Prevalence of Burnout Among Cardiothoracic Radiologists: Stress Factors, Career Satisfaction, and Modality-specific Imaging Volumes.

PURPOSE: We investigated the impact of modality-specific volumes and other potential stressors on burnout and career-choice satisfaction. MATERIALS AND METHODS: An anonymous survey of 36 questions was sent by email to all 875 faculty members of the STR. These included 11 multiple-choice questions, 23 Likert questions, and 2 free-text questions. The Maslach Burnout Index was used to assess the prevalence of the 3 components of burnout (emotional exhaustion, depersonalization, and low professional accomplishment), and we assessed variations among the potential sources of stress with respect to the respondent sex, career stage, and practice setting. Respondents were asked to estimate daily work volume as if interpreting only chest radiographs (CXRs) or only chest/cardiac computed tomography (CT). Statistical analysis was performed using Excel (Microsoft), open-source statistical computing package pandas and SciPy for Python, and Jupyter Notebook, an open-source interactive computing platform. RESULTS: Although financial concerns (49.3%), lack of input into decisions (48.6%), and inadequate staffing (45.2%) were additional stressors, the major sources were work-life balance (67.4%) and workload (66.8%), which were more frequently cited by women than men (78.9% vs. 60.8%, P=0.001). Emotional exhaustion and depersonalization were related to higher CXR volumes. Although 83.2% were satisfied being a diagnostic radiologist, 18.8% had thought of leaving medicine. More than half of all radiologists interpreted ≥150 CXRs daily (51.1% vs. 53.6%); more in private practice read ≥200 CXRs (23.2% vs. 14.7%). Of the academic radiologists, 80.2% interpreted 21 to 49 CTs; twice as many in private practice read ≥50 CTs (25.5% vs. 12.7%). CONCLUSIONS: The contributing factors to cardiothoracic radiologist burnout vary by sex, career stage, and practice setting. Several stressors, especially work-life balance, were associated with higher burnout prevalence. Most respondents expressed career-choice satisfaction. Defining threshold work volumes associated with higher rates of burnout is an important first step in defining burnout prevention guardrails.

Interstitial Lung Disease in Firefighters: An Emerging Occupational Hazard.

Introduction: Occupational risk factors for interstitial lung disease (ILD) are a remediable aspect of this progressive pulmonary disorder. The association between firefighting and ILD is unknown. Our objective was to assess the characteristics of firefighters with ILD from a large single-center ILD registry. Methods: The University of Chicago ILD database was reviewed for patients with a history of firefighting. Clinical information was abstracted from the medical record. The prevalence rate ratio of firefighters in the database compared to the baseline prevalence of firefighting in the Chicago metropolitan area was calculated via the Poisson distribution. Results: Nineteen firefighters were identified; all were men. A variety of ILD subtypes were seen across the cohort, including four patients with a diagnosis of connective tissue disease. Patients had mild forced vital capacity (FVC) and moderate diffusing capacity for carbon monoxide (DLCO) decrements on presentation; three patients died and two received lung transplantation over an average follow-up time of 76 months. Firefighters were seen at a greater proportion in the ILD registry than in the general population with a prevalence rate ratio of 3.98. Conclusions: Firefighting was overrepresented in our cohort compared to the general population, suggesting that there may be a causative association between firefighting and the presence of ILD. The wide variety of ILD subtypes observed suggest that all ILD patients should be asked about their occupational history. Further investigation to identify occupational exposures and determine the benefit of remediation is needed.

Computed Tomography Findings Suggestive of Connective Tissue Disease in the Setting of Usual Interstitial Pneumonia.

PURPOSE: A usual interstitial pneumonia (UIP) pattern is common in idiopathic pulmonary fibrosis (IPF) and connective tissue disease-related interstitial lung disease (CTD-ILD). The purpose of the study was to validate imaging findings differentiating CTD-ILD from IPF in UIP. METHODS: Patients with a multidisciplinary diagnosis of CTD-ILD or IPF and a UIP pattern on computed tomography and/or pathology were included in this study. Prevalence of 3 computed tomography findings shown to be associated with CTD-ILD (the straight edge sign [SES], the exuberant honeycombing sign, and the anterior upper lobe sign [AULS]) were tabulated in CTD-ILD and IPF subjects. The ability of each of these signs to discriminate between CTD-ILD and IPF was evaluated. Survival analysis was also performed using log-rank analysis. RESULTS: The study cohort included 50 CTD-ILD and 100 IPF subjects with UIP. The SES and the AULS were more common in CTD-ILD than IPF (prevalence, 36.0% and 34.9% in CTD-ILD vs 8.3% and 17.2% in IPF, respectively [P = 0.0105 - <0.001]). The highest specificity (95.7%) of CTD-ILD diagnosis was seen with bilateral SES. Moreover, the SES was associated with improved survival (P = 0.0383), which appeared to be largely because of improvement in survival in IPF subjects. The presence of AULS was associated with pulmonary functional abnormalities. CONCLUSIONS: A radiographic UIP pattern with evidence of SES or the AULS should raise suspicion for CTD-ILD rather than IPF. Patients with IPF and SES have an attenuated disease course and might represent a different phenotype than those without the SES.

