hegemann
  • Article
    | Open Access

    Cystic fibrosis is caused by mutations in the CFTR chloride channel. Here, the authors develop a gene therapy approach using the programmable nuclease AsCas12a to correct a splicing mutation in CFTR, and show efficient repair of the mutation and recovery of CFTR function in patient-derived organoids and airway epithelial cells.

    • Giulia Maule
    • , Antonio Casini
    •  & Anna Cereseto
  • Article
    | Open Access

    Identification of host factors associated with severe influenza infection could provide insights into treatment options. Here, the authors provide transcriptomic analyses of blood from >100 influenza infected patients and show that changes in circulating neutrophils are associated with severe influenza infection.

    • Benjamin M. Tang
    • , Maryam Shojaei
    •  & Klaus Schughart
  • Article
    | Open Access

    Mitochondria of alveolar type 2 epithelial cells (AEC2) in the lung have been suggested to play a role in the development of idiopathic pulmonary fibrosis (IPF). Here the authors show that loss of mitofusin1 and mitofusin2 in murine AEC2 cells leads to the development of lung fibrosis through the regulation of surfactant lipids.

    • Kuei-Pin Chung
    • , Chia-Lang Hsu
    •  & Augustine M. K. Choi
  • Article
    | Open Access

    Altered iron homeostasis resulting in excessive oxidative stress has been implicated in smoke-induced lung diseases. Here the authors show that ferroptosis of lung epithelial cells, potentially resulting from excessive ferritinophagy, is involved in the pathogenesis of COPD.

    • Masahiro Yoshida
    • , Shunsuke Minagawa
    •  & Kazuyoshi Kuwano
  • Article
    | Open Access

    Streptococcus pneumoniae is a common coloniser of the human nasopharynx, but it also causes severe diseases. Here, Weight et al. use an experimental human pneumococcal carriage model to show that bacterial colonisation is associated with invasion of the epithelium and enhancement of immune responses.

    • Caroline M. Weight
    • , Cristina Venturini
    •  & Robert S. Heyderman
  • Article
    | Open Access

    Epigenetic differences in nasal epithelium have been proposed as a biomarker for lower airway disease and asthma. Here, in epigenome-wide association studies for asthma and other airway traits using nasal swabs, the authors identify differentially methylated CpGs that highlight genes involved in TH2 response.

    • Andres Cardenas
    • , Joanne E. Sordillo
    •  & Diane R. Gold
  • Article
    | Open Access

    Idiopathic pulmonary fibrosis is associated with myofibroblast activation in the lungs and metabolic alterations. Here, the authors show that the antidiabetic drug metformin has antifibrotic effects in human-derived samples and mouse models, by modulating a number of metabolic pathways to induce lipogenic transdifferentiation of myofibroblasts.

    • Vahid Kheirollahi
    • , Roxana M. Wasnick
    •  & Elie El Agha
  • Article
    | Open Access

    Idiopathic pulmonary fibrosis (IPF) is a lethal disease with insufficient treatment strategies. Here the authors show that reduction of the microRNA MIRLET7D and hyperactivation of EP300 contribute to impaired epigenetic silencing by the MiCEE complex in pulmonary fibroblasts of IPF patients, and demonstrate the benefit of inhibiting EP300 for the treatment of IPF.

    • Karla Rubio
    • , Indrabahadur Singh
    •  & Guillermo Barreto
  • Article
    | Open Access

    Pulmonary hypertension is characterized by a metabolic switch similar to the Warburg effect in cancer. Here Dabral et al. describe a RASSF1a-HIF-1α feedforward loop driving the Warburg effect both in a mouse model of hypoxia-induced pulmonary hypertension and a subset of human cancer cells.

    • Swati Dabral
    • , Christian Muecke
    •  & Soni S. Pullamsetti
  • Article
    | Open Access

    Gastric aspiration severely injures donor lungs, frequently making them unacceptable for transplantation. Here the authors show that an interventional cross-circulation platform enables the regeneration of severely damaged lungs in a swine model of gastric aspiration injury.

    • Brandon A. Guenthart
    • , John D. O’Neill
    •  & Matthew Bacchetta
  • Article
    | Open Access

    Personalized approaches to diagnosis and treatment monitoring could improve the management of cystic fibrosis patients. Here the authors show that multiscale differential dynamic microscopy can assess changes in cilia beating dynamics and coordination in patient-derived airway epithelial cells, in response to different CFTR-modulating drugs, in a patient-specific manner.

    • M. Chioccioli
    • , L. Feriani
    •  & P. Cicuta
  • Review Article
    | Open Access

    How can scientists and policymakers work together to reduce the health impacts of air pollution? In this review paper, the authors discuss the interplay between advances in environmental exposure assessment and policy advances to tackle pollution in a focused way.

    • Andrew Caplin
    • , Masoud Ghandehari
    •  & George Thurston
  • Article
    | Open Access

    The burden of asthma varies between ancestries, but GWAS have so far focused on mainly European ancestry populations. Here, Daya et al. perform GWAS for asthma in 14,654 individuals of African ancestry and, besides confirming previously known loci, identify two potentially African ancestry-specific loci.

    • Michelle Daya
    • , Nicholas Rafaels
    •  & Maria Yazdanbakhsh
  • Article
    | Open Access

    The PI3K/Akt/mTOR pathway has been previously implicated in fibrosis and a pan-PI3K/mTOR inhibitor is currently under clinical evaluation for the treatment of IPF. Here the authors show that the mTORC1/4E-BP1 axis is critical for TGF-β1-induced fibrogenesis in in vitro and ex vivo models and that canonical PI3K/Akt signalling is dispensable.

    • Hannah V. Woodcock
    • , Jessica D. Eley
    •  & Rachel C. Chambers
  • Article
    | Open Access

    The promoter variant rs35705950 confers a gain of function to the MUC5B gene and is the dominant risk factor for idiopathic pulmonary fibrosis. Here the authors show that mice overexpressing Muc5b in distal airspaces show impaired mucociliary clearance and increased susceptibility to bleomycin-induced lung fibrosis, and that both characteristics are reduced by treatment with a mucolytic agent.

    • Laura A. Hancock
    • , Corinne E. Hennessy
    •  & David A. Schwartz
  • Article
    | Open Access

    Silica particles induce intereukin-1 (IL-1) response to contribute to lung inflammation, but the underlying mechanism is unclear. Here the authors show that silica induces cell death and release of mitochondria and genomic DNA, which are sensed by STING with or without involving cGAS, respectively, for IL-1 induction and lung inflammation.

    • Sulayman Benmerzoug
    • , Stéphanie Rose
    •  & Valerie F. J. Quesniaux