Estimating the Clinical Impact of Photon-Counting-Detector CT in Diagnosing Usual Interstitial Pneumonia.

OBJECTIVE: The aim of this study was to evaluate the clinical impact of a higher spatial resolution, full field-of-view investigational photon-counting detector computed tomography (PCD-CT) on radiologist confidence in imaging findings and diagnosis of usual interstitial pneumonia (UIP) compared with conventional energy-integrating detector CT (EID-CT). MATERIALS AND METHODS: Patients suspected of interstitial lung disease were scanned on a PCD-CT system after informed consent and a clinically indicated EID-CT. In 2 sessions, 3 thoracic radiologists blinded to clinical history and scanner type evaluated CT images of the right and left lungs separately on EID- or PCD-CT, reviewing each lung once/session, rating confidence in imaging findings of reticulation, traction bronchiectasis, honeycombing, ground-glass opacities (GGOs), mosaic pattern, and lower lobe predominance (100-point scale: 0-33, likely absent; 34-66, indeterminate; 67-100, likely present). Radiologists also rated confidence for the probability of UIP (0-20, normal; 21-40, inconsistent with UIP; 41-60, indeterminate UIP; 61-81; probable UIP; 81-100, definite UIP) and graded image quality. Because a confidence scale of 50 represented completely equivocal findings, magnitude score (the absolute value of confidence scores from 50) was used for analysis (higher scores were more confident). Image noise was measured for each modality. The magnitude score was compared using linear mixed effects regression. The consistency of findings and diagnosis between 2 scanners were evaluated using McNemar test and weighted κ statistics, respectively. RESULTS: A total of 30 patients (mean age, 68.8 ± 11.0 years; M:F = 18:12) underwent conventional EID-CT (median CTDI vol , 7.88 mGy) and research PCD-CT (median CTDI vol , 6.49 mGy). The magnitude scores in PCD-CT were significantly higher than EID-CT for imaging findings of reticulation (40.7 vs 38.3; P = 0.023), GGO (34.4 vs 31.7; P = 0.019), and mosaic pattern (38.6 vs 35.9; P = 0.013), but not for other imaging findings ( P ≥ 0.130) or confidence in UIP (34.1 vs 22.2; P < 0.059). Magnitude score of probability of UIP in PCD-CT was significantly higher than EID-CT in one reader (26.0 vs 21.5; P = 0.009). Photon-counting detector CT demonstrated a decreased number of indeterminate GGO (17 vs 26), an increased number of unlikely GGO (74 vs 50), and an increased number of likely reticulations (140 vs 130) relative to EID-CT. Interobserver agreements among 3 readers for imaging findings and probability of UIP were similar between PCD-CT and EID-CT (intraclass coefficient: 0.507-0.818 vs 0.601-0.848). Photon-counting detector CT had higher scores in overall image quality (4.84 ± 0.38) than those in EID-CT (4.02 ± 0.40; P < 0.001) despite increased image noise (mean 85.5 vs 36.1 HU). CONCLUSIONS: Photon-counting detector CT provided better image quality and improved the reader confidence for presence or absence of imaging findings of reticulation, GGO, and mosaic pattern with idiosyncratic improvement in confidence in UIP presence.

Excipient lung disease secondary to intravenous heroin use.

We present a case of a woman who had progressive shortness of breath and wheezing with a mild restrictive pulmonary function pattern. She was initially diagnosed with eosinophilic granulomatosis with polyangiitis on the basis of peripheral eosinophilia, bronchoalveolar lavage eosinophilia (47%) and surgical lung biopsy findings. Six months following her diagnosis, the patient returned because of persistent symptoms, and a second review of the lung biopsy revealed thrombotic lesions in the pulmonary vessels with polarisable foreign body materials, associated giant cell reactions and numerous eosinophil infiltrates, consistent with intravenous drug abuse. Further investigation showed that she had a history of intravenous heroin overdose, and the diagnosis of excipient lung disease was made. This case highlights the importance of expert pathological, radiological and clinical review of complex presentations and the need for a thorough medication and drug use history review.

International expert consensus recommendations for the diagnosis and treatment of Langerhans cell histiocytosis in adults.