Differentiation of Idiopathic Pulmonary Fibrosis from Connective Tissue Disease-Related Interstitial Lung Disease Using Quantitative Imaging.

A usual interstitial pneumonia (UIP) imaging pattern can be seen in both idiopathic pulmonary fibrosis (IPF) and connective tissue disease-related interstitial lung disease (CTD-ILD). The purpose of this multicenter study was to assess whether quantitative imaging data differ between IPF and CTD-ILD in the setting of UIP. Patients evaluated at two medical centers with CTD-ILD or IPF and a UIP pattern on CT or pathology served as derivation and validation cohorts. Chest CT data were quantitatively analyzed including total volumes of honeycombing, reticulation, ground-glass opacity, normal lung, and vessel related structures (VRS). VRS was compared with forced vital capacity percent predicted (FVC%) and percent predicted diffusing capacity of the lungs for carbon monoxide (DLCO%). There were 296 subjects in total, with 40 CTD-ILD and 85 IPF subjects in the derivation cohort, and 62 CTD-ILD and 109 IPF subjects in the validation cohort. VRS was greater in IPF across the cohorts on univariate (p < 0.001) and multivariable (p < 0.001-0.047) analyses. VRS was inversely correlated with DLCO% in both cohorts on univariate (p < 0.001) and in the derivation cohort on multivariable analysis (p = 0.003) but not FVC%. Total volume of normal lung was associated with DLCO% (p < 0.001) and FVC% (p < 0.001-0.009) on multivariable analysis in both cohorts. VRS appears to have promise in differentiating CTD-ILD from IPF. The underlying pathophysiological relationship between VRS and ILD is complex and is likely not explained solely by lung fibrosis.

Vessel-related structures predict UIP pathology in those with a non-IPF pattern on CT.

OBJECTIVES: To determine if a quantitative imaging variable (vessel-related structures [VRS]) could identify subjects with a non-IPF diagnosis CT pattern who were highly likely to have UIP histologically. METHODS: Subjects with a multidisciplinary diagnosis of interstitial lung disease including surgical lung biopsy and chest CT within 1 year of each other were included in the study. Non-contrast CT scans were analyzed using the Computer-Aided Lung Informatics for Pathology Evaluation and Rating (CALIPER) program, which quantifies the amount of various abnormal CT patterns on chest CT. Quantitative data were analyzed relative to pathological diagnosis as well as the qualitative CT pattern. RESULTS: CALIPER-derived volumes of reticulation (p = 0.012), honeycombing (p = 0.017), and VRS (p < 0.001) were associated with a UIP pattern on pathology on univariate analysis but only VRS was associated with a UIP pathology on multivariable analysis (p = 0.013). Using a VRS cut-off of 173 cm3, the sensitivity and specificity for pathological UIP were similar to those for standard qualitative CT assessment (55.9% and 80.4% compared to 60.6% and 80.4%, respectively). VRS differentiated pathological UIP cases in those with a non-IPF diagnosis CT category (p < 0.001) but not in other qualitative CT patterns (typical UIP, probable UIP, and indeterminate for UIP). The rate of pathological UIP in those with VRS greater than 173 cm3 (84.2%) was nearly identical to those who had a qualitative CT pattern of probable UIP (88.9%). CONCLUSIONS: VRS may be an adjunct to CT in predicting pathology in patients with interstitial lung disease. KEY POINTS: • Volume of vessel-related structures (VRS) was associated with usual interstitial pneumonia (UIP) on pathology. • This differentiation arose from those with CT scans with a non-IPF diagnosis imaging pattern. • Higher VRS has similar diagnostic ramifications for UIP as probable UIP, transitively suggesting in patients with high VRS, pathology may be obviated.

