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1.
Wilhelm Ammenwerth Henrik Wurps Mark A. Klemens Catharina Crolow Jeanette Schulz-Menger Nicolas Sch?nfeld Roland C. Bittner Torsten T. Bauer 《PloS one》2014,9(7)
Background
The non-invasive diagnosis of cardiac sarcoidosis (CS) is difficult. Cardiovascular magnetic resonance (CMR) has become a very valuable diagnostic tool in patients with suspected CS, but usually a combination of different tests is used. Oxygen uptake efficiency slope (OUES) is a parameter of cardiopulmonary exercise testing (CPET), which is used as an indicator for cardiovascular impairment. We investigated the predictive value of OUES for the diagnosis of myocardial involvement in sarcoid patients.Methods
Retrospectively 37 consecutive patients (44.9±13.8 years) with histologically confirmed sarcoidosis and clinical suspicion of heart involvement underwent noninvasive diagnostic testing including CMR. CS was diagnosed according to the guidelines from the Japanese Society of Sarcoidosis and other Granulomatous Disorders with additional consideration of CMR findings. Furthermore, CPET with calculation of predicted OUES according to equations by Hollenberg et al. was carried out.Results
Patients with CS (11/37; 30%) had a worse cardiovascular response to exercise. OUES was significantly lower in CS-group compared to non-CS-group (59.3±19.1 vs 88.0±15.4%pred., p<0.0001). ROC curve method identified 70%pred. as the OUES cut-off point, which maximized sensitivity and specificity for detection of CS (96% sensitivity, 82% specificity, 89% overall accuracy). OUES <70%pred. was the single best predictor of CS (Odds ratio: 100.43, 95% CI: 1.99 to 5064, p<0.001) even in multivariate analyses.Conclusion
OUES assessed in CPET may be helpful in identifying patient with cardiac involvement of sarcoidosis. Patient selection for CMR may be assisted by CPET findings in patients with sarcoidosis. 相似文献2.
Marc Miravitlles Heinrich Worth Juan José Soler Catalu?a David Price Fernando De Benedetto Nicolas Roche Nina Skavlan Godtfredsen Thys van der Molen Claes-G?ran L?fdahl Laura Padullés Anna Ribera 《Respiratory research》2014,15(1)
Background
Few studies have investigated the 24-hour symptom profile in patients with COPD or how symptoms during the 24-hour day are inter-related. This observational study assessed the prevalence, severity and relationship between night-time, early morning and daytime COPD symptoms and explored the relationship between 24-hour symptoms and other patient-reported outcomes.Methods
The study enrolled patients with stable COPD in clinical practice. Baseline night-time, early morning and daytime symptoms (symptom questionnaire), severity of airflow obstruction (FEV1), dyspnoea (modified Medical Research Council Dyspnoea Scale), health status (COPD Assessment Test), anxiety and depression levels (Hospital Anxiety and Depression Scale), sleep quality (COPD and Asthma Sleep Impact Scale) and physical activity level (sedentary, moderately active or active) were recorded.Results
The full analysis set included 727 patients: 65.8% male, mean ± standard deviation age 67.2 ± 8.8 years, % predicted FEV1 52.8 ± 20.5%.In each part of the 24-hour day, >60% of patients reported experiencing ≥1 symptom in the week before baseline. Symptoms were more common in the early morning and daytime versus night-time (81.4%, 82.7% and 63.0%, respectively). Symptom severity was comparable for each period assessed. Overall, in the week before baseline, 56.7% of patients had symptoms throughout the whole 24-hour day (3 parts of the day); 79.9% had symptoms in ≥2 parts of the 24-hour day. Symptoms during each part of the day were inter-related, irrespective of disease severity (all p < 0.001).Early morning and daytime symptoms were associated with the severity of airflow obstruction (p < 0.05 for both). Night-time, early morning and daytime symptoms were all associated with worse dyspnoea, health status and sleep quality, and higher anxiety and depression levels (all p < 0.001 versus patients without symptoms in each corresponding period). In each part of the 24-hour day, there was also an association between symptoms and a patient’s physical activity level (p < 0.05 for each period).Conclusions
More than half of patients experienced COPD symptoms throughout the whole 24-hour day. There was a significant relationship between night-time, early morning and daytime symptoms. In each period, symptoms were associated with worse patient-reported outcomes, suggesting that improving 24-hour symptoms should be an important consideration in the management of COPD.Electronic supplementary material
The online version of this article (doi:10.1186/s12931-014-0122-1) contains supplementary material, which is available to authorized users. 相似文献3.
