David A Lynch

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

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Publications (234)949.58 Total impact

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    ABSTRACT: Background:The current UIP/IPF CT classification system excludes probable UIP as a diagnostic category. We sought to determine the predictive effect of probable CT UIP on histology, and to determine the effect of the promoter polymorphism in the MUC5B gene (rs35705950) on histologic and CT UIP diagnosis. Methods:The cohort included 201 subjects with pulmonary fibrosis who had lung tissue samples obtained within one year of chest CT. UIP diagnosis on CT was categorized as inconsistent with, indeterminate, probable, or definite UIP by 2-3 pulmonary radiologists. Tissue slides were scored by two expert pulmonary pathologists. All subjects with available DNA (N=200) were genotyped for rs35705950. Results:The proportion of CT diagnoses were as follows: inconsistent with 69/201 (34.3%), indeterminate 72/201 (35.8%), probable 34/201 (16.9%), and definite 26/201 (12.9%) UIP. Subjects with probable CT UIP were more likely to have histologic probable/definite UIP than subjects with indeterminate CT UIP (82.4% [28/34] versus 54.2% [39/72]; p-value 0.01). CT and microscopic honeycombing were not associated with each other (p-value 0.76). The minor (T) allele of the MUC5B polymorphism was associated with concordant CT and histologic UIP diagnosis (p-value: 0.03). Conclusions:Probable CT UIP is associated with a higher rate of histologic UIP than indeterminate CT UIP suggesting that they are distinct groups and should not be combined into a single CT category as currently recommended by guidelines. CT and microscopic honeycombing may be dissimilar entities. The T allele at rs35705950 predicts a UIP diagnosis by both chest CT and histology.
    Chest 10/2014; · 7.13 Impact Factor
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    ABSTRACT: Rationale and Objectives: Asthma is associated with chronic airflow obstruction (CAO). Our goal was to assess the association of computed tomographic (CT) measures of airway wall volume (WV) and lumen volume (LV) with the forced expiratory volume in one second (FEV1) and CAO in smokers with childhood-onset asthma (CA). Methods: We analyzed clinical, lung function, and volumetric CT airway volumes data from 7,266 smokers including 590 with CA. Small WV and small LV of segmental airways were defined as measures 1 SD below the mean. We assessed the association between small WV, small LV, FEV1 and CAO (post-bronchodilator FEV1/forced vital capacity ratio <0.7) using linear and logistic models. Measurements and Main Results: CA subjects had smaller WV and LV than those without CA (mean ± SD, 371.3 ± 92.5mm3 vs. 388.7 ± 94.0mm3, P<0.0001; 230.8 ± 76.9 mm3 vs. 257.4 ± 80.9mm3, P<0.0001). Among CA subjects, those with the smallest WV and LV had the lowest FEV1 and greatest odds of CAO. A similar tendency was seen in those without CA. When comparing these 2 groups, small WV and small LV were more strongly associated with FEV1 (for WV, β [95%CI] -331ml [-488 - -174] vs. -244ml [-294 - -194]; for LV, -534ml [-669 - -398] vs. -435ml [-485 - -386] and CAO (Odds ratio 2.10 (1.27-3.46) vs. 2.02 [1.72-2.36]; 4.32 [2.64-7.08] vs. 3.55 [3.00-4.19], respectively) among CA subjects in multivariate models. Conclusion: In smokers with CA smaller airways are associated with reduced lung function and chronic airflow obstruction.
    Annals of the American Thoracic Society. 10/2014;
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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; · 7.13 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; · 2.73 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; · 7.13 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: Chronic obstructive pulmonary disease (COPD) has been classically divided into blue bloaters and pink puffers. The utility of these clinical subtypes is unclear. However, the broader distinction between airway-predominant and emphysema-predominant COPD may be clinically relevant. The objective was to define clinical features of emphysema-predominant and non-emphysematous COPD patients.
    BMC Pulmonary Medicine 01/2014; 14(1):164. · 2.76 Impact Factor
  • Chronic Obstructive Pulmonary Diseases: Journal of the COPD Foundation. 01/2014; 1(1):105-114.
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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

Publication Stats

5k Citations
949.58 Total Impact Points

Institutions

  • 2009–2014
    • National Research Center (CO, USA)
      Boulder, Colorado, United States
    • National Jewish Health
      • Division of Radiology
      Denver, 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
  • 2012
    • Duke University Medical Center
      Durham, North Carolina, United States
  • 2011–2012
    • Brigham and Women's Hospital
      • Department of Medicine
      Boston, MA, United States
    • University of Iowa
      Iowa City, Iowa, United States
    • University of Michigan
      • Department of Internal Medicine
      Ann Arbor, MI, United States
    • Seoul Medical Center
      Sŏul, Seoul, South Korea
  • 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