David A Lynch

National Research Center (CO, USA), Boulder, Colorado, United States

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Publications (178)903.66 Total impact

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    ABSTRACT: Rationale: Although occupational exposure to dust and fumes is considered a risk factor for COPD, this determination has been limited by reliance on spirometry alone to assess disease severity in predominantly male populations. Methods: COPDGene is a multicenter study of current and former smokers that underwent standardized volumetric chest CT scans to assess airways, %-emphysema and %-gas-trapping. Spirometry and a respiratory questionnaire including occupational history were also analyzed in 9,614 subjects (4,496 women). Logistic regression and analysis of covariance was used to assess associations with exposure. Results: Occupational exposure to both dust and fumes was reported by 47.9% of men and 20.1% of women. Adjusting for age, race, BMI, education, and current and lifetime smoking, the odds ratios (OR) for persons with dust and fume exposures for chronic cough, chronic phlegm, persistent wheeze, and >GOLD Stages 2 COPD were significantly elevated and similar for men (1.83, 1.84, 2.0, 1.61, respectively) and women (1.65, 1.82, 1.98, 1.90, respectively). The %-predicted FEV1 was similarly lower in those with exposure in men (70.7±0.8 vs. 76.0±0.9; p<0.001) and women (70.5± 0.8 vs. 77.2±0.8; p<0.001). Percent emphysema and gas trapping was greater in those exposed to dust and fumes in men and women. In men, but not in women, persons with exposure had a greater mean square root wall area of 10-mm internal perimeter airways. Conclusions: Occupational exposure to dust and fumes in men and women is similarly associated with airflow obstruction, respiratory symptoms, more emphysema, gas trapping in men and women. Abstract word count: 247.
    American Journal of Respiratory and Critical Care Medicine 08/2014; · 11.04 Impact Factor
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    ABSTRACT: Pulmonary hypertension (PH) is associated with advanced chronic obstructive pulmonary disease (COPD) though pulmonary vascular changes occur early in the course of the disease. Pulmonary artery enlargement (PAE) measured by computed tomography (CT) correlates with PH and COPD exacerbation frequency. Genome-wide association studies (GWASs) of PAE in COPD subjects have not been reported. To investigate whether genetic variants are associated with PAE within subjects with COPD, we investigated data from current and former smokers from the COPDGene Study and the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE). The ratio of the diameter of the pulmonary artery to the diameter of the aorta (PA/A) was measured using CT. PAE was defined as PA/A >1. A GWAS for COPD with PAE was performed using COPD subjects without PAE (PA/A ≤1) as a control group. A secondary analysis used smokers with normal spirometry as a control group. Genotyping was performed on Illumina platforms. The results were summarized using fixed-effect meta-analysis. Both meta-analyses revealed a genome-wide significant locus on chromosome 15q25.1 in IREB2 [COPD with PAE vs. without PAE, rs7181486, odds ratio (OR) = 1.32, P = 2.10×10(-8); vs. smoking controls, rs2009746, OR = 1.42, P = 1.32×10(-9)]. PAE was also associated with a region on 14q31.3 near the GALC gene (rs7140285, OR = 1.55, P = 3.75×10(-8)). Genetic variants near IREB2 and GALC likely contribute to genetic susceptibility to PAE associated with COPD. This study provides evidence for genetic heterogeneity associated with a clinically important COPD vascular subtype.