4.
Carlos H Martinez Yuka Okajima Susan Murray George R Washko Fernando J Martinez Edwin K Silverman Jin Hwa Lee Elizabeth A Regan James D Crapo Jeffrey L Curtis Hiroto Hatabu MeiLan K Han 《Respiratory research》2014,15(1):62
Background
The coexistence of gastroesophageal reflux disease (GERD) and COPD has been recognized, but there has been no comprehensive evaluation of the impact of GERD on COPD-related health status and patient-centered outcomes.Methods
Cross-sectional and longitudinal study of 4,483 participants in the COPDGene cohort who met GOLD criteria for COPD. Physician-diagnosed GERD was ascertained by questionnaire. Clinical features, spirometry and imaging were compared between COPD subjects without versus with GERD. We evaluated the relationship between GERD and symptoms, exacerbations and markers of microaspiration in univariate and multivariate models. Associations were additionally tested for the confounding effect of covariates associated with a diagnosis of GERD and the use of proton-pump inhibitor medications (PPIs). To determine whether GERD is simply a marker for the presence of other conditions independently associated with worse COPD outcomes, we also tested models incorporating a GERD propensity score.Results
GERD was reported by 29% of subjects with female predominance. Subjects with GERD were more likely to have chronic bronchitis symptoms, higher prevalence of prior cardiovascular events (combined myocardial infarction, coronary artery disease and stroke 21.3% vs. 13.4.0%, p < 0.0001). Subjects with GERD also had more severe dyspnea (MMRC score 2.2 vs. 1.8, p < 0.0001), and poorer quality of life (QOL) scores (St. George’s Respiratory Questionnaire (SGRQ) total score 41.8 vs. 34.9, p < 0.0001; SF36 Physical Component Score 38.2 vs. 41.4, p < 0.0001). In multivariate models, a significant relationship was detected between GERD and SGRQ (3.4 points difference, p < 0.001) and frequent exacerbations at baseline (≥2 exacerbation per annum at inclusion OR 1.40, p = 0.006). During a mean follow-up time of two years, GERD was also associated with frequent (≥2/year exacerbations OR 1.40, p = 0.006), even in models in which PPIs, GERD-PPI interactions and a GERD propensity score were included. PPI use was associated with frequent exacerbator phenotype, but did not meaningfully influence the GERD-exacerbation association.Conclusions
In COPD the presence of physician-diagnosed GERD is associated with increased symptoms, poorer QOL and increased frequency of exacerbations at baseline and during follow-up. These associations are maintained after controlling for PPI use. The PPI-exacerbations association could result from confounding-by-indication. 相似文献5.
6.
Stefano Aliberti Anna Maria Brambilla James D Chalmers Catia Cilloniz Julio Ramirez Angelo Bignamini Elena Prina Eva Polverino Paolo Tarsia Alberto Pesci Antoni Torres Francesco Blasi Roberto Cosentini 《Respiratory research》2014,15(1):27
Background
Acute respiratory failure (ARF) and severe sepsis (SS) are possible complications in patients with community-acquired pneumonia (CAP). The aim of the study was to evaluate prevalence, characteristics, risk factors and impact on mortality of hospitalized patients with CAP according to the presence of ARF and SS on admission.Methods
This was a multicenter, observational, prospective study of consecutive CAP patients admitted to three hospitals in Italy, Spain, and Scotland between 2008 and 2010. Three groups of patients were identified: those with neither ARF nor SS (Group A), those with only ARF (Group B) and those with both ARF and SS (Group C) on admission.Results
Among the 2,145 patients enrolled, 45% belonged to Group A, 36% to Group B and 20% to Group C. Patients in Group C were more severe than patients in Group B. Isolated ARF was correlated with age (p < 0.001), COPD (p < 0.001) and multilobar infiltrates (p < 0.001). The contemporary occurrence of ARF and SS was associated with age (p = 0.002), residency in nursing home (p = 0.007), COPD (p < 0.001), multilobar involvement (p < 0.001) and renal disease (p < 0.001). 4.2% of patients in Group A died, 9.3% in Group B and 26% in Group C, p < 0.001. After adjustment, the presence of only ARF had an OR for in-hospital mortality of 1.85 (p = 0.011) and the presence of both ARF and SS had an OR of 6.32 (p < 0.001).Conclusions
The identification of ARF and SS on hospital admission can help physicians in classifying CAP patients into three different clinical phenotypes. 相似文献7.
