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Background Hypersensitivity pneumonitis (HP) is an interstitial lung disease with a better prognosis, on average, than idiopathic pulmonary fibrosis (IPF). We compare survival time and pulmonary function trajectory in patients with HP and IPF by radiologic phenotype. Methods HP (n = 117) was diagnosed if surgical/transbronchial lung biopsy, BAL, and exposure history results suggested this diagnosis. IPF (n = 152) was clinically and histopathologically diagnosed. All participants had a baseline high-resolution CT (HRCT) scan and FVC % predicted. Three thoracic radiologists documented radiologic features. Survival time is from HRCT scan to death or lung transplant. Cox proportional hazards models identify variables associated with survival time. Linear mixed models compare post-HRCT scan FVC % predicted trajectories. Results Subjects were grouped by clinical diagnosis and three mutually exclusive radiologic phenotypes: honeycomb present, non-honeycomb fibrosis (traction bronchiectasis and reticulation) present, and nonfibrotic. Nonfibrotic HP had the longest event-free median survival (> 14.73 years) and improving FVC % predicted (1.92%; 95% CI, 0.49-3.35; P = .009). HP with non-honeycomb fibrosis had longer survival than IPF (> 7.95 vs 5.20 years), and both groups experienced a significant decline in FVC % predicted. Subjects with HP and IPF with honeycombing had poor survival (2.76 and 2.81 years, respectively) and significant decline in FVC % predicted. Conclusions Three prognostically distinct, radiologically defined phenotypes are identified among patients with HP. The importance of pursuing a specific diagnosis (eg, HP vs IPF) among patients with non-honeycomb fibrosis is highlighted. When radiologic honeycombing is present, invasive diagnostic testing directed at determining the diagnosis may be of limited value given a uniformly poor prognosis.

Hypersensitivity pneumonitis (HP) is an interstitial lung disease with a better prognosis, on average, than idiopathic pulmonary fibrosis (IPF). We compare survival time and pulmonary function trajectory in patients with HP and IPF by radiologic phenotype.HP (n = 117) was diagnosed if surgical/transbronchial lung biopsy, BAL, and exposure history results suggested this diagnosis. IPF (n = 152) was clinically and histopathologically diagnosed. All participants had a baseline high-resolution CT (HRCT) scan and FVC % predicted. Three thoracic radiologists documented radiologic features. Survival time is from HRCT scan to death or lung transplant. Cox proportional hazards models identify variables associated with survival time. Linear mixed models compare post-HRCT scan FVC % predicted trajectories.Subjects were grouped by clinical diagnosis and three mutually exclusive radiologic phenotypes: honeycomb present, non-honeycomb fibrosis (traction bronchiectasis and reticulation) present, and nonfibrotic. Nonfibrotic HP had the longest event-free median survival (14.73 years) and improving FVC % predicted (1.92%; 95% CI, 0.49-3.35; P = .009). HP with non-honeycomb fibrosis had longer survival than IPF (7.95 vs 5.20 years), and both groups experienced a significant decline in FVC % predicted. Subjects with HP and IPF with honeycombing had poor survival (2.76 and 2.81 years, respectively) and significant decline in FVC % predicted.Three prognostically distinct, radiologically defined phenotypes are identified among patients with HP. The importance of pursuing a specific diagnosis (eg, HP vs IPF) among patients with non-honeycomb fibrosis is highlighted. When radiologic honeycombing is present, invasive diagnostic testing directed at determining the diagnosis may be of limited value given a uniformly poor prognosis.

BACKGROUND The National Heart, Lung, and Blood Institute-sponsored IPF Clinical Research Network (IPFnet) studies enrolled subjects with idiopathic pulmonary fibrosis (IPF) to evaluate drug therapies in treatment trials. An adjudication committee (AC) provided a structured review of cases in which there was uncertainty or disagreement regarding diagnosis or clinical event classification. This article describes the diagnosis and adjudication processes. METHODS The diagnostic process was based on review of clinical data and high-resolution CT scans with central review of lung biopsies when available. The AC worked closely with the data coordinating center to obtain clinical, radiologic, and histologic data and to communicate with the clinical centers. The AC used a multidisciplinary discussion model with four clinicians, one radiologist, and one pathologist to adjudicate diagnosis and outcome measures. RESULTS The IPFnet trials screened 1,015 subjects; of these, 23 cases required review by the AC to establish eligibility. The most common diagnosis for exclusion was suspected chronic hypersensitivity pneumonitis. The AC reviewed 88 suspected acute exacerbations (AExs), 93 nonelective hospitalizations, and 16 cases of bleeding. Determination of AEx presented practical challenges to adjudicators, as necessary clinical data were often not collected, particularly when subjects were evaluated outside of the primary study site. CONCLUSIONS The IPFnet diagnostic process was generally efficient, but a multidisciplinary adjudication committee was critical to assure correct phenotype for study enrollment. The AC was key in adjudicating all adverse outcomes in two IPFnet studies terminated early because of safety issues. Future clinical trials in IPF should consider logistical and cost issues as they incorporate AExs and hospitalizations as outcome measures. TRIAL REGISTRY ClinicalTrials.gov; No.: NCT00517933, NCT00650091, NCT00957242; URL: www.clinicaltrials.gov

To determine whether intrathoracic fat volumes are associated with presence and chronicity of atrial fibrillation (AF) and radiofrequency ablation (RFA) treatment outcome. IRB approval was obtained and patient consent was waived for this HIPAA-compliant retrospective study. 169 patients with AF (75 non-paroxysmal and 94 paroxysmal) and 62 control patients underwent cardiac CT examination. Extrapericardial (EPFV) and epicardial fat volumes (EFV) were measured on CT, the sum of which is the total intrathoracic fat volume. Associations between these three fat volumes and presence and chronicity of AF, and outcome after RFA, were evaluated using logistic regression analysis. EFV was significantly associated with presence [OR 1.01 (95 % CI 1.003–1.03), p = 0.01], chronicity of AF [1.008 (1.001–1.020), p = 0.03] and AF recurrence after RFA [1.009 (1.001–1.01), p = 0.02] after adjustment for age, gender and BMI. Patients with a larger EFV had a shorter time to AF recurrence (p = 0.017) and a higher rate of recurrence (54 % vs 46 %) (p = 0.002) after RFA. EPFV had no significant associations. Increased epicardial fat is associated with the presence and chronicity of AF, a higher probability of AF recurrence after RFA and a shorter AF-free interval. • Increased epicardial fat is associated with presence and chronicity of atrial fibrillation • Extensive epicardial fat is associated with earlier recurrences of AF after ablation • Extensive epicardial fat may reduce transmurality of ablation by affecting current dynamics

Intrathoracic fat volume, more specifically, epicardial fat volume, is an emerging imaging biomarker of adverse cardiovascular events. The purpose of this work is to show the feasibility and reproducibility of intrathoracic fat volume measurement applied to contrast-enhanced multidetector computed tomography images. A retrospective cohort study of 62 subjects free of cardiovascular disease (55% females, age = 49 ± 11 years) conducted from 2008 to 2011 formed the study group. Intrathoracic fat volume was defined as all fat voxels measuring −50 to −250 Hounsfield Unit within the intrathoracic cavity from the level of the pulmonary artery bifurcation to the heart apex. The intrathoracic fat was separated into epicardial and extrapericardial fat by tracing the pericardium. The measurements were obtained by 2 readers and compared for interrater reproducibility. The fat volume measurements for the study group were 141 ± 72 cm3 for intrathoracic fat, 58 ± 27 cm3 for epicardial fat, and 84 ± 50 cm3 for extrapericardial fat. There was no statistically significant difference in intrathoracic fat volume measurements between the 2 readers, with correlation coefficients of 0.88 (P = .55) for intrathoracic fat volume and −0.12 (P = .33) for epicardial fat volume. Voxel-based measurement of intrathoracic fat, including the separation into epicardial and extrapericardial fat, is feasible and highly reproducible from multidetector computed tomography scans.