    American Journal of Respiratory Cell and Molecular Biology 08/2014; · 4.15 Impact Factor
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    ABSTRACT: Background Preserved Ratio Impaired Spirometry (PRISm), defined as a reduced FEV1 in the setting of a preserved FEV1/FVC ratio, is highly prevalent and is associated with increased respiratory symptoms, systemic inflammation, and mortality. Studies investigating quantitative chest tomographic features, genetic associations, and subtypes in PRISm subjects have not been reported.Methods Data from current and former smokers enrolled in COPDGene (n¿=¿10,192), an observational, cross-sectional study which recruited subjects aged 45¿80 with ¿10 pack years of smoking, were analyzed. To identify epidemiological and radiographic predictors of PRISm, we performed univariate and multivariate analyses comparing PRISm subjects both to control subjects with normal spirometry and to subjects with COPD. To investigate common genetic predictors of PRISm, we performed a genome-wide association study (GWAS). To explore potential subgroups within PRISm, we performed unsupervised k-means clustering.ResultsThe prevalence of PRISm in COPDGene is 12.3%. Increased dyspnea, reduced 6-minute walk distance, decreased percent emphysema and total lung capacity, as well as increased segmental bronchial wall area percentage were significant predictors (p-value <0.05) of PRISm status when compared to control subjects in multivariate models. Although no common genetic variants were identified on GWAS testing, a significant association with Klinefelter¿s syndrome (47XXY) was observed (p-value¿<¿0.001). Subgroups identified through k-means clustering include a putative ¿COPD-subtype¿, ¿Restrictive-subtype¿, and a highly symptomatic ¿Metabolic-subtype¿.ConclusionsPRISm subjects are clinically and genetically heterogeneous. Future investigations into the pathophysiological mechanisms behind and potential treatment options for subgroups within PRISm are warranted.Trial registrationClinicaltrials.gov Identifier: NCT000608764.
    Respiratory research. 08/2014; 15(1):89.
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    ABSTRACT: Cigarette smoking is a key factor in the development of numerous pulmonary diseases. An international group of clinicians, radiologists and pathologists evaluated patients with previously identified idiopathic interstitial pneumonia (IIP) to determine unique features of cigarette smoking. Phase 1 (derivation group) identified smoking-related features in patients with a history of smoking (n = 41). Phase 2 (validation group) determined if these features correctly predicted the smoking status of IIP patients (n = 100) to participants blinded to smoking history. Finally, the investigators sought to determine if a new smoking-related interstitial lung disease phenotype could be defined. Phase 1 suggested that preserved forced vital capacity with disproportionately reduced diffusing capacity of the lung for carbon monoxide, and various radiographic and histopathological findings were smoking-related features. In phase 2, the kappa coefficient among clinicians was 0.16 (95% CI 0.11-0.21), among the pathologists 0.36 (95% CI 0.32-0.40) and among the radiologists 0.43 (95% CI 0.35-0.52) for smoking-related features. Eight of the 100 cases were felt to represent a potential smoking-related interstitial lung disease. Smoking-related features of interstitial lung disease were identified in a minority of smokers and were not specific for smoking. This study is limited by its retrospective design, the potential for recall bias in smoking history and lack of information on second-hand smoke exposure. Further research is needed to understand the relationship between smoking and interstitial lung disease.
    The European respiratory journal. 07/2014;
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    ABSTRACT: Background:The risk factors for acute episodes of respiratory disease in current and former smokers who do not chronic obstructive pulmonary disease (COPD) are unknown. Methods:8246 non-Hispanic White and African American current and former smokers in the COPDGene cohort had longitudinal follow up (LFU) every six months to determine acute respiratory episodes requiring antibiotics or systemic corticosteroids, an emergency room visit, or hospitalization. Negative binomial regression was used to determine factors associated with acute respiratory episodes. A Cox-proportional hazards model was used to determine adjusted hazard ratios (HR) for time to first episode and an acute episode of respiratory disease risk score. Results:At enrollment, 4442 subjects did not have COPD, 658 had mild and 3146 had moderate or worse COPD. 9303 acute episodes of respiratory disease and 2707 hospitalizations were reported in LFU (3044 acute episodes of respiratory disease and 827 hospitalizations in those without COPD). Major predictors included: acute episodes of respiratory disease in year prior to enrollment (HR 1.20; 95% CI 1.15-1.24 per exacerbation), airflow obstruction (HR 0.94; 95% CI 0.91-0.96 per 10% change in %predicted forced expiratory volume at 1 second), and poor health related quality of life (HR 1.07; 95% CI 1.06-1.08 for each 4 unit increase in St. George's Respiratory Questionnaire Score). Risks were similar for those with and without COPD. Conclusions:Although acute episodes of respiratory disease rates are higher in subjects with COPD, risk factors are similar and at a population level there are more episodes in smokers without COPD.
