Susan J. Copley

Interstitial Lung Disease in Systemic Sclerosis A Simple Staging System

RATIONALE In interstitial lung disease complicating systemic sclerosis (SSc-ILD), the optimal prognostic use of baseline pulmonary function tests (PFTs) and high-resolution computed tomography (HRCT) is uncertain. OBJECTIVES To construct a readily applicable prognostic algorithm in SSc-ILD, integrating PFTs and HRCT. METHODS The prognostic value of baseline PFT and HRCT variables was quantified in patients with SSc-ILD (n = 215) against survival and serial PFT data. MEASUREMENTS AND MAIN RESULTS Increasingly extensive disease on HRCT was a powerful predictor of mortality (P < 0.0005), with an optimal extent threshold of 20%. In patients with HRCT extent of 10-30% (termed indeterminate disease), an FVC threshold of 70% was an adequate prognostic substitute. On the basis of these observations, SSc-ILD was staged as limited disease (minimal disease on HRCT or, in indeterminate cases, FVC >or= 70%) or extensive disease (severe disease on HRCT or, in indeterminate cases, FVC < 70%). This system (hazards ratio [HR], 3.46; 95% confidence interval [CI], 2.19-5.46; P < 0.0005) was more discriminatory than an HRCT threshold of 20% (HR, 2.48; 95% CI, 1.57-3.92; P < 0.0005) or an FVC threshold of 70% (HR, 2.11; 95% CI, 1.34-3.32; P = 0.001). The system was evaluated by four trainees and four practitioners, with minimal and severe disease on HRCT defined as clearly < 20% or clearly > 20%, respectively, and the use of an FVC threshold of 70% in indeterminate cases. The staging system was predictive of mortality for all scorers, with prognostic separation higher for practitioners (HR, 3.39-3.82) than trainees (HR, 1.87-2.60). CONCLUSIONS An easily applicable limited/extensive staging system for SSc-ILD, based on combined evaluation with HRCT and PFTs, provides discriminatory prognostic information.

Significance of connective tissue disease features in idiopathic interstitial pneumonia

In idiopathic interstitial pneumonia (IIP), the significance of connective tissue disease (CTD) features in the absence of a specific CTD diagnosis remains unclear. We studied the clinical and prognostic utility of a diagnosis of undifferentiated CTD (UCTD) in patients with biopsy-proven IIP. IIP patients undergoing surgical lung biopsy (1979–2005) were studied (nonspecific interstitial pneumonia (NSIP), n=45; idiopathic pulmonary fibrosis, n=56). UCTD was considered present when serum autoantibodies were present and symptoms or signs suggested CTD. The relationship between UCTD and NSIP histology was evaluated. A clinical algorithm that best predicted NSIP histology was constructed using a priori variables. The prognostic utility of UCTD, and of this algorithm, was evaluated. UCTD was present in 14 (31%) NSIP and seven (13%) IPF patients. UCTD was not associated with a survival benefit. The algorithm predictive of NSIP (OR 10.4, 95% CI 3.21–33.67; p<0.0001) consisted of the absence of typical high-resolution computed tomography (HRCT) features for IPF and 1) a compatible demographic profile (females aged <50 yrs) or 2) Raynaud’s phenomenon. In patients with an HRCT scan not typical for IPF, this algorithm predicted improved survival (hazard ratio 0.35, 95% CI 0.14–0.85; p=0.02) independent of IIP severity. UCTD is associated with NSIP histology. However, the diagnostic and prognostic significance of UCTD in IIP patients remains unclear.

Lung Morphology in the Elderly: Comparative CT Study of Subjects over 75 Years Old versus Those under 55 Years Old

PURPOSE To describe thin-section pulmonary computed tomographic (CT) features in asymptomatic elderly individuals. MATERIALS AND METHODS Institutional review board approval was given, and informed consent was obtained. Two study groups (older group, over 75 years of age; younger group, under 55 years) were prospectively identified from outpatient requests for CT of the abdomen or brain. Fifty-six consecutive volunteers (older group: n = 40, 18 men, 22 women; younger group: n = 16, eight men, eight women) with no known respiratory disease were included. Prone thin-section CT imaging was performed, and two observers independently scored images for the presence and extent of CT features (including reticular pattern, ground glass opacity, and thin-walled cystic air spaces). Group comparisons were made, and logistic regression analysis was used to assess relationships between CT findings and age and smoking history. RESULTS A limited predominantly subpleural basal reticular pattern was identified in the majority (24 of 40, 60%) of individuals in the older group and was absent (zero of 16) in the younger group (P < .001). Cysts were seen in 10 (25%) of the 40 subjects in the older group but were seen in none of the subjects in the younger group (P = .02). Bronchial dilation and wall thickening were also seen significantly more frequently (P < .001) in the older group (24 [60%] and 22 [55%] of 40, respectively) than in the younger group (both one [6%] of 16). All findings were independent of pack-year smoking history with multiple logistic regression analysis. CONCLUSION Thin-section CT findings usually associated with interstitial lung disease are frequently seen in asymptomatic elderly individuals and are absent in younger subjects. Therefore, these findings may not necessarily represent clinically relevant disease.