Background Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing lung disease of unknown etiology. Inter-society consensus guidelines on IPF diagnosis and management outline radiologic patterns including definite usual interstitial pneumonia (UIP), possible UIP, and inconsistent with UIP. We evaluate these diagnostic categories as prognostic markers among patients with IPF. Methods Included subjects had biopsy-proven UIP, a multidisciplinary team diagnosis of IPF, and a baseline high-resolution computed tomography (HRCT). Thoracic radiologists assigned the radiologic pattern and documented the presence and extent of specific radiologic findings. The outcome of interest was lung transplant-free survival. Results IPF patients with a possible UIP pattern on HRCT had significantly longer Kaplan-Meier event-free survival compared to those with definite UIP pattern (5.21 and 3.57 years, respectively, p = 0.002). In a multivariable Cox proportional hazards model adjusted for baseline age, gender, %-predicted FVC, and %-predicted DLCO via the GAP Stage, extent of fibrosis (via the traction bronchiectasis score) and ever-smoker status, possible UIP pattern on HRCT (versus definite UIP) was associated with reduced hazard of death or lung transplant (HR = 0.42, CI 95% 0.23–0.78, p = 0.006). Conclusions Radiologic diagnosis categories outlined by inter-society consensus guidelines is a widely-reported and potentially useful prognostic marker in IPF patients, with possible UIP pattern on HRCT associated with a favorable prognosis compared to definite UIP pattern, after adjusting for relevant covariates.

Rationale and Objectives To assess whether left atrial (LA) volume, function, and diameter as determined by multidetector computed tomography (MDCT) are associated with the presence and chronicity of atrial fibrillation (AF). Materials and Methods A total of 232 subjects, 156 with AF (43 with chronic and 113 with paroxysmal) and 76 normal subjects, formed the study population. AF subjects underwent MDCT of the pulmonary veins and LA, and normal subjects underwent coronary computed tomography (CT), on which LA volume, function, and diameter were measured. Associations between each MDCT LA parameter and presence and chronicity of AF were assessed using logistic regression analysis. Results The indexed LA maximum volume (odds ratio [OR] = 2.42; 95% confidence interval [CI], 1.43–4.08; P = .0009) was significantly associated with chronicity and presence of AF (OR = 1.06; 95% CI, 1.03–1.10; P = .0003) after adjustment for traditional risk factors. The LA function was associated with presence of AF (OR = 0.93; 95% CI, 0.89–0.97; P = .0005), but not with AF chronicity (OR = 1.12; 95% CI, 0.93–1.33; P = .21). Conclusions Decreased LA function is associated with presence of AF, and increased LA maximum volume is associated with presence and chronicity of AF, independent of traditional risk factors.

Introduction: Left ventricular (LV) and right ventricular (RV) volumetric and functional parameters are important biomarkers for morbidity and mortality in patients with heart failure. Purpose: To retrospectively determine reference mean values of LV and RV volume, function and mass normalised by age, gender and body surface area (BSA) from retrospectively electrocardiographically gated 64-slice cardiac computed tomography (CCT) by using automated analysis software in healthy adults. Materials and Methods: The study was approved by the institutional review board with a waiver of informed consent. Seventy-four healthy subjects (49% female, mean age 49.6 ± 11) free of hypertension and hypercholesterolaemia with a normal CCT formed the study population. Analyses of LV and RV volume (end-diastolic, end-systolic and stroke volumes), function (ejection fraction), LV mass and inter-rater reproducibility were performed with commercially available analysis software capable of automated contour detection. General linear model analysis was performed to assess statistical significance by age group after adjustment for gender and BSA. Bland–Altman analysis assessed the inter-rater agreement. Results: The reference range for LV and RV volume, function, and LV mass was normalised to age, gender and BSA. Statistically significant differences were noted between genders in both LV mass and RV volume (P-value < 0.0001). Age, in concert with gender, was associated with significant differences in RV end-diastolic volume and LV ejection fraction (P-values 0.027 and 0.03). Bland–Altman analysis showed acceptable limits of agreement (±1.5% for ejection fraction) without systematic error. Conclusion: LV and RV volume, function and mass normalised to age, gender and BSA can be reported from CCT datasets, providing additional information important for patient management.

The contribution of immune activation to accelerated HIV-disease progression in older individuals has not been delineated.Prospective multicenter cohort of older (≥45 years) and younger (18-30 years) HIV-infected adults initiating 192 weeks of antiretroviral therapy (ART). Longitudinal models of CD4 cell restoration examined associations with age-group, thymic volume, immune activation, and viral load.Forty-five older and 45 younger adults (median age 50 and 26 years, respectively) were studied. Older patients had fewer naive CD4 cells (P0.001) and higher HLA-DR/CD38 expression on CD4 (P=0.05) and CD8 cells (P=0.07) than younger patients at any time on ART. The rate of naive and total CD4 cell increase was similar between age groups, but older patients had a faster mean rate of B-cell increase (by +0.7 cells/week; P=0.01), to higher counts than healthy controls after 192 weeks (P=0.003). Naive CD4 increases from baseline were associated with immune activation reductions (as declines from baseline of %CD8 cells expressing HLA-DR/CD38; P0.0001), but these increases were attenuated in older patients, or in those with small thymuses. A 15% reduction in activation was associated with naive gains of 29.9 and 6.2 cells/μl in younger, versus older patients, or with gains of 25.7, 23.4, and 2.1 cells/μl in patients with the largest, intermediate, and smallest thymuses, respectively (P0.01 for interactions between activation reduction and age-group or thymic volume).Older patients had significant B-cell expansion, higher levels of immune activation markers, and significantly attenuated naive CD4 cell gains associated with activation reduction.

OBJECTIVE. The purpose of this study was to retrospectively determine CT-based normal reference values of left atrial volume, function, and diameter normalized by age, sex, and body surface area. MATERIALS AND METHODS. The study group consisted of 74 subjects with normal findings at ECG-gated coronary CT angiography performed with retrospective gating. Analy sis of left atrial volume (end-diastolic, end-systolic, and stroke volume) and function (ejection fraction) was performed with the Simpson method. Left atrial diameter was measured in the anteroposterior dimension. General linear model analysis was performed to model the data and assess statistical significance by age group after adjustment for sex and body surface area. RESULTS. The reference range for left atrial volume, function, and diameter was normalized (indexed) to age, sex, and body surface area in healthy subjects. A statistically signifi cant difference was noted between left atrial volume and age without adjustment for sex and body surface area, but no statistically significant difference was found after adjustment for these variables. Sex and body surface area had a significant influence on left atrial volume, function, and diameter. CONCLUSION. Left atrial volume, function, and diameter normalized to age, sex, and body surface area can be reported from CTA datasets and may provide information important for patient care.

Birt-Hogg-Dubé syndrome manifests in the thorax as lung cysts. The purpose of this article is to describe the CT characteristics of cysts in patients with Birt-Hogg-Dubé syndrome and to note other thoracic findings.The thoracic CT examinations of 17 patients with Birt-Hogg-Dubé syndrome were reviewed retrospectively for the presence, anatomic distribution (upper lung predominant, lower lung predominant, or diffuse), extent (size, number), and morphology (shape, wall thickness) of cysts. Any additional thoracic findings were also noted.The study population consisted of 13 women (76%) and four men (24%) with a mean age of 50.2 ±15.2 years. Two patients (12%) had normal findings on CT. Fifteen patients had cystic lung disease, all of whom had more than one cyst. Most patients had bilateral (13/15, 87%) and lower lung-predominant cysts (13/15, 87%). The cysts varied in size from 0.2 to 7.8 cm. The largest cysts were located in the lower lobes of 14 of 15 patients (93%). Of the nine patients with large cysts, most had at least one multiseptated cyst (7/9, 78%). Five of 15 patients (33%) had more than 20 cysts. Cyst shape varied among the 15 patients and also within individual patients (10/15, 67%) ranging from round to oval, lentiform, and multiseptated. Cysts showed no central or peripheral predominance.Discrete thin-walled cysts in patients with Birt-Hogg-Dubé syndrome are more numerous and larger in the lower lobes and vary in size and shape. Large lung cysts are frequently multiseptated. These features may aid in differentiating Birt-Hogg-Dubé syndrome from other more common cystic lung diseases.