Langerhans cell histiocytosis (LCH) can affect children and adults with a wide variety of clinical manifestations, including unifocal, single-system multifocal, single-system pulmonary (smoking-associated), or multisystem disease. The existing paradigms in the management of LCH in adults are mostly derived from the pediatric literature. Over the last decade, the discovery of clonality and MAPK-ERK pathway mutations in most cases led to the recognition of LCH as a hematopoietic neoplasm, opening the doors for treatment with targeted therapies. These advances have necessitated an update of the existing recommendations for the diagnosis and treatment of LCH in adults. This document presents consensus recommendations that resulted from the discussions at the annual Histiocyte Society meeting in 2019, encompassing clinical features, classification, diagnostic criteria, treatment algorithm, and response assessment for adults with LCH. The recommendations favor the use of 18F-Fluorodeoxyglucose positron emission tomography-based imaging for staging and response assessment in the majority of cases. Most adults with unifocal disease may be cured by local therapies, while the first-line treatment for single-system pulmonary LCH remains smoking cessation. Among patients not amenable or unresponsive to these treatments and/or have multifocal and multisystem disease, systemic treatments are recommended. Preferred systemic treatments in adults with LCH include cladribine or cytarabine, with the emerging role of targeted (BRAF and MEK inhibitor) therapies. Despite documented responses to treatments, many patients struggle with a high symptom burden from pain, fatigue, and mood disorders that should be acknowledged and managed appropriately.

Langerhans cell histiocytosis with lung involvement in isolation and multisystem disease: Staging, natural history, and comparative survival.

Langerhans cell histiocytosis (LCH) is a histiocytic neoplasm that can involve the lungs as single system (LCH-SSL) or multisystem disease (LCH-MSL). The role of full-body radiographic staging to determine whether patients have LCH-SSL or LCH-MSL is unclear. Long-term outcomes of LCH-SSL versus LCH-MSL and multisystem without lung involvement (LCH-MSNL) are unknown. A retrospective study of adult LCH patients seen at our center from January 2000 to 2020 was performed. In Part 1, we addressed utility of whole-body staging imaging among those presenting with isolated pulmonary signs or symptoms. Staging was defined as fluorodeoxyglucose positron emission tomography-computed tomography (CT) or whole-body CT obtained within 3 months of diagnosis. In Part 2, we examined the frequency of developing extra-pulmonary disease over time and mortality in patients with LCH-SSL. In Part 3, we compared the overall survival of LCH-SSL, LCH-MSL, and LCH-MSNL. Part 1: 240 patients with LCH were identified. A total of 112 (47%) had pulmonary signs or symptoms at presentation. Thirty-four (30%) underwent radiographic staging and only one showed evidence of extra-pulmonary disease. Part 2: 108 (45%) were LCH-SSL. Median follow-up duration of 4.5 years (95% confidence interval [CI]: 2.9-6.0). None developed extra-pulmonary disease. Part 3: 5-year survival: 94% (95% CI: 84%-98%) for LCH-SSL, 78% (95% CI: 59%-90%) for LCH-MSL, and 75% (95% CI: 53%-89%) for LCH-MSNL. LCH patients presenting with isolated pulmonary signs or symptoms rarely have extra-pulmonary involvement at the time of diagnosis and generally do not develop extra-pulmonary progression. LCH-SSL has the best overall survival, while LCH-MSL and LCH-MSNL have similar clinical outcomes.

Diffuse Pulmonary Ossification on High-Resolution Computed Tomography in Idiopathic Pulmonary Fibrosis, Systemic Sclerosis-Related Interstitial Lung Disease, and Chronic Hypersensitivity Pneumonitis: A Comparative Study.

OBJECTIVE: The aim of the study was to compare the prevalence of diffuse pulmonary ossification (DPO) in idiopathic pulmonary fibrosis (IPF), systemic sclerosis (SSc)-related interstitial lung disease (ILD), and chronic hypersensitivity pneumonitis (HP). METHODS: High-resolution computed tomography (HRCT) from 71 IPF, 67 SSc-ILD, and 75 HP cases were independently evaluated by 2 thoracic radiologists blinded to patient data. Studies were assessed for the presence of DPO, HRCT scanning pattern, stigmata of granulomatous infection, and honeycombing. RESULTS: The prevalence of DPO was significantly higher in cases of IPF and SSc compared with HP, although there was no significant difference in prevalence between the IPF and SSc groups, even when accounting for the presence of prior granulomatous infection. Interobserver agreement for the presence of DPO was substantial. CONCLUSIONS: Although prevalence DPO on HRCT varies between some forms of ILD, the use of DPO to influence characterization of ILD should be considered with caution.

