Findings on High Resolution Computed Tomography in Symptomatic Veterans with Deployment-Related Lung Disease.

PURPOSE: Military deployment to dusty, austere environments in Southwest Asia and Afghanistan is associated with symptomatic airways diseases including asthma and bronchiolitis. The utility of chest high-resolution computed tomographic (HRCT) imaging in lung disease diagnosis in this population is poorly understood. We investigated visual assessment of HRCT for identifying deployment-related lung disease compared with healthy controls. MATERIALS AND METHODS: Chest HRCT images from 46 healthy controls and 45 symptomatic deployed military personnel with clinically confirmed asthma and/or biopsy-confirmed distal lung disease were scored by 3 independent thoracic radiologists. We compared demographic and clinical characteristics and frequency of imaging findings between deployers and controls, and between deployers with asthma and those with biopsy-confirmed distal lung disease, using χ2, Fisher exact or t tests, and logistic regression where appropriate. We also analyzed inter-rater agreement for imaging findings. RESULTS: Expiratory air trapping was the only chest CT imaging finding that was significantly more frequent in deployers compared with controls. None of the 24 deployers with biopsy-confirmed bronchiolitis and/or granulomatous pneumonitis had HRCT findings of inspiratory mosaic attenuation or centrilobular nodularity. Only 2 of 21 with biopsy-proven emphysema had emphysema on HRCT. CONCLUSIONS: Compared with surgical lung biopsy, visual assessment of HRCT showed few abnormalities in this small cohort of previously deployed symptomatic veterans with normal or near-normal spirometry.

Parameter D: New Measure of Airflow Obstruction.

Rationale: Currently used spirometry measures of airflow obstruction are influenced by demographics, predominantly by age, complicating selection of diagnostic thresholds for the presence of airflow obstruction. Objectives: To develop diagnostic thresholds for Parameter D, a new metric for detection of airflow obstruction, which quantifies the rate of rise of expiratory volume over time. Methods: We analyzed spirometry data of normal subjects enrolled in the 2007-2008, 2009-2010, and 2011-2012 NHANES (National Health and Nutrition Examination Survey) cohorts and calculated Parameter D using the expiratory volume-time curve. Relationships between demographics and lung function (forced expiratory volume in 1 second [FEV1], FEV1/forced vital capacity [FVC], and Parameter D) were tested using generalized linear models in NHANES and UK Biobank. The variation in lung function explained by demographics was estimated using R2. A diagnostic threshold was developed for Parameter D using population-based percentiles. Based on concordance between the lower limit of normal (LLN) for FEV1/FVC and the Parameter D threshold, four groups were identified: normal (no airflow obstruction by either criterion), D+chronic obstructive pulmonary disease (D+COPD; positive by Parameter D only), D-COPD (positive by LLN only), and COPD (positive by both criteria), and associations with structural lung disease, exacerbations, and mortality were tested using multivariable analyses. Results: In contrast to FEV1 and FEV1/FVC, demographics cumulatively explained only 9% of the variance in Parameter D in NHANES (n = 4,945) and 3% in UK BioBank (n = 109,623). In COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease) (n = 9,542), a diagnostic threshold of -3.15 resulted in the identification of an additional 10.8% of participants with airflow obstruction. A total of 3.7% had FEV1/FVC < LLN but were missed by the Parameter D threshold. Compared with subjects in the normal group, after adjustment for age, sex, race, body mass index, pack-years of smoking, and current smoking status, D+COPD was associated with worse structural lung disease (odds ratio [OR] for ⩾5% emphysema, 1.71; 95% confidence interval [CI], 1.37-2.12; OR for functional small airway disease ⩾ 15%, 2.1; 95% CI, 1.79-2.67) and significant symptoms (OR for modified Medical Research Council dyspnea score ⩾ 2, 1.25; 95% CI, 1.07-1.47; OR for St. George's respiratory questionnaire ⩾ 25, 1.31; 95% CI, 1.13-1.53), a greater frequency of exacerbations (incidence rate ratio, 1.26; 95% CI, 1.10-1.46), and higher mortality (hazard ratio, 1.32; 95% CI, 1.10-1.57). Over 5 years, 28% of the D+COPD group versus 8% of normal group progressed to COPD by traditional criteria. Conclusions: Parameter D is not affected by age, and a normal population-based diagnostic threshold results in the early identification of additional individuals with airflow obstruction with a substantial amount of structural lung disease and respiratory symptoms.