Characteristics and Prevalence of Domestic and Occupational Inhalational Exposures Across Interstitial Lung Diseases.

BACKGROUND: Inhalational exposures are increasingly recognized as contributing factors in interstitial lung disease (ILD). However, the characteristics of both exposures and exposed patients are not well understood. We hypothesized that domestic and occupational inhalational exposures would be common and associated with differences in demographics, clinical characteristics, and transplant-free survival in patients with all forms of ILD. RESEARCH QUESTION: What is the prevalence of inhalational exposures across all ILD diagnoses, and are these exposures associated with differences in demographics, clinical characteristics, and transplant-free survival? STUDY DESIGN AND METHODS: Patients from a tertiary ILD clinic underwent an interview designed to capture inhalational exposures including occupational, home, hobbies, and tobacco. Demographic and survival data were collected from the electronic medical record. Survival analysis was performed using Cox regression to compare exposed vs unexposed patients and adjusted for gender-age-physiology score and smoking. RESULTS: One hundred and fifty-six patients seen between May and October 2018 were analyzed. Patients had a wide variety of multidisciplinary diagnoses, with a minority of patients with hypersensitivity pneumonitis (14%). One hundred and one patients (65%) had potentially relevant inhalational exposures. More men than women had a history of any exposure (82% vs 51%; P < .001), occupational exposure (66% vs 14%, P < .001), and multiple exposures (56% vs 26%, P < .001), respectively. White race was associated with bird and hobby exposure. Patients with any exposure had worse transplant-free survival (unadjusted hazard ratio, 2.58; 95% CI, 1.13-5.92; P = .025), but this was not statistically significant after adjustment (hazard ratio, 1.82; 95% CI, 0.77-4.27; P = .17). INTERPRETATION: A standardized interview revealed most patients across all types of ILD had potentially relevant inhalational exposures. Exposures were markedly different based on demographics and were associated with worse transplant-free survival, but this survival difference was not significant after multivariable adjustment. Identification and avoidance of exposures represent actionable targets in ILD management.

Prevalence of Burnout Among Cardiothoracic Radiologists.

PURPOSE: Burnout is a psychological syndrome in response to chronic occupational stressors. The prevalence of burnout among medical professionals has been increasing, and recent studies have shown that radiologists are among those affected. We investigated the prevalence of burnout and assessed associated factors among cardiothoracic radiologists. MATERIALS AND METHODS: Society of Thoracic Radiology members were invited to complete an anonymous cross-sectional survey that included an adapted Maslach Burnout Inventory and questions about demographics, work place characteristics, and stressors. RESULTS: The survey response rate was 33.1% (290/874). Per-item response rate ranged from 94% to 100% with a median of 99%. The prevalence of emotional exhaustion was 66.8% (186/283), depersonalization was 79% (223/283), and low personal accomplishment was 23% (65/280). There were no statistically significant differences between academic and private practice. There was a trend toward worse burnout in women, but this was not statistically significant. Being in early career (0 to 10 y since fellowship) was associated with low personal accomplishment [odds ratio (OR): 2.07, 95% confidence interval (CI): 1.08-3.99]. Those working fewer than 51 hours per week were significantly less likely to report emotional exhaustion (OR: 0.55, 95% CI: 0.33-0.90). The odds of emotional exhaustion for those producing fewer than 7500 work relative value units per year were approximately half of those exceeding that number (OR: 0.46, 95% CI: 0.22-0.95). CONCLUSIONS: The prevalence of burnout among cardiothoracic radiologists is comparable to that reported for radiologists in other subspecialties such as musculoskeletal and interventional radiology. High work relative value unit productivity and longer work hours are associated with higher prevalence of burnout.

Automated CT Analysis of Major Forms of Interstitial Lung Disease.