ACR Appropriateness Criteria® Occupational Lung Diseases.

Ordering the appropriate diagnostic imaging for occupational lung disease requires a firm understanding of the relationship between occupational exposure and expected lower respiratory track manifestation. Where particular inorganic dust exposures typically lead to nodular and interstitial lung disease, other occupational exposures may lead to isolated small airway obstruction. Certain workplace exposures, like asbestos, increase the risk of malignancy, but also produce pulmonary findings that mimic malignancy. This publication aims to delineate the common and special considerations associated with occupational lung disease to assist the ordering physician in selecting the most appropriate imaging study, while still stressing the importance of a multidisciplinary approach. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Pulmonary Low Attenuation Areas on CT in ANCA-associated Vasculitis: A quantitative and semi-quantitative analysis correlated with pulmonary function testing for obstructive airway disease.

OBJECTIVE: A subset of ANCA-associated vasculitis (AAV) patients are known to manifest obstructive airway disease. Using low attenuation areas (LAA) in the lung on HRCT as an imaging marker for obstructive airway disease, we analyze HRCT studies in AAV patients compared to a matched non-AAV group using visual semi-quantitative and automated quantitative analysis for presence and severity of LAA. Furthermore, HRCT and pulmonary function testing are compared to assess agreement between tests for airway obstruction. MATERIALS AND METHODS: 100 randomly selected AAV patients with HRCT were compared to 100 best-fit matched control subjects. HRCT cases were visually assessed for LAA, along with additional pulmonary patterns. Automated quantitative software analyzed images for texture features and volume of attenuation values of -950 HU or less (e-950). Evidence of obstructive airway disease established by pulmonary function testing, when available, was compared to HRCT analysis for LAA. Additional clinical information, diagnostic testing and mortality data were also compared. RESULTS: Both study groups were comprised of 57 females and 43 males with 35 smokers averaging 10.7 pk/yrs, with average age for the AAV and control groups being 59.4 yrs and 61.9 yrs, respectively. Visually, 46 AAV patients demonstrated LAA on HRCT compared to 25 control patients (p=0.0017) with the difference in LAA presence entirely within the non-smoking subgroup (25 to 3, respectively, p=<0.0001). Quantitatively, greater than 5% e-950 demonstrated similar significant differences between AAV (36/100) and controls (19/100) (p=0.0065), predominantly in non-smokers (p=0.006). Obstruction on PFTs was significantly increased in AAV (p=0.002) with moderate agreement of obstructive disease with visual LAA on CT (Kappa 0.509). Of the obstructive disease metrics, visual LAA on CT correlated best with mortality (p=0.0085). CONCLUSION: Visual LAA and automated quantitative analysis for e-950 on HRCT demonstrate statistically significant increases in AAV patients compared to age, gender and smoking matched controls, with differences primarily seen in the non-smoking subset. AAV revealed statistically significant greater obstructive pulmonary disease on PFTs (Sarcoidosis Vasc Diffuse Lung Dis 2020; 37 (4): e2020016).

Spontaneous Pneumomediastinum in Connective Tissue Diseases.

BACKGROUND: Spontaneous pneumomediastinum (SP) is an uncommon disorder but has been described in cases with connective tissue diseases (CTDs), most commonly dermatomyositis and polymyositis. We aimed to explore this relationship by analyzing the characteristics of CTD patients with SP. METHODS: Using a computer-assisted search, we identified 25 patients with CTD and SP evaluated between January 1997 and December 2016 at our institution. Clinicoradiologic characteristics, treatment, and outcomes were extracted and chest computed tomography studies analyzed. RESULTS: We identified 25 patients with CTD and SP. Median (range) age at SP occurrence was 55 (18-82) years, and 60% of the patients were women. Smoking history was present in 37%. Spontaneous pneumomediastinum was symptomatic in 56% of patients. Eighteen patients (72%) had a known CTD diagnosis, and 20 patients (80%) manifested radiologic evidence of interstitial lung disease. Spontaneous pneumomediastinum diagnosis was achieved with chest radiography in 20% of cases and chest computed tomography in the other cases. Spontaneous pneumomediastinum was managed with expectant observation alone in 22 cases (88%). Four patients (16%) had concomitant pneumothorax, 1 of whom required chest tube drainage. There were no deaths attributable to SP during the median (range) follow-up of 13 (0-174) months. Cumulative survival was 52% at 1 year and 40% at 2 years. CONCLUSIONS: Spontaneous pneumomediastinum is an uncommon manifestation of CTD and usually occurs in the presence of interstitial lung disease. Although SP seems to be associated with a relatively benign short-term course, occurrence of SP in CTD patients may be a poor prognostic factor.

