Thomas E. Hartman

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.

High Frequency of Pulmonary Lymphangioleiomyomatosis in Women With Tuberous Sclerosis Complex

OBJECTIVE To determine the frequency of pulmonary lymphangioleiomyomatosis (LAM), a rare cystic lung disorder that occurs almost exclusively in women of reproductive age, in women with tuberous sclerosis complex (TSC), an inheritable multiorgan hamartomatosis. PATIENTS AND METHODS In this retrospective cohort study, the medical records of 78 women with definite TSC were reviewed, and pertinent information was recorded, including the demographic data, clinical manifestations, results of lung biopsies and autopsies, and findings on imaging studies of the chest and abdomen. All available computed tomographic (CT) scans of the chest and abdomen were reviewed. RESULTS Of 78 women with definite TSC seen from 1977 to 1998, 20 (26%) had evidence of LAM. Surgical lung biopsy or autopsy in 7 patients confirmed the diagnosis of their lung disease. Characteristic CT findings of LAM were noted in 13 additional patients. Twelve of these 20 patients with TSC-associated LAM had respiratory symptoms, including exertional shortness of breath and spontaneous pneumothorax, that eventually led to their pulmonary diagnosis. CONCLUSIONS The frequency of lung involvement (LAM) in women with TSC is substantially higher than previously suspected and may be even higher than reported in this retrospective study. These findings support the recommendation for a screening CT of the chest for all women with TSC.

High short-term mortality following lung biopsy for usual interstitial pneumonia

Usual interstitial pneumonia (UIP) is a specific histological pattern of interstitial pneumonia most often associated with the clinical syndrome of idiopathic pulmonary fibrosis (IPF). There is controversy regarding the use of surgical lung biopsy in the diagnosis of UIP, and the risk of lung biopsy in these patients is largely unknown. This study investigated the 30 day surgical mortality rate in patients undergoing surgical lung biopsy for UIP. Patients undergoing surgical lung biopsy over a 10-yr period from 1986-1995 with the ultimate diagnosis of UIP (with or without underlying connective tissue disease) were identified. Pathology, computed tomography, medical records, and survival were assessed. Ten of sixty patients with usual interstitial pneumonia were found to be dead within 30 days of surgical biopsy. All of these were patients with idiopathic UIP, unassociated with connective tissue disease (clinical condition of IPF). In conclusion, patients with usual interstitial pneumonia of the idiopathic type, who present with atypical features, may be at higher risk for death following surgical biopsy than patients presenting with more typical features or patients with other interstitial illnesses.

Clinical features and outcomes in combined pulmonary fibrosis and emphysema in idiopathic pulmonary fibrosis

BACKGROUND Combined pulmonary fibrosis and emphysema (CPFE) is increasingly recognized, but its prevalence and prognosis remain unclear. We sought to determine the prevalence, clinical features, and prognosis of CPFE in idiopathic pulmonary fibrosis (IPF), using a standardized and reproducible definition. METHODS Patients with IPF were identified from two ongoing cohorts. Two radiologists scored emphysema and fibrosis severity on high-resolution CT (HRCT) scans. CPFE was defined as ≥10% emphysema on HRCT scan. Clinical characteristics and outcomes of patients with CPFE and IPF and those with non-CPFE IPF were compared with unadjusted analysis and then analysis after adjustment for HRCT fibrosis score. Mortality was compared using competing risks regression to handle lung transplantation. Sensitivity analyses were performed using Cox proportional hazards, including time to death (transplantation censored) and time to death or transplant. RESULTS CPFE criteria were met in 29 of 365 patients with IPF (8%), with high agreement between radiologists (κ=0.74). Patients with CPFE had less fibrosis on HRCT scans and higher FVC, but greater oxygen requirements (P≤.01 for all comparisons). Findings were maintained with adjustment for fibrosis severity. Inhaled therapies for COPD were used by 53% of patients with CPFE. There was no significant difference in mortality comparing patients with CPFE and IPF to those with non-CPFE IPF (hazard ratio, 1.14; 95% CI, 0.61-2.13; P=.69). CONCLUSIONS CPFE was identified in 8% of patients with IPF and is a distinct, clinical phenotype with potential therapies that remain underutilized. Patients with CPFE and IPF and those with non-CPFE IPF have similar mortality.