Sex Differences in Airways at Chest CT: Results from the COPDGene Cohort.

Background The prevalence of chronic obstructive pulmonary disease (COPD) in women is fast approaching that in men, and women experience greater symptom burden. Although sex differences in emphysema have been reported, differences in airways have not been systematically characterized. Purpose To evaluate whether structural differences in airways may underlie some of the sex differences in COPD prevalence and clinical outcomes. Materials and Methods In a secondary analyses of a multicenter study of never-, current-, and former-smokers enrolled from January 2008 to June 2011 and followed up longitudinally until November 2020, airway disease on CT images was quantified using seven metrics: airway wall thickness, wall area percent, and square root of the wall thickness of a hypothetical airway with internal perimeter of 10 mm (referred to as Pi10) for airway wall; and lumen diameter, airway volume, total airway count, and airway fractal dimension for airway lumen. Least-squares mean values for each airway metric were calculated and adjusted for age, height, ethnicity, body mass index, pack-years of smoking, current smoking status, total lung capacity, display field of view, and scanner type. In ever-smokers, associations were tested between each airway metric and postbronchodilator forced expiratory volume in 1 second (FEV1)-to-forced vital capacity (FVC) ratio, modified Medical Research Council dyspnea scale, St George's Respiratory Questionnaire score, and 6-minute walk distance. Multivariable Cox proportional hazards models were created to evaluate the sex-specific association between each airway metric and mortality. Results In never-smokers (n = 420), men had thicker airway walls than women as quantified on CT images for segmental airway wall area percentage (least-squares mean, 47.68 ± 0.61 [standard error] vs 45.78 ± 0.55; difference, -1.90; P = .02), whereas airway lumen dimensions were lower in women than men after accounting for height and total lung capacity (segmental lumen diameter, 8.05 mm ± 0.14 vs 9.05 mm ± 0.16; difference, -1.00 mm; P < .001). In ever-smokers (n = 9363), men had greater segmental airway wall area percentage (least-squares mean, 52.19 ± 0.16 vs 48.89 ± 0.18; difference, -3.30; P < .001), whereas women had narrower segmental lumen diameter (7.80 mm ± 0.05 vs 8.69 mm ± 0.04; difference, -0.89; P < .001). A unit change in each of the airway metrics (higher wall or lower lumen measure) resulted in lower FEV1-to-FVC ratio, more dyspnea, poorer respiratory quality of life, lower 6-minute walk distance, and worse survival in women compared with men (all P < .01). Conclusion Airway lumen sizes quantified at chest CT were smaller in women than in men after accounting for height and lung size, and these lower baseline values in women conferred lower reserves against respiratory morbidity and mortality for equivalent changes compared with men. © RSNA, 2022 Online supplemental material is available for this article.

Structural airway imaging metrics are differentially associated with persistent chronic bronchitis.