High-pitch versus standard mode CT pulmonary angiography: a comparison of indeterminate studies.

PURPOSE: To compare the causes of indeterminate CT pulmonary angiograms using standard mode and high-pitch mode, and determine at what level of the pulmonary arterial tree studies were non-diagnostic. METHODS: IRB approval was obtained. A retrospective review of patients at our institution who underwent a CT pulmonary angiogram, between November 1, 2015 and February 10, 2016 was performed. CT pulmonary angiograms using both high-pitch mode and standard mode were evaluated with positive and indeterminate rates calculated. Causes of indeterminate studies and the level of the pulmonary arterial tree at which the study became non-diagnostic were determined by a board certified radiologist by looking at the images of each indeterminate study. The indeterminate rates were compared between high-pitch and standard modes using a generalized estimating equation. RESULTS: Five hundred fifty-nine CT pulmonary angiograms using high-pitch mode were evaluated, while 661 standard mode scans were evaluated. 69/559 (12.3%) scans with high-pitch mode were positive and 84/661 (12.7%) scans with standard mode were positive (not statistically significant, p > 0.05). There was a higher rate of indeterminate scans with standard mode compared to the high-pitch mode (80 [12.1%] standard vs. 25 [4.5%] high-pitch, p value < 0.0001). Findings were indeterminate at the lobar level in 4 (16%), at the segmental level in 11 (44%), and at the subsegmental level in 10 (40%) using high-pitch mode. The most common causes of an indeterminate scan using high-pitch mode were motion in 11 (44%), transient interruption of contrast in 6 (24%), and contrast timing in 5 (20%). Findings were indeterminate at the main pulmonary artery level in 1 (1.3%), at the lobar level in 13 (16.3%), at the segmental level in 28 (35.0%), and at the subsegmental level in 38 (47.5%) using the standard mode. The most common causes of an indeterminate scan using the standard mode were motion in 53 (66.3%), transient interruption of contrast in 19 (23.8%), and contrast timing in 15 (18.8%). CONCLUSIONS: High-pitch mode results in statistically significant fewer indeterminate studies compared with standard mode. Furthermore, there were statistically significant fewer indeterminate studies due to motion artifact with high-pitch mode compared with standard mode.

Radiologic and pathologic characteristics of myeloperoxidase-antineutrophil cytoplasmic antibody-associated interstitial lung disease: a retrospective analysis.

Background: The association between interstitial lung disease (ILD) and myeloperoxidase (MPO)-antineutrophil cytoplasmic antibodies (ANCAs) has been described, but pathologic characteristics are not well characterized. Objectives: We assessed the radiologic and pathologic characteristics of ILD in MPO-ANCA-positive patients and the association between ILD and vasculitis, particularly microscopic polyangiitis (MPA). Methods: We retrospectively searched electronic health records to identify MPO-ANCA-positive patients with ILD who underwent surgical lung biopsy at our institution from January 1997 through August 2017. Demographic, clinical, imaging, and pathologic characteristics were analyzed. Results: We identified 18 MPO-ANCA-positive patients with ILD. The median (range) age was 58 (43-75) years, and the cohort included 10 men (56%), 10 former smokers (56%), and 11 patients (61%) had clinical evidence of systemic vasculitis (MPA) at the time of diagnosis of ILD. On high-resolution computed tomography, the most common radiologic pattern was "inconsistent with usual interstitial pneumonia" (UIP) (n=14 [78%]); the other 4 patients (22%) fulfilled the radiologic criteria for the UIP pattern. Honeycombing was seen in 15 patients (83%). Ten patients (56%) had the UIP pattern on biopsy: 4 of these patients had additional inflammatory changes that were not typical of UIP (as seen in patients with idiopathic pulmonary fibrosis), and the other 6 patients had other inflammatory patterns or findings. The presence or absence of MPA did not correlate with pathologic findings. Conclusions: MPO-ANCA-positive patients with ILD do not show the typical UIP pattern as seen in patients with idiopathic pulmonary fibrosis on surgical lung biopsy.