    Chest 06/2014; · 5.85 Impact Factor
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    ABSTRACT: Abstract Introduction: Smoking is a major risk factor for both cardiovascular disease (CVD) and chronic obstructive pulmonary disease (COPD). More individuals with COPD die from CVD than respiratory causes and the risk of developing CVD appears to be independent of smoking burden. Although CVD is a common comorbid condition within COPD, the nature of its relationships to COPD affection status and severity, and functional status is not well understood. Methods: The first 2,500 members of the COPDGene cohort were evaluated. Subjects were current and former smokers with a minimum 10 pack-year history of cigarette smoking. COPD was defined by spirometry as an FEV1/FVC < lower limit of normal (LLN) with further identification of severity by FEV1 percent of predicted (GOLD stages 2, 3, and 4) for the main analysis. The presence of physician-diagnosed self-reported CVD was determined from a medical history questionnaire administered by a trained staff member. Results: A total of 384 (15%) had pre-existing CVD. Self-reported CVD was independently related to COPD (Odds Ratio = 1.61, 95% CI = 1.18-2.20, p = 0.01) after adjustment for covariates with CHF having the greatest association with COPD. Within subjects with COPD, pre-existing self-reported CVD placed subjects at greater risk of hospitalization due to exacerbation, higher BODE index, and greater St. George's questionnaire score. The presence of self-reported CVD was associated with a shorter six-minute walk distance in those with COPD (p < 0.05). Conclusions: Self-reported CVD was independently related to COPD with presence of both self-reported CVD and COPD associated with a markedly reduced functional status and reduced quality of life. Identification of CVD in those with COPD is an important consideration in determining functional status.
    COPD Journal of Chronic Obstructive Pulmonary Disease 05/2014; · 2.31 Impact Factor
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    ABSTRACT: Chronic bronchitis (CB) has been related to poor outcomes in Chronic Obstructive Pulmonary Disease (COPD). From a clinical standpoint, we have shown that subjects with CB in a group with moderate to severe airflow obstruction were younger, more likely to be current smokers, male, Caucasian, had worse health related quality of life, more dyspnea, and increased exacerbation history compared to those without CB. We sought to further refine our clinical characterization of chronic bronchitics in a larger cohort and analyze the CT correlates of CB in COPD subjects. We hypothesized that COPD patients with CB would have thicker airways and a greater history of smoking, acute bronchitis, allergic rhinitis, and occupational exposures compared to those without CB. We divided 2703 GOLD 1-4 subjects in the Genetic Epidemiology of COPD (COPDGene(R)) Study into two groups based on symptoms: chronic bronchitis (CB+, n = 663, 24.5%) and no chronic bronchitis (CB-, n = 2040, 75.5%). Subjects underwent extensive clinical characterization, and quantitative CT analysis to calculate mean wall area percent (WA%) of 6 segmental airways was performed using VIDA PW2 (http://www.vidadiagnostics.com). Square roots of the wall areas of bronchi with internal perimeters 10 mm and 15 mm (Pi10 and Pi15, respectively),%emphysema,%gas trapping, were calculated using 3D Slicer (http://www.slicer.org). There were no differences in%emphysema (11.4 +/- 12.0 vs. 12.0 +/- 12.6%, p = 0.347) or%gas trapping (35.3 +/- 21.2 vs. 36.3 +/- 20.6%, p = 0.272) between groups. Mean segmental WA% (63.0 +/- 3.2 vs. 62.0 +/- 3.1%, p < 0.0001), Pi10 (3.72 +/- 0.15 vs. 3.69 +/- 0.14 mm, p < 0.0001), and Pi15 (5.24 +/- 0.22 vs. 5.17 +/- 0.20, p < 0.0001) were greater in the CB + group. Greater percentages of gastroesophageal reflux, allergic rhinitis, histories of asthma and acute bronchitis, exposures to dusts and occupational exposures, and current smokers were seen in the CB + group. In multivariate binomial logistic regression, male gender, Caucasian race, a lower FEV1%, allergic rhinitis, history of acute bronchitis, current smoking, and increased airway wall thickness increased odds for having CB. Histories of asthma, allergic rhinitis, acute bronchitis, current smoking, a lower FEV1%, Caucasian race, male gender, and increased airway wall thickness are associated with CB. These data provide clinical and radiologic correlations to the clinical phenotype of CB.
