Subsolid Nodules: Significance and Current Understanding.

Subsolid nodules are heterogeneously appearing and behaving entities, commonly encountered incidentally and in high-risk populations. Accurate characterization of subsolid nodules, and application of evolving surveillance guidelines, facilitates evidence-based and multidisciplinary patient-centered management.

Quantitative interstitial lung disease scores in idiopathic inflammatory myopathies: longitudinal changes and clinical implications.

OBJECTIVES: To investigate computer-aided quantitative scores from high-resolution CT (HRCT) images and determine their longitudinal changes and clinical significance in patients with idiopathic inflammatory myopathies (IIMs)-related interstitial lung disease (IIMs-ILD). METHODS: The clinical data and HRCT images of 80 patients with IIMs who underwent serial HRCT scans at least twice were retrospectively analysed. Quantitative ILD (QILD) scores (%) were calculated as the sum of the extent of lung fibrosis, ground-glass opacity, and honeycombing. The individual time-estimated ΔQILD between two consecutive scans was derived using a linear approximation of yearly changes. RESULTS: The baseline median QILD (interquartile range) scores in the whole lung were 28.1% (19.1-43.8). The QILD was significantly correlated with forced vital capacity (r = -0.349, P = 0.002) and diffusing capacity for carbon monoxide (r = -0.381, P = 0.001). For ΔQILD between the first two scans, according to the visual ILD subtype, QILD aggravation was more frequent in patients with usual interstitial pneumonia (UIP) than non-UIP (80.0% vs 44.4%, P = 0.013). Multivariable logistic regression analyses identified UIP was significantly related to radiographic ILD progression (ΔQILD >2%, P = 0.015). Patients with higher baseline QILD scores (>28.1%) had a higher risk of lung transplantation or death (P = 0.015). In the analysis of three serial HRCT scans (n = 41), dynamic ΔQILD with four distinct patterns (improving, worsening, convex and concave) was observed. CONCLUSION: QILD changes in IIMs-ILD were dynamic, and baseline UIP patterns seemed to be related to a longitudinal progression in QILD. These may be potential imaging biomarkers for lung function, changes in ILD severity and prognosis in IIMs-ILD.

The disconnect between visual assessment of air trapping and lung physiology for assessment of small airway disease in scleroderma-related interstitial lung disease: An observation from the Scleroderma Lung Study II Cohort.

Objective: To explore the presence of small airway disease (SAD) and emphysema in scleroderma-related interstitial lung disease (SSc-ILD) and to evaluate the physiologic and clinical correlates of SAD in SSc-ILD. Methods: Thoracic high-resolution computed tomography (HRCT) images obtained from the Scleroderma Lung Study II (SLSII) participants were reviewed by a group of thoracic radiologists. The presence of SAD was assessed by visual assessment for air trapping. HRCT scans were also evaluated for the presence of emphysema. The association of the presence of air trapping and emphysema with physiological measures of airway disease and clinical variables was evaluated. Results: A total of 155 baseline HRCT scans were reviewed. For assessment of air trapping, images needed to be adequate end-expiratory examinations, leaving 123 scans. Air trapping was seen in 13/123 (10.6%) of the SSc-ILD cohort and was independent of smoking history, asthma or the presence of gastroesophageal reflux. Air trapping on HRCT was not associated with physiologic evidence of SAD. We also identified 8/155 (5.2%) patients with emphysema on HRCT, which was independent of SAD and found mostly in prior smokers. Conclusion: We report the first study of air trapping on standardized, high-quality HRCT images as a reflection of SAD in a relatively large, well characterized SSc-ILD cohort. The presence of SAD in non-smoking SSc-ILD patients supports that SSc may cause not only restrictive lung disease (SSc-ILD), but also, to a lesser extent, obstructive disease. Physiologic measures alone may be inadequate to detect airway disease in patients with SSc-ILD.

Quantitative Image Analysis at Chronic Lung Allograft Dysfunction Onset Predicts Mortality.

