Brian J. Bartholmai

Incidence, Prevalence, and Clinical Course of Idiopathic Pulmonary Fibrosis: A Population-Based Study

BACKGROUND Limited data exist regarding the population-based epidemiology of idiopathic pulmonary fibrosis (IPF). The objective of the study was to describe the trends in the incidence, prevalence, and clinical course of IPF in the community. METHODS We conducted a population-based study of adult patients with IPF in Olmsted County, Minnesota, from 1997 to 2005. Two methods were used to identify IPF cases, as defined by the 2002 American Thoracic Society/European Respiratory Society consensus statement: (1) usual interstitial pneumonia (UIP) on a surgical lung biopsy specimen or a definite UIP pattern on a high-resolution CT image (narrow criteria) and (2) UIP on a surgical lung biopsy specimen or a definite or possible UIP pattern on CT image (broad criteria). RESULTS Of 596 patients screened for the possibility of pulmonary disease or pulmonary fibrosis over 9 years of follow-up, 47 cases had IPF. Of these, 24 met the narrow criteria. The age- and sex-adjusted incidence was 8.8/100,000 and 17.4/100,000 person-years, for narrow and broad criteria, respectively. The age-adjusted incidence was higher in men than in women, and among patients aged 70-79 years. During the study period, the incidence of IPF decreased (P < .001). On December 31, 2005, the age- and sex-adjusted prevalence was 27.9/100,000 and 63/100,000 persons by narrow and broad criteria, respectively. Thirty-seven patients experienced a total of 53 respiratory exacerbations (26 IPF related, 27 non-IPF related), and 34 (72%) patients died. The primary cause of death was IPF related in 16 (47%) patients. Median survival for narrow-criteria and broad-criteria incidence cases was 3.5 and 4.4 years, respectively. CONCLUSIONS The incidence of IPF in Olmsted County decreased over the study period. Nonprimary IPF respiratory exacerbations are as frequent as primary IPF respiratory exacerbations and an important cause of death.

Mortality Associated With Nephropathy After Radiographic Contrast Exposure

OBJECTIVE To define outcomes from contrast-induced nephropathy (CIN) after both intra-arterial and intravenous administration of contrast medium. PATIENTS AND METHODS We performed a retrospective case-matched cohort study at Mayo Clinics site in Rochester, MN, from April 1, 2004, to March 31, 2006. All contrast procedures were evaluated for inclusion. Contrast-induced nephropathy was defined as creatinine elevation of 25% or more after contrast exposure or of more than 0.5 mg/dL within 7 days of contrast exposure. Cases of CIN were matched 1:3 with controls by age, sex, pre-procedure creatinine elevation, diabetes mellitus, and type of imaging procedure. RESULTS A total of 809 patients who developed CIN were matched to 2427 patients who did not develop CIN after contrast exposure. In multivariate analyses, CIN was significantly associated with 30-day mortality (odds ratio, 3.37; 95% confidence interval [CI], 2.58-4.41; P<.001) and overall mortality (hazard ratio, 1.57; 95% CI, 1.32-1.86; P<.001) after adjustment for heart failure, hypertension, medications, total hydration, iodine load, prior contrast exposure, and all matched variables during the study period. Intravenous contrast administration was a risk factor for 30-day mortality (odds ratio, 2.91; 95% CI, 1.17-7.23; P=.02) and overall mortality (hazard ratio, 3.02; 95% CI, 1.89-4.82; P<.001) compared with intra-arterial administration of contrast after adjustment for heart failure, hypertension, medications, total hydration, iodine load, prior contrast exposure, and all matched variables during the study period. CONCLUSION Contrast-induced nephropathy after administration of contrast medium is associated with increased mortality. This risk is higher in patients in whom contrast medium is administered intravenously than in those in whom it is administered intra-arterially.

Sodium bicarbonate is associated with an increased incidence of contrast nephropathy: a retrospective cohort study of 7977 patients at mayo clinic.