    Respiratory research 04/2014; 15(1):52. · 3.64 Impact Factor
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    ABSTRACT: ABSTRACT BACKGROUND. In the acute respiratory distress syndrome (ARDS), the extent of fibroproliferative activity on chest HRCT has been reported to correlate with poorer short-term outcomes and pulmonary-associated quality of life. However, clinical factors associated with HRCT fibroproliferation are incompletely characterized. We questioned if lung compliance assessed at the bedside would be associated with fibroproliferation on HRCT obtained during the resolution phase of ARDS. METHODS. We utilized data from a published randomized, controlled clinical trial in ARDS. All patients were cared for using a low tidal volume strategy. Demographic data and ventilator parameters were examined in association with radiologic scores from chest HRCTs obtained 14 days after diagnosis. RESULTS. Data from 82 ARDS patients were analyzed. Average static respiratory compliance over the first 14 days after diagnosis was inversely associated with chest HRCT reticulation (rho=-0.46); this relationship persisted in multivariable analysis including APACHE II scores, initial PaO2/FiO2, pneumonia diagnosis and ventilator days. Average static respiratory compliance was also lower among patients with bronchiectasis at day 14 (p=0.007). Initial static respiratory compliance obtained within the first day after ARDS diagnosis was correlated inversely with the presence of HRCT reticulation (rho=-0.38), and was lower among patients who demonstrated bronchiectasis on the day 14 HRCT (p=0.008). CONCLUSIONS. In patients with ARDS, diminished lung compliance measured bedside was associated with radiologic fibroproliferation 14 days post diagnosis. Establishing factors that predispose to development of excessive fibroproliferation with subsequent confirmation by chest HRCT represents a promising strategy to identify ARDS patients at risk for poorer clinical outcomes.
    Chest 04/2014; · 5.85 Impact Factor
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    ABSTRACT: Present guidelines for the diagnosis of idiopathic pulmonary fibrosis require histological confirmation of surgical lung biopsy samples when high-resolution CT images are not definitive for usual interstitial pneumonia. We aimed to assess the predictive value of high-resolution CT in a cohort of patients with suspected idiopathic pulmonary fibrosis from a previous randomised trial. ARTEMIS-IPF was a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial of ambrisentan for adults aged 40-80 years with well-defined idiopathic pulmonary fibrosis and 5% or less honeycombing on high-resolution CT. In December, 2010, an interim analysis showed lack of efficacy and the trial was stopped. In the present follow-on analysis, we assessed patients who were screened for ARTEMIS-IPF who underwent high-resolution CT as part of screening and surgical lung biopsy as part of standard clinical care. A radiologist and a pathologist from a central panel independently assessed anonymised CT scans and biopsy samples. We calculated the positive and negative predictive value of high-resolution CT (classified as usual interstitial pneumonia, possible usual interstitial pneumonia, and inconsistent with usual interstitial pneumonia) for confirmation of histological patterns of usual interstitial pneumonia. This study is registered with ClinicalTrials.gov, number NCT00768300. 315 (29%) of 1087 consecutively screened patients in ARTEMIS-IPF had both high-resolution CT and surgical lung biopsy samples. 108 of 111 patients who met high-resolution CT criteria for usual interstitial pneumonia had histologically confirmed usual interstitial pneumonia (positive predictive value 97·3%, 95% CI 92·3-99·4), as did 79 of 84 patients who met high-resolution CT criteria for possible usual interstitial pneumonia (94·0%, 86·7-98·0). 22 of 120 patients had an inconsistent high-resolution CT pattern for usual interstitial pneumonia that was histologically confirmed as not or possible usual interstitial pneumonia (negative predictive value 18·3%, 95% CI 11·9-26·4). In the appropriate clinical setting, for patients with possible usual interstitial pneumonia pattern on high resolution CT, surgical lung biopsy sampling might not be necessary to reach a diagnosis of idiopathic pulmonary fibrosis if high-resolution CT scans are assessed by experts at regional sites familiar with patterns of usual interstitial pneumonia and management of idiopathic interstitial pneumonia. Gilead Sciences.
    The lancet. Respiratory medicine. 04/2014; 2(4):277-84.