Evolution of diagnostic UIP computed tomography patterns in idiopathic pulmonary fibrosis: Disease spectrum and implications for survival.

BACKGROUND: Whether current diagnostic computed tomography (CT) patterns in idiopathic pulmonary fibrosis (IPF) represent distinct clinical phenotypes or simply temporal evolution of the same underlying radiologic process is unknown. We studied IPF patients presenting with 'possible' or 'inconsistent' usual interstitial pneumonia (UIP) CT patterns and characterized the frequency and timing of evolution to 'consistent' UIP and its effect on survival. MATERIAL AND METHODS: Consecutive IPF patients seen at our institution from 1/1/2005 through 12/31/2013 were assessed for study inclusion. Presenting and serial CT scans were reviewed by two expert radiologists. Baseline and interval clinical data were collated. RESULTS: Ninety one patients (mean age 67.4 years, 59% male) met study criteria with 'possible' and 'inconsistent' UIP CT patterns present in 58 (64%) and 33 (36%) cases, respectively. Twenty nine (32%) transitioned to a 'consistent' UIP pattern over a median of 57 months (interquartile range 33-78 months). Decline in pulmonary function was statistically significant on interval follow-up for those with or without pattern evolution, but no different between them in terms of degree. Evolution to 'consistent' UIP did not confer worse survival from the date of disease diagnosis or date of first CT with 'consistent' UIP pattern. CONCLUSIONS: A portion of IPF patients with initial 'possible' or 'inconsistent' UIP CT pattern will go on to develop 'consistent' UIP CT pattern over months to years. Despite this, there appeared to be similar risk and cause of death in those with or without pattern evolution, suggesting similar morbidity across the radiologic spectrum in IPF.

Cowden Syndrome: A Cause of Pulmonary Cysts.

OBJECTIVE: To describe the pulmonary imaging findings in patients with Cowden syndrome (CS). MATERIALS AND METHODS: A retrospective review identified all patients with CS who underwent dedicated computed tomography examinations of the chest at our institution between January 2000 and October 2017. Patient demographics and imaging characteristics were identified through a review of the electronic medical record and relevant imaging. RESULTS: Fifteen patients (6 males/9 females; mean age 53 y) with a clinical diagnosis of CS were identified. Genetic confirmation of the PTEN mutation was available in 8/15 (50%) patients. Pulmonary cysts were present in 12/15 (80%) patients and in 8/8 (100%) patients with documented PTEN mutations. The cysts ranged in size from 4 to 63 mm and were <10 in 10/12 (83%). Cysts were distributed randomly in 10/12 (83%) cases. Solid pulmonary nodules were present in 13/15 (87%) patients and were distributed randomly in all cases. CONCLUSIONS: Pulmonary cysts and solid nodules are common in patients with CS. Cysts tend to be distributed randomly, few in number, and may have traversing vessels. These findings should not be interpreted as evidence of another underlying disorder in the setting of CS.

CT measurements of central pulmonary vasculature as predictors of severe exacerbation in COPD.

To identify a predictive value for the exacerbation status of chronic obstructive pulmonary disease (COPD) subjects, we evaluated the relationship between pulmonary vascular measurements on chest CT and severe COPD exacerbation.Six hundred three subjects enrolled in the COPDGene population were included and divided into nonexacerbator (n = 313) and severe exacerbator (n = 290) groups, based on whether they had an emergency room visit and/or hospitalization for COPD exacerbation. We measured the diameter of the main pulmonary artery (MPA) and ascending aorta (AA) at 2 different sites of the MPA (the tubular midportion and bifurcation) on both axial images and multiplanar reconstructions. Using multiple logistic regression analyses, we evaluated the relationship between each CT-measured pulmonary vasculature and exacerbation status.Axial and multiplanar MPA to AA diameter ratios (PA:AA ratios) at the tubular midportion and the axial PA:AA ratios at the bifurcation indicated significant association with severe exacerbation. The strongest association was found with the axial PA:mean AA ratio at the bifurcation (adjusted odds ratio [OR] = 12.53, 95% confidence interval [CI] = 2.35-66.74, P = .003) and the axial PA:major AA ratio at the tubular midportion (adjusted OR = 10.72, 95% CI = 1.99-57.86, P = .006). No differences were observed in the MPA diameter. Receiver operating characteristic analysis of these variables indicates that they may serve as a good predictive value for severe exacerbation (area under the curve, 0.77-0.78). The range of cut-off value for PA:AA ratio was 0.8 to 0.87.CT-measured PA:AA ratios at either the bifurcation or the tubular site, measured either on axial or multiplanar images, are useful for identification of the risk of severe exacerbation, and consequently can be helpful in guiding the management of COPD. Although CT measurement was used at the level of pulmonary bifurcation in previous studies, we suggest that future studies should monitor the tubular site of the MPA for maximum diagnostic value of CT in pulmonary hypertension or severe COPD exacerbation, as the tubular site of the MPA remains relatively constant on CT images.

