Global lung health: the dangers of mild lung function impairment

The relationship between low lung function and increased mortality risk, especially in the context of ageing and exposure to noxious particles and gases, was established several decades ago. However, it was not until recently that low peak lung function in early adulthood (and thus the vital lung function trajectory that followed, independently of the ageing process) was associated with an increased prevalence, and about a decade earlier incidence, of respiratory and cardiovascular abnormalities, as well as premature death

Cómo varían el riesgo y el pronóstico de covid-19 en un paciente de EPOC

El término EPOC significa Enfermedad Pulmonar Obstructiva Crónica. Se trata de una enfermedad muy frecuente que afecta a entre el 10 y el 12% de la población adulta. Además, está en alza: actualmente es la tercera causa de muerte en el mundo

Highlights and hot topics in the management of COPD: where are we heading?

Proceedings of the First World Lung Disease Summit, Lisbon, Portugal, November 2013 The First World Lung Disease Summit took place in Lisbon over two days in November 2013. This inaugural meeting, of what is hoped to be a long-running annual series, brought together experts in respiratory medicine to explore many of the issues and challenges faced by clinicians when managing lung diseases, particularly asthma and COPD. The aim of the series is to present and discuss innovative science through a scientifically balanced program, and to explore how recent developments can inform clinical practice and improve patient care. The program for the inaugural meeting emphasized ongoing work in basic, clinical, and translational science as it evolves to bring about a more complete understanding of the pathology of asthma and COPD

The Systemic Inflammome of Severe Obesity before and after Bariatric Surgery

Obesity is associated with low-grade systemic inflammation. The "inflammome" is a network layout of the inflammatory pattern. The systemic inflammome of obesity has not been described as yet. We hypothesized that it can be significantly worsened by smoking and other comorbidities frequently associated with obesity, and ameliorated by bariatric surgery (BS). Besides, whether or not these changes are mirrored in the lungs is unknown, but obesity is often associated with pulmonary inflammation and bronchial hyperresponsiveness. We sought to: (1) describe the systemic inflammome of morbid obesity; (2) investigate the effects of sex, smoking, sleep apnea syndrome, metabolic syndrome and BS upon this systemic inflammome; and, (3) determine their interplay with pulmonary inflammation. We studied 129 morbidly obese patients (96 females; age 46±12 years; body mass index [BMI], 46±6 kg/m 2) before and one year after BS, and 20 healthy, never-smokers, (43±7 years), with normal BMI and spirometry. Before BS, compared with controls, all obese subjects displayed a strong and coordinated (inflammome) systemic inflammatory response (adiponectin, C-reactive protein, interleukin (IL)-8, IL-10, leptin, soluble tumor necrosis factor-receptor 1(sTNF-R1), and 8-isoprostane). This inflammome was not modified by sex, smoking, or coexistence of obstructive sleep apnea and/or metabolic syndrome. By contrast, it was significantly ameliorated, albeit not completely abolished, after BS. Finally, obese subjects had evidence of pulmonary inflammation (exhaled condensate) that also decreased after BS. The systemic inflammome of morbid obesity is independent of sex, smoking status and/or comorbidities, it is significantly reduced by BS and mirrored in the lungs

Cellular Senescence in Lung Fibrosis

Fibrosing interstitial lung diseases (ILDs) are chronic and ultimately fatal age-related lung diseases characterized by the progressive and irreversible accumulation of scar tissue in the lung parenchyma. Over the past years, significant progress has been made in our incomplete understanding of the pathobiology underlying fibrosing ILDs, in particular in relation to diverse age-related processes and cell perturbations that seem to lead to maladaptation to stress and susceptibility to lung fibrosis. Growing evidence suggests that a specific biological phenomenon known as cellular senescence plays an important role in the initiation and progression of pulmonary fibrosis. Cellular senescence is defined as a cell fate decision caused by the accumulation of unrepairable cellular damage and is characterized by an abundant pro-inflammatory and pro-fibrotic secretome. The senescence response has been widely recognized as a beneficial physiological mechanism during development and in tumour suppression. However, recent evidence strengthens the idea that it also drives degenerative processes such as lung fibrosis, most likely by promoting molecular and cellular changes in chronic fibrosing processes. Here, we review how cellular senescence may contribute to lung fibrosis pathobiology, and we highlight current and emerging therapeutic approaches to treat fibrosing ILDs by targeting cellular senescence