This study aimed to determine diagnostic and prognostic differences in major forms of interstitial lung disease using quantitative CT imaging. A retrospective study of 225 subjects with a multidisciplinary diagnosis of idiopathic pulmonary fibrosis (IPF), interstitial pneumonia with autoimmune features (IPAF), connective tissue disease (CTD), or chronic hypersensitivity pneumonitis (cHP) was conducted. Non-contrast CT scans were analyzed using the Computer Aided Lung Informatics for Pathology Evaluation and Rating (CALIPER) program. Resulting data were analyzed statistically using ANOVA and Student's t-test. Univariate, multivariable, and receiver operating characteristic analyses were conducted on patient mortality data. CALIPER analysis of axial distribution on CT scans in those with IPF demonstrated greater peripheral volumes of reticulation than either CTD (p = 0.033) or cHP (p = 0.007). CTD showed lower peripheral ground-glass opacity than IPF (p = 0.005) and IPAF (p = 0.004). Statistical analysis of zonal distributions revealed reduced lower zone ground-glass opacity in cHP than IPF (p = 0.044) or IPAF (p = 0.018). Analysis of pulmonary vascular-related structure (VRS) volume by diagnosis indicated greater VRS volume in IPF compared to CTD (p = 0.003) and cHP (p = 0.003) as well as in IPAF compared to CTD (p = 0.007) and cHP (p = 0.007). Increased reticulation (p = 0.043) and ground glass opacity (p = 0.032) were predictive of mortality on univariate analysis. Increased pulmonary VRS volume was predictive of mortality (p < 0.001) even after multivariate analysis (p = 0.041). Quantitative CT imaging revealed significant differences between ILD diagnoses in specific CT findings in axial and, to a lesser degree, zonal distributions. Increased pulmonary VRS volume seems to be associated with both diagnosis and survival.

Ontology-Based Radiology Teaching File Summarization, Coverage, and Integration.

Radiology teaching file repositories contain a large amount of information about patient health and radiologist interpretation of medical findings. Although valuable for radiology education, the use of teaching file repositories has been hindered by the ability to perform advanced searches on these repositories given the unstructured format of the data and the sparseness of the different repositories. Our term coverage analysis of two major medical ontologies, Radiology Lexicon (RadLex) and Unified Medical Language System (UMLS) Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT), and two teaching file repositories, Medical Imaging Resource Community (MIRC) and MyPacs, showed that both ontologies combined cover 56.3% of terms in the MIRC and only 17.9% of terms in MyPacs. Furthermore, the overlap between the two ontologies (i.e., terms included by both the RadLex and UMLS SNOMED CT) was a mere 5.6% for the MIRC and 2% for the RadLex. Clustering the content of the teaching file repositories showed that they focus on different diagnostic areas within radiology. The MIRC teaching file covers mostly pediatric cases; a few cases are female patients with heart-, chest-, and bone-related diseases. The MyPacs contains a range of different diseases with no focus on a particular disease category, gender, or age group. MyPacs also provides a wide variety of cases related to the neck, face, heart, chest, and breast. These findings provide valuable insights on what new cases should be added or how existent cases may be integrated to provide more comprehensive data repositories. Similarly, the low-term coverage by the ontologies shows the need to expand ontologies with new terminology such as new terms learned from these teaching file repositories and validated by experts. While our methodology to organize and index data using clustering approaches and medical ontologies is applied to teaching file repositories, it can be applied to any other medical clinical data.

Anti-RNA binding protein positivity in idiopathic interstitial pneumonia.

INTRODUCTION: Idiopathic interstitial pneumonias (IIP) are diffuse lung diseases whose cause is unknown and often present with features of autoimmunity despite not meeting criteria for a connective tissue disease (CTD). Recent studies suggest that anti-RNA binding protein (anti-RBP) antibodies, which include anti-SSA, anti-SSB, anti-Sm, and anti-RNP, play a role in the loss of immune tolerance and severity of pulmonary hypertension (PH) in CTDs. We hypothesized that anti-RBP positive (RBP+) subjects would have worse measures of lung function, radiographic findings, PH, and survival than anti-RBP negative (RBP-) subjects. METHODS: Subjects with both IIP and serologies for review were identified retrospectively and stratified based on anti-RBP antibody seropositivity. Baseline cohort characteristics, pulmonary function tests (PFT), ambulatory oxygen requirement, radiographic characteristics, markers of PH, and transplant-free survival were compared between anti-RBP positive and negative groups. RESULTS: Five hundred twenty patients with IIP were identified, of which ten percent (n = 53) were anti-RBP positive. RBP+ as compared to RBP- subjects had significantly worse PFTs as indicated by FEV1 (59.6 vs. 64.9, p = 0.046) and FVC (71.6 vs. 78.8, p = 0.018). There was a higher prevalence of radiographic honeycombing (49.1% vs. 38.3%, p = 0.006) and emphysema (22.6% vs. 5.1%, p < 0.001) in the RBP+ group despite no difference in smoking history. The Pulmonary Artery-Aorta ratio was also larger in the RBP+ group (0.93 vs. 0.88, p = 0.040). There was no difference in transplant-free survival between groups (log rank = 0.912). CONCLUSION: Anti-RBP+ IIP patients may have worse lung function, increased chest radiographic abnormalities, and PH compared with those without these antibodies.