BACKGROUND: Chronic bronchitis (CB) is strongly associated with cigarette smoking, but not all smokers develop CB. We aimed to evaluate whether measures of structural airway disease on CT are differentially associated with CB. METHODS: In smokers between ages 45 and 80 years, and with Global Initiative for Obstructive Lung Disease stages 0-4, CB was defined by the classic definition. Airway disease on CT was quantified by (i) wall area percent (WA%) of segmental airways; (ii) Pi10, the square root of the wall area of a hypothetical airway with 10 mm internal perimeter; (iii) total airway count (TAC) and (iv) airway fractal dimension (AFD), a measure of the complex branching pattern and remodelling of airways. CB was also assessed at the 5-year follow-up visit. MEASUREMENTS AND MAIN RESULTS: Of 8917 participants, 1734 (19.4%) had CB at baseline. Airway measures were significantly worse in those with CB compared with those without CB: WA% 54.5 (8.8) versus 49.8 (8.3); Pi10 2.58 (0.67) versus 2.28 (0.59) mm; TAC 156.7 (81.6) versus 177.8 (91.1); AFD 1.477 (0.091) versus 1.497 (0.092) (all p<0.001). On follow-up of 5517 participants at 5 years, 399 (7.2%) had persistent CB. With adjustment for between-visits changes in smoking status and lung function, greater WA% and Pi10 were associated with significantly associated with persistent CB, adjusted OR per SD change 1.75, 95% CI 1.56 to 1.97; p<0.001 and 1.66, 95% CI 1.42 to 1.86; p<0.001, respectively. Higher AFD and TAC were associated with significantly lower odds of persistent CB, adjusted OR per SD change 0.76, 95% CI 0.67 to 0.86; p<0.001 and 0.69, 95% CI 0.60 to 0.80; p<0.001, respectively. CONCLUSIONS: Higher baseline AFD and TAC are associated with a lower risk of persistent CB, irrespective of changes in smoking status, suggesting preserved airway structure can confer a reserve against CB.

Deep neural network analyses of spirometry for structural phenotyping of chronic obstructive pulmonary disease.

BACKGROUNDCurrently recommended traditional spirometry outputs do not reflect the relative contributions of emphysema and airway disease to airflow obstruction. We hypothesized that machine-learning algorithms can be trained on spirometry data to identify these structural phenotypes.METHODSParticipants enrolled in a large multicenter study (COPDGene) were included. The data points from expiratory flow-volume curves were trained using a deep-learning model to predict structural phenotypes of chronic obstructive pulmonary disease (COPD) on CT, and results were compared with traditional spirometry metrics and an optimized random forest classifier. Area under the receiver operating characteristic curve (AUC) and weighted F-score were used to measure the discriminative accuracy of a fully convolutional neural network, random forest, and traditional spirometry metrics to phenotype CT as normal, emphysema-predominant (>5% emphysema), airway-predominant (Pi10 > median), and mixed phenotypes. Similar comparisons were made for the detection of functional small airway disease phenotype (>20% on parametric response mapping).RESULTSAmong 8980 individuals, the neural network was more accurate in discriminating predominant emphysema/airway phenotypes (AUC 0.80, 95%CI 0.79-0.81) compared with traditional measures of spirometry, FEV1/FVC (AUC 0.71, 95%CI 0.69-0.71), FEV1% predicted (AUC 0.70, 95%CI 0.68-0.71), and random forest classifier (AUC 0.78, 95%CI 0.77-0.79). The neural network was also more accurate in discriminating predominant emphysema/small airway phenotypes (AUC 0.91, 95%CI 0.90-0.92) compared with FEV1/FVC (AUC 0.80, 95%CI 0.78-0.82), FEV1% predicted (AUC 0.83, 95%CI 0.80-0.84), and with comparable accuracy with random forest classifier (AUC 0.90, 95%CI 0.88-0.91).CONCLUSIONSStructural phenotypes of COPD can be identified from spirometry using deep-learning and machine-learning approaches, demonstrating their potential to identify individuals for targeted therapies.TRIAL REGISTRATIONClinicalTrials.gov NCT00608764.FUNDINGThis study was supported by NIH grants K23 HL133438 and R21EB027891 and an American Thoracic Foundation 2018 Unrestricted Research Grant. The COPDGene study is supported by NIH grants NHLBI U01 HL089897 and U01 HL089856. The COPDGene study (NCT00608764) is also supported by the COPD Foundation through contributions made to an Industry Advisory Committee comprising AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Novartis, and Sunovion.