Biopsy-proved Idiopathic Pulmonary Fibrosis: Spectrum of Nondiagnostic Thin-Section CT Diagnoses

PURPOSE To document the spectrum of misleading thin-section computed tomographic (CT) diagnoses in patients with biopsy-proved idiopathic pulmonary fibrosis (IPF). MATERIALS AND METHODS This study had institutional review board approval, and patient consent was not required. Three observers, blinded to any clinical information and the purpose of the study, recorded thin-section CT differential diagnoses and assigned a percentage likelihood to each for a group of 123 patients (79 men, 44 women; age range, 27-82 years) with various chronic interstitial lung diseases, including a core group of 55 biopsy-proved cases of IPF. Patients with IPF in the core group, in whom IPF was diagnosed as low-grade probability (<30%) by at least two observers, were considered to have atypical IPF cases, and the alternative diagnoses were analyzed further. RESULTS Thirty-four (62%) of 55 biopsy-proved IPF cases were regarded as alternative diagnoses. In these atypical IPF cases, the first-choice diagnoses, expressed with high degree of probability, were nonspecific interstitial pneumonia (NSIP; 18 [53%] of 34), chronic hypersensitivity pneumonitis (HP; four [12%] of 34), sarcoidosis (three [9%] of 34), and organizing pneumonia (one [3%] of 34); in eight (23%) of 34 cases, no single diagnosis was favored by more than one observer. Frequent differential diagnoses, although not always the first-choice diagnosis, were NSIP (n = 29), chronic HP (n = 23), and sarcoidosis (n = 9). CONCLUSION In the correct clinical setting, a diagnosis of IPF is not excluded by thin-section CT appearances more suggestive of NSIP, chronic HP, or sarcoidosis. (c) RSNA, 2010.

A comparison of serial computed tomography and functional change in bronchiectasis

In bronchiectasis the morphological determinants of (marginal) fluctuations in pulmonary function tests are uncertain. The aim of the present study was to evaluate serial computed tomography (CT) changes in relation to pulmonary function trends in patients with bronchiectasis. The relationships between pulmonary function indices and CT scans in 48 adult patients with bronchiectasis were evaluated at baseline and at follow-up, at a median interval of 28 months (range 6–74 months). Two independent observers semiquantitatively scored CT features of bronchial and small airways disease. At initial assessment, the severity of airflow obstruction was linked primarily to the extent of mosaic attenuation. However, serial changes in pulmonary function indices were only associated with serial changes in mucous plugging scores. Alterations in mucous plugging on serial CT were associated with changes in the severity of bronchiectasis and bronchial wall thickness. Greater severity of all three morphological abnormalities at baseline CT were predictive of significant declines in forced expiratory volume in one second, with severe bronchial wall thickness being the most adverse prognostic determinant. Variations in mucous plugging on computed tomography correlate with minor fluctuations in pulmonary function tests in bronchiectasis. However, the severity of bronchial wall thickness is the primary determinant of subsequent major functional decline.

An integrated clinicoradiological staging system for pulmonary sarcoidosis: a case-cohort study

BACKGROUND Mortality in pulmonary sarcoidosis is highly variable and a reliable prognostic algorithm for disease staging and for guiding management decisions is needed. The objective of this study is to derive and test a staging system for determining prognosis in pulmonary sarcoidosis. METHODS We identified the prognostic value of high-resolution computed tomography (HRCT) patterns and pulmonary function tests, including the composite physiological index (CPI) in patients with pulmonary sarcoidosis. We integrated prognostic physiological and HRCT variables to form a clinical staging algorithm predictive of mortality in a test cohort. The staging system was externally validated in a separate cohort by the same methods of discrimination used in the primary analysis and tested for clinical applicability by four test observers. FINDINGS The test cohort included 251 patients with pulmonary sarcoidosis in the study referred to the Sarcoidosis clinic at the Royal Brompton Hospital, UK, between Jan 1, 2000, and June 30, 2010. The CPI was the strongest predictor of mortality (HR 1·04, 95% CI 1·02-1·06, p<0·0001) in the test cohort. An optimal CPI threshold of 40 units was identified (HR 4·24, 2·84-6·33, p<0·0001). The CPI40, main pulmonary artery diameter to ascending aorta diameter ratio (MPAD/AAD), and an extent of fibrosis threshold of 20% were combined to form a staging algorithm. When assessed in the validation cohort (n=252), this staging system was strikingly more predictive of mortality than any individual variable alone (HR 5·89, 2·68-10·08, p<0·0001). The staging system was successfully applied to the test and validation cohorts combined, by two radiologists and two physicians. INTERPRETATION A clear prognostic separation of patients with pulmonary sarcoidosis is provided by a simple staging system integrating the CPI and two HRCT variables.