Computed Tomography Honeycombing Identifies a Progressive Fibrotic Phenotype with Increased Mortality across Diverse Interstitial Lung Diseases.

Rationale: Honeycombing on chest computed tomography (CT) has been described in diverse forms of interstitial lung disease (ILD); however, its prevalence and association with mortality across the spectrum of ILD remains unclear. Objective: To determine the prevalence and prognostic value of CT honeycombing and characterize associated mortality patterns across diverse ILD subtypes in a multicenter cohort. Methods: This was an observational cohort study of adult participants with multidisciplinary or adjudicated ILD diagnosis and documentation of chest CT imaging at index diagnosis across five U.S. hospitals (one tertiary and four nontertiary medical centers). Participants were stratified based on presence or absence of CT honeycombing. Vital status was determined from review of medical records and social security death index. Transplant-free survival was analyzed using univariate and multivariable Cox regression. Results: The sample comprised 1,330 participants (mean age, 66.8 yr; 50% men) with 4,831 person-years of follow-up. The prevalences of CT honeycombing were 42.0%, 41.9%, 37.6%, and 28.6% in chronic hypersensitivity pneumonitis, connective tissue disease-related ILD (CTD-ILD), idiopathic pulmonary fibrosis (IPF), and unclassifiable/other ILDs, respectively. Among those with CT honeycombing, cumulative mortality hazards were similar across ILD subtypes, except for CTD-ILD, which had a lower mortality hazard. Overall, the mean survival time was shorter among those with CT honeycombing (107 mo; 95% confidence interval [CI], 92-122 mo) than those without CT honeycombing (161 mo; 95% CI, 147-174 mo). CT honeycombing was associated with an increased mortality rate (hazard ratio, 1.72; 95% CI, 1.38-2.14) even after adjustment for center, sex, age, forced vital capacity, diffusing capacity, ILD subtype, and use of immunosuppressive therapy (hazard ratio, 1.62; 95% CI, 1.29-2.02). CT honeycombing was associated with an increased mortality rate within non-IPF ILD subgroups (chronic hypersensitivity pneumonitis, CTD-ILD, and unclassifiable/other ILD). In IPF, however, mortality rates were similar between those with and without CT honeycombing. Conclusions: CT honeycombing is prevalent in diverse forms of ILD and uniquely identifies a progressive fibrotic ILD phenotype with a high mortality rate similar to IPF. CT honeycombing did not confer additional risk in IPF, which is already known to be a progressive fibrotic ILD phenotype regardless of the presence of CT honeycombing.

Prognosticating Outcomes in Interstitial Lung Disease by Mediastinal Lymph Node Assessment. An Observational Cohort Study with Independent Validation.

RATIONALE: Mediastinal lymph node (MLN) enlargement on chest computed tomography (CT) is prevalent in patients with interstitial lung disease (ILD) and may reflect immunologic activation and subsequent cytokine-mediated immune cell trafficking. OBJECTIVES: We aimed to determine whether MLN enlargement on chest CT predicts clinical outcomes and circulating cytokine levels in ILD. METHODS: MLN measurements were obtained from chest CT scans of patients with ILD at baseline evaluation over a 10-year period. Patients with sarcoidosis and drug toxicity-related ILD were excluded. MLN diameter and location were assessed. Plasma cytokine levels were analyzed in a subset of patients. The primary outcome was transplant-free survival (TFS). Secondary outcomes included all-cause and respiratory hospitalizations, lung function, and plasma cytokine concentrations. Cox regression was used to assess mortality risk. Outcomes were assessed in three independent ILD cohorts. MEASUREMENTS AND MAIN RESULTS: Chest CT scans were assessed in 1,094 patients (mean age, 64 yr; 52% male). MLN enlargement (≥10 mm) was present in 66% (n = 726) and strongly predicted TFS (hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.12-2.10; P = 0.008) and risk of all-cause and respiratory hospitalizations (internal rate of return [IRR], 1.52; 95% CI, 1.17-1.98; P = 0.002; and IRR, 1.71; 95% CI, 1.15-2.53; P = 0.008, respectively) when compared with subjects with MLN <10 mm. Patients with MLN enlargement had lower lung function and decreased plasma concentrations of soluble CD40L (376 pg/ml vs. 505 pg/ml, P = 0.001) compared with those without MLN enlargement. Plasma IL-10 concentration >45 pg/ml predicted mortality (HR, 4.21; 95% CI, 1.21-14.68; P = 0.024). Independent analysis of external datasets confirmed these findings. CONCLUSIONS: MLN enlargement predicts TFS and hospitalization risk in ILD and is associated with decreased levels of a key circulating cytokine, soluble CD40L. Incorporating MLN and cytokine findings into current prediction models might improve ILD prognostication.