The Four Corners Sign: A Specific Imaging Feature in Differentiating Systemic Sclerosis-related Interstitial Lung Disease From Idiopathic Pulmonary Fibrosis.

PURPOSE: Differentiating between systemic sclerosis-related interstitial lung disease (SSc-ILD) and idiopathic pulmonary fibrosis (IPF) is important because of the differences in workup, prognosis, and treatment. However, there is much overlap in the appearance of these 2 entities on high-resolution computed tomography. We propose that inflammation and/or fibrosis focally or disproportionately involving the bilateral anterolateral upper lobes and posterosuperior lower lobes ["Four Corners" Sign (FCS)] is specific for SSc-ILD. MATERIALS AND METHODS: Randomized high-resolution computed tomography studies from 74 IPF and 73 SSc-ILD cases were evaluated by 2 thoracic radiologists blinded to all patient data. For each case the reviewers noted whether the FCS was present and assigned a confidence level on the basis of a 7-point Likert scale. The same process was then performed on a randomized external validation group of 42 SSc-ILD and 42 IPF cases. RESULTS: For Likert scores of 6 or 7 ("mostly agree" or "entirely agree" that the FCS is present, respectively) the sensitivity in SSc was 16.4% (95% confidence interval, 9.7%, 26.6%), specificity 100.0% (95% confidence interval, 95.1%, 100.0%). There was a significant association between a confidently present FCS and SSc compared with a confidently present FCS and IPF (P=0.0003). Analysis on an external validation group of 42 SSc and 42 IPF cases conferred similarly high specificity for SSc in cases characterized as FCS with high confidence. CONCLUSION: The FCS, a pattern of focal or disproportionate inflammation and/or fibrosis involving the bilateral anterolateral upper lobes and posterosuperior lower lobes, is specific for SSc-ILD when readers are confident of its presence.

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.

Clinical features and outcomes of interstitial lung disease in anti-Jo-1 positive antisynthetase syndrome.

BACKGROUND: Interstitial lung disease (ILD) is a common extra-muscular manifestation of antisynthetase (AS) syndrome. ILD prevalence is higher with anti-Jo-1 antibody positivity. Data on long-term outcomes in these patients are lacking. METHODS: Over 15 years, we identified subjects with anti-Jo-1 positive AS syndrome and ILD. Demographics, pulmonary function testing (PFT), high-resolution computed tomography (HRCT), histopathology, and long-term survival were analyzed. RESULTS: We identified 103 subjects (mean age 49.2 years, female predominance [70%]). The predominant myopathy was polymyositis (64%) followed by dermatomyositis (24%). In approximately half of studied subjects, AS syndrome and ILD were diagnosed within 6 months of each other. The majority had restriction on PFTs (98%). Non-specific interstitial pneumonia (NSIP) was the most common HRCT pattern (52%), followed by NSIP overlapping with organizing pneumonia (OP) (22%). Thirty-nine subjects had biopsy data. Ten-year survival was 68%. Multivariable analysis adjusted for age at ILD diagnosis, gender, FVC and DLCO, revealed that male gender (HR = 2.60, p = 0.04) and DLCO at presentation (HR = 0.94, p = 0.05) significantly predicted mortality. CONCLUSIONS: We present a large cohort of anti-Jo-1 positive AS syndrome with ILD and note good overall survival.

