共查询到20条相似文献,搜索用时 31 毫秒
1.
Onno M. Mets Pim A. de Jong Bram van Ginneken Cas L. J. J. Kruitwagen Mathias Prokop Matthijs Oudkerk Jan-Willem J. Lammers Pieter Zanen 《PloS one》2013,8(4)
Purpose
We aimed to study the association between lung function decline and quantitative computed tomography (CT) air trapping.Materials and Methods
Current and former heavy smokers in a lung cancer screening trial underwent volumetric low-dose CT in inspiration and expiration. Spirometry was obtained at baseline and after 3 years. The expiratory to inspiratory ratio of mean lung density (E/I-ratioMLD) was used to quantify air trapping. CT emphysema was defined as voxels in inspiratory CT below −950 Hounsfield Unit. Linear mixed modeling was used to determine the association between CT air trapping and lung function.Results
We included 985 subjects with a mean age of 61.3 years. Independent of CT emphysema, CT air trapping was significantly associated with a reduction in forced expiratory volume in one second (FEV1) and the ratio of FEV1 over the forced vital capacity (FEV1/FVC); FEV1 declines with 33 mL per percent increase in CT air trapping, while FEV1/FVC declines 0.58% per percent increase (both p<0.001). CT air trapping further elicits accelerated loss of FEV1/FVC (additional 0.24% reduction per percent increase; p = 0.014).Conclusion
In a lung cancer screening cohort, quantitatively assessed air trapping on low-dose CT is independently associated with reduced lung function and accelerated decline of FEV1/FVC. 相似文献2.
Akkelies E Dijkstra Dirkje S Postma Nick ten Hacken Judith M Vonk Matthijs Oudkerk Peter MA van Ooijen Pieter Zanen Firdaus A Mohamed Hoesein Bram van Ginneken Michael Schmidt Harry JM Groen 《Respiratory research》2013,14(1):11
Background
Increased airway wall thickness (AWT) and parenchymal lung destruction both contribute to airflow limitation. Advances in computed tomography (CT) post-processing imaging allow to quantify these features. The aim of this Dutch population study is to assess the relationships between AWT, lung function, emphysema and respiratory symptoms.Methods
AWT and emphysema were assessed by low-dose CT in 500 male heavy smokers, randomly selected from a lung cancer screening population. AWT was measured in each lung lobe in cross-sectionally reformatted images with an automated imaging program at locations with an internal diameter of 3.5 mm, and validated in smaller cohorts of patients. The 15th percentile method (Perc15) was used to assess the severity of emphysema. Information about respiratory symptoms and smoking behavior was collected by questionnaires and lung function by spirometry.Results
Median AWT in airways with an internal diameter of 3.5 mm (AWT3.5) was 0.57 (0.44 - 0.74) mm. Median AWT in subjects without symptoms was 0.52 (0.41-0.66) and in those with dyspnea and/or wheezing 0.65 (0.52-0.81) mm (p<0.001). In the multivariate analysis only AWT3.5 and emphysema independently explained 31.1%and 9.5%of the variance in FEV1%predicted, respectively, after adjustment for smoking behavior.Conclusions
Post processing standardization of airway wall measurements provides a reliable and useful method to assess airway wall thickness. Increased airway wall thickness contributes more to airflow limitation than emphysema in a smoking male population even after adjustment for smoking behavior. 相似文献3.