African-American race and mortality in interstitial lung disease: a multicentre propensity-matched analysis.

We studied whether African-American race is associated with younger age and decreased survival time at diagnosis of interstitial lung disease (ILD).We performed a multicentre, propensity score-matched analysis of patients with an ILD diagnosis followed at five US hospitals between 2006 and 2016. African-Americans were matched with patients of other races based on a time-dependent propensity score calculated from multiple patient, physiological, diagnostic and hospital characteristics. Multivariable logistic regression models were used. All-cause mortality and hospitalisations were compared between race-stratified patient cohorts with ILD, and sensitivity analyses were performed.The study included 1640 patients with ILD, 13% of whom were African-American, followed over 5041 person-years. When compared with patients of other races, African-Americans with ILD were younger at diagnosis (56 years versus 67 years), but in the propensity-matched analyses had greater survival (hazard ratio 0.46, 95% CI 0.28-0.77; p=0.003) despite similar risk of respiratory hospitalisations (relative risk 1.04, 95% CI 0.83-1.31; p=0.709), and similar GAP-ILD (gender-age-physiology-ILD) scores at study entry. Sensitivity analyses in a separate cohort of 9503 patients with code-based ILD diagnosis demonstrated a similar association of baseline demographic characteristics with all-cause mortality.We conclude that African-Americans demonstrate a unique phenotype associated with younger age at ILD diagnosis and perhaps longer survival time.

Differentiating Usual Interstitial Pneumonia From Nonspecific Interstitial Pneumonia Using High-resolution Computed Tomography: The "Straight-edge Sign".

PURPOSE: The purpose of this article was to determine whether a novel finding on coronal computed tomography (CT) can help differentiate usual interstitial pneumonia (UIP) from nonspecific interstitial pneumonia (NSIP) in order to obviate lung biopsy. MATERIALS AND METHODS: Two chest radiologists, blinded to clinical data, reviewed 3 preselected coronal images from CT scans, performed within 1 year of surgical lung biopsy (SLB), from 51 patients with biopsy-proven UIP and 15 with biopsy-proven NSIP. The 198 (66×3) images were anonymized and randomized. The radiologists assessed each coronal image for the presence or absence of the straight-edge sign (SES) on both the right and left sides, anecdotally thought to be more common in NSIP than in UIP. The SES was defined as reticulation isolated to the lung bases with sharp demarcation in the craniocaudal plane and without substantial extension along the lateral margins of the lungs. A validation cohort from a second medical center was also evaluated to reassess our findings. RESULTS: The absence of a bilateral SES yielded a sensitivity, specificity, positive predictive value (PPV), and negative predictive value of 56.9%, 93.3%, 96.7%, and 38.9%, respectively, for UIP on SLB. The unilateral or bilateral absence of the SES yielded a sensitivity, specificity, PPV, and negative predictive value of 76.5%, 66.7%, 88.6%, and 45.5%, respectively, for UIP on SLB. For the 11 subjects with an overall CT pattern consistent with NSIP but a pathologic diagnosis of UIP, the SES was absent in 6 (54.5%) subjects. In the validation cohort, the SES was much more common in NSIP than in UIP (46.6% compared with 3.3%, respectively; P<0.001). CONCLUSION: The absence of the SES has a high PPV for biopsy-proven UIP. Bilateral absence of the SES has high specificity (93.3%) for biopsy-proven UIP. The SES may be useful for differentiating UIP from NSIP.

CT-Pathologic Correlation of Major Types of Pulmonary Fibrosis: Insights for Revisions to Current Guidelines.