Characterization of the Solitary Pulmonary Nodule: 18F-FDG PET Versus Nodule-Enhancement CT

OBJECTIVE The purpose of this study was to directly compare nodule-enhancement CT and 18F-FDG PET in the characterization of indeterminate solitary pulmonary nodules (SPNs) greater than 7 mm in size. MATERIALS AND METHODS Examinations from patients undergoing both nodule-enhancement CT and 18F-FDG PET to characterize the same indeterminate SPN were reviewed. For nodule-enhancement CT, an SPN was considered malignant when it showed an unenhanced to peak contrast-enhanced increase in attenuation greater than 15 H. Fluorine-18-FDG PET studies were blindly reinterpreted by two qualified nuclear radiologists. SPNs qualitatively showing hypermetabolic activity greater than the mediastinal blood pool were interpreted as malignant. These interpretations were compared with the original prospective clinical readings and to semiquantitative standardized uptake value (SUV) analysis. Results were compared with pathologic and clinical follow-up. RESULTS Forty-two pulmonary nodules were examined. Twenty-five (60%) were malignant, and 17 (40%) were benign. Nodule-enhancement CT was positive in all 25 malignant nodules and in 12 benign nodules, with sensitivity and specificity of 100% and 29%, respectively, and with a positive predictive value (PPV) and negative predictive value (NPV) of 68% and 100%, respectively. Qualitative 18F-FDG PET interpretations were positive in 24 of the 25 malignant nodules and in four benign nodules. Fluorine-18-FDG PET was considered negative in one malignant nodule and in 13 of the 17 benign nodules. This correlates with a sensitivity and specificity of 96% and 76%, respectively, and with a PPV and NPV of 86% and 93%, respectively. Original prospective 18F-FDG PET and semiquantitative SUV analysis showed sensitivity, specificity, PPV, and NPV of 88%, 76%, 85%, and 81% and 84%, 82%, 88%, and 78%, respectively. CONCLUSION Due to its much higher specificity and only slightly reduced sensitivity, 18F-FDG PET is preferable to nodule-enhancement CT in evaluating indeterminate pulmonary nodules. However, nodule-enhancement CT remains useful due to its high NPV, convenience, and lower cost. Qualitative 18F-FDG PET interpretation provided the best balance of sensitivity and specificity when compared with original prospective interpretation or SUV analysis.

Primary pulmonary carcinoma in patients with idiopathic pulmonary fibrosis

OBJECTIVE To identify distinguishing characteristics between patients with idiopathic pulmonary fibrosis (IPF) and primary lung carcinoma and patients with either IPF or carcinoma alone. PATIENTS AND METHODS The study group consisted of 24 patients with histologically proven usual interstitial pneumonia and lung carcinoma identified through a search of the Rochester Mayo Clinic database for 1990 to 1998. Medical records, radiographs, and histological slides were reviewed. Several variables including survival were compared in 2 control groups, IPF only and carcinoma only, by using various statistical methods. RESULTS Our study group included 21 men and 3 women (mean age, 72.3 years). Twenty-two were past or current smokers. Approximately half of the lung carcinomas were incidental findings. Of the 14 patients with preoperative computed tomographic scans, 12 had peripheral tumors situated in areas of fibrosis. Squamous cell carcinoma was the most common histological type, accounting for 16 cases. Almost all patients underwent surgical treatment; nearly 40% developed postoperative complications, and 3 died within 30 days of surgery. The ratio of men to women in patients with IPF and carcinoma was 7:1 compared with 1:1 in patients with IPF only (P=.003). Patients with IPF and carcinoma were also older, with a mean age of 72.3 years compared with 64.4 years (P=.001), and were more often smokers (P=.002). Carcinomas involved the lower lobes in 42% of patients with IPF and carcinoma compared with 29% of patients with carcinoma only (P=.004) and were mainly composed of squamous cell carcinoma (P=.004). Mean survival in patients with IPF and lung carcinoma was 2.3 years after the diagnosis of IPF and 1.6 years after that of carcinoma. This finding did not differ significantly from survival of patients with either IPF or carcinoma alone. However, statistical power was limited. CONCLUSION Carcinoma in patients with IPF arises in older male smokers and usually presents as peripheral squamous cell carcinoma. The prognosis is poor.