BACKGROUND: Chronic lung allograft dysfunction (CLAD) phenotype determines prognosis and may have therapeutic implications. Despite the clarity achieved by recent consensus statement definitions, their reliance on radiologic interpretation introduces subjectivity. The Center for Computer Vision and Imaging Biomarkers at the University of California, Los Angeles (UCLA) has established protocols for chest high-resolution computed tomography (HRCT)-based computer-aided quantification of both interstitial disease and air-trapping. We applied quantitative image analysis (QIA) at CLAD onset to demonstrate radiographic phenotypes with clinical implications. METHODS: We studied 47 first bilateral lung transplant recipients at UCLA with chest HRCT performed within 90 d of CLAD onset and 47 no-CLAD control HRCTs. QIA determined the proportion of lung volume affected by interstitial disease and air-trapping in total lung capacity and residual volume images, respectively. We compared QIA scores between no-CLAD and CLAD, and between phenotypes. We also assigned radiographic phenotypes based solely on QIA, and compared their survival outcomes. RESULTS: CLAD onset HRCTs had more lung affected by the interstitial disease (P = 0.003) than no-CLAD controls. Bronchiolitis obliterans syndrome (BOS) cases had lower scores for interstitial disease as compared with probable restrictive allograft syndrome (RAS) (P < 0.0001) and mixed CLAD (P = 0.02) phenotypes. BOS cases had more air-trapping than probable RAS (P < 0.0001). Among phenotypes assigned by QIA, the relative risk of death was greatest for mixed (relative risk [RR] 11.81), followed by RAS (RR 6.27) and BOS (RR 3.15). CONCLUSIONS: Chest HRCT QIA at CLAD onset appears promising as a method for precise determination of CLAD phenotypes with survival implications.

Birt-Hogg-Dubé Syndrome presenting with chronic progressive dyspnea.

Birt-Hogg-Dubé Syndrome (BHDS) is a rare autosomal dominant disease which manifests with cutaneous hamartomas, lung cysts and renal carcinomas. A wide spectrum of phenotypic expression and few visible manifestations makes BHDS a likely under-recognized entity. Diffuse cystic lung disease (DCLD) is the typical pulmonary manifestation of BHDS, which in the absence of other specific findings carries a broad differential diagnosis. Unlike many other causes of DCLD, BHDS is not known to present with symptomatic pulmonary dysfunction. We report a typical case of BHDS with an atypical presentation - chronic progressive dyspnea. The unusual presentation provides an opportunity to discuss the differential for DCLD and highlights the importance of maintaining an index of suspicion for BHDS even when symptoms appear inconsistent with the diagnosis. Also examined is the management of BHDS patients and their immediate relatives, and recommendations for the treatment of obstructive sleep apnea (OSA) with continuous positive airway pressure (CPAP) given the potential risk of pneumothorax in this group.

Case 286: Sarcoidlike Granulomatosis and Lymphadenopathy-Thoracic Manifestations of Nivolumab Drug Toxicity.

History A 70-year-old man had a posterior left thigh lesion confirmed to be biopsy-proven melanoma. The patient underwent wide excision and sentinel node biopsy, which showed absence of residual melanoma. Two years later, the patient noticed a subcentimeter subcutaneous lump in his thigh. Repeat excisional biopsy showed involvement of the surrounding soft tissue, consistent with a satellite lesion. Follow-up combined PET/CT revealed satellite nodules around the primary lesion, enabling confirmation of subcutaneous metastatic disease. The patient was subsequently started on nivolumab, an anti-programmed cell death 1 (PD-1) immune checkpoint inhibitor that blocks PD-1 and is approved as a first-line treatment in patients with advanced metastatic melanoma. On the baseline scan prior to starting nivolumab, there were no CT findings that suggested metastatic disease, nor were there enlarged mediastinal or hilar lymph nodes. Five months after initiation of nivolumab treatment, the first follow-up chest CT scan was performed and showed new findings in the mediastinum and bilateral lungs. The patient remained asymptomatic during the treatment period. Furthermore, the subcutaneous metastatic disease remained stable during the treatment period, and no other site of metastatic disease was noted on follow-up CT scans obtained during the first 5 months of treatment. The patient had no prior history of infectious or occupational exposures. During the nivolumab treatment cycle, his pertinent laboratory values and physical examination findings were unremarkable.

The MUC5B promoter variant does not predict progression of interstitial lung disease in systemic sclerosis.

OBJECTIVE: To investigate the prevalence of the MUC5B promoter variant rs35705950 in patients with systemic sclerosis-interstitial lung disease (SSc-ILD) and whether its presence predicts response to immunosuppression with cyclophosphamide (CYC) and mycophenolate (MMF). METHODS: SSc-ILD patients who participated in Scleroderma Lung Study (SLS) II (MMF versus CYC) were included in this study (N = 142). TaqMan Genotyping Assays were used to determine the MUC5B rs35705950 single nucleotide polymorphism. Joint models were created to examine how the presence of this variant affected the course of the forced vital capacity (FVC) over 2 years. Linear regression models were used to investigate the relationship between the presence of this variant and the change in quantitative radiographic fibrosis. RESULTS: Among 128 participants who were tested for this variant, 18% possessed at least one copy of the MUC5B minor allele. Patients with at least one copy of this allele were similar to those without the allele with respect to age, sex, SSc subtype, ILD disease severity; however, this variant was rare among African Americans (3.7%). The presence of the MUC5B variant did not affect the course of the FVC, nor the change in quantitative radiographic fibrosis, ground glass or ILD scores in either treatment arm. CONCLUSION: In the context of a randomized controlled trial for SSc-ILD, the presence of the MUC5B variant did not predict disease severity, nor affect treatment response to MMF or CYC. Future studies are needed to determine whether this variant affects ILD progression in other SSc cohorts and in patients receiving anti-fibrotic therapy.

