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Carlos H Martinez,
Ya-Hong Chen,
Phillip M Westgate,
Lyrica X Liu, Susan Murray,
Jeffrey L Curtis,
Barry J Make,
Ella A Kazerooni,
David A Lynch,
Nathaniel Marchetti,
George R Washko,
Fernando J Martinez,
Meilan K Han
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ABSTRACT: The value of quantitative CT (QCT) to identify chronic obstructive pulmonary disease (COPD) phenotypes is increasingly appreciated. The authors hypothesised that QCT-defined emphysema and airway abnormalities relate to St George's Respiratory Questionnaire (SGRQ) and Body-Mass Index, Airflow Obstruction, Dyspnea and Exercise Capacity Index (BODE).
1200 COPDGene subjects meeting Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria for COPD with QCT analysis were included. Total lung emphysema was measured using the density mask technique with a -950 Hounsfield unit threshold. An automated programme measured mean wall thickness (WT), wall area percentage (WA%) and 10 mm lumenal perimeter (pi10) in six segmental bronchi. Separate multivariate analyses examined the relative influence of airway measures and emphysema on SGRQ and BODE.
In separate models predicting SGRQ score, a 1 unit SD increase in each airway measure predicted higher SGRQ scores (for WT, 1.90 points higher, p=0.002; for WA%, 1.52 points higher, p=0.02; for pi10, 2.83 points higher p<0.001). The comparable increase in SGRQ for a 1 unit SD increase in emphysema percentage in these models was relatively weaker, significant only in the pi10 model (for emphysema percentage, 1.45 points higher, p=0.01). In separate models predicting BODE, a 1 unit SD increase in each airway measure predicted higher BODE scores (for WT, 1.07-fold increase, p<0.001; for WA%, 1.20-fold increase, p<0.001; for pi10, 1.16-fold increase, p<0.001). In these models, emphysema more strongly influenced BODE (range 1.24-1.26-fold increase, p<0.001).
Emphysema and airway disease both relate to clinically important parameters. The relative influence of airway disease is greater for SGRQ; the relative influence of emphysema is greater for BODE.
Thorax 05/2012; 67(5):399-406. · 6.84 Impact Factor
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Meilan K Han,
Ella A Kazerooni,
David A Lynch,
Lyrica X Liu, Susan Murray,
Jeffrey L Curtis,
Gerard J Criner,
Victor Kim,
Russell P Bowler,
Nicola A Hanania,
Antonio R Anzueto,
Barry J Make,
John E Hokanson,
James D Crapo,
Edwin K Silverman,
Fernando J Martinez,
George R Washko
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ABSTRACT: To test the hypothesis-given the increasing emphasis on quantitative computed tomographic (CT) phenotypes of chronic obstructive pulmonary disease (COPD)-that a relationship exists between COPD exacerbation frequency and quantitative CT measures of emphysema and airway disease.
This research protocol was approved by the institutional review board of each participating institution, and all participants provided written informed consent. One thousand two subjects who were enrolled in the COPDGene Study and met the GOLD (Global Initiative for Chronic Obstructive Lung Disease) criteria for COPD with quantitative CT analysis were included. Total lung emphysema percentage was measured by using the attenuation mask technique with a -950-HU threshold. An automated program measured the mean wall thickness and mean wall area percentage in six segmental bronchi. The frequency of COPD exacerbation in the prior year was determined by using a questionnaire. Statistical analysis was performed to examine the relationship of exacerbation frequency with lung function and quantitative CT measurements.
In a multivariate analysis adjusted for lung function, bronchial wall thickness and total lung emphysema percentage were associated with COPD exacerbation frequency. Each 1-mm increase in bronchial wall thickness was associated with a 1.84-fold increase in annual exacerbation rate (P = .004). For patients with 35% or greater total emphysema, each 5% increase in emphysema was associated with a 1.18-fold increase in this rate (P = .047).
Greater lung emphysema and airway wall thickness were associated with COPD exacerbations, independent of the severity of airflow obstruction. Quantitative CT can help identify subgroups of patients with COPD who experience exacerbations for targeted research and therapy development for individual phenotypes.