  • Christian W Cox, Cecile S Rose, David A Lynch
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    ABSTRACT: Imaging of occupational lung disease, often perceived as a static discipline, continues to evolve with changes in industry and imaging technology. The challenge of accurately identifying an occupational exposure as the cause of lung disease demands a team approach, requiring integration of imaging features with exposure type, time course, and severity. Increasing use of computed tomography has demonstrated that specific occupational exposures can result in a variety of patterns of lung injury. The radiologist must understand the spectrum of expected imaging patterns related to known occupational exposures and must also recognize newly described occupational exposure risks, often related to recent changes in industrial practices. © RSNA, 2014.
    Radiology 03/2014; 270(3):681-96. · 6.34 Impact Factor
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    ABSTRACT: There is notable heterogeneity in the clinical presentation of patients with COPD. To characterise this heterogeneity, we sought to identify subgroups of smokers by applying cluster analysis to data from the COPDGene study. We applied a clustering method, k-means, to data from 10 192 smokers in the COPDGene study. After splitting the sample into a training and validation set, we evaluated three sets of input features across a range of k (user-specified number of clusters). Stable solutions were tested for association with four COPD-related measures and five genetic variants previously associated with COPD at genome-wide significance. The results were confirmed in the validation set. We identified four clusters that can be characterised as (1) relatively resistant smokers (ie, no/mild obstruction and minimal emphysema despite heavy smoking), (2) mild upper zone emphysema-predominant, (3) airway disease-predominant and (4) severe emphysema. All clusters are strongly associated with COPD-related clinical characteristics, including exacerbations and dyspnoea (p<0.001). We found strong genetic associations between the mild upper zone emphysema group and rs1980057 near HHIP, and between the severe emphysema group and rs8034191 in the chromosome 15q region (p<0.001). All significant associations were replicated at p<0.05 in the validation sample (12/12 associations with clinical measures and 2/2 genetic associations). Cluster analysis identifies four subgroups of smokers that show robust associations with clinical characteristics of COPD and known COPD-associated genetic variants.
    Thorax 02/2014; · 8.38 Impact Factor
  • David A Lynch, Jason M Huckleberry
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    ABSTRACT: The computed tomography appearances of usual interstitial pneumonia (UIP) are usually characteristic, with basal-predominant, peripheral-predominant reticular abnormality and honeycombing. Important complications that may be detected by the radiologist include pulmonary hypertension, lung cancer, and acute exacerbation. As the number of surgical lung biopsies performed for typical UIP declines, histologic findings of UIP are increasingly found in subjects with atypical computed tomographic features. Potential reasons for such discordance may include variability in pathologist interpretation, sampling error on biopsy, biopsy obtained from nonrepresentative site, coexistence of multiple pathologies within the same lung, and familial pulmonary fibrosis. Multidisciplinary diagnosis is critical in resolving these cases.
    Seminars in ultrasound, CT, and MR. 02/2014; 35(1):12-23.
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    ABSTRACT: Rationale The forced vital capacity (FVC) is a difficult maneuver for many patients, and the forced expiratory volume in 6 seconds (FEV6) has been proposed as a surrogate for FVC for the diagnosis of chronic obstructive pulmonary disease (COPD). Previous studies performed head to head comparisons of these thresholds but did not examine their relationships with structural lung disease, symptoms or exacerbations. Objectives: To compare FEV1/FEV6 with FEV1/FVC in the diagnosis of COPD-related morbidity and structural lung disease as assessed by CT Methods We analyzed data from a large multicenter cohort study (COPDGene), which included current and former smokers (age 45 to 80 years). Accuracy and concordance between the two ratios in diagnosing structural COPD was compared using CT measures of emphysema and airway disease and COPD-related morbidity to assess how the two ratios compare in defining disease. Results: 10,018 subjects were included. FEV1/FEV6 showed excellent accuracy in diagnosing airflow obstruction using FEV1/FVC <0.70 as reference (area under curve 0.99; 95%CI = 0.989 to 0.992,p<0.001). FEV1/FEV6 <0.73 had the best sum of sensitivity (92.1%; 95%CI 90.8 to 92.4) and specificity (97.3%; 95%CI 97.3 to 98.1). There was excellent agreement between the two diagnostic cutoffs (kappa = 0.90; 95%CI 0.80 to 0.91,p<0.001). In comparison with both controls and those positive by FEV1/FVC alone, subjects positive by FEV1/FEV6 alone had greater gas trapping and airway wall thickness, worse functional capacity, and had greater number of exacerbations on follow up. These relationships held true when disease definitions were made using the lower limits of normal. Conclusions FEV1/FEV6 can be substituted for FEV1/FVC in diagnosing airflow obstruction and may better predict COPD-related pathology and morbidity.