The National Lung Screening Trial (NLST) is a randomized multicenter study comparing low-dose helical computed tomography (CT) with chest radiography in the screening of older current and former heavy smokers for early detection of lung cancer, which is the leading cause of cancer-related death in the United States. Five-year survival rates approach 70% with surgical resection of stage IA disease; however, more than 75% of individuals have incurable locally advanced or metastatic disease, the latter having a 5-year survival of less than 5%. It is plausible that treatment should be more effective and the likelihood of death decreased if asymptomatic lung cancer is detected through screening early enough in its preclinical phase. For these reasons, there is intense interest and intuitive appeal in lung cancer screening with low-dose CT. The use of survival as the determinant of screening effectiveness is, however, confounded by the well-described biases of lead time, length, and overdiagnosis. Despite previous attempts, no test has been shown to reduce lung cancer mortality, an endpoint that circumvents screening biases and provides a definitive measure of benefit when assessed in a randomized controlled trial that enables comparison of mortality rates between screened individuals and a control group that does not undergo the screening intervention of interest. The NLST is such a trial. The rationale for and design of the NLST are presented.

The composite physiologic index (CPI) was derived to represent the extent of fibrosis on high-resolution computed tomography (HRCT), adjusting for emphysema in patients with idiopathic pulmonary fibrosis (IPF). We hypothesised that longitudinal change in CPI would better predict mortality than forced expiratory volume in 1 s (FEV(1)), forced vital capacity (FVC) or diffusing capacity of the lung for carbon monoxide (D(L,CO)) in all patients with IPF, and especially in those with combined pulmonary fibrosis and emphysema (CPFE). Cox proportional hazard models were performed on pulmonary function data from IPF patients at baseline (n = 321), 6 months (n = 211) and 12 months (n = 144). Presence of CPFE was determined by HRCT. A five-point increase in CPI over 12 months predicted subsequent mortality (HR 2.1, p = 0.004). At 12 months, a 10% relative decline in FVC, a 15% relative decline in D(L,CO) or an absolute increase in CPI of five points all discriminated median survival by 2.1 to 2.2 yrs versus patients with lesser change. Half our cohort had CPFE. In patients with moderate/severe emphysema, only a 10% decline in FEV(1) predicted mortality (HR 3.7, p = 0.046). In IPF, a five-point increase in CPI over 12 months predicts mortality similarly to relative declines of 10% in FVC or 15% in D(L,CO). For CPFE patients, change in FEV(1) was the best predictor of mortality.

The purpose of this study was to use volumetric, 1.25 mm collimation MDCT read as softcopy and using a 2D and 3D viewer tool, to establish the frequency of normal and accessory fissures, the continuity of the fissures, whether the fissures are visible as a thin line, a hypovascular region, or both, and also to establish the interobserver agreement of readers. 150 consecutive MDCT examinations were retrospectively assessed. Interobserver agreement for each of these fissures was evaluated using the Kappa statistic. All subjects had a right and a left major fissure. 96.7% of subjects also had a right minor fissure. 40% had an accessory fissure, the most common, the left minor in 16% of subjects. Most of the three usual fissures were continuous, whereas fewer than half of accessory fissures were continuous. The majority (54–100%) of normal and accessory fissures were visualized as a thin line. There was substantial to excellent interobserver agreement on the presence or absence of fissures their continuity (k = 0.96), and fair to excellent agreement on fissure morphology (k = 0.37–1.0). The prevalence of fissures on MDCT, equivalent to autopsy studies, visualizing fissures as a thin line and high interobserver agreement is probably due to the high sensitivity of MDCT, secondary to thin-section volumetric imaging.

High-resolution computed tomography (HRCT) may be useful for diagnosing hypersensitivity pneumonitis. Here, we develop and validate a radiological diagnosis model and model-based points score.Patients with interstitial lung disease seen at the University of Michigan Health System (derivation cohort) or enrolling in the Lung Tissue Research Consortium (validation cohort) were included. A thin-section, inspiratory HRCT scan was required. Thoracic radiologists documented radiological features.The derivation cohort comprised 356 subjects (33.9% hypersensitivity pneumonitis) and the validation cohort comprised 424 subjects (15.5% hypersensitivity pneumonitis). An age-, sex- and smoking status-adjusted logistic regression model identified extent of mosaic attenuation or air trapping greater than that of reticulation ("MA-ATReticulation"; OR 6.20, 95% CI 3.53-10.90; p0.0001) and diffuse axial disease distribution (OR 2.33, 95% CI 1.31-4.16; p=0.004) as hypersensitivity pneumonitis predictors (area under the receiver operating characteristic curve 0.814). A model-based score2 (1 point for axial distribution, 2 points for "MA-ATReticulation") has specificity 90% and positive predictive value (PPV) 74% in the derivation cohort and specificity 96% and PPV 44% in the validation cohort. Similar model performance is seen with population restriction to those reporting no exposure (score2: specificity 91%).When radiological mosaic attenuation or air trapping are more extensive than reticulation and disease has diffuse axial distribution, hypersensitivity pneumonitis specificity is high and false diagnosis risk low (10%), but PPV is diminished in a low-prevalence setting.

The purpose of this study was to evaluate the agreement between axial, multiplanar reformatted (MPR) and semi-automated software measurements of pulmonary vein ostial diameters and distance to the first bifurcation. CT examinations of the thorax were retrospectively reviewed in 150 consecutive patients. The pulmonary vein ostial diameter and distance to the first bifurcation of the four main pulmonary veins were independently measured. The three measurement methods were compared using a Bland-Altman test. There was no significant variation between pulmonary vein ostial diameter measurements for the superior pulmonary veins across the three measurement methods. There was significant variation between the semi-automated program and both the axial (p=0.001) and MPR (p

Rationale: Idiopathic pulmonary fibrosis (IPF) is characterized by progressive dyspnea, impaired gas exchange, and ultimate mortality. Objectives: To test the hypothesis that maximal oxygen uptake during cardiopulmonary exercise testing at baseline and with short-term longitudinal measures would predict mortality in patients with idiopathic pulmonary fibrosis. Methods: Data from 117 patients with IPF and longitudinal cardiopulmonary exercise tests were examined retrospectively. Survival was calculated from the date of the first cardiopulmonary exercise test. Measurements and Main Results: Patients with baseline maximal oxygen uptake less than 8.3 ml/kg/min had an increased risk of death (n = 8; hazard ratio, 3.24; 95% confidence interval, 1.10–9.56; P = 0.03) after adjusting for age, gender, smoking status, baseline forced vital capacity, and baseline diffusion capacity for carbon monoxide. We were unable to define a unit change in maximal oxygen uptake that predicted survival in our cohort. Conclusions: We conclude that a threshold maximal oxygen uptake of 8.3 ml/kg/min during cardiopulmonary exercise testing at baseline adds prognostic information for patients with IPF.

In idiopathic pulmonary fibrosis, incidence is higher in males, and females may have better survival. The aim of the present study was to determine whether the rate of increase in desaturation during serial 6-min walk testing would be greater, and survival worse, for males versus females. Serial changes in the percentage of maximum desaturation area (DA) over 1 yr were estimated using mixed models in 215 patients. DA was defined as the total area above the curve created using desaturation percentage values observed during each minute of the 6-min walk test. Multivariate Cox regression assessed survival differences. Adjusting for baseline DA, 6-min walk distance, change in 6-min walk distance over time and smoking history, the percentage of maximum DA increased by an average of 2.83 and 1.37% per month for males and females, respectively. Females demonstrated better survival overall, which was more pronounced in patients who did not desaturate below 88% on ambulation at baseline and after additionally adjusting for 6-month relative changes in DA and forced vital capacity. These data suggest that differences in disease progression contribute to, but do not completely explain, better survival of females with idiopathic pulmonary fibrosis.