Radiology 07/2011; 261(1):274-82. · 5.73 Impact Factor
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ABSTRACT: Most multiple imputation (MI) methods for censored survival data either ignore patient characteristics when imputing a likely event time, or place quite restrictive modeling assumptions on the survival distributions used for imputation. In this research, we propose a robust MI approach that directly imputes restricted lifetimes over the study period based on a model of the mean restricted life as a linear function of covariates. This method has the advantages of retaining patient characteristics when making imputation choices through the restricted mean parameters and does not make assumptions on the shapes of hazards or survival functions. Simulation results show that our method outperforms its closest competitor for modeling restricted mean lifetimes in terms of bias and efficiency in both independent censoring and dependent censoring scenarios. Survival estimates of restricted lifetime model parameters and marginal survival estimates regain much of the precision lost due to censoring. The proposed method is also much less subject to dependent censoring bias captured by covariates in the restricted mean model. This particular feature is observed in a full statistical analysis conducted in the context of the International Breast Cancer Study Group Ludwig Trial V using the proposed methodology.
Statistics in Medicine 05/2011; 30(12):1339-50. · 1.88 Impact Factor
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ABSTRACT: Prolonged mechanical ventilation and home ventilation impose unique challenges on patients, families, and the healthcare system. In the absence of a centralized database to track prolonged and home ventilation, there has been a paucity of prevalence studies, and what is known is outdated. We surveyed respiratory care managers working in the state of Massachusetts to estimate the prevalence and locations of prolonged and home ventilation in 2006.
We invited 113 respiratory care managers practicing in acute-care hospitals, long-term acute-care facilities (also known as weaning units, step-down units, and long-term-ventilation units), and home-care companies to participate in a Web-based survey. We matched the responses to their respective institutions and analyzed the results according to hospital size, location (urban or suburban), and whether the institution was a teaching institution.
In December of 2006 there were 817 ventilated patients, of whom 460 met the criteria for prolonged ventilation (> 21 d for at least 6 h/d) and 221 met the criteria for home ventilation (ventilation for any period of time at home). Of the 239 patients not at home, 64 were in acute-care hospitals, 175 in long-term acute-care facilities, and 221 at home. The survey response rate was 86% for acute-care hospitals with ≥ 400 beds, 48% for acute-care hospitals with < 400 beds, 65% for long-term acute-care facilities, and 67% for home-care companies. The non-respondents were primarily smaller, suburban, non-teaching hospitals, which have a low prevalence of prolonged-ventilation patients. Among the home-ventilation patients, the majority had neuromuscular diseases, were < 65 years old, and were ventilated via tracheostomy tube. The most important limitations to transitioning prolonged-ventilation patients to home ventilation appeared to be lack of family and/or economic support.
In Massachusetts, the estimated prevalence of prolonged and home ventilation increased from 2.8/100,000 inhabitants in 1983 to 7.1/100,000 inhabitants in 2006, and the majority of them are in long-term acute-care facilities, large urban teaching hospitals, and at home.
Respiratory care 12/2010; 55(12):1693-8. · 2.01 Impact Factor
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Linda Badri, Susan Murray,
Lyrica X Liu,
Natalie M Walker,
Andrew Flint,
Anish Wadhwa,
Kevin M Chan,
Galen B Toews,
David J Pinsky,
Fernando J Martinez,
Vibha N Lama
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ABSTRACT: Bronchoalveolar lavage fluid (BAL) from human lung allografts demonstrates the presence of a multipotent mesenchymal stromal cell population. However, the clinical relevance of this novel cellular component of BAL and its association with bronchiolitis obliterans syndrome (BOS), a disease marked by progressive airflow limitation secondary to fibrotic obliteration of the small airways, remains to be determined.
In this study we investigate the association of number of mesenchymal stromal cells in BAL with development of BOS in human lung transplant recipients.
Mesenchymal colony-forming units (CFUs) were quantitated in a cohort of 405 BAL samples obtained from 162 lung transplant recipients. Poisson generalized estimating equations were used to determine the predictors of BAL mesenchymal CFU count.
Higher CFU counts were noted early post-transplantation; time from transplant to BAL of greater than 3 months predicted 0.4-fold lower CFU counts (P = 0.0001). BOS diagnosis less than or equal to 365 days before BAL was associated with a 2.11-fold higher CFU count (P = 0.02). There were 2.62- and 2.70-fold higher CFU counts noted in the presence of histologic diagnosis of bronchiolitis obliterans (P = 0.05) and organizing pneumonia (0.0003), respectively. In BAL samples obtained from BOS-free patients greater than 6 months post-transplantation (n = 173), higher mesenchymal CFU counts (≥10) significantly predicted BOS onset in both univariate (hazard ratio, 5.61; 95% CI, 3.03-10.38; P < 0.0001) and multivariate (hazard ratio, 5.02; 95% CI, 2.40-10.51; P < 0.0001) Cox regression analysis.