    Annals of the American Thoracic Society. 01/2014;
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    ABSTRACT: Bronchial wall area percent (WA%=100 × wall area/total bronchial cross sectional area) is a standard computed tomographic (CT) measure of central airway morphology utilized in smokers with chronic obstructive pulmonary disease (COPD). While providing significant clinical correlations, the range of reported WA% is narrow. This suggests limited macroscopic change in response to smoking or that remodeling proportionally affects the airway wall and lumen dimensions such that their ratio is preserved. The objective of this study is to assess central airway wall area (WA), lumen area (Ai), and total bronchial area (Ao) from CT scans of 5179 smokers and 92 never smoking normals. In smokers, WA, Ai, and Ao were positively correlated with FEV1 expressed as a percent of predicted (FEV1%), and the WA% was negatively correlated with FEV1% (p<0.0001 for all comparisons). Importantly, smokers with lower FEV1% tended to have airways of smaller cross sectional area with lower WA. The increases in the WA% across GOLD stages of COPD can therefore not be due to increases in WA. The data suggest two possible origins for the WA% increases: (1) central airway remodeling resulting in overall reductions in airway caliber in excess of the decreased WA, or (2) those with COPD had smaller native airways before they began smoking. In both cases these observations provide an explanation for the limited range of values of WA% across stages of COPD.
    Journal of Applied Physiology 01/2014; · 3.48 Impact Factor
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    ABSTRACT: Within the COPD Genetic Epidemiology (COPDGene(®)) study population of cigarette smokers, 9% were found to be unclassifiable by the Global Initiative for chronic Obstructive Lung Disease (GOLD) criteria. This study was to identify the differences in computed tomography (CT) findings between this nonobstructed (GOLDU) group and a control group of smokers with normal lung function. This research was approved by the institutional review board of each institution. CT images of 400 participants in the COPDGene(®) study (200 GOLDU, 200 smokers with normal lung function) were retrospectively evaluated in a blinded fashion. Visual CT assessment included lobar analysis of emphysema (type, extent), presence of paraseptal emphysema, airway wall thickening, expiratory air trapping, centrilobular nodules, atelectasis, non-fibrotic and fibrotic interstitial lung disease (ILD), pleural thickening, diaphragmatic eventration, vertebral body changes and internal thoracic diameters (in mm). Univariate comparisons of groups for each CT parameter and multiple logistic regression were performed to determine the imaging features associated with GOLDU. When compared with the control group, GOLDU participants had a significantly higher prevalence of unilateral diaphragm eventration (30% vs. 16%), airway wall thickening, centrilobular nodules, reticular abnormality, paraseptal emphysema (33% vs. 17%), linear atelectasis (60% vs. 35.6%), kyphosis (12% vs. 4%), and a smaller internal transverse thoracic diameter (255 ± 22.5 [standard deviation] vs. 264.8 ± 22.4, mm) (all p<0.05). With multiple logistic regression, all of these CT parameters, except non-fibrotic ILD and kyphosis, remained significantly associated with GOLDU status (p<0.05). In cigarette smokers, chest wall abnormalities and parenchymal lung disease, which contribute to restrictive physiologic impairment, are associated with GOLD-nonobstructed status.
    Chronic obstructive pulmonary diseases (Miami, Fla.). 01/2014; 1(1):88-96.
