The airway epithelium is now considered to be central to the orchestration of pulmonary inflammatory and immune responses, and is also key to tissue remodelling. It acts as the first barrier in the ...defence against a wide range of inhaled challenges, and is critically involved in the regulation of both innate and adaptive immune responses to these challenges. Recent progress in our understanding of the developmental regulation of this tissue, the differentiation pathways, recognition of pathogens and antimicrobial responses is now exploited to help understand how epithelial cell function and dysfunction contributes to the pathogenesis of a variety of inflammatory lung diseases. Herein, advances in our knowledge of the biology of airway epithelium, as well as its role and (dys)function in asthma, chronic obstructive pulmonary fibrosis and cystic fibrosis will be discussed.
The epithelial lining of the airway forms the first barrier against environmental insults, such as inhaled cigarette smoke, which is the primary risk factor for the development of chronic obstructive ...pulmonary disease (COPD). The barrier is formed by airway epithelial junctions, which are interconnected structures that restrict permeability to inhaled pathogens and environmental stressors. Destruction of the epithelial barrier not only exposes subepithelial layers to hazardous agents in the inspired air, but also alters the normal function of epithelial cells, which may eventually contribute to the development of COPD. Of note, disruption of epithelial junctions may lead to modulation of signaling pathways involved in differentiation, repair, and proinflammatory responses. Epithelial barrier dysfunction may be particularly relevant in COPD, where repeated injury by cigarette smoke exposure, pathogens, inflammatory mediators, and impaired epithelial regeneration may compromise the barrier function. In the current review, we discuss recent advances in understanding the mechanisms of barrier dysfunction in COPD, as well as the molecular mechanisms that underlie the impaired repair response of the injured epithelium in COPD and its inability to redifferentiate into a functionally intact epithelium.
It is increasingly recognized that the ubiquity of convenient single-use plastic has resulted in a global plastic pollution challenge, with substantial environmental and health consequences. ...Physical, chemical, and biological processes result in plastic weathering, with eventual formation of debris in the micro to nano size range. There is an increasing awareness that plastic fragments are dispersed in the air and can be inhaled by humans, which may cause adverse effects on the respiratory system and on other systems. Urban environments are often characterized by high concentrations of fine airborne dust from various sources. To date, however, there is limited information on the distribution, shape, and size of microplastics in the air in urban and other environments. In this article, we review and discuss our current understanding of the exposure characteristics of airborne plastic debris in urbanized areas, focusing on concentration, size, morphology, presence of additives and distributions of different polymers. The natural and extend data are compiled and compared to laboratory-based analyses to further our understanding of the potential adverse effects of inhaled plastic particles on human health.
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•Plastic fragments are dispersed in air, and can be inhaled.•There is limited information on the distribution of microplastics in air samples.•They may cause adverse effects on the respiratory system and beyond.•The exposure risk of inhaled MPs for human (respiratory) health is unresolved.
There is a marked increase in the development and use of electronic nicotine delivery systems or electronic cigarettes (ECIGs). This statement covers electronic cigarettes (ECIGs), defined as ..."electrical devices that generate an aerosol from a liquid" and thus excludes devices that contain tobacco. Database searches identified published articles that were used to summarise the current knowledge on the epidemiology of ECIG use; their ingredients and accompanied health effects; second-hand exposure; use of ECIGs for smoking cessation; behavioural aspects of ECIGs and social impact;
and animal studies; and user perspectives.ECIG aerosol contains potentially toxic chemicals. As compared to conventional cigarettes, these are fewer and generally in lower concentrations. Second-hand exposures to ECIG chemicals may represent a potential risk, especially to vulnerable populations. There is not enough scientific evidence to support ECIGs as an aid to smoking cessation due to a lack of controlled trials, including those that compare ECIGs with licenced stop-smoking treatments. So far, there are conflicting data that use of ECIGs results in a renormalisation of smoking behaviour or for the gateway hypothesis. Experiments in cell cultures and animal studies show that ECIGs can have multiple negative effects. The long-term effects of ECIG use are unknown, and there is therefore no evidence that ECIGs are safer than tobacco in the long term. Based on current knowledge, negative health effects cannot be ruled out.
Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and likely includes a subgroup that is biologically comparable to asthma. Studying asthma-associated gene expression changes in ...COPD could add insight into COPD pathogenesis and reveal biomarkers that predict a favorable response to corticosteroids.
To determine whether asthma-associated gene signatures are increased in COPD and associated with asthma-related features.
We compared disease-associated airway epithelial gene expression alterations in an asthma cohort (n = 105) and two COPD cohorts (n = 237, 171). The T helper type 2 (Th2) signature (T2S) score, a gene expression metric induced in Th2-high asthma, was evaluated in these COPD cohorts. The T2S score was correlated with asthma-related features and response to corticosteroids in COPD in a randomized, placebo-controlled trial, the Groningen and Leiden Universities study of Corticosteroids in Obstructive Lung Disease (GLUCOLD; n = 89).
The 200 genes most differentially expressed in asthma versus healthy control subjects were enriched among genes associated with more severe airflow obstruction in these COPD cohorts (P < 0.001), suggesting significant gene expression overlap. A higher T2S score was associated with decreased lung function (P < 0.001), but not asthma history, in both COPD cohorts. Higher T2S scores correlated with increased airway wall eosinophil counts (P = 0.003), blood eosinophil percentage (P = 0.03), bronchodilator reversibility (P = 0.01), and improvement in hyperinflation after corticosteroid treatment (P = 0.019) in GLUCOLD.