Alejandro A Diaz Farbod N Rahaghi James C Ross Rola Harmouche Juerg Tschirren Raul San José Estépar George R Washko for the COPD Gene investigators 《Respiratory research》2015,16(1)
Background
Computed tomographic (CT) airway lumen narrowing is associated with lower lung function. Although volumetric CT measures of airways (wall volume [WV] and lumen volume [LV]) compared to cross sectional measures can more accurately reflect bronchial morphology, data of their use in never smokers is scarce. We hypothesize that native tracheobronchial tree morphology as assessed by volumetric CT metrics play a significant role in determining lung function in normal subjects. We aimed to assess the relationships between airway size, the projected branching generation number (BGN) to reach airways of <2mm lumen diameter –the site for airflow obstruction in smokers- and measures of lung function including forced expiratory volume in 1 second (FEV1) and forced expiratory flow between 25% and 75% of vital capacity (FEF 25–75).Methods
We assessed WV and LV of segmental and subsegmental airways from six bronchial paths as well as lung volume on CT scans from 106 never smokers. We calculated the lumen area ratio of the subsegmental to segmental airways and estimated the projected BGN to reach a <2mm-lumen-diameter airway assuming a dichotomized tracheobronchial tree model. Regression analysis was used to assess the relationships between airway size, BGN, FEF 25–75, and FEV1.Results
We found that in models adjusted for demographics, LV and WV of segmental and subsegmental airways were directly related to FEV1 (P <0.05 for all the models). In adjusted models for age, sex, race, LV and lung volume or height, the projected BGN was directly associated with FEF 25–75 and FEV1 (P = 0.001) where subjects with lower FEV1 had fewer calculated branch generations between the subsegmental bronchus and small airways. There was no association between airway lumen area ratio and lung volume.Conclusion
We conclude that in never smokers, those with smaller central airways had lower airflow and those with lower airflow had less parallel airway pathways independent of lung size. These findings suggest that variability in the structure of the tracheobronchial tree may influence the risk of developing clinically relevant smoking related airway obstruction.Electronic supplementary material
The online version of this article (doi:10.1186/s12931-015-0181-y) contains supplementary material, which is available to authorized users. 相似文献4.
Victor Kim Parag Desai John D Newell Barry J Make George R Washko Edwin K Silverman James D Crapo Surya P Bhatt Gerard J Criner 《Respiratory research》2014,15(1):84
Rationale
Bronchodilator responsiveness (BDR) is a common but variable phenomenon in COPD. The CT characteristics of airway dimensions that differentiate COPD subjects with BDR from those without BDR have not been well described. We aimed to assess airway dimensions in COPD subjects with and without BDR.Methods
We analyzed subjects with GOLD 1–4 disease in the COPDGene® study who had CT airway analysis. We divided patients into two groups: BDR + (post bronchodilator ΔFEV1 ≥ 10%) and BDR-(post bronchodilator ΔFEV1 < 10%). The mean wall area percent (WA%) of six segmental bronchi in each subject was quantified using VIDA. Using 3D SLICER, airway wall thickness was also expressed as the square root wall area of an airway of 10 mm (Pi10) and 15 mm (Pi15) diameter. %Emphysema and %gas trapping were also calculated.Results
2355 subjects in the BDR-group and 1306 in the BDR + group formed our analysis. The BDR + group had a greater Pi10, Pi15, and mean segmental WA% compared to the BDR-group. In multivariate logistic regression using gender, race, current smoking, history of asthma, %emphysema, %gas trapping, %predicted FEV1, and %predicted FVC, airway wall measures remained independent predictors of BDR. Using a threshold change in FEV1 ≥ 15% and FEV1 ≥ 12% and 200 mL to divide patients into groups, the results were similar.Conclusion
BDR in COPD is independently associated with CT evidence of airway pathology. This study provides us with greater evidence of changes in lung structure that correlate with physiologic manifestations of airflow obstruction in COPD. 相似文献5.
Tricia M McKeever Sarah A Lewis Henriette A Smit Peter Burney Patricia A Cassano John Britton 《Respiratory research》2008,9(1):67
Background
There is mounting evidence that estimates of intakes of a range of dietary nutrients are related to both lung function level and rate of decline, but far less evidence on the relation between lung function and objective measures of serum levels of individual nutrients. The aim of this study was to conduct a comprehensive examination of the independent associations of a wide range of serum markers of nutritional status with lung function, measured as the one-second forced expiratory volume (FEV1).Methods
Using data from the Third National Health and Nutrition Examination Survey, a US population-based cross-sectional study, we investigated the relation between 21 serum markers of potentially relevant nutrients and FEV1, with adjustment for potential confounding factors. Systematic approaches were used to guide the analysis.Results
In a mutually adjusted model, higher serum levels of antioxidant vitamins (vitamin A, beta-cryptoxanthin, vitamin C, vitamin E), selenium, normalized calcium, chloride, and iron were independently associated with higher levels of FEV1. Higher concentrations of potassium and sodium were associated with lower FEV1.Conclusion
Maintaining higher serum concentrations of dietary antioxidant vitamins and selenium is potentially beneficial to lung health. In addition other novel associations found in this study merit further investigation. 相似文献6.