Measurement of mesenchymal CFUs in the BAL provides predictive information regarding future BOS onset.
American Journal of Respiratory and Critical Care Medicine 12/2010; 183(8):1062-70. · 11.08 Impact Factor
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Christine M Freeman,
MeiLan K Han,
Fernando J Martinez, Susan Murray,
Lyrica X Liu,
Stephen W Chensue,
Timothy J Polak,
Joanne Sonstein,
Jill C Todt,
Theresa M Ames,
Douglas A Arenberg,
Catherine A Meldrum,
Christi Getty,
Lisa McCloskey,
Jeffrey L Curtis
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ABSTRACT: Lung CD8(+) T cells might contribute to progression of chronic obstructive pulmonary disease (COPD) indirectly via IFN-gamma production or directly via cytolysis, but evidence for either mechanism is largely circumstantial. To gain insights into these potential mechanisms, we analyzed clinically indicated lung resections from three human cohorts, correlating findings with spirometrically defined disease severity. Expression by lung CD8(+) T cells of IL-18R and CD69 correlated with severity, as did mRNA transcripts for perforin and granzyme B, but not Fas ligand. These correlations persisted after correction for age, smoking history, presence of lung cancer, recent respiratory infection, or inhaled corticosteroid use. Analysis of transcripts for killer cell lectin-like receptor G1, IL-7R, and CD57 implied that lung CD8(+) T cells in COPD do not belong to the terminally differentiated effector populations associated with chronic infections or extreme age. In vitro stimulation of lung CD8(+) T cells with IL-18 plus IL-12 markedly increased production of IFN-gamma and TNF-alpha, whereas IL-15 stimulation induced increased intracellular perforin expression. Both IL-15 and IL-18 protein expression could be measured in whole lung tissue homogenates, but neither correlated in concentration with spirometric severity. Although lung CD8(+) T cell expression of mRNA for both T-box transcription factor expressed in T cells and GATA-binding protein 3 (but not retinoic acid receptor-related orphan receptor gamma or alpha) increased with spirometric severity, stimulation of lung CD8(+) T cells via CD3epsilon-induced secretion of IFN-gamma, TNF-alpha, and GM-CSF, but not IL-5, IL-13, and IL-17A. These findings suggest that the production of proinflammatory cytokines and cytotoxic molecules by lung-resident CD8(+) T cells contributes to COPD pathogenesis.
The Journal of Immunology 06/2010; 184(11):6504-13. · 5.79 Impact Factor
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MeiLan K Han,
Jeffrey Swigris,
Lyrica Liu,
Brian Bartholmai, Susan Murray,
Nicholas Giardino,
Bruce Thompson,
Margaret Frederick,
Daner Li,
Marvin Schwarz,
Andrew Limper,
Kevin Flaherty,
Fernando J Martinez
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ABSTRACT: HRQL in IPF patients is impaired. Data from other respiratory diseases led us to hypothesize that significant gender differences in HRQL in IPF also exist.
Data were drawn from the NIH-sponsored Lung Tissue Research Consortium (LTRC). Demographic and pulmonary physiology data along with MMRC, SF-12, and SGRQ scores from women vs. men were compared with two-sample t-tests. Multivariate linear regression was used to examine the association between SF-12 component scores and gender while adjusting for other relevant variables.
The study sample consisted of 147 men and 74 women. Among several baseline variables, only DL(CO)% predicted differed between women and men, (43.7 vs. 38.0, p=0.03). In general, men exhibited lower (better) MMRC scores (1.7 vs. 2.4, p=0.02), particularly those with milder disease as measured by DL(CO)% predicted. In an adjusted analysis, SF-12 PCS scores in men were lower (worse) than women (p=0.01), an effect that was more pronounced in men with greater dyspnea scores. In a similar analysis, SF-12 MCS scores in women were lower than men (worse) (48.3 vs. 54.4, p=0.0004), an effect that was more pronounced in women with greater dyspnea scores.
