What have transgenic and knockout animals taught us about respiratory disease?


:Over the past decade there has been a significant shift to the use of murine models for investigations into the molecular basis of respiratory diseases, including asthma and chronic obstructive pulmonary disease. These models offer the exciting prospect of dissecting the complex interaction between cytokines, chemokines and growth related peptides in disease pathogenesis. Furthermore, the receptors and the intracellular signalling pathways that are subsequently activated are amenable for study because of the availability of monoclonal antibodies and techniques for targeted gene disruption and gene incorporation for individual mediators, receptors and proteins. However, it is clear that extrapolation from these models to the human condition is not straightforward, as reflected by some recent clinical disappointments. This is not necessarily a problem with the use of mice itself, but results from our continued ignorance of the disease process and how to improve the modelling of complex interactions between different inflammatory mediators that underlie clinical pathology. This review highlights some of the strengths and weaknesses of murine models of respiratory disease.


Respir Res


Respiratory research


Vasquez YR,Spina D





Has Abstract


2000-01-01 00:00:00












  • Pentraxin 3 promotes airway inflammation in experimental asthma.

    abstract:BACKGROUND:Pentraxin 3 (PTX3) regulates multiple aspects of innate immunity and tissue inflammation. Recently, it has been reported that PTX3 deficiency enhances interleukin (IL)-17A-dominant pulmonary inflammation in an ovalbumin (OVA)-induced mouse asthma model. However, whether PTX3 treatment would provide protectio...

    journal_title:Respiratory research

    pub_type: 杂志文章


    authors: Gao P,Tang K,Lu Y,Huang Z,Wang S,Wang M,Wang J,Zhao J,Xie J

    更新日期:2020-09-16 00:00:00

  • Impact of gastroesophageal reflux on longitudinal lung function and quantitative computed tomography in the COPDGene cohort.

    abstract:RATIONALE:Gastroesophageal reflux disease (GERD) is a common comorbidity in chronic obstructive pulmonary disease (COPD) and has been associated with increased risk of acute exacerbations, hospitalization, emergency room visits, costs, and quality-of-life impairment. However, it remains unclear whether GERD contributes...

    journal_title:Respiratory research

    pub_type: 杂志文章


    authors: Baldomero AK,Wendt CH,Petersen A,Gaeckle NT,Han MK,Kunisaki KM,COPDGene Investigators.

    更新日期:2020-08-03 00:00:00

  • COPD diagnosis related to different guidelines and spirometry techniques.

    abstract::The aim was to compare the diagnosis of COPD among smokers according to different international guidelines and to compare the outcome when using slow (SVC) and forced vital capacity (FVC). In order to find current smokers a questionnaire was sent to persons who had been on sick leave for more than two weeks. Those who...

    journal_title:Respiratory research

    pub_type: 杂志文章


    authors: Nathell L,Nathell M,Malmberg P,Larsson K

    更新日期:2007-12-04 00:00:00

  • Altered molecular specificity of surfactant phosphatidycholine synthesis in patients with acute respiratory distress syndrome.

    abstract:BACKGROUND:Acute respiratory distress syndrome (ARDS) is a life-threatening critical illness, characterised by qualitative and quantitative surfactant compositional changes associated with premature airway collapse, gas-exchange abnormalities and acute hypoxic respiratory failure. The underlying mechanisms for this dys...

    journal_title:Respiratory research

    pub_type: 杂志文章


    authors: Dushianthan A,Goss V,Cusack R,Grocott MP,Postle AD

    更新日期:2014-11-07 00:00:00

  • Nebulization of the acidified sodium nitrite formulation attenuates acute hypoxic pulmonary vasoconstriction.

    abstract:BACKGROUND:Generalized hypoxic pulmonary vasoconstriction (HPV) occurring during exposure to hypoxia is a detrimental process resulting in an increase in lung vascular resistance. Nebulization of sodium nitrite has been shown to inhibit HPV. The aim of this project was to investigate and compare the effects of nebuliza...

    journal_title:Respiratory research

    pub_type: 杂志文章


    authors: Egemnazarov B,Schermuly RT,Dahal BK,Elliott GT,Hoglen NC,Surber MW,Weissmann N,Grimminger F,Seeger W,Ghofrani HA