BACKGROUND AND OBJECTIVES The role of sodium bicarbonate in preventing contrast nephropathy needs to be evaluated in clinical settings. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We performed a retrospective cohort study at Mayo Clinic in Rochester, Minnesota, to assess the risk of contrast nephropathy associated with the use of sodium bicarbonate, N-acetylcysteine, and the combination of sodium bicarbonate with N-acetylcysteine from April 2004 to May 2005. Contrast nephropathy was defined as postexposure creatinine elevation of > or =25% or >0.5 mg/dl within 7 d of contrast exposure. RESULTS A total of 11,516 contrast exposures in 7977 patients had creatinine values available for review before and after contrast exposure. More than 90% of exposures to agents prophylactic for contrast nephropathy were available for analysis. Sodium bicarbonate was used in 268 cases, N-acetylcysteine was used in 616 cases, and both agents were used in combination in 221 cases of contrast exposure. After adjustment for total volume of hydration, medications, age, gender, prior creatinine, contrast iodine load, prior exposure to contrast material, type of imaging study, heart failure, hypertension, renal failure, multiple myeloma, and diabetes mellitus, use of sodium bicarbonate alone was associated with an increased risk of contrast nephropathy compared with no treatment (odds ratio 3.10, 95% confidence interval 2.28 to 4.18; P < 0.001). N-acetylcysteine alone and in combination with sodium bicarbonate was not associated with any significant difference in the incidence of contrast nephropathy. CONCLUSIONS The use of intravenous sodium bicarbonate was associated with increased incidence of contrast nephropathy. Use of sodium bicarbonate to prevent contrast nephropathy should be evaluated further rather than adopted into clinical practice.

Clinical Significance of Radiologic Characterizations in COPD

ABSTRACT COPD is a heterogeneous disorder with clinical assessment becoming increasingly multidimensional. We hypothesized HRCT phenotype would strongly influence clinical outcomes including health status, exacerbation frequency, and BODE. COPD subjects were characterized via the SF-12, SGRQ, MMRC, physiologic testing, and standardized volumetric chest HRCT. Visual semi-quantitative estimation of bronchial wall thickness (VBT) and automated quantification of emphysema percent and bronchial wall thickness were generated. Multivariate modeling compared emphysema severity and airway abnormality with clinical outcome measures. Poisson models were used to analyze exacerbation frequency. SGRQ and SF-12 physical component scores were influenced by FEV1% predicted, emphysema percent, and VBT. VBT scores > 2 (scale 0–48) were associated with increased exacerbation frequency (p = 0.009) in the preceding year adjusting for age, gender, emphysema percent, smoking history and FEV1% predicted, although this effect was attenuated by age. Emphysema percent correlated with total BODE score in unadjusted (r = 0.73; p < 0.0001) and adjusted (p < 0.0001) analyses and with BODE individual components. HRCT provides unique COPD phenotyping information. Radiographic quantification of emphysema and bronchial thickness are independently associated with SGRQ and physical component score of the SF-12. Bronchial thickness but not emphysema is associated with exacerbation frequency, whereas emphysema is a stronger predictor of BODE and its systemic components MMRC, 6MWT, and BMI. Future research should clarify whether CT parameters complement BODE score in influencing survival.

Are airflow obstruction and radiographic evidence of emphysema risk factors for lung cancer? A nested case-control study using quantitative emphysema analysis.

OBJECTIVES Several studies have identified airflow obstruction as a risk factor for lung cancer independent of smoking history, but the risk associated with the presence of radiographic evidence of emphysema has not been extensively studied. We proposed to assess this risk using a quantitative volumetric CT scan analysis. METHODS Sixty-four cases of lung cancer were identified from a prospective cohort of 1,520 participants enrolled in a spiral CT scan lung cancer screening trial. Each case was matched to six control subjects for age, sex, and smoking history. Quantitative CT scan analysis of emphysema was performed. Spirometric measures were also conducted. Data were analyzed using conditional logistic regression making use of the 1:6 set groups of 64 cases and 377 matched control subjects. RESULTS Decreased FEV(1) and FEV(1)/FVC were significantly associated with a diagnosis of lung cancer with ORs of 1.15 (95% CI, 1.00-1.32; P = .046) and 1.29 (95% CI, 1.02-1.62; P = .031), respectively. The quantity of radiographic evidence of emphysema was not found to be a significant risk for lung cancer with OR of 1.042 (95% CI, 0.816-1.329; P = .743). Additionally, there was no significant association between severe emphysema and lung cancer with OR of 1.57 (95% CI, 0.73-3.37). CONCLUSIONS We confirm previous observations that airflow obstruction is an independent risk factor for lung cancer. The absence of a clear relationship between radiographic evidence of emphysema and lung cancer using an automated quantitative volumetric analysis may result from different population characteristics than those of prior studies, radiographic evidence of emphysema quantitation methodology, or absence of any relationship between emphysema and lung cancer risk.