Simon E Brill Anant RC Patel Richa Singh Alexander J Mackay Jeremy S Brown John R Hurst 《Respiratory research》2015,16(1)
Background
Exacerbations of non-cystic fibrosis bronchiectasis cause significant morbidity but there are few detailed data on their clinical course and associated physiological changes. The biology of an exacerbation has not been previously described.The purpose of this study was to describe changes in lung function, symptoms, health status and inflammation during the development and recovery from community-treated exacerbations.Methods
This was a prospective observational cohort study of 32 outpatients with non-cystic fibrosis bronchiectasis conducted between August 2010 and August 2012. Patients completed a symptom diary card and measured their peak expiratory flow rate (PEFR) daily. Exacerbations were defined as oral antibiotic treatment taken for a worsening of respiratory symptoms. Symptoms and peak flow at exacerbation were analysed, and further measurements including the COPD Assessment Test (CAT) and inflammatory markers were also compared to baseline values.Results
At baseline, health status was significantly related to lung function, prognostic severity and systemic inflammation. 51 exacerbations occurred in 22 patients. Exacerbation symptoms began a median (interquartile range) of 4 (2, 7) days before treatment started and the median exacerbation duration was 16 (10, 29) days. 16% had not recovered by 35 days. At exacerbation, mean PEFR dropped by 10.6% (95% confidence interval 6.9-14.2, p < 0.001) and mean CAT score increased by 6.3 units (3.6-9.1, p = 0.001), median symptom count by 4 (2.25, 6, p < 0.001), and mean CRP by 9.0mg/L (2.3-15.8, p = 0.011). Exacerbations where PEFR fell by ≥10% were longer with more symptoms at onset.Conclusion
Exacerbations of non-CF bronchiectasis are inflammatory events, with worsened symptoms, lung function and health status, and a prolonged recovery period. Symptom diary cards, PEFR and CAT scores are responsive to changes at exacerbation and may be useful tools for their detection and monitoring.Electronic supplementary material
The online version of this article (doi:10.1186/s12931-015-0167-9) contains supplementary material, which is available to authorized users. 相似文献8.
Michiko Mori Cecilia K Andersson Gerard J Graham Claes-G?ran L?fdahl Jonas S Erjef?lt 《Respiratory research》2013,14(1):65
Background
De novo lymphatic vessel formation has recently been observed in lungs of patients with moderate chronic obstructive pulmonary disease (COPD). However, the distribution of lymphatic vessel changes among the anatomical compartments of diseased lungs is unknown. Furthermore, information regarding the nature of lymphatic vessel alterations across different stages of COPD is missing. This study performs a detailed morphometric characterization of lymphatic vessels in major peripheral lung compartments of patients with different severities of COPD and investigates the lymphatic expression of molecules involved in immune cell trafficking.Methods
Peripheral lung resection samples obtained from patients with mild (GOLD stage I), moderate-severe (GOLD stage II-III), and very severe (GOLD stage IV) COPD were investigated for podoplanin-immunopositive lymphatic vessels in distinct peripheral lung compartments: bronchioles, pulmonary blood vessels and alveolar walls. Control subjects with normal lung function were divided into never smokers and smokers. Lymphatics were analysed by multiple morphological parameters, as well as for their expression of CCL21 and the chemokine scavenger receptor D6.Results
The number of lymphatics increased by 133% in the alveolar parenchyma in patients with advanced COPD compared with never-smoking controls (p < 0.05). In patchy fibrotic lesions the number of alveolar lymphatics increased 20-fold from non-fibrotic parenchyma in the same COPD patients. The absolute number of lymphatics per bronchiole and artery was increased in advanced COPD, but numbers were not different after normalization to tissue area. Increased numbers of CCL21- and D6-positive lymphatics were observed in the alveolar parenchyma in advanced COPD compared with controls (p < 0.01). Lymphatic vessels also displayed increased mean levels of immunoreactivity for CCL21 in the wall of bronchioles (p < 0.01) and bronchiole-associated arteries (p < 0.05), as well as the alveolar parenchyma (p < 0.001) in patients with advanced COPD compared with never-smoking controls. A similar increase in lymphatic D6 immunoreactivity was observed in bronchioles (p < 0.05) and alveolar parenchyma (p < 0.01).Conclusions
This study shows that severe stages of COPD is associated with increased numbers of alveolar lymphatic vessels and a change in lymphatic vessel phenotype in major peripheral lung compartments. This novel histopathological feature is suggested to have important implications for distal lung immune cell traffic in advanced COPD. 相似文献9.