Significant gender differences in HRQL exist in IPF. As compared to women, men reported less severe dyspnea, had worse SF-12 PCS scores, but better SF-12 MCS scores. Dyspnea appears to have a greater impact on the physical HRQL of men and the emotional HRQL of women. An improved understanding of the mechanism behind these differences is needed to better target interventions.
Respiratory medicine 05/2010; 104(5):724-30. · 2.33 Impact Factor
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Charlene D Fell,
Fernando J Martinez,
Lyrica X Liu, Susan Murray,
Meilan K Han,
Ella A Kazerooni,
Barry H Gross,
Jeffrey Myers,
William D Travis,
Thomas V Colby,
Galen B Toews,
Kevin R Flaherty
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ABSTRACT: Idiopathic pulmonary fibrosis (IPF) and other idiopathic interstitial pneumonias (IIPs) have similar clinical and radiographic features, but their histopathology, response to therapy, and natural history differ. A surgical lung biopsy is often required to distinguish between these entities.
We sought to determine if clinical variables could predict a histopathologic diagnosis of IPF in patients without honeycomb change on high-resolution computed tomography (HRCT).
Data from 97 patients with biopsy-proven IPF and 38 patients with other IIPs were examined. Logistic regression models were built to identify the clinical variables that predict histopathologic diagnosis of IPF.
Increasing age and average total HRCT interstitial score on HRCT scan of the chest may predict a biopsy confirmation of IPF. Sex, pulmonary function, presence of desaturation, or distance walked during a 6-minute walk test did not help discriminate pulmonary fibrosis from other IIPs.
Clinical data may be used to predict a diagnosis of IPF over other IIPs. Validation of these data with a prospective study is needed.
American Journal of Respiratory and Critical Care Medicine 04/2010; 181(8):832-7. · 11.08 Impact Factor
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Nicholas Giardino,
Jeffrey Curtis,
Adin-Cristian Andrei,
Vincent Fan,
Joshua Benditt,
Mark Lyubkin,
Keith Naunheim,
Gerard Criner,
Barry Make,
Robert Wise, Susan Murray,
Alfred Fishman,
Frank Sciurba,
Israel Liberzon,
Fernando Martinez
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ABSTRACT: Abstract
Background
Anxiety in patients with chronic obstructive pulmonary disease (COPD) is associated with self-reported disability. The purpose of this study is to determine whether there is an association between anxiety and functional measures, quality of life and dyspnea.
Methods
Data from 1828 patients with moderate to severe emphysema enrolled in the National Emphysema Treatment Trial (NETT), collected prior to rehabilitation and randomization, were used in linear regression models to test the association between anxiety symptoms, measured by the Spielberger State Trait Anxiety Inventory (STAI) and: (a) six-minute walk distance test (6 MWD), (b) cycle ergometry peak workload, (c) St. Georges Respiratory Questionnaire (SRGQ), and (d) UCSD Shortness of Breath Questionnaire (SOBQ), after controlling for potential confounders including age, gender, FEV<sub>1 </sub>(% predicted), DL<sub>CO </sub>(% predicted), and the Beck Depression Inventory (BDI).
Results
Anxiety was significantly associated with worse functional capacity [6 MWD (B = -0.944, p < .001), ergometry peak workload (B = -.087, p = .04)], quality of life (B = .172, p < .001) and shortness of breath (B = .180, p < .001). Regression coefficients show that a 10 point increase in anxiety score is associated with a mean decrease in 6 MWD of 9 meters, a 1 Watt decrease in peak exercise workload, and an increase of almost 2 points on both the SGRQ and SOBQ.
Conclusion
In clinically stable patients with moderate to severe emphysema, anxiety is associated with worse exercise performance, quality of life and shortness of breath, after accounting for the influence of demographic and physiologic factors known to affect these outcomes.