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    ABSTRACT: Clinical trial design in interstitial lung diseases (ILDs) has been hampered by lack of consensus on appropriate outcome measures for reliably assessing treatment response. In the setting of connective tissue diseases (CTDs), some measures of ILD disease activity and severity may be confounded by non-pulmonary comorbidities. The Connective Tissue Disease associated Interstitial Lung Disease (CTD-ILD) working group of Outcome Measures in Rheumatology-a non-profit international organisation dedicated to consensus methodology in identification of outcome measures-conducted a series of investigations which included a Delphi process including >248 ILD medical experts as well as patient focus groups culminating in a nominal group panel of ILD experts and patients. The goal was to define and develop a consensus on the status of outcome measure candidates for use in randomised controlled trials in CTD-ILD and idiopathic pulmonary fibrosis (IPF). A core set comprising specific measures in the domains of lung physiology, lung imaging, survival, dyspnoea, cough and health-related quality of life is proposed as appropriate for consideration for use in a hypothetical 1-year multicentre clinical trial for either CTD-ILD or IPF. As many widely used instruments were found to lack full validation, an agenda for future research is proposed. Identification of consensus preliminary domains and instruments to measure them was attained and is a major advance anticipated to facilitate multicentre RCTs in the field.
    Thorax 12/2013; · 8.38 Impact Factor
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    ABSTRACT: The purpose of this study was to describe a characteristic magnetic resonance imaging (MRI) appearance of lymphadenopathy in sarcoidosis-the dark lymph node sign (DLNS)-and to determine its prevalence in a retrospective review of cardiopulmonary MRI examinations obtained in patients with sarcoidosis. Fifty-one adult patients with a clinical history of sarcoidosis were evaluated with thoracic MRI during a 15-month span; 29 patients were men, and 22 patients were women. The average age of patients was 53.7±11.2 years. Patients were considered to have the DLNS on MRI if mediastinal or hilar lymph nodes demonstrated internal low intensity with a peripheral circumferential rim of hyperintensity (relative to paraspinal muscle) on post-gadolinium volume-interpolated 3-dimensional gradient echo (3D-GRE/VIBE) and fat-saturated T2-weighted fast spin echo (T2-FSE/BLADE) sequences. Univariate analyses and a logistic regression were used to determine how variables of interest related to the DLNS. Of the 51 patients with sarcoidosis, 49% (25 patients) demonstrated the DLNS. Nodal calcification was present on computed tomography in 45.7% (16/35) of patients with computed tomography scans obtained within 90 days of MRI. The DLNS sign was not more common in those with nodal calcification. When the DLNS occurred in conjunction with calcified nodes, the extent of hypointensity on MRI was not strictly limited to the calcified portions of the lymph node in 71.4% (5/7) of such cases. The DLNS is commonly present on MRI examinations of patients with sarcoidosis, occurring in approximately half of the participants in our study.
    Journal of thoracic imaging 10/2013; · 1.42 Impact Factor
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    ABSTRACT: Background: In 2002 the American Thoracic Society/European Respiratory Society (ATS/ERS) classification of idiopathic interstitial pneumonias (IIPs) defined seven specific entities, and provided standardized terminology and diagnostic criteria. In addition, the historical "gold standard" of histologic diagnosis was replaced by a multidisciplinary approach. Since 2002 many publications have provided new information about IIPs. Purpose: The objective of this statement is to update the 2002 ATS/ERS classification of IIPs. Methods: An international multidisciplinary panel was formed and developed key questions that were addressed through a review of the literature published between 2000 and 2011. Results: Substantial progress has been made in IIPs since the previous classification. Nonspecific interstitial pneumonia is now better defined. Respiratory bronchiolitis-interstitial lung disease is now commonly diagnosed without surgical biopsy. The clinical course of idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia is recognized to be heterogeneous. Acute exacerbation of IIPs is now well defined. A substantial percentage of patients with IIP are difficult to classify, often due to mixed patterns of lung injury. A classification based on observed disease behavior is proposed for patients who are difficult to classify or for entities with heterogeneity in clinical course. A group of rare entities, including pleuroparenchymal fibroelastosis and rare histologic patterns, is introduced. The rapidly evolving field of molecular markers is reviewed with the intent of promoting additional investigations that may help in determining diagnosis, and potentially prognosis and treatment. Conclusions: This update is a supplement to the previous 2002 IIP classification document. It outlines advances in the past decade and potential areas for future investigation.
