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1.
Sci Rep ; 10(1): 17415, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-33060632

RESUMO

Hyperinflation contributes to dyspnea intensity in COPD. Little is known about the molecular mechanisms underlying hyperinflation and how inhaled corticosteroids (ICS) affect this important aspect of COPD pathophysiology. To investigate the effect of ICS/long-acting ß2-agonist (LABA) treatment on both lung function measures of hyperinflation, and the nasal epithelial gene-expression profile in severe COPD. 117 patients were screened and 60 COPD patients entered a 1-month run-in period on low-dose ICS/LABA budesonide/formoterol (BUD/F) 200/6 one inhalation b.i.d. Patients were then randomly assigned to 3-month treatment with either a high dose BDP/F 100/6 two inhalations b.i.d. (n = 31) or BUD/F 200/6 two inhalations b.i.d. (n = 29). Lung function measurements and nasal epithelial gene-expression were assessed before and after 3-month treatment and validated in independent datasets. After 3-month ICS/LABA treatment, residual volume (RV)/total lung capacity (TLC)% predicted was reduced compared to baseline (p < 0.05). We identified a nasal gene-expression signature at screening that associated with higher RV/TLC% predicted values. This signature, decreased by ICS/LABA treatment was enriched for genes associated with increased p53 mediated apoptosis was replicated in bronchial biopsies of COPD patients. Finally, this signature was increased in COPD patients compared to controls in nasal, bronchial and small airways brushings. Short-term ICS/LABA treatment improves RV/TLC% predicted in severe COPD. Furthermore, it decreases the expression of genes involved in the signal transduction by the p53 class mediator, which is a replicable COPD gene expression signature in the upper and lower airways.Trial registration: ClinicalTrials.gov registration number NCT01351792 (registration date May 11, 2011), ClinicalTrials.gov registration number NCT00848406 (registration date February 20, 2009), ClinicalTrials.gov registration number NCT00158847 (registration date September 12, 2005).

2.
Respirology ; 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33078507

RESUMO

BACKGROUND AND OBJECTIVE: Cigarette smoking is one of the most prevalent causes of preventable deaths worldwide, leading to chronic diseases, including chronic obstructive pulmonary disease (COPD). Cigarette smoke is known to induce significant transcriptional modifications throughout the respiratory tract. However, it is largely unknown how genetic profiles influence the smoking-related transcriptional changes and how changes in gene expression translate into altered alveolar epithelial repair responses. METHODS: We performed a candidate-based acute cigarette smoke-induced eQTL study, investigating the association between SNP and differential gene expression of FPR family members in bronchial epithelial cells isolated 24 h after smoking and after 48 h without smoking. The effects FPR1 on lung epithelial integrity and repair upon damage in the presence and absence of cigarette smoke were studied in CRISPR-Cas9-generated lung epithelial knockout cells. RESULTS: One significant (FDR < 0.05) inducible eQTL (rs3212855) was identified that induced a >2-fold change in gene expression. The minor allele of rs3212855 was associated with significantly higher gene expression of FPR1, FPR2 and FPR3 upon smoking. Importantly, the minor allele of rs3212855 was also associated with lower lung function. Alveolar epithelial FPR1 knockout cells were protected against CSE-induced reduction in repair capacity upon wounding. CONCLUSION: We identified a novel smoking-related inducible eQTL that is associated with a smoke-induced increase in the expression of FPR1, FPR2 and FPR3, and with lowered lung function. in vitro FPR1 down-regulation protects against smoke-induced reduction in lung epithelial repair.

3.
Sci Rep ; 10(1): 16980, 2020 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-33046825

RESUMO

Macrophage migration inhibitory factor (MIF) is a cytokine found to be associated with chronic obstructive pulmonary disease (COPD). However, there is no consensus on how MIF levels differ in COPD compared to control conditions and there are no reports on MIF expression in lung tissue. Here we studied gene expression of members of the MIF family MIF, D-Dopachrome Tautomerase (DDT) and DDT-like (DDTL) in a lung tissue dataset with 1087 subjects and identified single nucleotide polymorphisms (SNPs) regulating their gene expression. We found higher MIF and DDT expression in COPD patients compared to non-COPD subjects and found 71 SNPs significantly influencing gene expression of MIF and DDTL. Furthermore, the platform used to measure MIF (microarray or RNAseq) was found to influence the splice variants detected and subsequently the direction of the SNP effects on MIF expression. Among the SNPs found to regulate MIF expression, the major LD block identified was linked to rs5844572, a SNP previously found to be associated with lower diffusion capacity in COPD. This suggests that MIF may be contributing to the pathogenesis of COPD, as SNPs that influence MIF expression are also associated with symptoms of COPD. Our study shows that MIF levels are affected not only by disease but also by genetic diversity (i.e. SNPs). Since none of our significant eSNPs for MIF or DDTL have been described in GWAS for COPD or lung function, MIF expression in COPD patients is more likely a consequence of disease-related factors rather than a cause of the disease.