Trail Registration
ClinicalTrials.gov NCT00000606
Respiratory Research. 01/2010;
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MeiLan K Han,
Brian Bartholmai,
Lyrica X Liu, Susan Murray,
Jeffrey L Curtis,
Frank C Sciurba,
Ella A Kazerooni,
Bruce Thompson,
Margaret Frederick,
Daner Li,
Marvin Schwarz,
Andrew Limper,
Christine Freeman,
Rodney J Landreneau,
Robert Wise,
Fernando J Martinez
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ABSTRACT: COPD is a heterogeneous disorder with clinical assessment becoming increasingly multidimensional. We hypothesized HRCT phenotype would strongly influence clinical outcomes including health status, exacerbation frequency, and BODE. COPD subjects were characterized via the SF-12, SGRQ, MMRC, physiologic testing, and standardized volumetric chest HRCT. Visual semi-quantitative estimation of bronchial wall thickness (VBT) and automated quantification of emphysema percent and bronchial wall thickness were generated. Multivariate modeling compared emphysema severity and airway abnormality with clinical outcome measures. Poisson models were used to analyze exacerbation frequency. SGRQ and SF-12 physical component scores were influenced by FEV(1)% predicted, emphysema percent, and VBT. VBT scores > 2 (scale 0-48) were associated with increased exacerbation frequency (p = 0.009) in the preceding year adjusting for age, gender, emphysema percent, smoking history and FEV(1)% predicted, although this effect was attenuated by age. Emphysema percent correlated with total BODE score in unadjusted (r = 0.73; p < 0.0001) and adjusted (p < 0.0001) analyses and with BODE individual components. HRCT provides unique COPD phenotyping information. Radiographic quantification of emphysema and bronchial thickness are independently associated with SGRQ and physical component score of the SF-12. Bronchial thickness but not emphysema is associated with exacerbation frequency, whereas emphysema is a stronger predictor of BODE and its systemic components MMRC, 6MWT, and BMI. Future research should clarify whether CT parameters complement BODE score in influencing survival.
COPD Journal of Chronic Obstructive Pulmonary Disease 12/2009; 6(6):459-67. · 1.79 Impact Factor
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Charlene D Fell,
Lyrica Xiaohong Liu,
Caroline Motika,
Ella A Kazerooni,
Barry H Gross,
William D Travis,
Thomas V Colby, Susan Murray,
Galen B Toews,
Fernando J Martinez,
Kevin R Flaherty
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ABSTRACT: Idiopathic pulmonary fibrosis (IPF) is characterized by progressive dyspnea, impaired gas exchange, and ultimate mortality.
To test the hypothesis that maximal oxygen uptake during cardiopulmonary exercise testing at baseline and with short-term longitudinal measures would predict mortality in patients with idiopathic pulmonary fibrosis.
Data from 117 patients with IPF and longitudinal cardiopulmonary exercise tests were examined retrospectively. Survival was calculated from the date of the first cardiopulmonary exercise test.
Patients with baseline maximal oxygen uptake less than 8.3 ml/kg/min had an increased risk of death (n = 8; hazard ratio, 3.24; 95% confidence interval, 1.10-9.56; P = 0.03) after adjusting for age, gender, smoking status, baseline forced vital capacity, and baseline diffusion capacity for carbon monoxide. We were unable to define a unit change in maximal oxygen uptake that predicted survival in our cohort.
We conclude that a threshold maximal oxygen uptake of 8.3 ml/kg/min during cardiopulmonary exercise testing at baseline adds prognostic information for patients with IPF.
American Journal of Respiratory and Critical Care Medicine 01/2009; 179(5):402-7. · 11.08 Impact Factor
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Fernando J Martinez,
Meilan K Han,
Adin-Cristian Andrei,
Robert Wise, Susan Murray,
Jeffrey L Curtis,
Alice Sternberg,
Gerard Criner,
Steven E Gay,
John Reilly,
Barry Make,
Andrew L Ries,
Frank Sciurba,
Gail Weinmann,
Zab Mosenifar,
Malcolm DeCamp,
Alfred P Fishman,
Bartolome R Celli
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ABSTRACT: The predictive value of longitudinal change in BODE (Body mass index, airflow Obstruction, Dyspnea, and Exercise capacity) index has received limited attention. We hypothesized that decrease in a modified BODE (mBODE) would predict survival in National Emphysema Treatment Trial (NETT) patients.
To determine how the mBODE score changes in patients with lung volume reduction surgery versus medical therapy and correlations with survival.
Clinical data were recorded using standardized instruments. The mBODE was calculated and patient-specific mBODE trajectories during 6, 12, and 24 months of follow-up were estimated using separate regressions for each patient. Patients were classified as having decreasing, stable, increasing, or missing mBODE based on their absolute change from baseline. The predictive ability of mBODE change on survival was assessed using multivariate Cox regression models. The index of concordance was used to directly compare the predictive ability of mBODE and its separate components.