The Peak Index: Spirometry Metric for Airflow Obstruction Severity and Heterogeneity.

Rationale: Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation. Spirometry loops are not smooth curves and have undulations and peaks that likely reflect heterogeneity of airflow.Objectives: To assess whether the Peak Index, the number of peaks adjusted for lung size, is associated with clinical outcomes.Methods: We analyzed spirometry data of 9,584 participants enrolled in the COPDGene study and counted the number of peaks in the descending part of the expiratory flow-volume curve from the peak expiratory flow to end-expiration. We adjusted the peaks count for the volume of the lungs from peak expiratory flow to end-expiration to derive the Peak Index. Multivariable regression analyses were performed to test associations between the Peak Index and lung function, respiratory morbidity, structural lung disease on computed tomography (CT), forced expiratory volume in 1 second (FEV1) decline, and mortality.Results: The Peak Index progressively increased from Global Initiative for Chronic Obstructive Lung Disease stage 0 through 4 (P < 0.001). On multivariable analysis, the Peak Index was significantly associated with CT emphysema (adjusted ß = 0.906; 95% confidence interval [CI], 0.789 to 1.023; P < 0.001) and small airways disease (adjusted ß = 1.367; 95% CI, 1.188 to 1.545; P < 0.001), St. George's Respiratory Questionnaire score (adjusted ß = 1.075; 95% CI, 0.807 to 1.342; P < 0.001), 6-minute-walk distance (adjusted ß = -1.993; 95% CI, -3.481 to -0.506; P < 0.001), and FEV1 change over time (adjusted ß = -1.604; 95% CI, -2.691 to -0.516; P = 0.004), after adjustment for age, sex, race, body mass index, current smoking status, pack-years of smoking, and FEV1. The Peak Index was also associated with the BODE (body mass index, airflow obstruction, dyspnea, and exercise capacity) index and mortality (P < 0.001).Conclusions: The Peak Index is a spirometry metric that is associated with CT measures of lung disease, respiratory morbidity, lung function decline, and mortality.Clinical trial registered with www.clinicaltrials.gov (NCT00608764).

New Spirometry Indices for Detecting Mild Airflow Obstruction.

The diagnosis of chronic obstructive pulmonary disease (COPD) relies on demonstration of airflow obstruction. Traditional spirometric indices miss a number of subjects with respiratory symptoms or structural lung disease on imaging. We hypothesized that utilizing all data points on the expiratory spirometry curves to assess their shape will improve detection of mild airflow obstruction and structural lung disease. We analyzed spirometry data of 8307 participants enrolled in the COPDGene study, and derived metrics of airflow obstruction based on the shape on the volume-time (Parameter D), and flow-volume curves (Transition Point and Transition Distance). We tested associations of these parameters with CT measures of lung disease, respiratory morbidity, and mortality using regression analyses. There were significant correlations between FEV1/FVC with Parameter D (r = -0.83; p < 0.001), Transition Point (r = 0.69; p < 0.001), and Transition Distance (r = 0.50; p < 0.001). All metrics had significant associations with emphysema, small airway disease, dyspnea, and respiratory-quality of life (p < 0.001). The highest quartile for Parameter D was independently associated with all-cause mortality (adjusted HR 3.22,95% CI 2.42-4.27; p < 0.001) but a substantial number of participants in the highest quartile were categorized as GOLD 0 and 1 by traditional criteria (1.8% and 33.7%). Parameter D identified an additional 9.5% of participants with mild or non-recognized disease as abnormal with greater burden of structural lung disease compared with controls. The data points on the flow-volume and volume-time curves can be used to derive indices of airflow obstruction that identify additional subjects with disease who are deemed to be normal by traditional criteria.

Paratracheal Paraseptal Emphysema and Expiratory Central Airway Collapse in Smokers.