These data identify airway gene expression alterations that can co-occur in asthma and COPD. The association of the T2S score with increased severity and "asthma-like" features (including a favorable corticosteroid response) in COPD suggests that Th2 inflammation is important in a COPD subset that cannot be identified by clinical history of asthma.
Electronic cigarettes (e-cigarettes, ECIGs) were introduced into the market a decade ago as an alternative to tobacco smoking. Whether ECIGs are safe and whether they qualify as smoking cessation ...tool is currently unknown. Their use has markedly expanded in that period, despite the fact that potential toxic effects of the vapour created by the e-cigarette and the nicotine-containing cartridge fluid have been incompletely studied. Marketing targets diverse groups including older smokers but also young people. Whereas the adverse health effects of nicotine inhaled by users of ECIGs has been well documented, less is known about the other components. An increasing number of in vitro and in vivo studies demonstrate a range of adverse effects of both the vapour created by ECIGs as well as the nicotine-containing fluid. Importantly, these studies demonstrate that toxicity from ECIGs, although this may be less than that caused by tobacco products, not only arises from its nicotine content. Furthermore, there are no data on the long-term consequences of ECIG use. The wide range of ECIG products available to consumers and the lack of standardisation of toxicological approaches towards ECIG evaluation complicates the assessment of adverse health effects of their use. Here we review the current data on preclinical studies on ECIGs describing their effects in cell culture and animal models.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) seems an important clinical phenotype, but multiple definitions have been proposed. This study's objectives were to assess ...the effect of different ACOS definitions on prevalence, patient characteristics and exacerbations.5675 individuals aged 45-65 years, with 846 asthma/COPD patients, were included in the Netherlands Epidemiology of Obesity study between 2008 and 2012, and followed-up for a median of 1.8 years. ACOS was defined by recent consensus criteria and five other definitions, based on registry, questionnaires and lung function.Prevalence of ACOS in the asthma/COPD population ranged between 4.4% and 38.3%, depending on the definition used. Agreement between registry-based and self-reported ACOS was 0.04 and 0.41 when lung function (forced expiratory volume in 1 s (FEV
)/forced vital capacity (FVC) <0.7) was added. With registry or self-report defined ACOS, only 51% and 33% had FEV
/FVC <0.7. Patient characteristics were similar, but asthma duration was longer with self-reported compared with registry-based ACOS (mean difference 22 years (95% CI 12-33)). Exacerbation risk was highest with registry-based ACOS compared with asthma (adjusted incidence rate ratio 1.6 (95% CI 1.2-2.1)).This study adds important knowledge about agreement between ACOS definitions and their relation with exacerbations. Given the low agreement, differences in prevalence, patient characteristics and risk of exacerbations, consensus about ACOS definition in different care settings is urgently needed.
Cationic host defence peptides (CHDPs), also known as antimicrobial peptides, exhibit a wide range of activities contributing to immune responses and resolution of infections. CHDPs are expressed ...across diverse species, are generally amphipathic with less than 50 amino acids in length, and differ significantly in sequence and structure. This chapter focuses on the role of these peptides in immunity. CHDPs are known to function in both innate and adaptive immune responses. These peptides exert both pro- and anti-inflammatory properties, which are likely context dependent based on cell and tissue type, concentration of the peptides, and its interaction with other factors in the microenvironment. Furthermore, the crosstalk between CHDPs and the microbiome and how this may influence mucosal immunity is a rapidly emerging field of research. Overall, the immunomodulatory functions of CHDPs play an important role in the control of infections, regulation of inflammation, and maintaining immune homeostasis. It is thus not surprising that dysregulation of expression of CHDPs is implicated in the susceptibility, pathology, and progression of various diseases. In this chapter, we summarize the immunomodulatory functions of CHDPs, its clinical relevance, and the translational opportunities that these peptides provide for the development of new therapies.
Chronic exposure to environmental pollutants is a major contributor to the development and progression of obstructive airway diseases, including asthma and COPD. Understanding the mechanisms ...underlying the development of obstructive lung diseases upon exposure to inhaled pollutants will lead to novel insights into the pathogenesis, prevention and treatment of these diseases. The respiratory epithelial lining forms a robust physicochemical barrier protecting the body from inhaled toxic particles and pathogens. Inhalation of airborne particles and gases may impair airway epithelial barrier function and subsequently lead to exaggerated inflammatory responses and airway remodelling, which are key features of asthma and COPD. In addition, air pollutant-induced airway epithelial barrier dysfunction may increase susceptibility to respiratory infections, thereby increasing the risk of exacerbations and thus triggering further inflammation. In this review, we discuss the molecular and immunological mechanisms involved in physical barrier disruption induced by major airborne pollutants and outline their implications in the pathogenesis of asthma and COPD. We further discuss the link between these pollutants and changes in the lung microbiome as a potential factor for aggravating airway diseases. Understanding these mechanisms may lead to identification of novel targets for therapeutic intervention to restore airway epithelial integrity in asthma and COPD.
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