    American Journal of Respiratory and Critical Care Medicine 09/2013; 188(6):733-48. · 11.04 Impact Factor
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    ABSTRACT: OBJECTIVE. This study evaluates the relationships between quantitative CT (QCT) and spirometric measurements of disease severity in cigarette smokers with and without chronic obstructive pulmonary disease (COPD). MATERIALS AND METHODS. Inspiratory and expiratory CT scans of 4062 subjects in the Genetic Epidemiology of COPD (COPDGene) Study were evaluated. Measures examined included emphysema, defined as the percentage of low-attenuation areas ≤ -950 HU on inspiratory CT, which we refer to as "LAA-950I"; air trapping, defined as the percentage of low-attenuation areas ≤ -856 HU on expiratory CT, which we refer to as "LAA-856E"; and the inner diameter, inner and outer areas, wall area, airway wall thickness, and square root of the wall area of a hypothetical airway of 10-mm internal perimeter of segmental and subsegmental airways. Correlations were determined between spirometry and several QCT measures using statistics software (SAS, version 9.2). RESULTS. QCT measurements of low-attenuation areas correlate strongly and significantly (p < 0.0001) with spirometry. The correlation between LAA-856E and forced expiratory volume in 1 second (FEV1) and the ratio of FEV1 to forced vital capacity (FVC) (r = -0.77 and -0.84, respectively) is stronger than the correlation between LAA-950I and FEV1 and FEV1/FVC (r = -0.67 and r = -0.76). Inspiratory and expiratory volume changes decreased with increasing disease severity, as measured by the Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) staging system (p < 0.0001). When airway variables were included with low-attenuation area measures in a multiple regression model, the model accounted for a statistically greater proportion of variation in FEV1 and FEV1/FVC (R(2) = 0.72 and 0.77, respectively). Airway measurements alone are less correlated with spirometric measures of FEV1 (r = 0.15 to -0.44) and FEV1/FVC (r = 0.19 to -0.34). CONCLUSION. QCT measurements are strongly associated with spirometric results showing impairment in smokers. LAA-856E strongly correlates with physiologic measurements of airway obstruction. Airway measurements can be used concurrently with QCT measures of low-attenuation areas to accurately predict lung function.
    American Journal of Roentgenology 09/2013; 201(3):W460-70. · 2.90 Impact Factor
  • David A Lynch
    Journal of thoracic imaging 09/2013; 28(5):264-5. · 1.42 Impact Factor

Publication Stats

4k Citations
903.66 Total Impact Points


  • 2009–2014
    • National Research Center (CO, USA)
      Boulder, Colorado, United States
  • 1992–2014
    • University of Colorado
      • • Department of Radiology
      • • Division of Pulmonary Sciences and Critical Care Medicine
      Denver, Colorado, United States
  • 2013
    • Ulsan University Hospital
      Urusan, Ulsan, South Korea
    • Harvard University
      Cambridge, Massachusetts, United States
    • Harvard Medical School
      • Department of Medicine
      Boston, Massachusetts, United States
  • 2009–2013
    • National Jewish Health
      • Division of Radiology
      Denver, CO, United States
  • 2012
    • Duke University Medical Center
      Durham, North Carolina, United States
  • 2011
    • Seoul Medical Center
      Sŏul, Seoul, South Korea
    • University of Michigan
      • Department of Internal Medicine
      Ann Arbor, MI, United States
    • Brigham and Women's Hospital
      • Department of Medicine
      Boston, MA, United States
  • 2008–2009
    • University of California, Los Angeles
      • • School of Public Health
      • • Department of Radiology
      Los Angeles, CA, United States
  • 2007
    • Concordia University–Ann Arbor
      Ann Arbor, Michigan, United States
    • University of California, San Francisco
      • Division of Hospital Medicine
      San Francisco, CA, United States
  • 2005
    • University of Washington Seattle
      • Department of Radiology
      Seattle, WA, United States
    • University of Alberta
      • Department of Radiology and Diagnostic Imaging
      Edmonton, Alberta, Canada
  • 2003
    • Yamaguchi University
      • Division of Radiology
      Yamaguti, Yamaguchi, Japan
  • 1995
    • University of Santiago, Chile
      • Departamento de Física
      CiudadSantiago, Santiago, Chile