Sabine Dettmer Lars Peters Claudia de Wall Cornelia Schaefer-Prokop Michael Schmidt Gregor Warnecke Jens Gottlieb Frank Wacker Hoen-oh Shin 《PloS one》2014,9(4)
Objectives
To prospectively evaluate quantitative airway wall measurements of thin-section CT for the diagnosis of Bronchiolitis Obliterans Syndrome (BOS) following lung transplantation.Materials and Methods
In 141 CT examinations, bronchial wall thickness (WT), the wall area percentage (WA%) calculated as the ratio of the bronchial wall area and the total area (sum of bronchial wall area and bronchial lumen area) and the difference of the WT on inspiration and expiration (WTdiff) were automatically measured in different bronchial generations. The measurements were correlated with the lung function parameters. WT and WA% in CT examinations of patients with (n = 25) and without (n = 116) BOS, were compared using the unpaired t-test and univariate analysis of variance, while also considering the differing lung volumes.Results
Measurements could be performed in 2,978 bronchial generations. WT, WA%, and WTdiff did not correlate with the lung function parameters (r<0.5). The WA% on inspiration was significantly greater in patients with BOS than in patients without BOS, even when considering the dependency of the lung volume on the measurements. WT on inspiration and expiration and WA% on expiration did not show significant differences between the groups.Conclusion
WA% on inspiration was significantly greater in patients with than in those without BOS. However, WA% measurements were significantly dependent on lung volume and showed a high variability, thus not allowing the sole use of bronchial wall measurements to differentiate patients with from those without BOS. 相似文献7.
Ren Yuan Taishi Nagao Peter D Paré James C Hogg Don D Sin Mark W Elliott Leanna Loy Li Xing Steven E Kalloger John C English John R Mayo Harvey O Coxson 《Respiratory research》2010,11(1):153
Objective
To refine the CT prediction of emphysema by comparing histology and CT for specific regions of lung. To incorporate both regional lung density measured by CT and cluster analysis of low attenuation areas for comparison with histological measurement of surface area per unit lung volume.Methods
The histological surface area per unit lung volume was estimated for 140 samples taken from resected lung specimens of fourteen subjects. The region of the lung sampled for histology was located on the pre-operative CT scan; the regional CT median lung density and emphysematous lesion size were calculated using the X-ray attenuation values and a low attenuation cluster analysis. Linear mixed models were used to examine the relationships between histological surface area per unit lung volume and CT measures.Results
The median CT lung density, low attenuation cluster analysis, and the combination of both were important predictors of surface area per unit lung volume measured by histology (p < 0.0001). Akaike''s information criterion showed the model incorporating both parameters provided the most accurate prediction of emphysema.Conclusion
Combining CT measures of lung density and emphysematous lesion size provides a more accurate estimate of lung surface area per unit lung volume than either measure alone. 相似文献8.
Firdaus AA Mohamed Hoesein Pieter Zanen Pim A de Jong Bram van Ginneken H Marike Boezen Harry JM Groen Mathijs Oudkerk Harry J de Koning Dirkje S Postma Jan-Willem J Lammers 《Respiratory research》2013,14(1):55
Background
Little is known about the factors associated with CT-quantified emphysema progression in heavy smokers. The objective of this study was to investigate the effect of length of smoking cessation and clinical / demographical factors on the rate of emphysema progression and FEV1-decline in male heavy smokers.Methods
3,670 male smokers with mean (SD) 40.8 (17.9) packyears underwent chest CT scans and pulmonary function tests at baseline and after 1 and 3 years follow-up. Smoking status (quitted ≥5, ≥1-<5, <1 years or current smoker) was noted. Rate of progression of emphysema and FEV1-decline after follow-up were assessed by analysis of variance adjusting for age, height, baseline pulmonary function and emphysema severity, packyears, years in study and respiratory symptoms. The quitted ≥5 group was used as reference.Results
Median (Q1-Q3) emphysema severity,<-950 HU, was 8.8 (5.1 – 14.1) and mean (SD) FEV1 was 3.4 (0.73) L or 98.5 (18.5) % of predicted. The group quitted ‘>5 years’ showed significantly lower rates of progression of emphysema compared to current smokers, 1.07% and 1.12% per year, respectively (p<0.001). Current smokers had a yearly FEV1-decline of 69 ml, while subjects quit smoking >5 years had a yearly decline of 57.5 ml (p<0.001).Conclusion
Quit smoking >5 years significantly slows the rate of emphysema progression and lung function decline.Trial registration
Registered at http://www.trialregister.nl with trial number ISRCTN63545820. 相似文献9.