Haemophilus influenzae induces steroid-resistant inflammatory responses in COPD.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is an inflammatory disorder partially resistant to glucocorticoids. A reduced histone deacetylase (HDAC) activity has been proposed to explain this resistance. Haemophilus influenzae frequently colonizes the airways of COPD patients, where it enhances inflammation. The effects of Haemophilus influenzae on HDAC activity have not been investigated before. METHODS: The effects of the presence or absence of Haemophilus influenzae ex-vivo and in vitro were studied. To this end, we determined: (1) cytokine release in alveolar macrophages (AM) from 7 patients with COPD, 5 healthy smokers, 6 healthy non-smokers and (2) HDAC activity, nuclear factor kappa B (NF-κB) activation in a macrophage-like cell line (PMA-transformed U937 cells) co-cultured with epithelial cells. Experiments were repeated with dexamethasone (1 μM) and/or the HDAC enhancer theophylline (10 μM). RESULTS: Haemophilus influenzae induced a steroid-resistant inflammatory response in AM from COPD and controls and decreased HDAC activity, activated NF-κB and induced the secretion of several cytokines (IL-6, IL-8, IL-1β, IL-10 and TNF-α) (p < 0.001 for all comparisons) in the macrophage-like cell line. Dexamethasone reduced NF-κB activation but it did not modify HDAC activity. The addition of theophylline to dexamethasone increased HDAC activity and suppressed cytokine release completely, without modifying NF-κB activation. CONCLUSIONS: These results indicate that Haemophilus influenzae reduces HDAC activity and induces a NF-κB mediated inflammatory response that is only partially suppressed by glucocorticoids irrespective of having COPD. Yet, the latter can be fully restored by targeting HDAC activity

Pathogenesis of chronic obstructive pulmonary disease: understanding the contributions of gene-environment interactions across the lifespan

The traditional view of chronic obstructive pulmonary disease (COPD) as a self-inflicted disease caused by tobaccosmoking in genetically susceptible individuals has been challenged by recent research findings. COPD can instead beunderstood as the potential end result of the accumulation of gene–environment interactions encountered by anindividual over the lifetime. Integration of a time axis in pathogenic models of COPD is necessary because thebiological responses to and clinical consequences of different exposures might vary according to the age of anindividual at which a given gene–environment interaction occurs, as well as to the cumulative history of previousgene–environment interactions. Future research should aim to understand the effects of dynamic interactionsbetween genes (G) and the environment (E) by integrating information from basic omics (eg, genomics, epigenomics,proteomics) and clinical omics (eg, phenomics, physiomics, radiomics) with exposures (the exposome) over time(T)—an approach that we refer to as GETomics. In the context of this approach, we argue that COPD should beviewed not as a single disease, but as a clinical syndrome characterised by a recognisable pattern of chronic symptomsand structural or functional impairments due to gene–environment interactions across the lifespan that influencenormal lung development and ageing

Effect of aclidinium bromide on exacerbations in patients with moderate to severe COPD: a pooled analysis of five Phase III, randomized, placebo-controlled studies