RATIONALE: Expiratory central airway collapse is associated with respiratory morbidity independent of underlying lung disease. However, not all smokers develop expiratory central airway collapse, and the etiology of expiratory central airway collapse in adult smokers is unclear. Paraseptal emphysema in the paratracheal location, by untethering airway walls, may predispose smokers to developing expiratory central airway collapse. OBJECTIVES: To evaluate whether paratracheal paraseptal emphysema is associated with expiratory central airway collapse. METHODS: We analyzed paired inspiratory and expiratory computed tomography scans from participants enrolled in a multicenter study (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease) of smokers aged 45 to 80 years. Expiratory central airway collapse was defined as greater than or equal to 50% reduction in cross-sectional area of the trachea during expiration. In a nested case-control design, participants with and without expiratory central airway collapse were included in a 1:2 fashion, and inspiratory scans were further analyzed using the Fleischner Society criteria for presence of centrilobular emphysema, paraseptal emphysema, airway wall thickening, and paratracheal paraseptal emphysema (maximal diameter ≥ 0.5 cm). RESULTS: A total of 1,320 patients were included, 440 with and 880 without expiratory central airway collapse. Those with expiratory central airway collapse were older, had higher body mass index, and were less likely to be men or current smokers. Paratracheal paraseptal emphysema was more frequent in those with expiratory central airway collapse than control subjects (16.6 vs. 11.8%; P = 0.016), and after adjustment for age, race, sex, body mass index, smoking pack-years, and forced expiratory volume in 1 second, paratracheal paraseptal emphysema was independently associated with expiratory central airway collapse (adjusted odds ratio, 1.53; 95% confidence interval, 1.18-1.98; P = 0.001). Furthermore, increasing size of paratracheal paraseptal emphysema (maximal diameter of at least 1 cm and 1.5 cm) was associated with greater odds of expiratory central airway collapse (adjusted odds ratio, 1.63; 95% confidence interval, 1.18-2.25; P = 0.003 and 1.77; 95% confidence interval, 1.19-2.64; P = 0.005, respectively). CONCLUSIONS: Paraseptal emphysema adjacent to the trachea is associated with expiratory central airway collapse. The identification of this risk factor on inspiratory scans should prompt further evaluation for expiratory central airway collapse. Clinical trial registered with ClinicalTrials.gov (NCT 00608764).

Association Between Expiratory Central Airway Collapse and Respiratory Outcomes Among Smokers.

IMPORTANCE: Central airway collapse greater than 50% of luminal area during exhalation (expiratory central airway collapse [ECAC]) is associated with cigarette smoking and chronic obstructive pulmonary disease (COPD). However, its prevalence and clinical significance are unknown. OBJECTIVE: To determine whether ECAC is associated with respiratory morbidity in smokers independent of underlying lung disease. DESIGN, SETTING, AND PARTICIPANTS: Analysis of paired inspiratory-expiratory computed tomography images from a large multicenter study (COPDGene) of current and former smokers from 21 clinical centers across the United States. Participants were enrolled from January 2008 to June 2011 and followed up longitudinally until October 2014. Images were initially screened using a quantitative method to detect at least a 30% reduction in minor axis tracheal diameter from inspiration to end-expiration. From this sample of screen-positive scans, cross-sectional area of the trachea was measured manually at 3 predetermined levels (aortic arch, carina, and bronchus intermedius) to confirm ECAC (>50% reduction in cross-sectional area). EXPOSURES: Expiratory central airway collapse. MAIN OUTCOMES AND MEASURES: The primary outcome was baseline respiratory quality of life (St George's Respiratory Questionnaire [SGRQ] scale 0 to 100; 100 represents worst health status; minimum clinically important difference [MCID], 4 units). Secondary outcomes were baseline measures of dyspnea (modified Medical Research Council [mMRC] scale 0 to 4; 4 represents worse dyspnea; MCID, 0.7 units), baseline 6-minute walk distance (MCID, 30 m), and exacerbation frequency (events per 100 person-years) on longitudinal follow-up. RESULTS: The study included 8820 participants with and without COPD (mean age, 59.7 [SD, 6.9] years; 4667 [56.7%] men; 4559 [51.7%] active smokers). The prevalence of ECAC was 5% (443 cases). Patients with ECAC compared with those without ECAC had worse SGRQ scores (30.9 vs 26.5 units; P < .001; absolute difference, 4.4 [95% CI, 2.2-6.6]) and mMRC scale scores (median, 2 [interquartile range [IQR], 0-3]) vs 1 [IQR, 0-3]; P < .001]), but no significant difference in 6-minute walk distance (399 vs 417 m; absolute difference, 18 m [95% CI, 6-30]; P = .30), after adjustment for age, sex, race, body mass index, forced expiratory volume in the first second, pack-years of smoking, and emphysema. On follow-up (median, 4.3 [IQR, 3.2-4.9] years), participants with ECAC had increased frequency of total exacerbations (58 vs 35 events per 100 person-years; incidence rate ratio [IRR], 1.49 [95% CI, 1.29-1.72]; P < .001) and severe exacerbations requiring hospitalization (17 vs 10 events per 100 person-years; IRR, 1.83 [95% CI, 1.51-2.21]; P < .001). CONCLUSIONS AND RELEVANCE: In a cross-sectional analysis of current and former smokers, the presence of ECAC was associated with worse respiratory quality of life. Further studies are needed to assess long-term associations with clinical outcomes.