Nicola Sverzellati Davide Colombi Giorgia Randi Antonio Pavarani Mario Silva Simon L. Walsh Massimo Pistolesi Veronica Alfieri Alfredo Chetta Mauro Vaccarezza Marco Vitale Ugo Pastorino 《PloS one》2013,8(7)
Background
Factors determining the shape of the human rib cage are not completely understood. We aimed to quantify the contribution of anthropometric and COPD-related changes to rib cage variability in adult cigarette smokers.Methods
Rib cage diameters and areas (calculated from the inner surface of the rib cage) in 816 smokers with or without COPD, were evaluated at three anatomical levels using computed tomography (CT). CTs were analyzed with software, which allows quantification of total emphysema (emphysema%). The relationship between rib cage measurements and anthropometric factors, lung function indices, and %emphysema were tested using linear regression models.Results
A model that included gender, age, BMI, emphysema%, forced expiratory volume in one second (FEV1)%, and forced vital capacity (FVC)% fit best with the rib cage measurements (R2 = 64% for the rib cage area variation at the lower anatomical level). Gender had the biggest impact on rib cage diameter and area (105.3 cm2; 95% CI: 111.7 to 98.8 for male lower area). Emphysema% was responsible for an increase in size of upper and middle CT areas (up to 5.4 cm2; 95% CI: 3.0 to 7.8 for an emphysema increase of 5%). Lower rib cage areas decreased as FVC% decreased (5.1 cm2; 95% CI: 2.5 to 7.6 for 10 percentage points of FVC variation).Conclusions
This study demonstrates that simple CT measurements can predict rib cage morphometric variability and also highlight relationships between rib cage morphometry and emphysema. 相似文献10.
Meng-Rui Lee Ching-Yao Yang Kai-Ping Chang Li-Ta Keng David Hung-Tsang Yen Jann-Yuan Wang Huey-Dong Wu Li-Na Lee Chong-Jen Yu 《PloS one》2013,8(3)
Background
There is paucity of risk factors on lung function decline among patients with non-tuberculous mycobacteria (NTM) pulmonary disease in literature.Methods
Patients with NTM pulmonary disease between January 2000 and April 2011 were retrospectively selected. Sixty-eight patients had at least two pulmonary function tests within a mean follow-up period of 47 months.Results
Sixty-eight patients were included. They had a median age of 65 years and 65% had impaired lung function (Forced expiratory volume in 1 second [FEV1] <80% of predicted value). The mean FEV1 decline was 48 ml/year. By linear regression, younger age (beta: 0.472, p<0.001), initial FEV1>50% of predicted value (beta: 0.349, p = 0.002), male sex (beta: 0.295, p = 0.018), bronchiectasis pattern (beta: 0.232, p = 0.035), and radiographic score >3 (beta: 0.217, p = 0.049) were associated with greater FEV1 decline. Initial FEV1>50% of predicted value (beta: 0.263, p = 0.032) was also associated with greater FVC annual decline, whereas M. kansasii pulmonary disease was marginally associated with greater annual FVC decline (beta: 0.227, p = 0.062).Conclusions
NTM pulmonary disease is associated with greater decline in lung function in patients who are young, male, with bronchiectasis, and with a high radiographic score. Special attention should be given to patients with these risk factors. 相似文献11.