Treatment and prognoses of diffuse parenchymal lung diseases (DPLDs) varies by diagnosis. Obtaining a uniform diagnosis among observers is difficult.Evaluate diagnostic agreement between academic and community-based physicians for patients with DPLDs, and determine if an interactive approach between clinicians, radiologists, and pathologists improved diagnostic agreement in community and academic centers.Retrospective review of 39 patients with DPLD. A total of 19 participants reviewed cases at 2 community locations and 1 academic location. Information from the history, physical examination, pulmonary function testing, high-resolution computed tomography, and surgical lung biopsy was collected. Data were presented in the same sequential fashion to three groups of physicians on separate days.Each observer's diagnosis was coded into one of eight categories. A kappa statistic allowing for multiple raters was used to assess agreement in diagnosis. Interactions between clinicians, radiologists, and pathologists improved interobserver agreement at both community and academic sites; however, final agreement was better within academic centers (kappa = 0.55-0.71) than within community centers (kappa = 0.32-0.44). Clinically significant disagreement was present between academic and community-based physicians (kappa = 0.11-0.56). Community physicians were more likely to assign a final diagnosis of idiopathic pulmonary fibrosis compared with academic physicians.Significant disagreement exists in the diagnosis of DPLD between physicians based in communities compared with those in academic centers. Wherever possible, patients should be referred to centers with expertise in diffuse parenchymal lung disorders to help clarify the diagnosis and provide suggestions regarding treatment options.

To evaluate the prevalence of thoracic lymph node enlargement (LNE) in usual (UIP) and nonspecific (NSIP) interstitial pneumonitis, change in LNE over time, and if LNE is related to disease activity.High-resolution CT scans (HRCT) in 20 patients each with UIP and NSIP were retrospectively reviewed. Two HRCT scans were reviewed for each patient, at diagnosis and a mean of 1 +/- 0.7 years later. Two thoracic radiologists independently recorded the location and size of thoracic lymph nodes (LNs)10-mm in short-axis diameter, using the American Thoracic Society lymph node mapping scheme. HRCT disease severity was scored for ground glass opacity and fibrosis. The number and size of enlarged LN stations were compared with HRCT scores.LNE was found on 44 HRCT examinations (21 baseline prevalence 52.5%, 23 follow-up, prevalence 57.5%), most common in the low right paratracheal (38%) and subcarinal (36%) regions. There was no significant difference in LN size or number of enlarged LN stations between baseline and follow-up CT. LNE prevalence was not different on baseline CT (P = 0.34) follow-up CT (P = 0.11) between UIP and NSIP patients. The mean size of the largest enlarged LN was 1.36 cm (1 to 2.1 cm) at baseline and 1.43 cm (1 to 1.9 cm) on follow-up CT. Mean CT ground glass and fibrosis scores were 1.98 and 1.6 when LNE was present, and 1.34 and 1.03 when absent (P = 0.008 and 0.003, respectively). The number and maximum size of enlarged LNs did not correlate with CT ground glass or fibrosis scores. Five patients who developed LNE between baseline and follow-up CT examinations had a greater increase in CT fibrosis scores than patients whose LNE status did not change (P = 0.004); CT ground glass scores were not significantly different. There was a trend for UIP patients to progress from absence of LNE to presence of LNE (4/20 patients or 20%).Intrathoracic LNE is common in both UIP and NSIP, and becomes increasingly prevalent in UIP patients over time. LNE is more prevalent with more severe lung disease. An increase in LNE over time is associated with the progression of fibrosis, and should not raise concern for co-existing infection or malignancy, in the absence of other clinical findings that would suggest this.

Rationale and Hypothesis: Idiopathic pulmonary fibrosis is a fatal disease with a variable rate of progression. We hypothesized that changes in distance walked and quantity of desaturation during a six-minute-walk test (6MWT) would add prognostic information to changes in FVC or diffusing capacity for carbon monoxide. Methods:Onehundredninety-sevenpatientswithidiopathicpulmonary fibrosis were evaluated. Desaturation during the 6MWT was associated with increased mortality even if a threshold of 88% was not reached. Baseline walk distance predicted subsequent walk distance but was not a reliable predictor of subsequent mortality in multivariate survival models. The predictive ability of serial changes in physiology varied when patients were stratified by the presence/absence of desaturation 88% during a baseline 6MWT. For patients with a baseline saturation 88% during a 6MWT, the strongest observed predictor of mortality was serial change in diffusing capacity for carbon monoxide. For patients with saturation 88% during their baseline walk test, serial decreases in FVC and increases in desaturation area significantly predicted subsequentmortality,whereas decreasesinwalk distanceandindiffusing capacity for carbon monoxide displayed less consistent statistical evidence of increasing mortality in our patients. Conclusion: These data highlight the importance of stratifying patients by degree of desaturation during a 6MWT before attributing prognostic value to serial changes in other physiologic variables.

(CHEST 2005; 127:1433–1436) A 70-year-old man presented with progressive mild dyspnea on exertion, cough, and low-grade fevers. He had a long history of atrial fibrillation, recurrent despite multiple cardioversions, and antiarrhythmics, and was currently rate controlled with amiodarone, 200 mg po tid. He also had a history of coronary artery disease documented by coronary angiography, asthma, and prior transurethral resection of prostate for benign prostatic hyperplasia. He was a lifelong nonsmoker with no occupational exposures. Physical examination revealed an elderly man in no acute distress. Heart rate was 82 beats/min, BP was 150/80 mm Hg, respiratory rate was 16 breaths/ min, and temperature was 37.1°C. Auscultation of the chest revealed mildly diminished breath sounds with otherwise normal lungs. The remainder of the physical examination was normal. Laboratory data were unremarkable, with a normal CBC, serum chemistry and liver function test results, and erythrocyte sedimentation rate. The chest radiograph (not shown) demonstrated a hazy mass at the peripheral aspect of the right lung base. The cardiac size was normal. CT scan of the thorax revealed subcarinal lymph node enlargement (Fig 1) and masses in the left upper, left lower, right lower, and right middle lobes (Fig 2), each approximately 1 cm in size. There was focal ground-glass opacity in the azygoesophageal recess (Fig 3). At bronchoscopy, there was no evidence of endobronchial lesions. Bronchial washings were negative for acid-fast bacilli and fungi, with rare atypical keratinizing squamous cells.

Objective To compare disease progression and mortality between idiopathic interstitial pneumonia (IIP) and interstitial lung disease (ILD) due to connective tissue diseases (CTD) including scleroderma, rheumatoid arthritis, systemic lupus, polymyositis, dermatomyositis, Sjogren's syndrome, and mixed CTD. Methods A case-control study of patients with CTD-ILD (n = 46) and IIP controls (n = 51), seen at the University of Michigan between July 1,1998 and June 30,1999 and followed until March 30, 2002, was conducted. Survival analysis and Cox regression were performed to estimate survival, accounting for demographic and clinical parameters, including pulmonary function tests and high resolution computed tomography (HRCT) diagnosis and scoring. Results Median followup time was 4.4 person-years. Five-year survival in the IIP group was 51.9% (95% confidence interval [95% CI] 30.8–69.4) versus 43.4% (95% CI 21.1–63.9) in the CTD-ILD group. There were no significant differences among HRCT diagnostic categories between IIP and CTD-ILD. A fibrotic score ≥2 was associated with decreased survival among the entire group. Age at diagnosis and most recent forced vital capacity were significant predictors of mortality when adjusted for IIP versus CTD-ILD diagnosis, sex, and interstitial score. Conclusion Contrary to expectation, CTD-ILD compared with IIP appears to be associated with a worse prognosis when adjusted for age. A higher fibrotic score is suggestive of decreased survival.