4.
Eur Respir J ; 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32907887

RESUMO

Periostin may serve as a biomarker for type-2-mediated eosinophilic airway inflammation in asthma. We hypothesised that type-2 cytokine IL-13 induces airway epithelial expression of periostin, which in turn contributes to epithelial changes observed in asthma.We studied the effect of IL-13 on periostin expression in BEAS-2B and air-liquid interface (ALI)-differentiated primary bronchial epithelial cells (PBECs). Additionally, effects of recombinant human periostin on epithelial-to-mesenchymal transition (EMT) markers and mucin genes were assessed. In bronchial biopsies and induced sputum from asthma patients and healthy controls, we analysed periostin single cell gene expression and protein levels.IL-13 increased POSTN expression in both cell types, which was accompanied by EMT-related features in BEAS-2B. In ALI-differentiated PBECs, IL-13 increased periostin basolateral and apical release. Apical administration of periostin increased the expression of MMP9, MUC5B and MUC5AC In bronchial biopsies, POSTN expression was mainly confined to basal epithelial cells, ionocytes, endothelial cells and fibroblasts, showing higher expression in basal epithelial cells from asthma patients versus controls. Higher protein levels of periostin, expressed in epithelial and subepithelial layers, was confirmed in bronchial biopsies from asthma patients compared to healthy controls. Although sputum periostin levels were not higher in asthma, levels correlated with eosinophil numbers and coughing up mucus.Periostin expression is increased by IL-13 in bronchial epithelial cells and higher in bronchial biopsies from asthma patients. This may have important consequences, as administration of periostin increased epithelial expression of mucin genes, supporting the relationship of periostin with type-2 mediated asthma and mucus secretion.

6.
Allergy ; 2020 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-32799375

RESUMO

BACKGROUND: The receptor for advanced glycation end products (RAGE) and Toll-like receptor 4 (TLR4) is implicated in COPD. Although these receptors share common ligands and signalling pathways, it is not known whether they act in concert to drive pathological processes in COPD. We examined the impact of RAGE and/or TLR4 gene deficiency in a mouse model of COPD and also determined whether expression of these receptors correlates with airway neutrophilia and airway hyperresponsiveness (AHR) in COPD patients. METHODS: We measured airway inflammation and AHR in wild-type, RAGE-/- , TLR4-/- and TLR4-/- RAGE-/- mice following acute exposure to cigarette smoke (CS). We also examined the impact of smoking status on AGER (encodes RAGE) and TLR4 bronchial gene expression in patients with and without COPD. Finally, we determined whether expression of these receptors correlates with airway neutrophilia and AHR in COPD patients. RESULTS: RAGE-/- mice were protected against CS-induced neutrophilia and AHR. In contrast, TLR4-/- mice were not protected against CS-induced neutrophilia and had more severe CS-induced AHR. TLR4-/- RAGE-/- mice were not protected against CS-induced neutrophilia but were partially protected against CS-induced mediator release and AHR. Current smoking was associated with significantly lower AGER and TLR4 expression irrespective of COPD status, possibly reflecting negative feedback regulation. However, consistent with preclinical findings, AGER expression correlated with higher sputum neutrophil counts and more severe AHR in COPD patients. TLR4 expression did not correlate with neutrophilic inflammation or AHR. CONCLUSIONS: Inhibition of RAGE but not TLR4 signalling may protect against airway neutrophilia and AHR in COPD.