David G Parr Martin Sevenoaks ChunQin Deng Berend C Stoel Robert A Stockley 《Respiratory research》2008,9(1):21
Background
Computer tomography (CT) densitometry is a potential tool for detecting the progression of emphysema but the optimum methodology is uncertain. The level of inspiration affects reproducibility but the ability to adjust for this variable is facilitated by whole lung scanning methods. However, emphysema is frequently localised to sub-regions of the lung and targeted densitometric sampling may be more informative than whole lung assessment.Methods
Emphysema progression over a 2-year interval was assessed in 71 patients (alpha 1-antitrypsin deficiency with PiZ phenotype) with CT densitometry, using the 15th percentile point (Perc15) and voxel index (VI) -950 Hounsfield Units (HU) and -910 HU (VI -950 and -910) on whole lung, limited single slices, and apical, central and basal thirds. The relationship between whole lung densitometric progression (ΔCT) and change in CT-derived lung volume (ΔCTVol) was characterised, and adjustment for lung volume using statistical modelling was evaluated.Results
CT densitometric progression was statistically significant for all methods. ΔCT correlated with ΔCTVol and linear regression indicated that nearly one half of lung density loss was secondary to apparent hyperinflation. The most accurate measure was obtained using a random coefficient model to adjust for lung volume and the greatest progression was detected by targeted sampling of the middle third of the lung.Conclusion
Progressive hyperinflation may contribute significantly to loss of lung density, but volume effects and absolute tissue loss can be identified by statistical modelling. Targeted sampling of the middle lung region using Perc15 appears to be the most robust measure of emphysema progression. 相似文献12.
I Curjuric M Imboden R Nadif A Kumar C Schindler M Haun F Kronenberg N Künzli H Phuleria DS Postma EW Russi T Rochat F Demenais NM Probst-Hensch 《PloS one》2012,7(7):e40175
Background
Oxidative stress related genes modify the effects of ambient air pollution or tobacco smoking on lung function decline. The impact of interactions might be substantial, but previous studies mostly focused on main effects of single genes.Objectives
We studied the interaction of both exposures with a broad set of oxidative-stress related candidate genes and pathways on lung function decline and contrasted interactions between exposures.Methods
For 12679 single nucleotide polymorphisms (SNPs), change in forced expiratory volume in one second (FEV1), FEV1 over forced vital capacity (FEV1/FVC), and mean forced expiratory flow between 25 and 75% of the FVC (FEF25-75) was regressed on interval exposure to particulate matter <10 µm in diameter (PM10) or packyears smoked (a), additive SNP effects (b), and interaction terms between (a) and (b) in 669 adults with GWAS data. Interaction p-values for 152 genes and 14 pathways were calculated by the adaptive rank truncation product (ARTP) method, and compared between exposures. Interaction effect sizes were contrasted for the strongest SNPs of nominally significant genes (pinteraction<0.05). Replication was attempted for SNPs with MAF>10% in 3320 SAPALDIA participants without GWAS.Results
On the SNP-level, rs2035268 in gene SNCA accelerated FEV1/FVC decline by 3.8% (pinteraction = 2.5×10−6), and rs12190800 in PARK2 attenuated FEV1 decline by 95.1 ml pinteraction = 9.7×10−8) over 11 years, while interacting with PM10. Genes and pathways nominally interacting with PM10 and packyears exposure differed substantially. Gene CRISP2 presented a significant interaction with PM10 (pinteraction = 3.0×10−4) on FEV1/FVC decline. Pathway interactions were weak. Replications for the strongest SNPs in PARK2 and CRISP2 were not successful.Conclusions
Consistent with a stratified response to increasing oxidative stress, different genes and pathways potentially mediate PM10 and tobacco smoke effects on lung function decline. Ignoring environmental exposures would miss these patterns, but achieving sufficient sample size and comparability across study samples is challenging. 相似文献13.