Automated quantification of radiological patterns predicts survival in idiopathic pulmonary fibrosis

Accurate assessment of prognosis in idiopathic pulmonary fibrosis remains elusive due to significant individual radiological and physiological variability. We hypothesised that short-term radiological changes may be predictive of survival. We explored the use of CALIPER (Computer-Aided Lung Informatics for Pathology Evaluation and Rating), a novel software tool developed by the Biomedical Imaging Resource Laboratory at the Mayo Clinic Rochester (Rochester, MN, USA) for the analysis and quantification of parenchymal lung abnormalities on high-resolution computed tomography. We assessed baseline and follow-up (time-points 1 and 2, respectively) high-resolution computed tomography scans in 55 selected idiopathic pulmonary fibrosis patients and correlated CALIPER-quantified measurements with expert radiologists’ assessments and clinical outcomes. Findings of interval change (mean 289 days) in volume of reticular densities (hazard ratio 1.91, p=0.006), total volume of interstitial abnormalities (hazard ratio 1.70, p=0.003) and per cent total interstitial abnormalities (hazard ratio 1.52, p=0.017) as quantified by CALIPER were predictive of survival after a median follow-up of 2.4 years. Radiologist interpretation of short-term global interstitial lung disease progression, but not specific radiological features, was also predictive of mortality. These data demonstrate the feasibility of quantifying interval short-term changes on high-resolution computed tomography and their possible use as independent predictors of survival in idiopathic pulmonary fibrosis. Short-term quantified CT changes are predictive of survival in IPF http://ow.ly/qmbjd

Computer-Aided Detection and Diagnosis at the Start of the Third Millennium

Computer-aided diagnosis has been under development for more than 3 decades. The rate of progress appears exponential, with either recent approval or pending approval for devices focusing on mammography, chest radiographs, and chest CT. Related technologies improve diagnosis for many other types of medical images including virtual colonography, vascular imaging, as well as automated quantitation of image-derived metrics. A variety of techniques are currently employed with success, likely reflecting the variety of imagery used, as well as the variety of tasks. Most areas of medical imaging have had efforts at computer assistance, and some have even received FDA approval and can be reimbursed. We anticipate that the rapid advance of these technologies will continue, and that application will broaden to cover much of medical imaging. Acceptance of, and integration of computer-aided diagnosis technology with the electronic radiology practice is a current challenge. These challenges will be overcome, and we expect that computer-aided diagnosis will be routinely applied to medical images.

Collapsibility of lung volume by paired inspiratory and expiratory CT scans: Correlations with lung function and mean lung density

RATIONALE AND OBJECTIVES To evaluate the relationship between measurements of lung volume (LV) on inspiratory/expiratory computed tomography (CT) scans, pulmonary function tests (PFT), and CT measurements of emphysema in individuals with chronic obstructive pulmonary disease. MATERIALS AND METHODS Forty-six smokers (20 females and 26 males; age range 46-81 years), enrolled in the Lung Tissue Research Consortium, underwent PFT and chest CT at full inspiration and expiration. Inspiratory and expiratory LV values were automatically measured by open-source software, and the expiratory/inspiratory (E/I) ratio of LV was calculated. Mean lung density (MLD) and low attenuation area percent (<-950 HU) were also measured. Correlations of LV measurements with lung function and other CT indices were evaluated by the Spearman rank correlation test. RESULTS LV E/I ratio significantly correlated with the following: the percentage of predicted value of forced expiratory volume in the first second (FEV(1)), the ratio of FEV(1) to forced vital capacity (FVC), and the ratio of residual volume (RV) to total lung capacity (TLC) (FEV(1)%P, R = -0.56, P < .0001; FEV(1)/FVC, r = -0.59, P < .0001; RV/TLC, r = 0.57, P < .0001, respectively). A higher correlation coefficient was observed between expiratory LV and expiratory MLD (r = -0.73, P < .0001) than between inspiratory LV and inspiratory MLD (r = -0.46, P < .01). LV E/I ratio showed a very strong correlation to MLD E/I ratio (r = 0.95, P < .0001). CONCLUSIONS LV E/I ratio can be considered to be equivalent to MLD E/I ratio and to reflect airflow limitation and air-trapping. Higher collapsibility of lung volume, observed by inspiratory/expiratory CT, indicates less severe conditions in chronic obstructive pulmonary disease.