Current guidelines recommend that the clinician, radiologist, and pathologist work together to establish a diagnosis of idiopathic interstitial pneumonia. Three clinicians, two radiologists, and two pathologists reviewed 58 consecutive cases of suspected idiopathic interstitial pneumonia. Each participant was provided information in a sequential manner and was asked to record their diagnostic impression and level of confidence at each step. Interobserver agreement improved from the beginning to the end of the review. After the presentation of histopathologic information, radiologists changed their diagnostic impression more often than did clinicians. In general, as more information was provided the confidence level for a given diagnosis improved, and the diagnoses rendered with a high level of confidence were more likely congruent with the final pathologic consensus diagnosis. The final consensus pathologist diagnosis was idiopathic pulmonary fibrosis in 30 cases. Clinicians identified 75% and radiologists identified 48% of these cases before presentation of the histopathologic information. Histopathologic information has the greatest impact on the final diagnosis, especially when the initial clinical/radiographic diagnosis is not idiopathic pulmonary fibrosis. We conclude that dynamic interactions between clinicians, radiologists, and pathologists improve interobserver agreement and diagnostic confidence.

Highly active antiretroviral therapy (HAART) initiated in advanced HIV disease is associated with CD4 lymphocyte increases (200-300 cells/ mm 3 after 2-4 years), although longer-term cellular dynamics have not been studied. We observed a significant median CD4 lymphocyte increase of 126 cells/mm 3 and 54 naive CD4 lymphocytes from year 3 to 6 of HAART among 20 individuals with pre-HAART CD4 cell counts of 100-300 cells/mm 3 . This cohort represents the longest prospective immunological follow-up of virologically suppressed patients on HAART.

Chemokines are increased and may exert effects on both inflammatory and remodeling events in idiopathic pulmonary pneumonia (IIP). Accordingly, we examined the concomitant expression of inflammatory CC chemotactic cytokines or chemokines and their corresponding receptors in surgical lung biopsies obtained at the time of disease diagnosis and pulmonary fibroblasts grown from these biopsies. By gene array analysis, upper and lower lobe biopsies and primary fibroblast lines from patients with usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia, and respiratory bronchiolitis-interstitial lung disease, but not patients without IIP, exhibited CCL7 gene expression. TAQMAN, immunohistochemical, and ELISA analyses confirmed that CCL7 was expressed at significantly higher levels in UIP lung biopsies compared with biopsies from patients with nonspecific interstitial pneumonia, respiratory bronchiolitis-interstitial lung disease, and from patients without IIP. Higher levels of CCL7 were present in cultures of IIP fibroblasts compared with non-IIP fibroblasts, and CCL5, a CCR5 agonist, significantly increased the synthesis of CCL7 by UIP fibroblasts. Together, these data suggest that CCL7 is highly expressed in biopsies and pulmonary fibroblast lines obtained from patients with UIP relative to patients with other IIP and patients without IIP, and that this CC chemokine may have a major role in the progression of fibrosis in this IIP patient group.

Background: Some idiopathic interstitial pneumonias (IIPs) are characterised by fibroproliferation and deposition of extracellular matrix. Because efficacious treatment options are limited, research has been directed towards understanding the cytokine networks that may affect fibroblast activation and, hence, the progression of certain IIPs. Aims: To examine the expression of interleukin 4 (IL-4), IL-13, and their corresponding receptor subunits in the various forms of IIP and normal patient groups. Methods: Molecular and immunohistochemical analysis of IL-4, interferon γ (IFNγ), IL-13, IL-4 receptor (IL-R), and IL-13 receptor subunits in surgical lung biopsies (SLBs) from 39 patients (21 usual interstitial pneumonia (UIP), six non-specific interstitial pneumonia (NSIP), eight respiratory bronchiolitic interstitial lung disease (RBILD), and five normal controls). Results: Molecular analysis demonstrated that IL-13Rα2, IL-13Rα1, and IL-4Rα were present in a greater proportion of upper and lower lobe biopsies from patients with UIP than patients with NSIP and RBILD. Immunohistochemical analysis of patients with UIP, NSIP, and RBILD revealed interstitial staining for all three receptor subunits, whereas such staining was only seen in mononuclear cells present in normal SLBs. Fibroblastic foci in patients with UIP strongly stained for IL-4Rα and IL-13Rα2. Localised expression of IL-4Rα was also seen in SLBs from patients with NSIP but not in other groups. Conclusion: Some histological subtypes of IIP are associated with increased pulmonary expression of receptor subunits responsive to IL-4 and IL-13. These findings may be of particular importance in understanding the pathogenesis of IIP and, more importantly, may provide important novel therapeutic targets.

Exercise-induced hypoxia is an index of the severity of interstitial lung disease. We hypothesized that desaturation during a 6-minute walk test would predict mortality for patients with usual interstitial pneumonia (n = 83) and nonspecific interstitial pneumonia (n = 22). Consecutive patients with biopsy-proven disease performed a 6-minute walk test between January 1996 and December 2001. Desaturation was defined as a fall in oxygen saturation to 88% or less during the 6-minute walk test. Desaturation was common (44 of 83 usual interstitial pneumonia and 8 of 22 nonspecific interstitial pneumonia; chi square, p = 0.39). Patients with usual interstitial pneumonia or nonspecific interstitial pneumonia who desaturated had a significantly higher mortality than patients who did not desaturate (respective log-rank tests, p = 0.0018, p = 0.0089). In patients with usual interstitial pneumonia, the presence of desaturation was associated with an increased hazard of death (hazard ratio, 4.2; 95% confidence interval, 1.40, 12.56; p = 0.01) after adjusting for age, sex, smoking, baseline diffusion capacity for carbon monoxide, FVC, and resting saturation. We conclude that knowledge of desaturation during a 6-minute walk test adds prognostic information for patients with usual interstitial pneumonia and nonspecific interstitial pneumonia.

Idiopathic interstitial pneumonias are a diverse group of lung diseases with varied prognoses. We hypothesized that changes in physiologic and radiographic parameters would predict survival. We retrospectively examined 80 patients with usual interstitial pneumonia and 29 patients with nonspecific interstitial pneumonia. Baseline characteristics were examined together with 6-month change in forced vital capacity, diffusing capacity for carbon monoxide, and ground glass infiltrate and fibrosis on high resolution computed tomography. Patients with usual interstitial pneumonia were more likely to have a statistically significant or marginally significant decline in lung volume, diffusing capacity for carbon monoxide, and an increase in ground glass infiltrates (por = 0.08) compared with patients with nonspecific interstitial pneumonia. For patients with usual interstitial pneumonia, change in forced vital capacity was the best physiologic predictor of mortality (p = 0.05). In a multivariate Cox proportional hazards model controlling for histopathologic diagnosis, gender, smoking history, baseline forced vital capacity, and 6-month change in forced vital capacity, a decrease in forced vital capacity remained an independent risk factor for mortality (decrease10%; hazard ratio 2.47; 95% confidence interval 1.29, 4.73; p = 0.006). We conclude that a 6-month change in forced vital capacity gives additional prognostic information to baseline features for patients with idiopathic interstitial pneumonia.

Older age is a strong predictor of accelerated human immunodeficiency virus (HIV) disease progression. We investigated the possible immunologic basis of this interaction by comparing older (>/=45 years) and younger (

A histologic feature of usual interstitial pneumonia is the presence of fibroblastic foci. As some patients with usual interstitial pneumonia and an underlying collagen vascular disease have a better prognosis, we hypothesized that they would have fewer fibroblastic foci. Pathologists reviewed surgical lung biopsies from 108 patients with usual interstitial pneumonia (nine with collagen vascular disease) and assigned a score (absent 0, mild 1, moderate 2, and marked 3) for fibroblastic foci. Patients with idiopathic usual interstitial pneumonia had a higher median profusion of fibroblastic foci (1.75 vs. 1.0, p = 0.003). Baseline characteristics were similar, although patients with a collagen vascular disease were younger, had a shorter duration of symptoms, and had a higher percentage of predicted total lung capacity. Profusion of fibroblastic foci was the most discriminative feature for separating idiopathic from collagen vascular disease-associated usual interstitial pneumonia (odds ratio 8.31; 95% confidence interval, 1.98, 59.42; p = 0.002 for a one-unit increase in fibroblastic foci score). No deaths were noted in the collagen vascular disease-associated usual interstitial pneumonia group; 52 deaths occurred in the idiopathic usual interstitial pneumonia group (log rank; p = 0.005). We conclude that patients with collagen vascular disease-associated usual interstitial pneumonia have fewer fibroblastic foci and improved survival.