8.
Artigo em Inglês | MEDLINE | ID: mdl-32442646

RESUMO

BACKGROUND: Asthma is a complex disease with multiple phenotypes that may differ in disease pathobiology and treatment response. IL33 single nucleotide polymorphisms (SNPs) have been reproducibly associated with asthma. IL33 levels are elevated in sputum and bronchial biopsies of patients with asthma. The functional consequences of IL33 asthma SNPs remain unknown. OBJECTIVE: This study sought to determine whether IL33 SNPs associate with asthma-related phenotypes and with IL33 expression in lung or bronchial epithelium. This study investigated the effect of increased IL33 expression on human bronchial epithelial cell (HBEC) function. METHODS: Association between IL33 SNPs (Chr9: 5,815,786-6,657,983) and asthma phenotypes (Lifelines/DAG [Dutch Asthma GWAS]/GASP [Genetics of Asthma Severity & Phenotypes] cohorts) and between SNPs and expression (lung tissue, bronchial brushes, HBECs) was done using regression modeling. Lentiviral overexpression was used to study IL33 effects on HBECs. RESULTS: We found that 161 SNPs spanning the IL33 region associated with 1 or more asthma phenotypes after correction for multiple testing. We report a main independent signal tagged by rs992969 associating with blood eosinophil levels, asthma, and eosinophilic asthma. A second, independent signal tagged by rs4008366 presented modest association with eosinophilic asthma. Neither signal associated with FEV1, FEV1/forced vital capacity, atopy, and age of asthma onset. The 2 IL33 signals are expression quantitative loci in bronchial brushes and cultured HBECs, but not in lung tissue. IL33 overexpression in vitro resulted in reduced viability and reactive oxygen species-capturing of HBECs, without influencing epithelial cell count, metabolic activity, or barrier function. CONCLUSIONS: We identify IL33 as an epithelial susceptibility gene for eosinophilia and asthma, provide mechanistic insight, and implicate targeting of the IL33 pathway specifically in eosinophilic asthma.

9.
Am J Physiol Lung Cell Mol Physiol ; 319(1): L48-L60, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32460521

RESUMO

Chronic obstructive pulmonary disease (COPD) is associated with features of accelerated aging, including cellular senescence, DNA damage, oxidative stress, and extracellular matrix (ECM) changes. We propose that these features are particularly apparent in patients with severe, early-onset (SEO)-COPD. Whether fibroblasts from COPD patients display features of accelerated aging and whether this is also present in relatively young SEO-COPD patients is unknown. Therefore, we aimed to determine markers of aging in (SEO)-COPD-derived lung fibroblasts and investigate the impact on ECM. Aging hallmarks and ECM markers were analyzed in lung fibroblasts from SEO-COPD and older COPD patients and compared with fibroblasts from matched non-COPD groups (n = 9-11 per group), both at normal culture conditions and upon Paraquat-induced senescence. COPD-related differences in senescence and ECM expression were validated in lung tissue. Higher levels of cellular senescence, including senescence-associated ß-galactosidase (SA-ß-gal)-positive cells (19% for COPD vs. 13% for control) and p16 expression, DNA damage (γ-H2A.X-positive nuclei), and oxidative stress (MGST1) were detected in COPD compared with control-derived fibroblasts. Most effects were also different in SEO-COPD, with SA-ß-gal-positive cells only being significant in SEO-COPD vs. matched controls. Lower decorin expression in COPD-derived fibroblasts correlated with higher p16 expression, and this association was confirmed in lung tissue. Paraquat treatment induced cellular senescence along with clear changes in ECM expression, including decorin. Fibroblasts from COPD patients, including SEO-COPD, display higher levels of cellular senescence, DNA damage, and oxidative stress. The association between cellular senescence and ECM expression changes may suggest a link between accelerated aging and ECM dysregulation in COPD.


Assuntos
Senescência Celular , Matriz Extracelular/metabolismo , Doença Pulmonar Obstrutiva Crônica/patologia , Adulto , Idade de Início , Biomarcadores/metabolismo , Células Cultivadas , Dano ao DNA , Feminino , Fibroblastos/patologia , Regulação da Expressão Gênica , Humanos , Pulmão/patologia , Pulmão/fisiopatologia , Masculino , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Pessoa de Meia-Idade , Neuropeptídeos/genética , Neuropeptídeos/metabolismo , Estresse Oxidativo , Paraquat/toxicidade , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/fisiopatologia
10.
Br J Pharmacol ; 177(20): 4809, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32436213

RESUMO

The above article from the British Journal of Pharmacology, published online on May 20, 2020 in Wiley Online Library (http://wileyonlinelibrary.com) has been withdrawn due to a lack of full disclosure of the chemical structure of the novel TRPA1 antagonist BI01305834, by agreement between the Editor-in-Chief and John Wiley & Sons Inc on behalf of The British Pharmacology Society.