Airway Count and Emphysema Assessed by Chest CT Imaging Predicts Clinical Outcome in Smokers

BACKGROUND Recently, it has been shown that emphysematous destruction of the lung is associated with a decrease in the total number of terminal bronchioles. It is unknown whether a similar decrease is visible in the more proximal airways. We aimed to assess the relationships between proximal airway count, CT imaging measures of emphysema, and clinical prognostic factors in smokers, and to determine whether airway count predicts the BMI, airflow obstruction, dyspnea, and exercise capacity (BODE) index. METHODS In 50 smokers, emphysema was measured on CT scans and airway branches from the third to eighth generations of the right upper lobe apical bronchus were counted manually. The sum of airway branches from the sixth to eighth generations represented the total airway count (TAC). For each subject, the BODE index was determined. We used logistic regression to assess the ability of TAC to predict a high BODE index (≥ 7 points). RESULTS TAC was inversely associated with emphysema (r = -0.54, P < .0001). TAC correlated with the modified Medical Research Council dyspnea score (r = -0.42, P = .004), FEV(1)% predicted (r = 0.52, P = .0003), 6-min walk distance (r = 0.36, P = .012), and BODE index (r = -0.55, P < .0001). The C-statistics, which correspond to the area under the receiver operating characteristic curve, for the ability of TAC alone and TAC, emphysema, and age to predict a high BODE index were 0.84 and 0.92, respectively. CONCLUSIONS TAC is lower in subjects with greater emphysematous destruction and is a predictor of a high BODE index. These results suggest that CT imaging-based TAC may be a unique COPD-related phenotype in smokers.

Iodixanol Versus Low-Osmolar Contrast Media for Prevention of Contrast Induced Nephropathy Meta-analysis of Randomized, Controlled Trials

Background—Contrast-induced nephropathy (CIN) is associated with significant morbidity and mortality. The objective of our meta-analysis was to assess the efficacy of iodixanol compared with low-osmolar contrast media (LOCM) for prevention of CIN. Methods and Results—We searched MEDLINE, the Cochrane Central Register of Controlled Trials, and internet sources of cardiology trial results for individual and relevant reviews of randomized, controlled trials, for the terms contrast media, contrast nephropathy, renal failure, iodixanol, Visipaque, and low-osmolar contrast media. All studies reported an incidence rate of CIN for each study group; there was no restriction on the definition of CIN. There were no restrictions on journal type or patient population. Overall, 36 trials were identified for analysis of aggregated summary data on 7166 patients; 3672 patients received iodixanol and 3494 patients received LOCM. Overall, iodixanol showed no statistically significant reduction in CIN incidence below that observed with heterogeneous comparator agents (P=0.11). Analysis of patient subgroups revealed that there was a significant benefit of iodixanol when compared with iohexol alone (odds ratio, 0.25; 95% confidence interval, 0.11 to 0.55; P<0.001) but not when compared with LOCM other than iohexol or with other ionic dimers or among patients receiving intra-arterial contrast injections or among patients undergoing coronary angiography with or without percutaneous intervention. Conclusions—Analysis of aggregated summary data from multiple randomized, controlled trials of iodixanol against diverse LOCMs for heterogeneous procedures and definitions of CIN show an iodixanol-associated reduction that is suggestive but statistically nonsignificant.