Diagnosis of Interstitial Lung Diseases

Interstitial lung diseases (ILDs), a broad heterogeneous group of parenchymal lung disorders, can be classified into those with known and unknown causes. The definitions and diagnostic criteria for several major forms of ILDs have been revised in recent years. Although well over 100 distinct entities of ILDs are recognized, a limited number of disorders, including idiopathic pulmonary fibrosis, sarcoidosis, and connective tissue disease-related ILDs, account for most ILDs encountered clinically. In evaluating patients with suspected ILD, the clinician should confirm the presence of the disease and then try to determine its underlying cause or recognized clinicopathologic syndrome. Clues from the medical history along with the clinical context and radiologic findings provide the initial basis for prioritizing diagnostic possibilities for a patient with ILD. High-resolution computed tomography of the chest has become an invaluable tool in the diagnostic process. A confident diagnosis can sometimes be made on the basis of high-resolution computed tomography and clinical context. Serologic testing can be helpful in selected cases. Histopathologic findings procured through bronchoscopic or surgical lung biopsy are often needed in deriving a specific diagnosis. An accurate prognosis and optimal treatment strategy for patients with ILDs depend on an accurate diagnosis, one guided by recent advances in our understanding of the causes and pathogenetic mechanisms of ILDs.

High-Resolution CT Findings of Parenchymal Fibrosis Correlate With Prognosis in Hypersensitivity Pneumonitis*

BACKGROUND Histopathologic evidence of fibrosis on surgical lung biopsy has been associated with reduced survival in patients with hypersensitivity pneumonitis (HP). Changes of pulmonary fibrosis detected on CT may also correlate with prognosis in patients with HP. METHODS We identified 69 consecutive patients with HP diagnosed between January 1997 and December 2002 at Mayo Clinic, Rochester, MN. Patients were stratified into fibrotic and nonfibrotic groups based on the CT findings. Fibrosis was defined by the presence of irregular linear opacities, traction bronchiectasis, or honeycombing. MEASUREMENTS AND MAIN RESULTS Of 69 patients, 26 were classified as fibrotic and 43 as nonfibrotic. Patients in the fibrotic group were older, had longer symptom duration, were more likely to have crackles on auscultation, more likely to be exposed to avian antigen, and had greater restrictive lung impairment (p<0.05 for all comparisons). There were 11 deaths in the fibrotic group and 1 death in the nonfibrotic group (p<0.0001). In the regression analysis, CT evidence of fibrosis, more severe pulmonary function abnormalities, and the presence of crackles on auscultation were predictive of reduced survival (p<0.05 for all). The presence as well as the extent of fibrosis on CT was associated with increased mortality. The age-adjusted hazard ratio for mortality in patients with fibrosis was 4.6 (95% confidence interval, 2.0 to 20.1; p<0.0001). CONCLUSION CT findings of parenchymal fibrosis are associated with reduced survival in patients with HP and may serve as a useful prognostic indicator.

CT mosaic pattern of lung attenuation: etiologies and terminology.

Areas of variable lung attenuation forming a “mosaic pattern” are occasionally seen on computed tomography (CT) or high-resolution CT (HRCT) images of the lungs. This CT mosaic pattern of lung attenuation is a nonspecific finding that can reflect the presence of vascular disease, airway abnormalities, or ground-glass interstitial or air-space infiltrates. However, it is often possible to distinguish among these categories. In small airways disease and pulmonary vascular disease, the pulmonary vessels within the lucent regions of lung are small relative to the vessels in the more opaque lung. In infiltrative diseases, the vessels are more uniform in size throughout the different regions of lung attenuation. The distinction of small airways disease from primary vascular disease requires the use of paired inspiratory/expiratory CT scans. The terms “mosaic perfusion” or “mosaic oligemia” have also been used to describe this heterogeneous pattern of lung attenuation. We believe that the term “mosaic pattern of lung attenuation” is preferable when describing areas of variable lung attenuation because the term “mosaic perfusion” implies pulmonary vascular pathology.

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