Firdaus A. A. Mohamed Hoesein Pim A. de Jong Jan-Willem J. Lammers Willem PThM Mali Michael Schmidt Harry J. de Koning Carlijn van der Aalst Matthijs Oudkerk Rozemarijn Vliegenthart Bram van Ginneken Eva M. van Rikxoort Pieter Zanen 《PloS one》2013,8(6)
Background
There is increasing evidence that structural lung changes may be present before the occurrence of airflow limitation as assessed by spirometry. This study investigated the prevalence of computed tomography (CT) quantified emphysema, airway wall thickening and gas trapping according to classification of airflow limitation (FEV1/FVC <70% and/or < the lower limit of normal (LLN)) in (heavy) smokers.Methods
A total number of 1,140 male former and current smokers participating in a lung cancer screenings trial (NELSON) were included and underwent chest CT scanning and spirometry. Emphysema was quantified by the 15th percentile, air way wall thickening by the square root of wall area for a theoretical airway with 10mm lumen perimeter (Pi10) and gas trapping by the mean lung density expiratory/inspiratory (E/I)-ratio. Participants were classified by entry FEV1/FVC: group 1>70%; group 2<70% but >LLN; and group 3<LLN. 32 restricted subjects, i.e. FEV1/FVC >70% but FEV1 <80% predicted, were excluded. Multivariate regression analysis correcting for covariates was used to asses the extent of emphysema, airway wall thickening and gas trapping according to three groups of airflow limitation.Results
Mean (standard deviation) age was 62.5 (5.2) years and packyears smoked was 41.0 (18.0). Group 2 subjects when compared to group 1 had a significantly lower 15th percentile, −920.6 HU versus −912.2 HU; a higher Pi10, 2.87 mm versus 2.57 mm; and a higher E/I-ratio, 88.6% versus 85.6% (all p<0.001).Conclusion
Subjects with an FEV1/FVC<70%, but above the LLN, have a significant greater degree of structural lung changes on CT compared to subjects without airflow limitation. 相似文献14.
Yuichi Higami Emiko Ogawa Yasushi Ryujin Kenichi Goto Ruriko Seto Hiroshi Wada Nguyen Van Tho Le Thi Tuyet Lan Peter D. Paré Yasutaka Nakano 《PloS one》2016,11(2)
Background
Epicardial adipose tissue (EAT) has been shown to be a non-invasive marker that predicts the progression of cardiovascular disease (CVD). It has been reported that the EAT volume is increased in patients with chronic obstructive pulmonary disease (COPD). However, little is known about which phenotypes of COPD are associated with increased EAT.Methods
One hundred and eighty smokers who were referred to the clinic were consecutively enrolled. A chest CT was used for the quantification of the emphysematous lesions, airway lesions, and EAT. These lesions were assessed as the percentage of low attenuation volume (LAV%), the square root of airway wall area of a hypothetical airway with an internal perimeter of 10 mm (√Aaw at Pi10) and the EAT area, respectively. The same measurements were made on 225 Vietnamese COPD patients to replicate the results.Results
Twenty-six of the referred patients did not have COPD, while 105 were diagnosed as having COPD based on a FEV1/FVC<0.70. The EAT area was significantly associated with age, BMI, FEV1 (%predicted), FEV1/FVC, self-reported hypertension, self-reported CVD, statin use, LAV%, and √Aaw at Pi10 in COPD patients. The multiple regression analyses showed that only BMI, self-reported CVD and √Aaw at Pi10 were independently associated with the EAT area (R2 = 0.51, p<0.0001). These results were replicated in the Vietnamese population.Conclusions
The EAT area is independently associated with airway wall thickness. Because EAT is also an independent predictor of CVD risk, these data suggest a mechanistic link between the airway predominant form of COPD and CVD. 相似文献15.