Yuan Zhang Xianqiu Chen Yang Hu Shanshan Du Li Shen Yifan He Yuxuan Zhang Xia Zhang Huiping Li Rex C Yung 《Respiratory research》2013,14(1):18
Background
The diagnosis of sarcoidosis is still a significant challenge in China because of the need to exclude other diseases including granulomatous infections and malignancies that may be clinically and radiographically similar. The specific aim of the study is to search for serum protein biomarkers of sarcoidosis and to validate their clinical usefulness in differential diagnosis.Methods
Serum samples were collected from patients with sarcoidosis (n = 37), and compared to those from patients with tuberculosis (n = 20), other pulmonary diseases (n = 20), and healthy volunteers (n = 20) for determination of sarcoidosis-specific or -associated protein expression profiles. The first part of this study focused on proteomic analysis of serum from patients with sarcoidosis to identify a pattern of peptides capable of differentiating the studied populations using the ClinProt profiling technology based on mass spectrometry. Enzyme Linked Immunosorbent Assay (ELISA) was then used to verify corresponding elevation of the serum protein concentration of the potential biomarkers in the same patients sets. Receiver operating characteristic curve (ROC) analyses was performed to determine the optimal cutoff value for diagnosis. Immunohistochemistry was carried out to further confirm the protein expression patterns of the biomarkers in lung tissue.Results
An unique protein peak of M/Z 3,210 Daltons (Da) was found to be differentially expressed between the sarcoidosis and control groups and was identified as the N-terminal peptide of 29 amino acids (94-122) of serum amyloid A (SAA). ELISA confirmed that the serum SAA level was significantly higher in the sarcoidosis group than that of the other 3 control groups (p < 0.05). The cutoff for serum SAA concentration determined by ROC analysis was 101.98 ng/ml, with the sensitivity and specificity of 96.3% and 52.5%, respectively. Immunohistochemical staining showed that the SAA depositions in lung tissue of the sarcoidosis patients were also significantly more intense than in non-sarcoid lung tissue (p < 0.05).Conclusion
This is the first study to investigate serum protein markers in Chinese subjects with sarcoidosis. This study shows that the serum SAA expression profiles were different between the sarcoidosis and non-sarcoidosis groups. SAA may be a potential serum biomarker for ruling-out the diagnosis of sarcoidosis in Chinese subjects. 相似文献10.
Zhike Liang Qingling Zhang Catherine MR Thomas Kirandeep K Chana David Gibeon Peter J Barnes Kian Fan Chung Pankaj K Bhavsar Louise E Donnelly 《Respiratory research》2014,15(1):72
Background
Bacteria are frequently cultured from sputum samples of severe asthma patients suggesting a defect in bacterial clearance from the airway. We measured the capacity of macrophages from patients with asthma to phagocytose bacteria.Methods
Phagocytosis of fluorescently-labelled polystyrene beads, Haemophilus influenzae or Staphylococcus aureus by broncholaveolar lavage alveolar macrophages (AM) and by monocyte-derived macrophages (MDM) from non-asthmatics, mild-moderate and severe asthmatic patients was assessed using fluorimetry.Results
There were no differences in phagocytosis of polystyrene beads by AMs or MDMs from any of the subject groups. There was reduced phagocytosis of Haemophilus influenzae and Staphylococcus aureus in MDMs from patients with severe asthma compared to non-severe asthma (p < 0.05 and p < 0.01, respectively) and healthy subjects (p < 0.01and p < 0.001, respectively). Phagocytosis of Haemophilus influenzae and Staphylococcus aureus by AM was also reduced in severe asthma compared to normal subjects (p < 0.05). Dexamethasone and formoterol did not suppress phagocytosis of bacteria by MDMs from any of the groups.Conclusions
Persistence of bacteria in the lower airways may result partly from a reduced phagocytic capacity of macrophages for bacteria. This may contribute to increased exacerbations, airway colonization and persistence of inflammation. 相似文献11.