    更新日期:2010-06-21 00:00:00

  • Role of SOD3 in silica-related lung fibrosis and pulmonary vascular remodeling.

    abstract:BACKGROUND:Work-place exposure to silica dust may lead to progressive lung inflammation culminating in the development of silicosis, an irreversible condition that can be complicated by onset of pulmonary hypertension (PH). The molecular mechanisms leading to the development of PH and lung fibrosis in response to silic...

    journal_title:Respiratory research

    pub_type: 杂志文章


    authors: Zelko IN,Zhu J,Roman J

    更新日期:2018-11-20 00:00:00

  • Cigarette smoke-induced accumulation of lung dendritic cells is interleukin-1α-dependent in mice.

    abstract:BACKGROUND:Evidence suggests that dendritic cells accumulate in the lungs of COPD patients and correlate with disease severity. We investigated the importance of IL-1R1 and its ligands IL-1α and β to dendritic cell accumulation and maturation in response to cigarette smoke exposure. METHODS:Mice were exposed to cigare...

    journal_title:Respiratory research

    pub_type: 杂志文章


    authors: Botelho FM,Nikota JK,Bauer CM,Morissette MC,Iwakura Y,Kolbeck R,Finch D,Humbles AA,Stämpfli MR

    更新日期:2012-09-19 00:00:00

  • The clinical course of idiopathic pulmonary fibrosis and its association to quality of life over time: longitudinal data from the INSIGHTS-IPF registry.

    abstract:BACKGROUND:Quality of life (QoL) is profoundly impaired in patients with idiopathic pulmonary fibrosis (IPF). However, data is limited regarding the course of QoL. We therefore analysed longitudinal data from the German INSIGHTS-IPF registry. METHODS:Clinical status and QoL were assessed at enrollment and subsequently...

    journal_title:Respiratory research

    pub_type: 杂志文章,多中心研究


    authors: Kreuter M,Swigris J,Pittrow D,Geier S,Klotsche J,Prasse A,Wirtz H,Koschel D,Andreas S,Claussen M,Grohé C,Wilkens H,Hagmeyer L,Skowasch D,Meyer JF,Kirschner J,Gläser S,Kahn N,Welte T,Neurohr C,Schwaiblmair M,Held

    更新日期:2019-03-15 00:00:00

  • Decline of COPD exacerbations in clinical trials over two decades - a systematic review and meta-regression.

    abstract:BACKGROUND:An important goal of chronic obstructive pulmonary disease (COPD) treatment is to reduce the frequency of exacerbations. Some observations suggest a decline in exacerbation rates in clinical trials over time. A more systematic understanding would help to improve the design and interpretation of COPD trials. ...

    journal_title:Respiratory research

    pub_type: 杂志文章,meta分析


    authors: Andreas S,Röver C,Heinz J,Straube S,Watz H,Friede T

    更新日期:2019-08-16 00:00:00

  • Real world evaluation of a novel lateral flow assay (AlphaKit® QuickScreen) for the detection of alpha-1-antitrypsin deficiency.

    abstract:BACKGROUND:Alpha-1-Antitrypsin (AAT) deficiency (AATD) is a hereditary disorder that manifests primarily as pulmonary emphysema and liver cirrhosis. The clinically most relevant mutation causing AATD is a single nucleotide polymorphism Glu342Lys (Z-mutation). Despite the recommendation to test every COPD patient, the c...

    journal_title:Respiratory research

    pub_type: 杂志文章,多中心研究


    authors: Greulich T,Rodríguez-Frias F,Belmonte I,Klemmer A,Vogelmeier CF,Miravitlles M

    更新日期:2018-08-13 00:00:00

  • Microbial dysbiosis and mortality during mechanical ventilation: a prospective observational study.

    abstract:BACKGROUND:Host-associated microbial communities have important roles in tissue homeostasis and overall health. Severe perturbations can occur within these microbial communities during critical illness due to underlying diseases and clinical interventions, potentially influencing patient outcomes. We sought to profile ...

    journal_title:Respiratory research

    pub_type: 杂志文章,随机对照试验


    authors: Lamarche D,Johnstone J,Zytaruk N,Clarke F,Hand L,Loukov D,Szamosi JC,Rossi L,Schenck LP,Verschoor CP,McDonald E,Meade MO,Marshall JC,Bowdish DME,Karachi T,Heels-Ansdell D,Cook DJ,Surette MG,PROSPECT Investigators.,C