Background: High resolution computed tomography (HRCT) has an important diagnostic role in idiopathic interstitial pneumonia (IIP). We hypothesised that the HRCT appearance would have an impact on survival in patients with IIP. Methods: HRCT scans from patients with histological usual interstitial pneumonia (UIP; n=73) or histological non-specific interstitial pneumonia (NSIP; n=23) were characterised as definite UIP, probable UIP, indeterminate, probable NSIP, or definite NSIP. Cox regression analysis examined the relationships between histopathological and radiological diagnoses and mortality, controlling for patient age, sex, and smoking status. Results: All 27 patients with definite or probable UIP on HRCT had histological UIP; 18 of 44 patients with probable or definite NSIP on HRCT had histological NSIP. Patients with HRCT diagnosed definite or probable UIP had a shorter survival than those with indeterminate CT (hazards ratio (HR) 2.43, 95% CI 1.06 to 5.58; median survival 2.08 v 5.76 years) or HRCT diagnosed definite or probable NSIP (HR 3.47, 95% CI 1.58 to 7.63; median survival 2.08 v 5.81 years). Patients with histological UIP with no HRCT diagnosis of probable or definite UIP fared better than patients with histological UIP and an HRCT diagnosis of definite or probable UIP (HR 0.49, 95% CI 0.25 to 0.98; median survival 5.76 v 2.08 years) and worse than those with a histological diagnosis of NSIP (HR 5.42, 95% CI 1.25 to 23.5; median survival 5.76 v >9 years). Conclusions: Patients with a typical HRCT appearance of UIP experience the highest mortality. A surgical lung biopsy is indicated for patients without an HRCT appearance of UIP to differentiate between histological UIP and NSIP.

Poor CD4 lymphocyte recovery on antiretroviral therapy (ART) is associated with reduced function of the thymus. Palifermin (keratinocyte growth factor), by providing support to the thymic epithelium, promotes lymphopoiesis in animal models of bone marrow transplantation and graft-versus-host disease.In AIDS Clinical Trials Group A5212, a randomized, double-blind, placebo-controlled study, 99 HIV-infected patients on ART with plasma HIV-1 RNA levels ≤200 copies per milliliter for ≥6 months and CD4 lymphocyte counts200 cells per cubic milliliter were randomized 1:1:1:1 to receive once daily intravenous administration of placebo or 20, 40, or 60 μg/kg of palifermin on 3 consecutive days.The median change in the CD4 T-cell count from baseline to week 12 was not significantly different between the placebo arm [15 (-16, 23) cells/mm] and the 20-μg/kg dose [11 (2, 32) cells/mm], the 40-μg/kg dose [12 (-2, 25) cells/mm], or the 60-μg/kg dose arm [8 (-13, 35) cells/mm] of palifermin. No significant changes were observed in thymus size or in the number of naive T cells or recent thymic emigrants.Palifermin in the doses studied was not effective in improving thymic function and did not raise CD4 lymphocyte counts in HIV-infected patients with low CD4 cell counts despite virologically effective ART.

Rationale and Objectives The purpose of this study was to determine relative rates of missed diagnoses for radiologists as a measure of competence in interpreting chest radiographs. Materials and Methods Cases involving differing interpretations of chest radiographs were collected from January 1994 through December 1999 by faculty (chest and nonchest radiology specialists) in an academic radiology department. A quarterly peer-review process designated cases months after the fact, and anonymously, as no miss or as class I (nondiagnosable), class II (very difficult diagnosis), class III (should be diagnosed most of time), or class IV (should almost always be diagnosed) missed diagnoses. The rates and classes of missed diagnoses were compared among chest faculty and for the nonchest radiology specialists as a group. Results Chest radiologists read 184,977 studies, and nonchest radiologists read 300,684 studies. Of these, 243 missed diagnoses were classified (classes I and II, 184 cases; class III, 50; and class IV, nine). No difference was detected in the rate of class III and IV misses among chest faculty, but nonchest faculty had significantly more class III ( P = .022) and class IV misses ( P = .016). Conclusion Random sampling of differing interpretations can yield a relative rate of missed diagnoses for radiologists. No difference was detected in clinically important misses (ie, classes III and IV) among chest radiologists, but a statistically significantly higher rate of seemingly obvious misdiagnoses was found for nonchest specialty radiologists. Potential biases may have influenced this analysis, including disease prevalence, sampling, clinical factors, observer variability, and truth-in-diagnosis.

Purpose We evaluated the risk and potential benefit of high-dose corticosteroid therapy in patients with idiopathic pulmonary fibrosis. Subjects and methods We prospectively studied 41 patients with previously untreated, biopsy-proven idiopathic pulmonary fibrosis. Before treatment, we calculated clinical, radiographic, and physiologic severity-of-illness scores for each patient. We scored high-resolution computerized tomographic (CT) scans for ground glass and interstitial opacity. We determined the extent of cellular infiltration, interstitial fibrosis, desquamation, and granulation in open lung biopsy samples. Patients were monitored monthly for steroid-related side effects, response to therapy at 3 months, and mortality. Results All patients experienced at least one steroid-induced side effect. Eleven (27%) patients were nonresponders, 11 (27%) were responders, and 19 (46%) remained stable. Of the 19 patients who died during a mean (+/- SD) follow-up of 3.3 +/- 2.3 years, 8 (42%) lost weight during the initial 3 months of steroid therapy; only 3 (14%) of the 22 patients still living (P = 0.08) experienced weight loss. In a multivariate analysis, greater fibrosis (hazard ratio [HR] = 1.4 per unit increase; 95% confidence interval [CI]: 1.0 to 1.9; P = 0.03) and cellularity (RR = 1.9 per unit increase; 95% CI: 1.3 to 2.8; 3, P Conclusion Corticosteroid treatment for idiopathic pulmonary fibrosis is associated with substantial morbidity. Patients who remain stable or respond to corticosteroid therapy have better survival than those who fail to respond. Whether this difference reflects an effect of treatment or less severe disease can be determined only in a randomized trial.

Left ventricular (LV) and right ventricular (RV) volumetric and functional parameters are important biomarkers for morbidity and mortality in patients with heart failure.To retrospectively determine reference mean values of LV and RV volume, function and mass normalised by age, gender and body surface area (BSA) from retrospectively electrocardiographically gated 64-slice cardiac computed tomography (CCT) by using automated analysis software in healthy adults.The study was approved by the institutional review board with a waiver of informed consent. Seventy-four healthy subjects (49% female, mean age 49.6 ± 11) free of hypertension and hypercholesterolaemia with a normal CCT formed the study population. Analyses of LV and RV volume (end-diastolic, end-systolic and stroke volumes), function (ejection fraction), LV mass and inter-rater reproducibility were performed with commercially available analysis software capable of automated contour detection. General linear model analysis was performed to assess statistical significance by age group after adjustment for gender and BSA. Bland-Altman analysis assessed the inter-rater agreement.The reference range for LV and RV volume, function, and LV mass was normalised to age, gender and BSA. Statistically significant differences were noted between genders in both LV mass and RV volume (P-value 0.0001). Age, in concert with gender, was associated with significant differences in RV end-diastolic volume and LV ejection fraction (P-values 0.027 and 0.03). Bland-Altman analysis showed acceptable limits of agreement (±1.5% for ejection fraction) without systematic error.LV and RV volume, function and mass normalised to age, gender and BSA can be reported from CCT datasets, providing additional information important for patient management.