Andrei Malinovschi Monica Masoero Michela Bellocchia Antonio Ciuffreda Paolo Solidoro Alessio Mattei Lorena Mercante Enrico Heffler Giovanni Rolla Caterina Bucca 《Respiratory research》2014,15(1)
Background
Acute exacerbations of COPD (AECOPD) are common and strongly influence disease severity and relative healthcare costs. Vitamin D deficiency is frequent among COPD patients and its contributory role in disease exacerbations is widely debated. Our aim was to assess the relationship of serum vitamin D levels with COPD severity and AECOPD.Methods
Serum vitamin D (25-hydroxyvitamin D) levels were measured in 97 COPD patients and related to lung function, comorbidities, FEV1 decline, AECOPD and hospital admission during the previous year.Results
Most patients (96%) had vitamin D deficiency, which was severe in 35 (36%). No significant relationship was found between vitamin D and FEV1 or annual FEV1 decline. No difference between patients with and without severe vitamin D deficiency was found in age, gender, BMI, smoking history, lung function, and comorbidities, apart from osteoporosis (60.9% in severe deficiency vs 22.7%, p = 0.001). In multiple logistic regression models, severe deficiency was independently associated with AECOPD [adjusted odds ratios (aOR) of 30.5 (95% CI 5.55, 168), p < 0.001] and hospitalization [aOR 3.83 (95% CI 1.29, 11.4), p = 0.02]. The odds ratio of being a frequent exacerbator if having severe vitamin D deficiency was 18.1 (95% CI 4.98, 65.8) (p < 0.001), while that of hospitalization was 4.57 (95% CI 1.83, 11.4) (p = 0.001).Conclusions
In COPD patients severe vitamin D deficiency was related to more frequent disease exacerbations and hospitalization during the year previous to the measurement of vitamin D. This association was independent of patients’ characteristics and comorbidities.Electronic supplementary material
The online version of this article (doi:10.1186/s12931-014-0131-0) contains supplementary material, which is available to authorized users. 相似文献12.
Elide Anna Pastorello Laura Farioli Laura Michelina Losappio Nuccia Morici Matteo Di Biase Michele Nichelatti Jan Walter Schroeder Luca Balossi Silvio Klugmann 《Clinical and molecular allergy : CMA》2015,13(1)
Background
One of the greatest challenges in cardiovascular medicine is to define the best tools for performing an accurate risk stratification for the recurrence of ischemic events in acute coronary syndrome (ACS) patients.Methods
We followed 65 ACS patients enrolled in a previous pilot study for 2 years after being discharged, focusing on the occurrence of major adverse cardiovascular events (MACE).The relationship between serum tryptase levels on admission, SYNergy between percutaneous coronary intervention with the TAXUS drug-eluting stent and the cardiac surgery score (SX-score), cardiovascular complexity and MACE at 2 years follow-up were analyzed.Results
The ACS population was divided in two groups: patients with MACE (n = 23) and patients without MACE (n = 42).The tryptase measurement at admission (T0) and at discharge (T3) and SX-score were higher in patients who experienced MACE than in those without (p = 0.0001, p < 0.0001 and p = 0.006, respectively). Conversely, we found no significant association between MACE and C-reactive protein (CRP), and between MACE and maximum level of high-sensitivity troponin (hs-Tn) values.Among all patients with MACE, 96% belonged to the group that presented with cardiovascular complexity at the beginning of ACS index admission (p < 0.0001).The predictive accuracy of serum tryptase for MACE at follow up set at the cut-off point of 4.95 ng/ml at T0 and of 5.2 ng/ml at T3. Interestingly, patients with both the above cut-off tryptase values at T0 and at T3 presented a 1320% increase in the odds of developing MACE (p < 0.0001).Conclusion
In ACS patients, serum tryptase measured during index admission is significantly correlated to the development of MACE up to 2 years, demonstrating a possible long-term prognostic role of this biomarker.Electronic supplementary material
The online version of this article (doi:10.1186/s12948-015-0013-0) contains supplementary material, which is available to authorized users. 相似文献13.