Michael H Cho George R Washko Thomas J Hoffmann Gerard J Criner Eric A Hoffman Fernando J Martinez Nan Laird John J Reilly Edwin K Silverman 《Respiratory research》2010,11(1):30
Background
Numerous studies have demonstrated associations between genetic markers and COPD, but results have been inconsistent. One reason may be heterogeneity in disease definition. Unsupervised learning approaches may assist in understanding disease heterogeneity.Methods
We selected 31 phenotypic variables and 12 SNPs from five candidate genes in 308 subjects in the National Emphysema Treatment Trial (NETT) Genetics Ancillary Study cohort. We used factor analysis to select a subset of phenotypic variables, and then used cluster analysis to identify subtypes of severe emphysema. We examined the phenotypic and genotypic characteristics of each cluster.Results
We identified six factors accounting for 75% of the shared variability among our initial phenotypic variables. We selected four phenotypic variables from these factors for cluster analysis: 1) post-bronchodilator FEV1 percent predicted, 2) percent bronchodilator responsiveness, and quantitative CT measurements of 3) apical emphysema and 4) airway wall thickness. K-means cluster analysis revealed four clusters, though separation between clusters was modest: 1) emphysema predominant, 2) bronchodilator responsive, with higher FEV1; 3) discordant, with a lower FEV1 despite less severe emphysema and lower airway wall thickness, and 4) airway predominant. Of the genotypes examined, membership in cluster 1 (emphysema-predominant) was associated with TGFB1 SNP rs1800470.Conclusions
Cluster analysis may identify meaningful disease subtypes and/or groups of related phenotypic variables even in a highly selected group of severe emphysema subjects, and may be useful for genetic association studies. 相似文献16.
Introduction
The percentage of neutrophils in sputum are increased in COPD patients, and may therefore be a biomarker of airway inflammation. We studied the relationships between sputum neutrophils and FEV1, health status, exacerbation rates, systemic inflammation and emphysema, and long term variability at 1 year.Methods
Sputum samples were obtained from 488 COPD patients within the ECLIPSE cohort. 359 samples were obtained at baseline, and 297 after 1 year. 168 subjects provided samples at both visits. Serum interleukin-6 (IL-6), IL-8, surfactant protein D and C-reactive protein levels were measured by immunoassays. Low-dose CT scans evaluated emphysema.Results
Sputum neutrophil % increased with GOLD stage. There was a weak association between % sputum neutrophils and FEV1 % predicted (univariate r2 = 0.025 and 0.094 at baseline and year 1 respectively, p < 0.05 after multivariate regression). Similar weak but significant associations were observed between neutrophil % and health status measured using the St Georges Respiratory Questionairre. There were no associations between neutrophils and exacerbation rates or emphysema. Associations between sputum neutrophils and systemic biomarkers were non-significant or similarly weak. The mean change over 1 year in neutrophil % was an increase of 3.5%.Conclusions
Sputum neutrophil measurements in COPD are associated weakly with FEV1 % predicted and health status. Sputum neutrophil measurements were dissociated from exacerbation rates, emphysema and systemic inflammation. 相似文献17.
Anna Nolan Sophia Kwon Soo Jung Cho Bushra Naveed Ashley L Comfort David J Prezant William N Rom Michael D Weiden 《Respiratory research》2014,15(1):5
Rationale
After 9/11/2001, most FDNY workers had persistent lung function decline but some exposed workers recovered. We hypothesized that the protease/anti-protease balance in serum soon after exposure predicts subsequent recovery.Methods
We performed a nested case–control study measuring biomarkers in serum drawn before 3/2002 and subsequent forced expiratory volume at one second (FEV1) on repeat spirometry before 3/2008. Serum was assayed for matrix metalloproteinases (MMP-1,2,3,7,8,9,12 and 13) and tissue inhibitors of metalloproteinases (TIMP-1,2,3,4). The representative sub-cohort defined analyte distribution and a concentration above 75th percentile defined elevated biomarker expression. An FEV1 one standard deviation above the mean defined resistance to airway injury. Logistic regression was adjusted for pre-9/11 FEV1, BMI, age and exposure intensity modeled the association between elevated biomarker expression and above average FEV1.Results
FEV1 in cases and controls declined 10% of after 9/11/2001. Cases subsequently returned to 99% of their pre-exposure FEV1 while decline persisted in controls. Elevated TIMP-1 and MMP-2 increased the odds of resistance by 5.4 and 4.2 fold while elevated MMP-1 decreased it by 0.27 fold.Conclusions
Resistant cases displayed healing, returning to 99% of pre-exposure values. High TIMP-1 and MMP-2 predict healing. MMP/TIMP balance reflects independent pathways to airway injury and repair after WTC exposure. 相似文献18.