The entire cohort (610 treated medically and 608 treated surgically) was characterized by severe airflow obstruction, moderate breathlessness, and increased mBODE at baseline. A wide distribution of change in mBODE was seen at follow-up. An increase in mBODE of more than 1 point was associated with increased mortality in surgically and medically treated patients. Surgically treated patients were less likely to experience death or an increase greater than 1 in mBODE. Indices of concordance showed that mBODE change predicted survival better than its separate components.
The mBODE demonstrates short- and intermediate-term responsiveness to intervention in severe chronic obstructive pulmonary disease. Increase in mBODE of more than 1 point from baseline to 6, 12, and 24 months of follow-up was predictive of subsequent mortality. Change in mBODE may prove a good surrogate measure of survival in therapeutic trials in severe chronic obstructive pulmonary disease. Clinical trial registered with www.clinicaltrials.gov (NCT 00000606).
American Journal of Respiratory and Critical Care Medicine 07/2008; 178(5):491-9. · 11.08 Impact Factor
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Fernando J Martinez,
Jeffrey L Curtis,
Frank Sciurba,
Jeanette Mumford,
Nicholas D Giardino,
Gail Weinmann,
Ella Kazerooni, Susan Murray,
Gerard J Criner,
Donald D Sin,
James Hogg,
Andrew L Ries,
MeiLan Han,
Alfred P Fishman,
Barry Make,
Eric A Hoffman,
Zab Mohsenifar,
Robert Wise
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ABSTRACT: Limited data on sex differences in advanced COPD are available.
To compare male and female emphysema patients with severe disease.
One thousand fifty-three patients (38.8% female) evaluated for lung volume reduction surgery as part of the National Emphysema Treatment Trial were analyzed.
Detailed clinical, physiological, and radiological assessment, including quantitation of emphysema severity and distribution from helical chest computed tomography, was completed. In a subgroup (n = 101), airway size and thickness was determined by histological analyses of resected tissue. Women were younger and exhibited a lower body mass index (BMI), shorter smoking history, less severe airflow obstruction, lower Dl(co) and arterial Po(2), higher arterial Pco(2), shorter six-minute walk distance, and lower maximal wattage during oxygen-supplemented cycle ergometry. For a given FEV(1)% predicted, age, number of pack-years, and proportion of emphysema, women experienced greater dyspnea, higher modified BODE, more depression, lower SF-36 mental component score, and lower quality of well-being. Overall emphysema was less severe in women, with the difference from men most evident in the outer peel of the lung. Females had thicker small airway walls relative to luminal perimeters.
In patients with severe COPD, women, relative to men, exhibit anatomically smaller airway lumens with disproportionately thicker airway walls, and emphysema that is less extensive and characterized by smaller hole size and less peripheral involvement.
American Journal of Respiratory and Critical Care Medicine 09/2007; 176(3):243-52. · 11.08 Impact Factor
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ABSTRACT: In this research we develop generalized linear regression models for the mean of a quality-of-life-adjusted restricted survival time. Parameter and standard error estimates could be obtained from generalized estimating equations applied to pseudo-observations. Simulation studies with moderate sample sizes are conducted and an example from the International Breast Cancer Study Group Ludwig Trial V is used to illustrate the newly developed methodology.
Biometrics 07/2007; 63(2):398-404. · 1.83 Impact Factor
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Kevin R Flaherty,
Adin-Cristian Andrei,
Talmadge E King,
Ganesh Raghu,
Thomas V Colby,
Athol Wells,
Nadir Bassily,
Kevin Brown,
Roland du Bois,
Andrew Flint, [......],
Andrew G Nicholson,
John Quick,
Victor J Thannickal,
William D Travis,
James Vyskocil,
Frazer A Wadenstorer,
Jeffrey Wilt,
Galen B Toews, Susan Murray,
Fernando J Martinez
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ABSTRACT: Treatment and prognoses of diffuse parenchymal lung diseases (DPLDs) varies by diagnosis. Obtaining a uniform diagnosis among observers is difficult.
Evaluate diagnostic agreement between academic and community-based physicians for patients with DPLDs, and determine if an interactive approach between clinicians, radiologists, and pathologists improved diagnostic agreement in community and academic centers.