    更新日期:2018-12-07 00:00:00

  • The natural history of progressive fibrosing interstitial lung diseases.

    abstract::A proportion of patients with certain types of interstitial lung disease (ILD), including chronic hypersensitivity pneumonitis and ILDs associated with autoimmune diseases, develop a progressive fibrosing phenotype that shows similarities in clinical course to idiopathic pulmonary fibrosis. Irrespective of the clinica...

    journal_title:Respiratory research

    pub_type: 杂志文章,评审


    authors: Kolb M,Vašáková M

    更新日期:2019-03-14 00:00:00

  • Indacaterol/glycopyrronium is cost-effective compared to salmeterol/fluticasone in COPD: FLAME-based modelling in a Swedish population.

    abstract:BACKGROUND:This study assessed the cost-effectiveness of indacaterol/glycopyrronium (IND/GLY) versus salmeterol/fluticasone (SFC) in chronic obstructive pulmonary disease (COPD) patients with moderate to very severe airflow limitation and ≥1 exacerbation in the preceding year. METHODS:A previously published and valida...

    journal_title:Respiratory research

    pub_type: 杂志文章,多中心研究,随机对照试验


    authors: Bjermer L,van Boven JFM,Costa-Scharplatz M,Keininger DL,Gutzwiller FS,Lisspers K,Mahon R,Olsson P,Roche N

    更新日期:2017-12-11 00:00:00

  • Differences in the risk of mood disorders in patients with asthma-COPD overlap and in patients with COPD alone: a nationwide population-based retrospective cohort study in Korea.

    abstract:BACKGROUND:Although feelings of anxiety and depression are common in patients with chronic obstructive pulmonary disease (COPD), little is known about the estimates of their incidence in patients with asthma-COPD overlap (ACO), which has been described and acknowledged as a distinct clinical entity. We aimed to estimat...

    journal_title:Respiratory research

    pub_type: 杂志文章


    authors: Kang HR,Hong SH,Ha SY,Kim TB,Lee EK

    更新日期:2019-04-30 00:00:00

  • Signaling and regulation of G protein-coupled receptors in airway smooth muscle.

    abstract::Signaling through G protein-coupled receptors (GPCRs) mediates numerous airway smooth muscle (ASM) functions including contraction, growth, and "synthetic" functions that orchestrate airway inflammation and promote remodeling of airway architecture. In this review we provide a comprehensive overview of the GPCRs that ...

    journal_title:Respiratory research

    pub_type: 杂志文章,评审


    authors: Billington CK,Penn RB

    更新日期:2003-01-01 00:00:00

  • Characteristics, disease burden and costs of COPD patients in the two years following initiation of long-acting bronchodilators in UK primary care.

    abstract:BACKGROUND:To assess the symptomatic and cost burden among patients initiating long-acting bronchodilator (LABD) therapy and impact of adherence on healthcare resource use and costs. METHODS:This retrospective cohort study identified patients with COPD who were newly prescribed a LABD (long-acting muscarinic antagonis...

    journal_title:Respiratory research

    pub_type: 杂志文章


    authors: Punekar YS,Landis SH,Wurst K,Le H

    更新日期:2015-11-16 00:00:00

  • Factors associated with hospitalization in bronchiectasis exacerbations: a one-year follow-up study.

    abstract:BACKGROUND:Bronchiectasis (BE) is a chronic structural lung disease with frequent exacerbations, some of which require hospital admission though no clear associated factors have been identified. We aimed to evaluate factors associated with hospitalization due to exacerbations during a 1-year follow-up period. METHODS:...

    journal_title:Respiratory research

    pub_type: 杂志文章,多中心研究


    authors: Menéndez R,Méndez R,Polverino E,Rosales-Mayor E,Amara-Elori I,Reyes S,Posadas T,Fernández-Barat L,Torres A

    更新日期:2017-09-30 00:00:00

  • Surfactant proteins, SP-A and SP-D, in respiratory fungal infections: their role in the inflammatory response.