Radiological correlates and clinical implications of the paradoxical lung function response to ß2 agonists: an observational study.

BACKGROUND: Bronchodilator response has been noted in a significant proportion of patients with chronic obstructive pulmonary disease (COPD). However, there are also reports of a paradoxical response to ß2 agonists resulting in bronchoconstriction. Asymptomatic bronchoconstriction is likely to be far more common than is symptomatic bronchoconstriction with ß2 agonists, but no systematic studies have been done. We assessed the prevalence of paradoxical response in current and former smokers with and without COPD, and its radiological correlates and clinical implications. METHODS: Non-Hispanic white and African-American patients (aged 45-80 years) from a large multicentre study COPDGene were classified into two groups on the basis of a paradoxical response, defined as at least a 12% and 200 mL reduction in forced expiratory volume in 1 sec (FEV1) or forced vital capacity (FVC), or both, after administration of a shortacting ß2 agonist (180 µg salbutamol). FINDINGS: Patients were recruited from January, 2008, to June, 2011. 9986 (96%) of 10,364 patients enrolled in the COPDGene study were included in the analysis population (mean age 59·6 years [SD 9·0]). Paradoxical response was noted in 453 (5%) of 9986 patients and the frequency was similar in patients with COPD (198 [4%] of 4439) and smokers without airflow obstruction (255 [5%] of 5547). Compared with white patients, a paradoxical response was twice as common in African-American patients (227 [7%] of 3282 vs 226 [3%] of 6704; p<0·0001). In the multivariate analyses, African-American ethnic origin (adjusted odds ratio 1·89, 95% CI 1·50-2·39; p<0·0001), less emphysema (0·96, 0·92-0·99; p=0·023), and increased wall-area percentage of the segmental airways (1·04, 1·01-1·08; p=0·023) were independently associated with a paradoxical response. A paradoxical response was independently associated with worse dyspnoea (adjusted ß for Modified Medical Research Council Dyspnoea Scale 0·12 [95% CI 0·00 to 0·24]; p=0·05), lower 6 min walk distance (-45·8 [-78·5 to -13·2]; p=0·006), higher Body Mass Index, Airflow Obstruction, Dyspnea, and Exercise Capacity (BODE) index (0·31 [0·19 to 0·43]; p<0·0001), and a greater frequency of severe exacerbations (increased by a factor of 1·35, 1·00-1·81; p=0·048). INTERPRETATION: Paradoxical response to ß2 agonists is associated with respiratory morbidity and is more common in African-Americans. These findings might have implications for the use of ß2agonists in some patients. FUNDING: National Institutes of Health.