12.
Sci Rep ; 10(1): 6754, 2020 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-32317758

RESUMO

Asthma is a heterogeneous disease characterized by chronic inflammation and structural changes in the airways. The airway smooth muscle (ASM) is responsible for airway narrowing and an important source of inflammatory mediators. We and others have previously shown that WNT5A mRNA and protein expression is higher in the ASM of asthmatics compared to healthy controls. Here, we aimed to characterize the functional role of (smooth muscle-derived) WNT5A in asthma. We generated a tet-ON smooth-muscle-specific WNT5A transgenic mouse model, enabling in vivo characterization of smooth-muscle-derived WNT5A in response to ovalbumin. Smooth muscle specific WNT5A overexpression showed a clear trend towards enhanced actin (α-SMA) expression in the ASM in ovalbumin challenged animals, but had no effect on collagen content. WNT5A overexpression in ASM also significantly enhanced the production of the Th2-cytokines IL4 and IL5 in lung tissue after ovalbumin exposure. In line with this, WNT5A increased mucus production, and enhanced eosinophilic infiltration and serum IgE production in ovalbumin-treated animals. In addition, CD4+ T cells of asthma patients and healthy controls were stimulated with WNT5A and changes in gene transcription assessed by RNA-seq. WNT5A promoted expression of 234 genes in human CD4+ T cells, among which the Th2 cytokine IL31 was among the top 5 upregulated genes. IL31 was also upregulated in response to smooth muscle-specific WNT5A overexpression in the mouse. In conclusion, smooth-muscle derived WNT5A augments Th2 type inflammation and remodelling. Our findings imply a pro-inflammatory role for smooth muscle-derived WNT5A in asthma, resulting in increased airway wall inflammation and remodelling.

13.
JCI Insight ; 5(8)2020 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-32324168

RESUMO

The IL1RL1 (ST2) gene locus is robustly associated with asthma; however, the contribution of single nucleotide polymorphisms (SNPs) in this locus to specific asthma subtypes and the functional mechanisms underlying these associations remain to be defined. We tested for association between IL1RL1 region SNPs and characteristics of asthma as defined by clinical and immunological measures and addressed functional effects of these genetic variants in lung tissue and airway epithelium. Utilizing 4 independent cohorts (Lifelines, Dutch Asthma GWAS [DAG], Genetics of Asthma Severity and Phenotypes [GASP], and Manchester Asthma and Allergy Study [MAAS]) and resequencing data, we identified 3 key signals associated with asthma features. Investigations in lung tissue and primary bronchial epithelial cells identified context-dependent relationships between the signals and IL1RL1 mRNA and soluble protein expression. This was also observed for asthma-associated IL1RL1 nonsynonymous coding TIR domain SNPs. Bronchial epithelial cell cultures from asthma patients, exposed to exacerbation-relevant stimulations, revealed modulatory effects for all 4 signals on IL1RL1 mRNA and/or protein expression, suggesting SNP-environment interactions. The IL1RL1 TIR signaling domain haplotype affected IL-33-driven NF-κB signaling, while not interfering with TLR signaling. In summary, we identify that IL1RL1 genetic signals potentially contribute to severe and eosinophilic phenotypes in asthma, as well as provide initial mechanistic insight, including genetic regulation of IL1RL1 isoform expression and receptor signaling.

14.
Am J Physiol Lung Cell Mol Physiol ; 318(6): L1222-L1228, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32320267