    abstract::Pulmonary surfactant is a complex fluid that comprises phospholipids and four proteins (SP-A, SP-B, SP-C, and SP-D) with different biological functions. SP-B, SP-C, and SP-D are essential for the lungs' surface tension function and for the organization, stability and metabolism of lung parenchyma. SP-A and SP-D, which...

    journal_title:Respiratory research

    pub_type: 杂志文章,评审


    authors: Carreto-Binaghi LE,Aliouat el M,Taylor ML

    更新日期:2016-06-01 00:00:00

  • The pathology of small airways disease in COPD: historical aspects and future directions.

    abstract::Small airways disease (SAD) is a cardinal feature of chronic obstructive pulmonary disease (COPD) first recognized in the nineteenth century. The diverse histopathological features associated with SAD underpin the heterogeneous nature of COPD. Our understanding of the key molecular mechanisms which drive the pathologi...

    journal_title:Respiratory research

    pub_type: 杂志文章,评审


    authors: Higham A,Quinn AM,Cançado JED,Singh D

    更新日期:2019-03-04 00:00:00

  • Comparing microbiota profiles in induced and spontaneous sputum samples in COPD patients.

    abstract:BACKGROUND:Induced and spontaneous sputum are used to evaluate the airways microbiota. Whether the sputum types can be used interchangeably in microbiota research is unknown. Our aim was to compare microbiota in induced and spontaneous sputum from COPD patients sampled during the same consultation. METHODS:COPD patien...

    journal_title:Respiratory research

    pub_type: 杂志文章


    authors: Tangedal S,Aanerud M,Grønseth R,Drengenes C,Wiker HG,Bakke PS,Eagan TM

    更新日期:2017-08-29 00:00:00

  • Acute exacerbations of chronic obstructive pulmonary disease are associated with decreased CD4+ & CD8+ T cells and increased growth & differentiation factor-15 (GDF-15) in peripheral blood.

    abstract:BACKGROUND:Although T cells, especially CD8+, have been implicated in chronic obstructive pulmonary disease (COPD) pathogenesis, their role during acute exacerbations (AE-COPD) is uncertain. METHODS:We recruited subjects with COPD and a history of previous AE-COPD and studied them quarterly to collect blood and sponta...

    journal_title:Respiratory research

    pub_type: 临床试验,杂志文章


    authors: Freeman CM,Martinez CH,Todt JC,Martinez FJ,Han MK,Thompson DL,McCloskey L,Curtis JL

    更新日期:2015-08-05 00:00:00

  • Exchange protein directly activated by cAMP (Epac) protects against airway inflammation and airway remodeling in asthmatic mice.

    abstract:BACKGROUND:β2 receptor agonists induce airway smooth muscle relaxation by increasing intracellular cAMP production. PKA is the traditional downstream signaling pathway of cAMP. Exchange protein directly activated by cAMP (Epac) was identified as another important signaling molecule of cAMP recently. The role of Epac in...

    journal_title:Respiratory research

    pub_type: 杂志文章


    authors: Chen YF,Huang G,Wang YM,Cheng M,Zhu FF,Zhong JN,Gao YD

    更新日期:2019-12-18 00:00:00

  • Serum surfactant protein D as a predictive biomarker for the efficacy of pirfenidone in patients with idiopathic pulmonary fibrosis: a post-hoc analysis of the phase 3 trial in Japan.

    abstract:BACKGROUND:Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal disorder with a variable disease course. The recent advancement of antifibrotic therapy has increased the need for reliable and specific biomarkers. This study aimed to assess alveolar epithelial biomarkers as predictors for the efficacy of the anti...

    journal_title:Respiratory research

    pub_type: 杂志文章


    authors: Ikeda K,Chiba H,Nishikiori H,Azuma A,Kondoh Y,Ogura T,Taguchi Y,Ebina M,Sakaguchi H,Miyazawa S,Suga M,Sugiyama Y,Nukiwa T,Kudoh S,Takahashi H,Pirfenidone Clinical Study Group in Japan.