Case 286.

History A 70-year-old man had a posterior left thigh lesion confirmed to be biopsy-proven melanoma. The patient underwent wide excision and sentinel node biopsy, which showed absence of residual melanoma. Two years later, the patient noticed a subcentimeter subcutaneous lump in his thigh. Repeat excisional biopsy showed involvement of the surrounding soft tissue, consistent with a satellite lesion. Follow-up combined PET/CT revealed satellite nodules around the primary lesion, enabling confirmation of subcutaneous metastatic disease. The patient was subsequently started on nivolumab, an anti-programmed cell death 1 (PD-1) immune checkpoint inhibitor that blocks PD-1 and is approved as a first-line treatment in patients with advanced metastatic melanoma. On the baseline scan prior to starting nivolumab, there were no CT findings that suggested metastatic disease, nor were there enlarged mediastinal or hilar lymph nodes. Five months after initiation of nivolumab treatment, the first follow-up chest CT scan was performed and showed new findings in the mediastinum (Fig 1) and bilateral lungs (Figs 2, 3). The patient remained asymptomatic during the treatment period. Furthermore, the subcutaneous metastatic disease remained stable during the treatment period, and no other site of metastatic disease was noted on follow-up CT scans obtained during the first 5 months of treatment. The patient had no prior history of infectious or occupational exposures. During the nivolumab treatment cycle, his pertinent laboratory values and physical examination findings were unremarkable.

Right atrial cavotricuspid isthmus: anatomic characterization with multi-detector row CT.

PURPOSE: To retrospectively evaluate the anatomic characteristics of the right atrial cavotricuspid isthmus (CTI) by using 64-section multi-detector row computed tomography (CT). MATERIALS AND METHODS: Institutional review board approval and waiver of informed consent were obtained for this HIPAA-compliant study. The anatomic region of the CTI was evaluated in 201 patients (116 men and 85 women; mean age, 58 years +/- 11 [standard deviation]) who underwent coronary multi-detector row CT. CTI length was assessed along three parallel isthmic levels (paraseptal, central, and inferolateral). Central isthmus depth was classified as straight (3 mm), concave (>3 to 5 mm). Measurements were obtained during three cardiac phases: midsystole, middiastole, and atrial contraction. Subthebesian recess dimensions and eustachian ridge width were measured. Distances from the atrioventricular node artery to the coronary sinus, from the right coronary artery (RCA) to the inferior vena cava, and from the RCA to the tricuspid valve annulus were measured. Software was used for statistical analysis. RESULTS: At middiastole, the paraseptal isthmus (mean length, 20 mm +/- 3.5; range, 11-34 mm) was significantly shorter than the central isthmus (24 mm +/- 4.3; range, 12-43 mm) and the central isthmus was shorter than the inferolateral isthmus (27 mm +/- 4.8; range, 13-45 mm) (P < .001). The longest CTI measurements were obtained during midsystole, and the shortest were obtained during atrial contraction (40% variation per cardiac cycle). Isthmus contraction occurred primarily in the posterior segment of the central isthmus (RCA to inferior vena cava distance). At middiastole, the central isthmus was straight in 8% of patients, concave in 47% of patients, and pouchlike (>5 mm) in 45% of patients. The mean depth was greater during atrial contraction (6.3 mm +/- 2.1) than in midsystole (4.3 mm +/- 1.5) and middiastole (5.1 mm +/- 1.8) (32% variation during cardiac cycle). A subthebesian recess greater than 5 mm deep was identified in 45% of patients. In 24% of patients, a thick eustachian ridge greater than 4 mm was seen. The atrioventricular node artery passed close to the coronary sinus wall (mean distance, 2.1 mm +/- 0.7; range, 1-6 mm). CONCLUSION: Cardiac multi-detector row CT provides extensive information regarding the size and morphology of the CTI and its related structures.