We investigated the effect of the long-acting muscarinic antagonist aclidinium bromide on chronic obstructive pulmonary disease (COPD) exacerbations by pooling data from five randomized, placebo-controlled,parallel-group Phase III studies of 3-6 months' duration. Data were pooled from the aclidinium 400 μg twice-daily (BID) and placebo arms (N = 2,521) and stratified by Global initiative for chronic Obstructive Lung Disease (GOLD) group (A, B, C and D). Results showed that fewer patients experienced 1 exacerbation with aclidinium (any severity: 12.5%; moderate to severe: 10.9%) compared with placebo (any severity: 15.7%; moderate to severe: 13.3%) and the odds of experiencing 1 exacerbation of any severity were reduced in patients receiving aclidinium (odds ratio = 0.78, p = 0.039). Furthermore, aclidinium reduced the rate of exacerbations compared with placebo (any severity: rate ratio = 0.79, p = 0.026; moderate to severe: 0.80, p = 0.044). The time to first exacerbation of any severity was delayed with aclidinium compared with placebo (hazard ratio = 0.79, p = 0.026) and there was a numerical delay in time to first moderate-to-severe exacerbation. Finally, the effects of aclidinium on exacerbations versus placebo were greater in patients in GOLD Groups B and D; however, it is of note that only 10.7% of patients were classified in Group A or C. In summary, the results indicate that aclidinium 400 μg BID reduces the frequency of COPD exacerbations compared with placebo and that these effects are greater in symptomatic patients

Enfermedad pulmonar obstructiva crónica. Actualización 2014

La enfermedad pulmonar obstructiva crónica (EPOC) es un problema socio-sanitario de primera magnitud por su elevada prevalencia (10% en nuestro País), incidencia creciente (la Organización Mundial de la Salud estima que será la tercera causa de muerte en el mundo en 2020) y elevados costes socio-económicos asociados. En los últimos años se han producido avances notables en el conocimiento y tratamiento de la enfermedad que es ya considerada una enfermedad "prevenible y tratable". El texto que sigue resume los principales aspectos diagnósticos y terapéuticos de la EPOC a partir de la última versión (2014) del documento de la estrategia GOLD (Global Strategy for the Diagnosis, Management and Prevention of chronic obstructive pulmonary disease), el documento de referencia mundial en este ámbito. Hace énfasis especial en la nueva forma de determinar la gravedad de la enfermedad, basada en una valoración multi-dimensional de la EPOC que tiene en cuenta no sólo la severidad de la limitación al flujo aéreo (como se había hecho tradicionalmente hasta ahora), sino que añade dos dimensiones de gran valor clínico y pronóstico (el nivel de síntomas del paciente y la historia previa de agudizaciones de la enfermedad). Con estas tres dimensiones, los pacientes con EPOC se clasifican actualmente en uno de cuatro posibles grupos (A, B, C o D) y el tratamiento farmacológico recomendado se ajusta a esta clasificación

The systemic inflammome of severe obesity before and after bariatric surgery

INTRODUCTION: Obesity is associated with low-grade systemic inflammation. The 'inflammome' is a network layout of the inflammatory pattern. The systemic inflammome of obesity has not been described as yet. We hypothesized that it can be significantly worsened by smoking and other comorbidities frequently associated with obesity, and ameliorated by bariatric surgery (BS). Besides, whether or not these changes are mirrored in the lungs is unknown, but obesity is often associated with pulmonary inflammation and bronchial hyperresponsiveness. OBJECTIVES: We sought to: (1) describe the systemic inflammome of morbid obesity; (2) investigate the effects of sex, smoking, sleep apnea syndrome, metabolic syndrome and BS upon this systemic inflammome; and, (3) determine their interplay with pulmonary inflammation. METHODS: We studied 129 morbidly obese patients (96 females; age 46 ± 12 years; body mass index [BMI], 46 ± 6 kg/m2) before and one year after BS, and 20 healthy, never-smokers, (43 ± 7 years), with normal BMI and spirometry. RESULTS: Before BS, compared with controls, all obese subjects displayed a strong and coordinated (inflammome) systemic inflammatory response (adiponectin, C-reactive protein, interleukin (IL)-8, IL-10, leptin, soluble tumor necrosis factor-receptor 1(sTNF-R1), and 8-isoprostane). This inflammome was not modified by sex, smoking, or coexistence of obstructive sleep apnea and/or metabolic syndrome. By contrast, it was significantly ameliorated, albeit not completely abolished, after BS. Finally, obese subjects had evidence of pulmonary inflammation (exhaled condensate) that also decreased after BS. CONCLUSIONS: The systemic inflammome of morbid obesity is independent of sex, smoking status and/or comorbidities, it is significantly reduced by BS and mirrored in the lungs