RESUMO

Parametric response mapping (PRM) is a computed tomography (CT)-based method to phenotype patients with chronic obstructive pulmonary disease (COPD). It is capable of differentiating emphysema-related air trapping with nonemphysematous air trapping (small airway disease), which helps to identify the extent and localization of the disease. Most studies evaluating the gene expression in smokers and COPD patients related this to spirometric measurements, but none have investigated the relationship with CT-based measurements of lung structure. The current study aimed to examine gene expression profiles of brushed bronchial epithelial cells in association with the PRM-defined CT-based measurements of emphysema (PRMEmph) and small airway disease (PRMfSAD). Using the Top Institute Pharma (TIP) study cohort (COPD = 12 and asymptomatic smokers = 32), we identified a gene expression signature of bronchial brushings, which was associated with PRMEmph in the lungs. One hundred thirty-three genes were identified to be associated with PRMEmph. Among the most significantly associated genes, CXCL11 is a potent chemokine involved with CD8+ T cell activation during inflammation in COPD, indicating that it may play an essential role in the development of emphysema. The PRMEmph signature was then replicated in two independent data sets. Pathway analysis showed that the PRMEmph signature is associated with proinflammatory and notch signaling pathways. Together these findings indicate that airway epithelium may play a role in the development of emphysema and/or may act as a biomarker for the presence of emphysema. In contrast, its role in relation to functional small airways disease is less clear.


Assuntos
Brônquios/diagnóstico por imagem , Brônquios/patologia , Perfilação da Expressão Gênica , Processamento de Imagem Assistida por Computador , Enfisema Pulmonar/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Idoso , Brônquios/fisiopatologia , Feminino , Volume Expiratório Forçado , Regulação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Enfisema Pulmonar/patologia , Enfisema Pulmonar/fisiopatologia
15.
FASEB J ; 34(6): 7703-7717, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32277855

RESUMO

Parasympathetic neurons in the airways control bronchomotor tone. Increased activity of cholinergic neurons are mediators of airway hyperresponsiveness (AHR) in asthma, however, mechanisms are not elucidated. We describe remodeling of the cholinergic neuronal network in asthmatic airways driven by brain-derived neurotrophic factor (BDNF) and Tropomyosin receptor kinase B (TrkB). Human bronchial biopsies were stained for cholinergic marker vesicular acetylcholine transporter (VAChT). Human lung gene expression and single nucleotide polymorphisms (SNP) in neuroplasticity-related genes were compared between asthma and healthy patients. Wild-type (WT) and mutated TrkB knock-in mice (Ntrk2tm1Ddg/J) with impaired BDNF signaling were chronically exposed to ovalbumin (OVA). Neuronal VAChT staining and airway narrowing in response to electrical field stimulation in precision cut lung slices (PCLS) were assessed. Increased cholinergic fibers in asthmatic airway biopsies was found, paralleled by increased TrkB gene expression in human lung tissue, and SNPs in the NTRK2 [TrkB] and BDNF genes linked to asthma. Chronic allergen exposure in mice resulted in increased density of cholinergic nerves, which was prevented by inhibiting TrkB. Increased nerve density resulted in AHR in vivo and in increased nerve-dependent airway reactivity in lung slices mediated via TrkB. These findings show cholinergic neuroplasticity in asthma driven by TrkB signaling and suggest that the BDNF-TrkB pathway may be a potential target.

16.
Thorax ; 75(4): 338-344, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31996401

RESUMO

Culture-independent microbial sequencing techniques have revealed that the respiratory tract harbours a complex microbiome not detectable by conventional culturing methods. The contribution of the microbiome to chronic obstructive pulmonary disease (COPD) pathobiology and the potential for microbiome-based clinical biomarkers in COPD are still in the early phases of investigation. Sputum is an easily obtainable sample and has provided a wealth of information on COPD pathobiology, and thus has been a preferred sample type for microbiome studies. Although the sputum microbiome likely reflects the respiratory microbiome only in part, there is increasing evidence that microbial community structure and diversity are associated with disease severity and clinical outcomes, both in stable COPD and during the exacerbations. Current evidence has been limited to mainly cross-sectional studies using 16S rRNA gene sequencing, attempting to answer the question 'who is there?' Longitudinal studies using standardised protocols are needed to answer outstanding questions including differences between sputum sampling techniques. Further, with advancing technologies, microbiome studies are shifting beyond the examination of the 16S rRNA gene, to include whole metagenome and metatranscriptome sequencing, as well as metabolome characterisation. Despite being technically more challenging, whole-genome profiling and metabolomics can address the questions 'what can they do?' and 'what are they doing?' This review provides an overview of the basic principles of high-throughput microbiome sequencing techniques, current literature on sputum microbiome profiling in COPD, and a discussion of the associated limitations and future perspectives.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala/métodos , Microbiota/genética , Doença Pulmonar Obstrutiva Crônica/microbiologia , RNA Ribossômico 16S/genética , Escarro/microbiologia , Estudos Transversais , Feminino , Humanos , Estudos Longitudinais , Masculino , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Sensibilidade e Especificidade , Análise de Sequência de RNA
17.
J Allergy Clin Immunol ; 145(6): 1655-1663, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31953105