    更新日期:2020-11-30 00:00:00

  • A probabilistic model of biological ageing of the lungs for analysing the effects of smoking, asthma and COPD.

    abstract:BACKGROUND:Although a large body of literature is available that describes the effects of smoking, asthma and COPD on lung function, most studies are restricted to a small age range and to one factor. As a consequence, available results are incomplete and often difficult to compare, also due to the ways the effects are...

    journal_title:Respiratory research

    pub_type: 杂志文章


    authors: Chiappa S,Winn J,Viñuela A,Tipney H,Spector TD

    更新日期:2013-05-30 00:00:00

  • Legionella pneumophila induces cathepsin B-dependent necrotic cell death with releasing high mobility group box1 in macrophages.

    abstract:BACKGROUND:Legionella pneumophila (LPN) can cause a lethal infectious disease with a marked inflammatory response in humans. However, the mechanism of this severe inflammation remains poorly understood. Since necrosis is known to induce inflammation, we investigated whether LPN induces necrosis in macrophages. We also ...

    journal_title:Respiratory research

    pub_type: 杂志文章


    authors: Morinaga Y,Yanagihara K,Nakamura S,Hasegawa H,Seki M,Izumikawa K,Kakeya H,Yamamoto Y,Yamada Y,Kohno S,Kamihira S

    更新日期:2010-11-22 00:00:00

  • Factors associated with change in exacerbation frequency in COPD.

    abstract:BACKGROUND:Patients with chronic obstructive pulmonary disease (COPD) can be categorized as having frequent (FE) or infrequent (IE) exacerbations depending on whether they respectively experience two or more, or one or zero exacerbations per year. Although most patients do not change category from year to year, some wi...

    journal_title:Respiratory research

    pub_type: 临床试验,杂志文章


    authors: Donaldson GC,Müllerova H,Locantore N,Hurst JR,Calverley PM,Vestbo J,Anzueto A,Wedzicha JA

    更新日期:2013-07-30 00:00:00

  • Induction and regulation of matrix metalloproteinase-12 in human airway smooth muscle cells.

    abstract:BACKGROUND:The elastolytic enzyme matrix metalloproteinase (MMP)-12 has been implicated in the development of airway inflammation and remodeling. We investigated whether human airway smooth muscle cells could express and secrete MMP-12, thereby participating in the pathogenesis of airway inflammatory diseases. METHODS...

    journal_title:Respiratory research

    pub_type: 杂志文章


    authors: Xie S,Issa R,Sukkar MB,Oltmanns U,Bhavsar PK,Papi A,Caramori G,Adcock I,Chung KF

    更新日期:2005-12-16 00:00:00

  • Withdrawal of inhaled corticosteroids in individuals with COPD--a systematic review and comment on trial methodology.

    abstract::Inhaled corticosteroids (ICS) reduce COPD exacerbation frequency and slow decline in health related quality of life but have little effect on lung function, do not reduce mortality, and increase the risk of pneumonia. We systematically reviewed trials in which ICS have been withdrawn from patients with COPD, with the ...

    journal_title:Respiratory research

    pub_type: 杂志文章,meta分析,评审


    authors: Nadeem NJ,Taylor SJ,Eldridge SM

    更新日期:2011-08-12 00:00:00

  • A 3D epithelial-mesenchymal co-culture model of human bronchial tissue recapitulates multiple features of airway tissue remodeling by TGF-β1 treatment.

    abstract:BACKGROUND:The collagen gel contraction assay measures gel size to assess the contraction of cells embedded in collagen gel matrices. Using the assay with lung fibroblasts is useful in studying the lung tissue remodeling process in wound healing and disease development. However, the involvement of bronchial epithelial ...

    journal_title:Respiratory research

    pub_type: 杂志文章


    authors: Ishikawa S,Ishimori K,Ito S

    更新日期:2017-11-22 00:00:00

  • MUC1 deficiency mediates corticosteroid resistance in chronic obstructive pulmonary disease.

    abstract:BACKGROUND:Lung inflammation in COPD is poorly controlled by inhaled corticosteroids (ICS). Strategies to improve ICS efficacy or the search of biomarkers who may select those patients candidates to receive ICS in COPD are needed. Recent data indicate that MUC1 cytoplasmic tail (CT) membrane mucin can mediate corticost...

    journal_title:Respiratory research

    pub_type: 杂志文章


    authors: Milara J,Díaz-Platas L,Contreras S,Ribera P,Roger I,Ballester B,Montero P,Cogolludo Á,Morcillo E,Cortijo J

    更新日期:2018-11-20 00:00:00