Retrospective review of 39 patients with DPLD. A total of 19 participants reviewed cases at 2 community locations and 1 academic location. Information from the history, physical examination, pulmonary function testing, high-resolution computed tomography, and surgical lung biopsy was collected. Data were presented in the same sequential fashion to three groups of physicians on separate days.
Each observer's diagnosis was coded into one of eight categories. A kappa statistic allowing for multiple raters was used to assess agreement in diagnosis. Interactions between clinicians, radiologists, and pathologists improved interobserver agreement at both community and academic sites; however, final agreement was better within academic centers (kappa = 0.55-0.71) than within community centers (kappa = 0.32-0.44). Clinically significant disagreement was present between academic and community-based physicians (kappa = 0.11-0.56). Community physicians were more likely to assign a final diagnosis of idiopathic pulmonary fibrosis compared with academic physicians.
Significant disagreement exists in the diagnosis of DPLD between physicians based in communities compared with those in academic centers. Wherever possible, patients should be referred to centers with expertise in diffuse parenchymal lung disorders to help clarify the diagnosis and provide suggestions regarding treatment options.
American Journal of Respiratory and Critical Care Medicine 06/2007; 175(10):1054-60. · 11.08 Impact Factor
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ABSTRACT: Bronchiolitis obliterans syndrome (BOS), defined by loss of lung function, develops in the majority of lung transplant recipients. However, there is a paucity of information on the subsequent course of lung function in these patients.
To characterize the course of FEV(1) over time after development of BOS and to determine the predictors that influence the rate of functional decline of FEV(1).
FEV(1)% predicted (FEV(1)%pred) trajectories were studied in 111 lung transplant recipients with BOS by multivariate, linear, mixed-effects statistical models.
FEV(1)%pred varied over time after BOS onset, with the steepest decline typically seen in the first 6 months (12% decline; p < 0.0001). Bilateral lung transplant recipients had significantly higher FEV(1)%pred at BOS diagnosis (71 vs. 47%; p < 0.0001) and at 24 months after BOS onset (58 vs. 41%; p = 0.0001). Female gender and pretransplant diagnosis of idiopathic pulmonary fibrosis were associated with a steeper decline in FEV(1)%pred in the first 6 months after BOS diagnosis (p = 0.02 and 0.04, respectively). A fall in FEV(1) greater than 20% in the 6 months preceding BOS (termed "rapid onset") was associated with shorter time to BOS onset (p = 0.01), lower FEV(1)%pred at BOS onset (p < 0.0001), steeper decline in the first 6 months (p = 0.03), and lower FEV(1)%pred at 2 years after onset (p = 0.0002).
Rapid onset of BOS, female gender, pretransplant diagnosis of idiopathic pulmonary fibrosis, and single-lung transplantation are associated with worse pulmonary function after BOS onset.
American Journal of Respiratory and Critical Care Medicine 06/2007; 175(11):1192-8. · 11.08 Impact Factor
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Vibha N Lama,
Lisa Smith,
Linda Badri,
Andrew Flint,
Adin-Cristian Andrei, Susan Murray,
Zhuo Wang,
Hui Liao,
Galen B Toews,
Paul H Krebsbach,
Marc Peters-Golden,
David J Pinsky,
Fernando J Martinez,
Victor J Thannickal
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ABSTRACT: The origin and turnover of connective tissue cells in adult human organs, including the lung, are not well understood. Here, studies of cells derived from human lung allografts demonstrate the presence of a multipotent mesenchymal cell population, which is locally resident in the human adult lung and has extended life span in vivo. Examination of plastic-adherent cell populations in bronchoalveolar lavage samples obtained from 76 human lung transplant recipients revealed clonal proliferation of fibroblast-like cells in 62% (106 of 172) of samples. Immunophenotyping of these isolated cells demonstrated expression of vimentin and prolyl-4-hydroxylase, indicating a mesenchymal phenotype. Multiparametric flow cytometric analyses revealed expression of cell-surface proteins, CD73, CD90, and CD105, commonly found on mesenchymal stem cells (MSCs). Hematopoietic lineage markers CD14, CD34, and CD45 were absent. Multipotency of these cells was demonstrated by their capacity to differentiate into adipocytes, chondrocytes, and osteocytes. Cytogenetic analysis of cells from 7 sex-mismatched lung transplant recipients harvested up to 11 years after transplant revealed that 97.2% +/- 2.1% expressed the sex genotype of the donor. The presence of MSCs of donor sex identity in lung allografts even years after transplantation provides what we believe to be the first evidence for connective tissue cell progenitors that reside locally within a postnatal, nonhematopoietic organ.