RESUMO

BACKGROUND: Epigenetic signatures in the nasal epithelium, which is a primary interface with the environment and an accessible proxy for the bronchial epithelium, might provide insights into mechanisms of allergic disease. OBJECTIVE: We aimed to identify and interpret methylation signatures in nasal epithelial brushes associated with rhinitis and asthma. METHODS: Nasal epithelial brushes were obtained from 455 children at the 16-year follow-up of the Dutch Prevention and Incidence of Asthma and Mite Allergy birth cohort study. Epigenome-wide association studies were performed on children with asthma, rhinitis, and asthma and/or rhinitis (AsRh) by using logistic regression, and the top results were replicated in 2 independent cohorts of African American and Puerto Rican children. Significant CpG sites were related to environmental exposures (pets, active and passive smoking, and molds) during secondary school and were correlated with gene expression by RNA-sequencing (n = 244). RESULTS: The epigenome-wide association studies identified CpG sites significantly associated with rhinitis (n = 81) and AsRh (n = 75), but not with asthma. We significantly replicated 62 of 81 CpG sites with rhinitis and 60 of 75 with AsRh, as well as 1 CpG site with asthma. Methylation of cg03565274 was negatively associated with AsRh and positively associated with exposure to pets during secondary school. DNA methylation signals associated with AsRh were mainly driven by specific IgE-positive subjects. DNA methylation related to gene transcripts that were enriched for immune pathways and expressed in immune and epithelial cells. Nasal CpG sites performed well in predicting AsRh. CONCLUSIONS: We identified replicable DNA methylation profiles of asthma and rhinitis in nasal brushes. Exposure to pets may affect nasal epithelial methylation in relation to asthma and rhinitis.

18.
Thorax ; 75(2): 180-183, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31937552

RESUMO

Translation of genomic alterations to protein changes in chronic obstructive pulmonary disease (COPD) is largely unexplored. Using integrated proteomic and RNA sequencing analysis of COPD and control lung tissues, we identified a protein signature in COPD characterised by extracellular matrix changes and a potential regulatory role for SUMO2. Furthermore, we identified 61 differentially expressed novel, non-reference, peptides in COPD compared with control lungs. This included two peptides encoding for a new splice variant of SORBS1, of which the transcript usage was higher in COPD compared with control lungs. These explorative findings and integrative proteogenomic approach open new avenues to further unravel the pathology of COPD.


Assuntos
Regulação da Expressão Gênica/genética , Proteínas dos Microfilamentos/genética , Isoformas de Proteínas/genética , Proteogenômica/métodos , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Idoso , Estudos de Casos e Controles , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Medição de Risco , Índice de Gravidade de Doença
20.
Eur Respir J ; 55(2)2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31772002

RESUMO

Oscillometry (also known as the forced oscillation technique) measures the mechanical properties of the respiratory system (upper and intrathoracic airways, lung tissue and chest wall) during quiet tidal breathing, by the application of an oscillating pressure signal (input or forcing signal), most commonly at the mouth. With increased clinical and research use, it is critical that all technical details of the hardware design, signal processing and analyses, and testing protocols are transparent and clearly reported to allow standardisation, comparison and replication of clinical and research studies. Because of this need, an update of the 2003 European Respiratory Society (ERS) technical standards document was produced by an ERS task force of experts who are active in clinical oscillometry research.The aim of the task force was to provide technical recommendations regarding oscillometry measurement including hardware, software, testing protocols and quality control.The main changes in this update, compared with the 2003 ERS task force document are 1) new quality control procedures which reflect use of "within-breath" analysis, and methods of handling artefacts; 2) recommendation to disclose signal processing, quality control, artefact handling and breathing protocols (e.g. number and duration of acquisitions) in reports and publications to allow comparability and replication between devices and laboratories; 3) a summary review of new data to support threshold values for bronchodilator and bronchial challenge tests; and 4) updated list of predicted impedance values in adults and children.

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