Giancarlo Todiere Lorena Pisciella Andrea Barison Annamaria Del Franco Elisabetta Zachara Paolo Piaggi Federica Re Alessandro Pingitore Michele Emdin Massimo Lombardi Giovanni Donato Aquaro 《PloS one》2014,9(10)
Background
Myocardial hyperintensity on T2-weighted short-tau inversion recovery (STIR) (HyT2) cardiac magnetic resonance (CMR) images has been demonstrated in patients with hypertrophic cardiomyopathy (HCM) and is considered a sign of acute damage. The aim of the current study was to evaluate the relationship between HyT2 and both a) markers of ventricular electrical instability and b) clinical and CMR parameters.Methods
Sixty-five patients underwent a thorough clinical examination, consisting of 24-h ECG recording and CMR examination including functional evaluation, T2-STIR images and late gadolinium enhancement (LGE).Results
HyT2 was detected in 27 patients (42%), and subjects with HyT2 showed a greater left ventricle (LV) mass index (p<0.001), lower LV ejection fraction (p = 0.05) and greater extent of LGE (p<0.001) compared to those without HyT2. Twenty-two subjects (34%) presented non-sustained ventricular tachycardia (NSVT) on the 24-h ECG recording, 21 (95%) of whom exhibited HyT2. Based on the logistic regression analysis, HyT2 (odds ratio [OR]: 165, 95% CI 11–2455, p<0.001) and LGE extent (1.1, 1.0–1.3, p<0.001) served as independent predictors of NSVT, while the presence of LGE was not associated with NSVT occurrence (p = 0.49). The presence of HyT2 was associated with lower heart rate variability (p = 0.006) and a higher number of arrhythmic risk factors (p<0.001).Conclusions
In HCM patients, HyT2 upon CMR examination is associated with more advanced disease and increased arrhythmic burden. 相似文献14.
Elisabeth APM Romme David A McAllister John T Murchison Edwin JR Van Beek George S Petrides Cameron OS Price Erica PA Rutten Frank WJM Smeenk Emiel FM Wouters William MacNee 《Respiratory research》2013,14(1):129
Background
Cardiovascular disease, osteoporosis and emphysema are associated with COPD. Associations between these factors and whether they predict all-cause mortality in COPD patients are not well understood. Therefore, we examined associations between markers of cardiovascular disease (coronary artery calcification [CAC], thoracic aortic calcification [TAC] and arterial stiffness), bone density (bone attenuation of the thoracic vertebrae), emphysema (PI-950 and 15th percentile) and all-cause mortality in a COPD cohort.Methods
We assessed CAC, TAC, bone attenuation of the thoracic vertebrae, PI-950 and 15th percentile on low-dose chest computed tomography in COPD subjects. We measured arterial stiffness as carotid-radial pulse wave velocity (PWV), and identified deaths from the national register.Results
We studied 119 COPD subjects; aged 67.8 ±7.3, 66% were males and mean FEV1% predicted was 46.0 ±17.5. Subjects were classified into three pre-specificed groups: CAC = 0 (n = 14), 0 < CAC ≤ 400 (n = 41) and CAC > 400 (n = 64). Subjects with higher CAC were more likely to be older (p < 0.001) and male (p = 0.03), and more likely to have higher systolic blood pressure (p = 0.001) and a history of hypertension (p = 0.002) or ischemic heart disease (p = 0.003). Higher CAC was associated with higher PWV (OR 1.62, p = 0.04) and lower bone attenuation (OR 0.32, p = 0.02), but not with 15th percentile, after adjustment for age, sex and pack-years of smoking. In a Cox proportional hazards model, CAC, TAC and 15th percentile predicted all-cause mortality (HR 2.01, 2.09 and 0.66, respectively).Conclusions
Increased CAC was associated with increased arterial stiffness and lower bone density in a COPD cohort. In addition, CAC, TAC and extent of emphysema predicted all-cause mortality.Trial registration
Lothian NHS Board, Lothian Research Ethics Committee, LREC/2003/8/28. 相似文献15.