Journal of Clinical Investigation 05/2007; 117(4):989-96. · 15.39 Impact Factor
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Andrew C Chang,
Kevin M Chan,
Robert J Lonigro,
Christine L Lau,
Vibha N Lama,
Kevin R Flaherty,
Ros Florn,
Allan Pickens, Susan Murray,
Fernando J Martinez,
Mark B Orringer
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ABSTRACT: Despite the potential limitation of organ availability, several surgical groups have advocated preferential bilateral lung transplantation because of its demonstrated long-term survival advantage. Comparative results for single and sequential double lung transplantation performed at a single center are evaluated to determine whether such a policy improves patient outcome.
A retrospective analysis of demographic and outcome data for patients undergoing lung transplantation was performed. Patients were grouped as single or double lung recipients and segregated into diagnostic categories according to the lung allocation scoring system. Era terciles were chosen on the basis of year of transplant, operating surgeon, and transplant volume.
Between November 1990 and September 2005, 344 lung transplant procedures were performed in 339 patients. Over three time periods evaluated, the proportion of patients undergoing double lung transplant procedures increased. Overall survivals at 3 months and 1, 3, and 5 years were 89%, 79%, 60%, and 52%, respectively. After adjusting for lung recipient characteristics, survival after double lung transplantation was improved when compared with single lung transplantation (P = .020). Overall patient survival among the three time periods was not significantly different at 30 days and 1 and 3 years despite increasing maximal donor organ ischemia times.
In this single-center study, despite longer median allograft ischemic times, as well as greater patient acuity as determined by listing diagnosis, overall early and midterm patient survival has remained higher than nationally reported figures. Bilateral lung transplantation in eligible patients is the procedure of choice.
The Journal of thoracic and cardiovascular surgery 03/2007; 133(2):532-40. · 3.41 Impact Factor
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Fernando J Martinez,
Jeffrey L Curtis,
Frank Sciurba,
Jeanette Mumford,
Nicholas D Giardino,
Gail Weinmann,
Ella Kazerooni, Susan Murray,
Gerard J Criner,
Donald D Sin,
James Hogg,
Andrew L Ries,
Meilan Han,
Alfred P Fishman,
Barry Make,
Eric A Hoffman,
Zab Mohsenifar,
Robert Wise
AJRCCM Articles in Press. Published on April. 01/2007; 12.
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Kevin R Flaherty,
Adin-Cristian Andrei, Susan Murray,
Chris Fraley,
Thomas V Colby,
William D Travis,
Vibha Lama,
Ella A Kazerooni,
Barry H Gross,
Galen B Toews,
Fernando J Martinez
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ABSTRACT: Idiopathic pulmonary fibrosis is a fatal disease with a variable rate of progression. We hypothesized that changes in distance walked and quantity of desaturation during a six-minute-walk test (6MWT) would add prognostic information to changes in FVC or diffusing capacity for carbon monoxide.
One hundred ninety-seven patients with idiopathic pulmonary fibrosis were evaluated. Desaturation during the 6MWT was associated with increased mortality even if a threshold of 88% was not reached. Baseline walk distance predicted subsequent walk distance but was not a reliable predictor of subsequent mortality in multivariate survival models. The predictive ability of serial changes in physiology varied when patients were stratified by the presence/absence of desaturation < or = 88% during a baseline 6MWT. For patients with a baseline saturation < or = 88% during a 6MWT, the strongest observed predictor of mortality was serial change in diffusing capacity for carbon monoxide. For patients with saturation > 88% during their baseline walk test, serial decreases in FVC and increases in desaturation area significantly predicted subsequent mortality, whereas decreases in walk distance and in diffusing capacity for carbon monoxide displayed less consistent statistical evidence of increasing mortality in our patients.
These data highlight the importance of stratifying patients by degree of desaturation during a 6MWT before attributing prognostic value to serial changes in other physiologic variables.
American Journal of Respiratory and Critical Care Medicine 10/2006; 174(7):803-9. · 11.08 Impact Factor