Human immunodeficiency virus (HIV) infection is associated with progressive loss of circulating CD4 + lymphocytes. Treatment with highly active antiretroviral therapy (HAART) has led to increases in CD4 + T lymphocytes of naive (CD45RA + 62L + ) and memory (CD45R0 + RA - ) phenotypes. Thymic computerized tomography scans were obtained on 30 individuals with HIV disease to investigate the role of the thymus in cellular restoration after 48 weeks of HAART. Individuals with abundant thymic tissue had higher naive CD4 + T lymphocyte counts at weeks 2-24 after therapy than individuals with minimal thymic tissue. Individuals with abundant thymic tissue had significantly larger increases in naive CD4 + cells during the first 4 weeks of therapy. These individuals were also more likely to experience viral rebound despite comparable initial declines in plasma HIV-1 RNA. These findings suggest that there is a complex relationship among the thymus, viral replication, and lymphocyte restoration after application of HAART in HIV disease.

The thymus in adults infected with the HIV-1 is generally thought to be inactive, both because of age-related involution and viral destruction. We have revisited the question of thymic function in adults, using chest-computed tomography (CT) to measure thymic tissue in HIV-1-seropositive (n = 99) or HIV-1-seronegative (n = 32) subjects, and correlating these results with the level of circulating CD4(+) and CD8(+) T cells that are phenotypically described as naive thymic emigrants. Abundant thymic tissue was detectable in many (47/99) HIV-1-seropositive adults, aged 20-59. Independent of age, radiographic demonstration of thymic tissue was significantly associated with both a higher CD4(+) T cell count (P = 0.02) and a higher percentage and absolute number of circulating naive (CD45RA+CD62L+) CD4(+) T cells (P 40 yr) regardless of CD4 count (P = 0.03). These studies suggest that the thymus is functional in some but not all adults with HIV-1 disease.

Because CT protocols for staging lung cancer vary and little information exists regarding the diagnostic importance of using i.v. contrast material, our intent was to evaluate intra- and interobserver agreement in the detection of enlarged mediastinal lymph nodes, comparing i.v. contrast-enhanced and unenhanced CT.Fifty patients with known or suspected bronchogenic carcinoma underwent unenhanced thoracic CT followed by contrast-enhanced CT. Three observers noted enlarged lymph nodes (10 mm in the short axis) and assigned the enlarged nodes to American Thoracic Society nodal station designations. Enlarged lymph nodes were grouped two ways: by assigning the exact number of enlarged lymph nodes found (zero, one, two, three, four or more), and by assigning whether at least one, or no, enlarged mediastinal lymph nodes were found at a station ("one or none"). Agreement levels were determined for inter- and intraobserver interpretations using weighted kappa statistics and the McNemar test.The number of enlarged lymph nodes with enhanced CT was 11% higher than on unenhanced studies (418 versus 377; p = .044). Numbers of enlarged lymph nodes were different for five stations; however, the numbers were small except for the right upper paratracheal station (2R) (contrast-enhanced, 68 enlarged lymph nodes; unenhanced, 44 enlarged lymph nodes; p = .014). With regard to all stations together, intraobserver agreement between contrast-enhanced and unenhanced studies was almost perfect (kappa range, .85-.94), and no difference was found for any observer in the proportion of patients with at least one enlarged lymph node. Interobserver agreement was substantial or almost perfect for the total number of enlarged lymph nodes. For specific stations, the lowest kappa value was .48 at 2R. One observer reported more patients with at least one enlarged lymph node with contrast enhancement at station 2R (p = .031). Greater agreement existed between two observers at station 2R with contrast enhancement versus no enhancement (kappa = .85 versus .48; p = .02). Conclusions matched, and calculations of estimated kappa values gave similar results for determination of the specific number of enlarged lymph nodes at a station and the "one or none" category.We found high agreement for intra- and interobserver interpretations for contrast-enhanced and unenhanced CT, although contrast-enhanced CT revealed more enlarged lymph nodes, especially at station 2R.

Idiopathic pulmonary fibrosis (IPF) is associated with significant morbidity and mortality despite aggressive therapy. Thirty-eight patients with biopsy-proven IPF were studied to identify pretreatment features that could be used to predict short-term improvement in pulmonary function and improved longer term survival. In all patients, a pretreatment clinical (dyspnea), radiographic (chest radiograph), and physiologic (pulmonary function including exercise saturation) score was generated (CRP). A high-resolution CT scan (HRCT) was independently scored by four radiologists for ground glass (CT-alv) and linear opacity (CT-fib) on a scale of 0-4. Open lung biopsy samples were scored for cellular infiltration, interstitial fibrosis, desquamation, and granulation by an experienced pulmonary pathologist. All patients were treated with 3 mo of high-dose steroids and the CRP scoring repeated. Patients were divided into three groups: responders with a greater than 10-point drop in CRP (n = 10); stable with +/- 10 point change in CRP (n = 14); and nonresponders with > 10 point rise in CRP or death (n = 14). Those responding to steroids were treated for 18 mo in a tapering fashion. In all others, steroids were tapered quickly and oral cyclophosphamide prescribed. Responders (10 of 38) had a lower age (45.1+/-4.3 yr) than nonresponders (61.4+/-3.5 yr) or those remaining stable (53.1+/-3.3 yr) (p = 0.01). Pretreatment CRP was higher in responders (58.8+/-5.6) than nonresponders (40.5+/-4.7) or stable individuals (37.6+/-4.7) (p = 0.01). Cellular infiltration score of the open lung biopsies was higher in responders (7.6+/-0.6) than stable individuals (5.7+/-0.5) (p = 0.04). The CT-alv scores were higher and CT-fib scores were lower in responders than nonresponders. Receiver operating curve (ROC) analysis was employed to identify pretreatment features of longer term survival (follow-up of 29.1+/-2.3 mo). Only CT-fib (p = 0.009) and pathology fibrosis score (p = 0.03) were able to predict mortality. A pretreatment CT-fib score > or = 2.0 demonstrated 80% sensitivity and 85% specificity in predicting survival. Those patients who did not respond to initial steroid therapy demonstrated a worse long-term survival and greater likelihood of decreased pulmonary function. We demonstrate that pretherapy pulmonary function, pathologic and radiographic parameters are different in individuals who respond to initial prednisone therapy. Only HRCT imaging and pathologic fibrosis were able to reliably predict long-term survival in patients with biopsy-proven IPF.

The purpose of our study was to determine if three-level thin-section CT depicts idiopathic pulmonary fibrosis (IPF) pathology as accurately as CT obtained at 10-mm increments throughout the entire lungs.Thin-section (1.0- to 1.5-mm) images at 10-mm increments were obtained and scored prospectively in 25 consecutive patients with newly diagnosed IPF who were participating in a Special Center of Research grant for interstitial lung disease. Each patient's lobe was scored by four thoracic radiologists on a scale of 0-5 for both ground-glass attenuation and fibrosis. The radiologists used three images (limited CT) and also used the entire data set (complete CT). CT scores were compared with pathology scores from 67 open and thoracoscopic biopsies. Limited and complete scores were compared with each other (Pearson correlation coefficient). Interobserver variation in the CT scoring system was assessed using kappa values.CT fibrosis scores strongly correlated with pathology fibrosis scores for complete (r = .53, p = .0001) and limited (r = .50, p = .0001) CT. CT ground-glass scores correlated with the histologic inflammatory scores for each lobe on complete (r = .27, p = .03) and limited (r = .26, p = .03) CT. The desquamative subcomponent of the pathology inflammatory score had the highest correlation with the CT ground-glass scores (complete: r = .29, p = .01; limited: r = .33, p = .007). Good interobserver agreement existed for both the alveolar and fibrosis components of the CT scoring system (kappa values ranging from .51 to .83) for each lobe of the lung on limited and complete CT.Limited thin-section CT reveals the pathologic changes associated with IPF as well as CT obtained at 10-mm increments. An added advantage of limited thin-section CT is that it exposes patients to less radiation.