FEV(1)/FEV(6) to diagnose airflow obstruction. Comparisons with computed tomography and morbidity indices.

RATIONALE: FVC is a difficult maneuver for many patients, and 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 have 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) that included current and former smokers (age 45-80 yr). 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: A total of 10,018 subjects were included. FEV1/FEV6 showed excellent accuracy in diagnosing airflow obstruction using FEV1/FVC < 0.70 as a reference (area under curve, 0.99; 95% confidence interval [CI], 0.989-0.992; P < 0.001). FEV1/FEV6 < 0.73 had the best sum of sensitivity (92.1%; 95% CI, 90.8-92.4) and specificity (97.3%; 95% CI, 97.3-98.1). There was excellent agreement between the two diagnostic cutoffs (κ = 0.90; 95% CI, 0.80-0.91; P < 0.001). In comparison with control subjects 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 a 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.

Relationships between airflow obstruction and quantitative CT measurements of emphysema, air trapping, and airways in subjects with and without chronic obstructive pulmonary disease.

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 (R2=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.

Oral food challenges in children with a diagnosis of food allergy.

OBJECTIVE: To assess the outcome of oral food challenges in patients placed on elimination diets based primarily on positive serum immunoglobulin E (IgE) immunoassay results. STUDY DESIGN: This is a retrospective chart review of 125 children aged 1-19 years (median age, 4 years) evaluated between January 2007 and August 2008 for IgE-mediated food allergy at National Jewish Health and who underwent an oral food challenge. Clinical history, prick skin test results, and serum allergen-specific IgE test results were obtained. RESULTS: The data were summarized for food avoidance and oral food challenge results. Depending on the reason for avoidance, 84%-93% of the foods being avoided were returned to the diet after an oral food challenge, indicating that the vast majority of foods that had been restricted could be tolerated at discharge. CONCLUSIONS: In the absence of anaphylaxis, the primary reliance on serum food-specific IgE testing to determine the need for a food elimination diet is not sufficient, especially in children with atopic dermatitis. In those circumstances, oral food challenges may be indicated to confirm food allergy status.

Mortality from pulmonary fibrosis increased in the United States from 1992 to 2003.

RATIONALE: From the late 1970s to the early 1990s, studies found that mortality rates for pulmonary fibrosis were increasing. Recent data for mortality from pulmonary fibrosis are unavailable. OBJECTIVES: We sought to determine mortality rates for pulmonary fibrosis in the United States from 1992 through 2003. METHODS: Using data from the National Center for Health Statistics, we calculated age-adjusted mortality rates from the deaths of persons with pulmonary fibrosis and stratified the data to determine differences in mortality rates by age, sex, race/ethnicity, and geography of the decedent. We developed a multivariable model to predict future mortality rates, and we determined the underlying cause of death in patients with pulmonary fibrosis. MEASUREMENTS AND MAIN RESULTS: From 1992 to 2003, there were 28,176,224 deaths in the United States and 175,088 decedents with pulmonary fibrosis. The average age- and sex-adjusted mortality rate was 50.8 per 1,000,000 people. The age-adjusted mortality rate increased 28.4% in men (from 40.2 deaths per 1,000,000 in 1992 to 61.9 deaths per 1,000,000 in 2003) and 41.3% in women (from 39.0 deaths per 1,000,000 in 1992 to 55.1 deaths per 1,000,000 in 2003). While increases were significant in both men and women (p < 0.0001), the rate of increase was higher in women (p < 0.0001). The most common cause of death in patients with pulmonary fibrosis was the disease itself. CONCLUSIONS: From 1992 to 2003, mortality rates for pulmonary fibrosis significantly increased. Further investigation is needed to determine the etiology of these trends, which are predicted to continue to increase.