Arjun K Ravi Shruti Khurana Jonathan Lemon Jonathan Plumb George Booth Louise Healy Matthew Catley J?rgen Vestbo Dave Singh 《Respiratory research》2014,15(1)
Background
COPD patients have increased numbers of macrophages and neutrophils in the lungs. Interleukin-6 (IL-6) trans-signaling via its soluble receptor sIL-6R, governs the influx of innate immune cells to inflammatory foci through regulation of the chemokine CCL3. We hypothesized that there would be enhanced levels of IL-6, sIL-6R and CCL3 in COPD sputum.Methods
59 COPD patients, 15 HNS and 15 S underwent sputum induction and processing with phosphate buffered saline to obtain supernatants for IL-6, sIL-6R and CCL3 analysis. Cytoslides were produced for differential cell counting and immunocytochemistry (COPD; n = 3) to determine cell type surface expression of the CCL3 receptors CCR5 and CCR1.Results
COPD patients expressed higher levels (p < 0.05) of sIL-6R and CCL3 compared to controls (sIL-6R medians pg/ml: COPD 166.4 vs S 101.1 vs HNS 96.4; CCL3 medians pg/ml: COPD 117.9 vs S 0 vs HNS 2.7). COPD sIL-6R levels were significantly correlated with sputum neutrophil (r = 0.5, p < 0.0001) and macrophage (r = 0.3, p = 0.01) counts. Immunocytochemical analysis revealed that CCR5 and CCR1 were exclusively expressed on airway macrophages.Conclusion
Enhanced airway generation of sIL-6R may promote IL-6 trans-signaling in COPD. Associated upregulation of CCL3 may facilitate the recruitment of macrophages into the airways by ligation of CCR1 and CCR5.Electronic supplementary material
The online version of this article (doi:10.1186/s12931-014-0103-4) contains supplementary material, which is available to authorized users. 相似文献16.
Richa Singh Alexander J Mackay Anant RC Patel Davinder S Garcha Beverly S Kowlessar Simon E Brill Louise E Donnelly Peter J Barnes Gavin C Donaldson Jadwiga A Wedzicha 《Respiratory research》2014,15(1)
Background
There has been increasing interest in the use of newer, culture-independent techniques to study the airway microbiome of COPD patients. We investigated the relationships between the three common potentially pathogenic microorganisms (PPMs) Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis, as detected by quantitative PCR (qPCR), and inflammation and health status in stable patients in the London COPD cohort.Methods
We prospectively collected sputum, serum and plasma samples for analysis of airway bacterial presence and load, and airway and systemic inflammation from 99 stable COPD patients between January 2011 and October 2012. Health status was measured with St George’s Respiratory Questionnaire and COPD Assessment Test.Results
Airway inflammation and plasma fibrinogen, but not C-reactive protein, were greater in samples with PPM detection (p < 0.001, p = 0.049 and p = 0.261, respectively). Increasing total bacterial load was associated with increasing airway (p < 0.01) but not systemic inflammation (p > 0.05). Samples with high total bacterial loads had significantly higher airway inflammation than both samples without PPM detection and those with lower loads. Haemophilus influenzae presence was associated with significantly higher levels of airway but not systemic inflammation for all given pathogen loads (p < 0.05), and was significantly greater than with other PPMs. No association was observed between inflammation and health status (p > 0.05).Conclusions
Airway and systemic inflammation, as measured by fibrinogen, is greater in stable COPD patients with PPMs detected using the culture-independent qPCR technique. The airway, but not systemic inflammatory response, appears to have a total pathogen-load threshold and appears attributable to Haemophilus influenzae. However, discordance between inflammation and health status was observed.Electronic supplementary material
The online version of this article (doi:10.1186/s12931-014-0114-1) contains supplementary material, which is available to authorized users. 相似文献17.
Anna-Karin Larsson-Callerfelt Oskar Hallgren Annika Andersson-Sj?land Lena Thiman Johan Bj?rklund Josefine Kron Kristian Nihlberg Leif Bjermer Claes-G?ran L?fdahl Gunilla Westergren-Thorsson 《Respiratory research》2013,14(1):21
Background
Prostacyclin analogs are potent vasodilators and possess anti-inflammatory properties. However, the effect of prostacyclin on extracellular matrix (ECM) in COPD is not well known. Collagen fibrils and proteoglycans are essential ECM components in the lung and fibroblasts are key players in regulating the homeostasis of ECM proteins. The aim was to study the synthesis of prostacyclin and its effect on fibroblast activity and ECM production, and in particular collagen I and the collagen-associated proteoglycans biglycan and decorin.Methods
Parenchymal lung fibroblasts were isolated from lungs from COPD patients (GOLD stage IV) and from lungs and transbronchial biopsies from control subjects. The prostacyclin analog iloprost was used to study the effect of prostacyclin on ECM protein synthesis, migration, proliferation and contractile capacity of fibroblasts.Results
TGF-β1 stimulation significantly increased prostacyclin synthesis in fibroblasts from COPD patients (p < 0.01), but showed no effect on fibroblasts from control subjects. Collagen I synthesis was decreased by iloprost in both control and COPD fibroblasts (p < 0.05). Conversely, iloprost significantly altered biglycan and decorin synthesis in control fibroblasts, but iloprost displayed no effect on these proteoglycans in COPD fibroblasts. Proliferation rate was reduced (p < 0.05) and contractile capacity was increased in COPD fibroblasts (p < 0.05) compared to control fibroblasts. Iloprost decreased proliferative rate in control fibroblasts (p < 0.05), whereas iloprost attenuated contraction capacity in both COPD (p < 0.01) and control fibroblasts (p < 0.05).Conclusions
Iloprost reduced collagen I synthesis and fibroblast contractility but did not affect the collagen-associated proteoglycans or proliferation rate in fibroblasts from COPD patients. Enhanced prostacyclin production could lead to improper collagen network fibrillogenesis and a more emphysematous lung structure in severe COPD patients. 相似文献18.