Objectives: To assess the sensitivity of high-resolution chest computed tomography (HRCT) in detecting idiopathic pulmonary fibrosis proved by biopsy specimen. To determine the degree of physiologic and pathologic abnormalities in patients with idiopathic pulmonary fibrosis who have a false-negative HRCT. Design: Prospective 2-year study. Setting: Tertiary care university hospital. Patients: All patients with dyspnea and suspected interstitial lung disease referred to the University of Michigan for enrollment in the Idiopathic Pulmonary Fibrosis Specialized Center of Research (SCOR) protocol were included; 25 underwent open lung biopsy and formed the final study group. Measurements: All patients underwent physiologic (pulmonary function, gas exchange, and exercise testing), radiologic (chest x-ray film and HRCT), and pathologic assessments (bronchoscopic and open lung biopsy). The results of HRCT were prospectively compared with results of standard pulmonary function tests, cardiopulmonary exercise testing, and open lung biopsy. Results: Of 25 patients who had both HRCT and open lung biopsy, 3 patients (12%) had HRCTs that demonstrated no evidence of interstitial lung disease. These three patients had less severe disease based on clinical, radiographic, and physiologic (CRP) scores, gas exchange abnormalities, and pathologic scoring of open lung biopsy specimens, compared with those with an abnormal HRCT. Conclusion: We conclude that in the evaluation of patients with dyspnea and abnormal results of pulmonary function studies, a normal HRCT does not exclude early and clinically significant interstitial lung disease. In our patient population, physiologic testing was more sensitive than HRCT in detecting mild abnormalities in patients with idiopathic pulmonary fibrosis proved by biopsy specimen.

Immunosuppressed patients are at high risk of developing fulminant, multiple, and recurrent infections. Some organisms are more common than others in this group of patients. Early diagnosis is essential for prompt, complete treatment. Imaging with high-resolution chest CT (HRCT) is a valuable diagnostic tool that may guide therapy. We discuss the imaging characteristics of the common organisms in the immunocompromised host as well as noninfectious causes that can have similar imaging features.

Chest CT has major advantages over conventional chest radiographs, including improved contrast resolution, tissue characterization capability, and cross-sectional anatomic display. For ICU patients, these advantages are counterbalanced by the need to transport such patients outside the ICU environment and also by increased expense and radiation dose. Most of all, chest CT is usually not necessary in ICU patients. The authors conclude that CT is especially helpful in patients whose clinical course is not explained by the available information or whose chest radiographs are difficult to interpret.

Computed tomographic (CT) scans were retrospectively reviewed for evidence of (a) intragastric soft-tissue mass or gastric wall thickening, (b) extragastric soft-tissue mass or mediastinal lymph node enlargement (local-regional disease), (c) abdominal lymph node enlargement, and (d) metastatic disease to distant organs.Fifty-eight patients with a clinical suspicion of recurrent esophageal carcinoma underwent CT. The thoracic level of local-regional recurrence was compared with the level of the primary tumor.Proof of recurrence status was obtained in 52 of 58 patients. Of the 58 patients, 36 (62%) had CT findings of recurrence, 16 (28%) had no CT findings of recurrence, and six (10%) had CT findings questionable for recurrence. CT accuracy for determining recurrence status was 87%. There was no correlation between the level of primary tumor and that of recurrence.At CT, tumor recurrences were most commonly seen as some combination of local-regional disease, distant metastases, and abdominal lymph node enlargement. CT findings isolated to one region were seen only occasionally.

Idiopathic pulmonary fibrosis is characterized by diffuse alveolar damage and severe fibrosis, resulting in a steady worsening of lung function and gas exchange. Because idiopathic pulmonary fibrosis is a generally progressive disorder with highly heterogeneous disease progression, we classified affected patients as either rapid or slow progressors over the first year of follow-up and then identified differences between the two groups to investigate the mechanism governing rapid progression. Previous work from our laboratory has demonstrated that Toll-like receptor 9 (TLR9), a pathogen recognition receptor that recognizes unmethylated CpG motifs in bacterial and viral DNA, promotes myofibroblast differentiation in lung fibroblasts cultured from biopsies of patients with idiopathic pulmonary fibrosis. Therefore, we hypothesized that TLR9 functions as both a sensor of pathogenic molecules and a profibrotic signal in rapidly progressive idiopathic pulmonary fibrosis. Indeed, TLR9 was present at higher concentrations in surgical lung biopsies from rapidly progressive patients than in tissue from slowly progressing patients. Moreover, fibroblasts from rapid progressors were more responsive to the TLR9 agonist, CpG DNA, than were fibroblasts from slowly progressing patients. Using a humanized severe combined immunodeficient mouse, we then demonstrated increased fibrosis in murine lungs receiving human lung fibroblasts from rapid progressors compared with mice receiving fibroblasts from slowly progressing patients. This fibrosis was exacerbated by intranasal CpG challenges. Furthermore, CpG induced the differentiation of blood monocytes into fibrocytes and the epithelial-to-mesenchymal transition of A549 lung epithelial cells. These data suggest that TLR9 may drive the pathogenesis of rapidly progressive idiopathic pulmonary fibrosis and may serve as a potential indicator for this subset of the disease.

Pilot studies have suggested that treatment with recombinant human growth hormone (rhGH) is associated with increased T-lymphocyte restoration and enhanced thymic output. We evaluated the immunologic effects of rhGH on HIV(+) subjects with incomplete immune reconstitution on antiretroviral therapy (ART). Sixty subjects were randomized to receive rhGH 1.5 mg scqd and ART for 48 weeks (Arm A) or continue ART alone for 24 weeks then add rhGH 3.0 mg scqd for 24 weeks (Arm B). Median baseline CD4 for Arms A and B were 223 and 219, respectively. There was little difference between Arm A and Arm B in change in total or naive CD4 cells or percentage from baseline to week 24. Only one subject in Arm A met the primary endpoint, an increase in naive CD4 percentage of at least 10 percentage points. By week 48 both Arms had statistically significant increases in naive CD4 cell count and percentage and thymus size. Within Arm B, treatment with rhGH was associated with significant increases in naive CD4(+) cell count and percentage compared with ART alone. Treatment with rhGH +ART may be associated with modest increases in CD4 lymphocytes over ART alone in subjects with CD4350, yet the origin of these naive cells and their impact on immune function require further investigation.

Objective To determine the optimal anatomic coverage at CT that would provide the most accurate staging for patients with non-small cell lung cancer. Methods We reviewed lung cancer staging PET-CT scans and correlated them with staging chest CT scans performed within 50 days of the PET-CT study. There were 113 patients who underwent both studies within our time frame. We reviewed the results of subsequent imaging studies and surgical and biopsy procedures to determine the final stage for each patient. This study was approved by the local institutional review board. Results In 86 (76%) of 113 patients, staging by PET-CT and by CT from the lung apices through the lung bases was identical. PET-CT upstaged 21 patients (19%) compared with CT findings; in 13 of these patients the PET-CT noted disease that was either outside of the anatomic range of any lung cancer staging CT or was within the area scanned by CT, but was not evident by CT. In the other 8 upstaged patients, extending the anatomic scope of the CT scan to the supraclavicular region (5), adrenal glands (2) or abdomen (1) would have resulted in correct staging. Conclusions CT scanning from the supraclavicular region through the caudal adrenal glands improves the accuracy of CT staging of lung cancer compared with scanning from the lung apices through the lung bases. Anatomic coverage beyond the adrenal glands has a low yield for improved staging, at the cost of requiring administration of oral contrast to all patients. Summary To determine the optimal anatomic coverage at CT that would provide the most accurate staging for patients with non-small cell lung cancer, we reviewed lung cancer staging PET-CT scans and correlated them with staging chest CT scans performed within 50 days of the PET-CT study. CT scanning from the supraclavicular region through the caudal adrenal glands improves the accuracy of CT staging of lung cancer compared with scanning from the lung apices through the lung bases. Anatomic coverage beyond the adrenal glands has a low yield for improved staging, at the cost of requiring administration of oral contrast to all patients undergoing lung cancer staging.