Clinical Predictors of a Diagnosis of Common Variable Immunodeficiency-related Granulomatous-Lymphocytic Interstitial Lung Disease.

RATIONALE: Granulomatous-lymphocytic interstitial lung disease (GLILD) has emerged as a major cause of morbidity in patients with common variable immunodeficiency (CVID). While GLILD is among the most serious noninfectious pulmonary complications of CVID, risk factors for this condition have not been reported. OBJECTIVES: To identify clinical, physiologic, and serologic risk factors for GLILD in adults with CVID. METHODS: Of 345 consecutive adult patients with CVID, we identified 34 in the National Jewish Health research database who had a radiographic-pathologic diagnosis of GLILD evaluated between 2002 and 2014. Each case was age and sex matched to 52 CVID control subjects. We used logistic regression to determine independent predictors of GLILD. A mixed effects model was used to estimate the longitudinal change in percent predicted FVC. MEASUREMENTS AND MAIN RESULTS: The mean time from CVID diagnosis to GLILD detection was 7.8 years. Compared with matched control subjects, cases were more likely to have a history of autoimmune cytopenia, hypersplenism, polyarthritis, lower marginal zone and switched memory B cells, and restrictive lung function. Multivariate analysis revealed that hypersplenism (odds ratio [OR], 24; 95% confidence interval [CI], 4.5-179.1), polyarthritis (OR, 19; 95% CI, 2.3-206.8), and percent predicted FVC (OR, 0.93; 95% CI, 0.87-0.98) were independently associated with the development of GLILD. The rate of change of percent predicted FVC (slope, P = 0.48) did not vary significantly in patients with GLILD over a mean follow-up of 7 years after diagnosis. CONCLUSIONS: Hypersplenism and polyarthritis are strong risk factors for GLILD in patients with CVID. Percent predicted FVC remained stable over time in patients with GLILD.

Improvement in Quality of Life after Therapy for Mycobacterium abscessus Group Lung Infection. A Prospective Cohort Study.

RATIONALE: Mycobacterium abscessus group lung infection is characterized by low cure rates. Improvement in quality of life may be a reasonable treatment goal. OBJECTIVES: The objective of this study was to evaluate change in quality of life in response to therapy, predictors of improvement in quality of life, and association of quality of life with traditional outcome measures. METHODS: Forty-seven patients were treated for Mycobacterium abscessus group lung infection (including one with Mycobacterium chelonae) and were followed prospectively for 2 years between December 2009 and May 2012. St. George's Respiratory Questionnaire (SGRQ) was administered, chest computed tomography (CT) imaging was carried out, and culture data were collected at multiple time points. Predictors of improvement in the SGRQ total score greater than or equal to a minimal clinically important difference (MCID) at 12 months were evaluated. MEASUREMENTS AND MAIN RESULTS: Patients were 85% female and 94% white, with a mean age of 65 years. Nine (20%) had a genetic diagnosis of cystic fibrosis (none F508del homozygous). Coinfection with Mycobacterium avium complex occurred in 28% and Pseudomonas in 26%. Chest CT imaging universally indicated bronchiectasis and nodules; 51% had lung cavities. Treatment included a mean of 17 months of antibiotics, and lung resection in 34%. Seventeen patients with M. avium complex (36%) and one with Mycobacterium kansasii were treated for coinfection. The mean SGRQ total score (SD) at baseline was 35 (20). At all follow-up time points, the mean SGRQ total score (SD) was significantly lower (better) than at baseline: 27 (17) at 3 months, P < 0.01; 27 (19) at 6 months, P < 0.01; 27 (20) at 12 months, P < 0.01; and 30 (22) at 24 months, P = 0.02. At 12 and 24 months, respectively, 60% and 56% had improvement greater than or equal to the MCID in SGRQ total score. Improvement greater than or equal to the MCID at 12 months was positively associated with a history of respiratory exacerbation, isolate susceptible to imipenem-cilastatin, and lung resection surgery, and negatively associated with nodules >4 mm in diameter on chest CT imaging, but these associations were not statistically significant in multivariable analysis. At 24 months, 16 patients (48%) with complete data were culture negative for 1 year and had discontinued M. abscessus group treatment. CONCLUSIONS: Quality of life was a sensitive indicator of treatment response and has the potential to be a useful parameter to guide treatment.