OBJECTIVE: The purpose of this study was to assess the diagnostic significance of CT patterns that cannot be classified according to current idiopathic pulmonary fibrosis (IPF) guidelines and of specific findings of the inconsistent with usual interstitial pneumonitis (UIP) pattern. MATERIALS AND METHODS: Subjects with a multidisciplinary diagnosis of interstitial lung disease who had undergone surgical lung biopsy and chest CT within 1 year of each other were included in the study. The predominant distribution and pattern of disease were scored. Cases were classified as UIP, possible UIP, or inconsistent with UIP at chest CT according to 2011 IPF guidelines. Cases that could not be confidently categorized with current guidelines were annotated as indeterminate. RESULTS: UIP, possible UIP, and inconsistent with UIP CT patterns were associated with pathologic UIP in 89.6%, 81.6%, and 60.0% of subjects. An indeterminate CT pattern (7.7% [20/259]) was associated with a UIP pathologic diagnosis in 55.0% of cases. This finding was not statistically different from the findings in the group with the inconsistent with UIP CT pattern (p = 0.677) but was different from the findings in the UIP (p < 0.001) and possible UIP (p = 0.031) groups. In regard to specific findings of the inconsistent with UIP CT category, ground-glass opacity, air-trapping, consolidation, and axial distribution were associated with a non-UIP pathologic diagnosis; however, there was no significant association with zonal distribution. CONCLUSION: A substantial minority of cases cannot be confidently categorized according to current guidelines for IPF and differ diagnostically from the possible UIP and UIP CT categories. The term "inconsistent with UIP" is misleading and should be renamed.

N-acetylcysteine exposure is associated with improved survival in anti-nuclear antibody seropositive patients with usual interstitial pneumonia.

BACKGROUND: Mortality is similarly high among individuals with usual interstitial pneumonia (UIP) due to idiopathic pulmonary fibrosis (IPF) and interstitial pneumonia with autoimmune features (IPAF). Circulating anti-nuclear antibodies (ANA) are commonly found in this patient population, suggesting possible aberrant immune activation. Because an environment of oxidative stress can result from immunologic activation, we hypothesized that ANA positive patients with UIP would have improved outcome when exposed to the antioxidant N-acetylcysteine (NAC) compared to ANA negative patients. METHODS: A single center, retrospective cohort analysis was performed. Patients with UIP due to IPF and IPAF were stratified according to ANA status to and NAC exposure. Transplant-free survival (TFS) was assessed using the Kaplan-Meier estimator and multivariable Cox regression adjusted for diagnosis, gender/age/physiology score, immunosuppressant exposure and anti-fibrotic exposure. RESULTS: Of 293 individuals with UIP due to IPF (74%) or IPAF (26%), NAC exposure was documented in 58 (19.8%). Among NAC exposed individuals, 33 (56.9%) were ANA seropositive and 25 (43.1%) were seronegative. NAC exposure was associated with improved TFS survival among ANA seropositive individuals in unadjusted analysis (plogrank = 0.02) and after multi-variable adjustment (HR 0.51, 95% CI 0.30-0.87; p = 0.01). There was no association between NAC exposure and TFS in ANA seronegative individuals (HR 1.26, 95% CI 0.69-2.32; p = 0.45). Formal interaction testing confirmed NAC*ANA interaction (p = 0.04) and sensitivity analysis demonstrated an increasing effect size associated with NAC therapy as ANA titer increased. Among patients with available genetic data, a marginally higher proportion of ANA positive patients (p = 0.08) carried the rs3750920 (TOLLIP) genotype previously shown to predict favorable outcome in NAC exposed patients. CONCLUSION: NAC exposure is associated with improved transplant-free survival ANA positive patients with UIP. These findings support the prospective collection of ANA data in in future NAC clinical trials performed in patients with UIP.

CT Features of the Usual Interstitial Pneumonia Pattern: Differentiating Connective Tissue Disease-Associated Interstitial Lung Disease From Idiopathic Pulmonary Fibrosis.