Chronic Lung Disease in Adolescents With Delayed Diagnosis of Vertically Acquired HIV Infection

A high burden of chronic lung disease (CLD) was found among 116 consecutive adolescents with vertically acquired human immunodeficiency virus in Zimbabwe. The main cause of HIV-associated CLD appears to be obliterative bronchiolitis, which has not previously been recognized among this patient group.

CARD15/NOD2 polymorphisms are associated with severe pulmonary sarcoidosis

Sarcoidosis and Crohn’s disease are heterogeneous systemic diseases characterised by granulomatous inflammation. Caspase recruitment domain (CARD)15 is a major susceptibility gene for Crohn’s disease, and specifically for ileal and fibrostenotic subtypes. The C-C chemokine receptor (CCR)5 gene has been associated with both parenchymal pulmonary sarcoidosis and perianal Crohn’s disease. This study explored associations between CARD15 polymorphisms, CCR5 haplotype and distinct pulmonary sarcoidosis subtypes. 185 Caucasian sarcoidosis patients were genotyped for CARD15 and CCR5 polymorphisms. The genetic data were compared with 347 healthy controls and were examined for associations with serial pulmonary function tests and chest radiographs. CARD15 genotypes did not differ between the unselected sarcoidosis cohort and controls. However, patients carrying the functional 2104T (702W) polymorphism were more likely to have radiographic stage IV disease at 4-yr follow-up. All patients possessing both CARD15 2104T and CCR5 HHC haplotype had stage IV disease at presentation. Carriage of 2104T was associated with worse forced expiratory volume in 1 s, whereas carriage of the CARD15 1761G (587R) polymorphism was associated with better lung function. For the first time, an association between two CARD15 polymorphisms and specific sarcoidosis phenotypes has been demonstrated, as well as an additive effect of possessing CARD15 2104T and CCR5 HHC haplotype.

Effect of aging on lung structure in vivo: assessment with densitometric and fractal analysis of high-resolution computed tomography data.

Purpose: To test the hypothesis that there is a difference between the lung computed tomography (CT) microstructure of asymptomatic older individuals and that of young individuals as evaluated by objective indices of complexity and density. Materials and Methods: Two study groups of nonsmoking urban-dwelling individuals over 75 years and under 55 years were prospectively identified. Thirty-three consecutive volunteers (21 older than 75 y and 12 less than 55 y) were included, and CTs were performed with concurrent pulmonary function testing. Pulmonary regions of interest (ROIs) were evaluated with fractal dimension (FD) analysis (an index of complexity), mean lung density (MLD), and percentage of pixels with lung density (LD) less than thresholds of −910 HU and −950 HU. The Student t test and the Mann-Whitney test were used to evaluate for differences in mean values between groups. The Pearson correlation coefficient was used to correlate mean FD value and LD data with pulmonary function. Results: Significant correlations of ROI MLD, LD −910 HU, and LD −950 HU with age and sex were shown (P=0.029–0.003). The ROI mean FD value was greater in younger individuals compared with older individuals (76.5±1.7 vs. 70.3±1.2; P=0.004). There was a correlation between Kco (gas-diffusing capacity adjusted for alveolar volume) and mean FD value (P=0.006) and MLD (P=0.015). Conclusion: The lung parenchyma of nonsmoking older urban-dwelling asymptomatic individuals has significantly different CT density and complexity compared with younger individuals.

Imaging appearance of thoracic amyloidosis.

Amyloidosis is a disease caused by the deposition of abnormal proteins within extracellular soft tissues, and affects the respiratory tract in 50% of cases. Pulmonary involvement may be secondary to systemic disease or due to the accumulation of locally produced amyloid, and this differentiation has important prognostic and therapeutic implications. This pictorial essay, using cases of biopsy-proven respiratory tract amyloidosis, aims to depict the spectrum of imaging findings, and those of CT in particular, that can be of use in distinguishing between the 2 typical patterns of the disease.