Bharat Thyagarajan Mary Wojczynski Ryan L Minster Jason Sanders Sandra Barral Lene Christiansen R Graham Barr CHARGE consortium SpiroMeta consortium Anne Newman 《Respiratory research》2014,15(1)
Background
Reduced forced expiratory volume in 1 second (FEV1) and the ratio of FEV1 to forced vital capacity (FVC) are strong predictors of mortality and lung function is higher among individuals with exceptional longevity. However, genetic factors associated with lung function in individuals with exceptional longevity have not been identified.Method
We conducted a genome wide association study (GWAS) to identify novel genetic variants associated with lung function in the Long Life Family Study (LLFS) (n = 3,899). Replication was performed using data from the CHARGE/SpiroMeta consortia. The association between SNPs and FEV1 and FEV1/FVC was analyzed using a linear mixed effects model adjusted for age, age2, sex, height, field center, ancestry principal components and kinship structure to adjust for family relationships separately for ever smokers and never smokers. In the linkage analysis, we used the residuals of the FEV1 and FEV1/FVC, adjusted for age, sex, height, ancestry principal components (PCs), smoking status, pack-years, and field center.Results
We identified nine SNPs in strong linkage disequilibrium in the CYP2U1 gene to be associated with FEV1 and a novel SNP (rs889574) associated with FEV1/FVC, none of which were replicated in the CHARGE/SpiroMeta consortia. Using linkage analysis, we identified a novel linkage peak in chromosome 2 at 219 cM for FEV1/FVC (LOD: 3.29) and confirmed a previously reported linkage peak in chromosome 6 at 28 cM (LOD: 3.33) for FEV1.Conclusion
Future studies need to identify the rare genetic variants underlying the linkage peak in chromosome 6 for FEV1.Electronic supplementary material
The online version of this article (doi:10.1186/s12931-014-0134-x) contains supplementary material, which is available to authorized users. 相似文献19.
Lystra P. Hayden Brian D. Hobbs Robyn T. Cohen Robert A. Wise William Checkley James D. Crapo Craig P. Hersh 《Respiratory research》2015,16(1)
Background
Development of adult respiratory disease is influenced by events in childhood. The impact of childhood pneumonia on chronic obstructive pulmonary disease (COPD) is not well defined. We hypothesize that childhood pneumonia is a risk factor for reduced lung function and COPD in adult smokers.Methods
COPD cases and control smokers between 45–80 years old from the United States COPDGene Study were included. Childhood pneumonia was defined by self-report of pneumonia at <16 years. Subjects with lung disease other than COPD or asthma were excluded. Smokers with and without childhood pneumonia were compared on measures of respiratory disease, lung function, and quantitative analysis of chest CT scans.Results
Of 10,192 adult smokers, 854 (8.4 %) reported pneumonia in childhood. Childhood pneumonia was associated with COPD (OR 1.40; 95 % CI 1.17-1.66), chronic bronchitis, increased COPD exacerbations, and lower lung function: post-bronchodilator FEV1 (69.1 vs. 77.1 % predicted), FVC (82.7 vs. 87.4 % predicted), FEV1/FVC ratio (0.63 vs. 0.67; p < 0.001 for all comparisons). Childhood pneumonia was associated with increased airway wall thickness on CT, without significant difference in emphysema. Having both pneumonia and asthma in childhood further increased the risk of developing COPD (OR 1.85; 95 % CI 1.10-3.18).Conclusions
Children with pneumonia are at increased risk for future smoking-related lung disease including COPD and decreased lung function. This association is supported by airway changes on chest CT scans. Childhood pneumonia may be an important factor in the early origins of COPD, and the combination of pneumonia and asthma in childhood may pose the greatest risk.Clinical trials registration
ClinicalTrials.gov, (Active since January 28, 2008). NCT00608764Electronic supplementary material
The online version of this article (doi:10.1186/s12931-015-0273-8) contains supplementary material, which is available to authorized users. 相似文献20.
Maria C Mirabelli Stephanie J London Luenda E Charles Lisa A Pompeii Lynne E Wagenknecht 《Respiratory research》2012,13(1):24