OBJECTIVE: A substantial proportion of cases of usual interstitial pneumonia (UIP) are due to connective tissue disease (CTD)-associated interstitial lung disease (ILD). The purpose of this study was to determine whether specific CT findings can help differentiate a UIP pattern of CTD-ILD from a UIP pattern of idiopathic pulmonary fibrosis (IPF) and whether these signs are associated with survival. MATERIALS AND METHODS: Adults visiting an ILD clinic from 2006 to 2015 enrolled in a research registry with a multidisciplinary diagnosis of CTD-ILD or IPF and a UIP pattern at high-resolution CT were included in the study. In these subjects with CT findings of UIP due to either IPF or CTD-ILD, three CT findings anecdotally associated with CTD-ILD were assessed for diagnostic accuracy: the "straight-edge" sign, the "exuberant honeycombing" sign, and the "anterior upper lobe" sign. Survival assessments were performed with univariate and multivariable techniques. RESULTS: The subjects included 63 patients who had CTD-ILD and 133 patients who had IPF with a UIP pattern at CT. All three CT signs were significantly more common in subjects with CTD-ILD than those with IPF (prevalence, 22.2-25.4% for CTD-ILD, 6.0-12.8% for IPF; p = 0.028 to < 0.001). The highest specificity (94.0%) and sensitivity (25.4%) were seen for the straight-edge sign. No CT sign was associated with survival in multivariable analysis. CONCLUSION: Although UIP is usually associated with IPF, the index of suspicion for CTD-ILD should be raised in the care of patients with any of the three CT signs. A thorough workup for CTD-ILD should be pursued, including referral to the rheumatology department.

Phenotypic Clusters Predict Outcomes in a Longitudinal Interstitial Lung Disease Cohort.

BACKGROUND: The current interstitial lung disease (ILD) classification has overlapping clinical presentations and outcomes. Cluster analysis modeling is a valuable tool in identifying distinct clinical phenotypes in heterogeneous diseases. However, this approach has yet to be implemented in ILD. METHODS: Using cluster analysis, novel ILD phenotypes were identified among subjects from a longitudinal ILD cohort, and outcomes were stratified according to phenotypic clusters compared with subgroups according to current American Thoracic Society/European Respiratory Society ILD classification criteria. RESULTS: Among subjects with complete data for baseline variables (N = 770), four clusters were identified. Cluster 1 (ie, younger white obese female subjects) had the highest baseline FVC and diffusion capacity of the lung for carbon monoxide (Dlco). Cluster 2 (ie, younger African-American female subjects with elevated antinuclear antibody titers) had the lowest baseline FVC. Cluster 3 (ie, elderly white male smokers with coexistent emphysema) had intermediate FVC and Dlco. Cluster 4 (ie, elderly white male smokers with severe honeycombing) had the lowest baseline Dlco. Compared with classification according to ILD subgroup, stratification according to phenotypic clusters was associated with significant differences in monthly FVC decline (Cluster 4, -0.30% vs Cluster 2, 0.01%; P < .0001). Stratification by using clusters also independently predicted progression-free survival (P < .001) and transplant-free survival (P < .001). CONCLUSIONS: Among adults with diverse chronic ILDs, cluster analysis using baseline characteristics identified four distinct clinical phenotypes that might better predict meaningful clinical outcomes than current ILD diagnostic criteria.

Autoimmune Hypothyroidism As a Predictor of Mortality in Chronic Hypersensitivity Pneumonitis.

BACKGROUND: Chronic hypersensitivity pneumonitis (CHP) is a fibrotic parenchymal lung disease that occurs when inhalation of environmental antigens leads to immune dysregulation. Autoimmune features have recently been identified as potentially important among patients with CHP. However, the relationship between hypothyroidism (HT) and CHP is unknown. In this study, we investigate the prevalence and impact of HT among patients with CHP. METHODS: We conducted a retrospective, case-control analysis. We identified 121 patients at the University of Chicago Interstitial Lung Disease Center with a multidisciplinary diagnosis of CHP. These patients were matched 3:1 according to age, sex, and race to 363 control subjects with asthma from 2006 to 2015. We analyzed demographics, clinical characteristics, and survival between both groups and assessed the relationship of HT with CHP. Survival analysis was performed using Cox proportional hazards modeling. RESULTS: Patients with CHP had higher prevalence of HT (25.6%, n = 31) compared to controls (10.7%, n = 39; OR, 2.86; 95% CI, 1.62-4.99; P < 0.0001). Compared to CHP alone, patients with CHP/HT were more likely to be female (80.6 vs 51.1%, P = 0.004), have increased incidence of autoimmune disease (19.4 vs 3.3%, P = 0.009), antinuclear antibody seropositivity (80.6 vs 57.0%, P = 0.019), and higher TSH levels (4.0 vs 1.9 mIU/L, P < 0.0001). HT was a significant independent predictor of mortality among CHP patients with seropositive ANA (HR, 3.39; 95% CI, 1.31-8.80; P = 0.012). CONCLUSION: HT is common in patients with CHP and may carry prognostic significance in patients with features of autoimmunity. Further research exploring common pathogenic pathways between autoimmune HT and CHP may illuminate the association of HT with survival.