Victor Pinto-Plata Ciro Casanova Hana Müllerova Juan P de Torres Henneth Corado Nerea Varo Elizabeth Cordoba Salah Zeineldine Hildegarde Paz Rebeca Baz Miguel Divo Felipe Cortopassi Bartolome R Celli 《Respiratory research》2012,13(1):71
Background
The relationship between serum biomarkers and clinical expressions of COPD is limited. We planned to further describe this association using markers of inflammation and injury and repair.Methods
We studied lung function, comorbidities, exercise tolerance, BODE index, and quality of life in 253 COPD patients and recorded mortality over three years. Serum levels of Interleukins 6,8 and16, tumor necrosis factor alpha (TNF α) [inflammatory panel], vascular endothelial growth factor (VEGF), and matrix metalloproteinase 9 (MMP-9) [injury and repair panel] and pulmonary and activation-regulated chemokine (PARC/CCL-18) and monocyte chemotactic protein 1 (MCP-1/CCL2) [chemoattractant panel] were measured. We related the pattern of the biomarker levels to minimal clinically important differences (MCID) using a novel visualization method [ObServed Clinical Association Results (OSCAR) plot].Results
Levels of the inflammatory markers IL-6, TNF α were higher and those of injury and repair lower (p < 0.01) with more advanced disease (GOLD 1 vs. 4). Using the OSCAR plot, we found that patients in the highest quartile of inflammatory and lowest quartile of injury and repair biomarkers level were more clinically compromised and had higher mortality (p < 0.05).Conclusions
In COPD, serum biomarkers of inflammation and repair are distinctly associated with important clinical parameters and survival. 相似文献19.
Renata Ferrari Suzana E Tanni Laura MO Caram Corina Corrêa Camila R Corrêa Irma Godoy 《Respiratory research》2013,14(1):24
Background
Past studies have shown that mean values of Interleukin-6 (IL-6) and C-reactive protein (CRP) do not change significantly in COPD patients over a one-year period. However, longer period follow-up studies are still lacking. Thus, the aim of this study is to evaluate plasma CRP and IL-6 concentration over three years in COPD patients and to test the association between these inflammatory mediators and disease outcome markers.Methods
A cohort of 77 outpatients with stable COPD was evaluated at baseline, and 53 (mean FEV1, 56% predicted) were included in the prospective study. We evaluated Interleukin-6 (IL-6), C-reactive protein (CRP), six-minute walking distance (6MWD), and body mass index (BMI) at baseline and after three years. Plasma concentration of IL-6 was measured by high sensitivity ELISA, and CRP was obtained by high sensitivity particle-enhanced immunonephelometry.Results
IL-6 increased significantly after 3 years compared to baseline measurements [0.8 (0.5-1.3) vs 2.4 (1.3-4.4) pg/ml; p < 0.001] and was associated with worse 6MWD performance. In the Cox regression, increased IL-6 at baseline was associated with mortality [Hazard Ratio (95% CI) = 2.68 (0.13, 1.84); p = 0.02]. CRP mean values did not change [5 (1.6-7.9) vs 4.7 (1.7-10) pg/L; p = 0.84], although eleven patients (21%) presented with changes >3 mg/L in CRP after 3 years.Conclusions
The systemic inflammatory process, evaluated by IL-6, seems to be persistent, progressive and associated with mortality and worse physical performance in COPD patients.Trial registration
No.: NCT00605540相似文献20.
Nils P Nickel Ralf Lichtinghagen Heiko Golpon Karen M Olsson Korbinian Brand Tobias Welte Marius M Hoeper 《Respiratory research》2013,14(1):130