Consensus Statements on Deployment-Related Respiratory Disease, Inclusive of Constrictive Bronchiolitis: A Modified Delphi Study.

BACKGROUND: The diagnosis of constrictive bronchiolitis (CB) in previously deployed individuals, and evaluation of respiratory symptoms more broadly, presents considerable challenges, including using consistent histopathologic criteria and clinical assessments. RESEARCH QUESTION: What are the recommended diagnostic workup and associated terminology of respiratory symptoms in previously deployed individuals? STUDY DESIGN AND METHODS: Nineteen experts participated in a three-round modified Delphi study, ranking their level of agreement for each statement with an a priori definition of consensus. Additionally, rank-order voting on the recommended diagnostic approach and terminology was performed. RESULTS: Twenty-five of 28 statements reached consensus, including the definition of CB as a histologic pattern of lung injury that occurs in some previously deployed individuals while recognizing the importance of considering alternative diagnoses. Consensus statements also identified a diagnostic approach for the previously deployed individual with respiratory symptoms, distinguishing assessments best performed at a local or specialty referral center. Also, deployment-related respiratory disease (DRRD) was proposed as a broad term to subsume a wide range of potential syndromes and conditions identified through noninvasive evaluation or when surgical lung biopsy reveals evidence of multicompartmental lung injury that may include CB. INTERPRETATION: Using a modified Delphi technique, consensus statements provide a clinical approach to possible CB in previously deployed individuals. Use of DRRD provides a broad descriptor encompassing a range of postdeployment respiratory findings. Additional follow-up of individuals with DRRD is needed to assess disease progression and to define other features of its natural history, which could inform physicians better and lead to evolution in this nosology.

Mosaic Attenuation Pattern: A Guide to Analysis with HRCT.

Mosaic attenuation pattern is commonly encountered on high-resolution computed tomography and has myriad causes. These diseases may involve small airways, vessels, alveoli, or interstitium, with some involving compartmental combinations. Small airways disease is caused by cellular bronchiolitis, infiltrated by inflammatory cells or constrictive bronchiolitis, resulting in fibrosis of the small airways. Any acute or chronic cause of ground-glass opacity can result in a mosaic pattern. Vascular causes of mosaic attenuation include chronic thromboembolic pulmonary hypertension and rarely other causes of pulmonary arterial hypertension. Ancillary CT findings along with the clinical history help narrow the differential diangosis. Biopsy is uncommonly required for definitiive diagnosis.

Human Oncoviruses and Thoracic Tumors: Understanding the Imaging Findings.

Approximately 1.4 million virus-induced cancers occur annually, representing roughly 10% of the cancer burden worldwide. Seven oncogenic DNA and RNA viruses (ie, oncoviruses) are implicated in approximately 12%-25% of all human cancers owing to a variety of mechanisms as uncommon consequences of the normal viral life cycle. These seven well-recognized human oncoviruses are Epstein-Barr virus (EBV), human T-lymphotropic virus 1, hepatitis B virus, hepatitis C virus, HIV, human papilloma virus (HPV), and human herpesvirus 8 (HHV-8). Several viruses-namely, EBV, HPV, and Kaposi sarcoma herpesvirus or HHV-8-are increasingly being recognized as being related to HIV and/or AIDS, the growing number of transplant cases, and the use of immunosuppressive therapies. Infectious and inflammatory processes, and the accompanying lymphadenopathy, are great mimickers of human oncovirus-related tumors. Although it is often difficult to differentiate these entities, the associated clinical setting and radiologic findings may provide clues for an accurate diagnosis and appropriate management. Malignant lymphoid lesions are best evaluated with multidetector chest CT. The radiologic findings of these lesions are often nonspecific and are best interpreted in correlation with clinical data and histopathologic findings. ©RSNA, 2022.

Demystifying idiopathic interstitial pneumonia: time for more etiology-focused nomenclature in interstitial lung disease.

INTRODUCTION: A major focus of interstitial lung disease (ILD) has centered on disorders termed idiopathic interstitial pneumonias (IIPs) which include, among others, idiopathic pulmonary fibrosis, idiopathic nonspecific interstitial pneumonia, cryptogenic organizing pneumonia, and respiratory bronchiolitis-interstitial lung disease. AREAS COVERED: We review the radiologic and histologic patterns for the nine disorders classified by multidisciplinary approach as IIP, and describe the remarkable amount of published epidemiologic, translational, and molecular studies demonstrating their associations with numerous yet definitive environmental exposures, occupational exposures, pulmonary diseases, systemic diseases, medication toxicities, and genetic variants. EXPERT OPINION: In the 21st century, these disorders termed IIPs are rarely idiopathic, but rather are well-described radiologic and histologic patterns of lung injury that are associated with a wide array of diverse etiologies. Accordingly, the idiopathic nomenclature is misleading and confusing, and may also promote a lack of inquisitiveness, suggesting the end rather than the beginning of a thorough diagnostic process to identify ILD etiology and initiate patient-centered management. A shift toward more etiology-focused nomenclature will be beneficial to all, including patients hoping for better life quality and disease outcome, general medicine and pulmonary physicians furthering their ILD knowledge, and expert ILD clinicians and researchers who are advancing the ILD field.

Autologous Stem Cell Transplantation in the Treatment of Pulmonary Light Chain Deposition Disease.

Light chain deposition disease is a rare condition that results in the deposition of light chains in organs and their subsequent dysfunction. It is often the consequence of unchecked light chain production by a plasma cell clone. Rarely does it manifest with solely pulmonary involvement, especially in the young otherwise healthy patient. This article highlights the presentation and diagnosis of pulmonary light chain deposition disease in an active duty solider, the discovery of a plasma cell clone responsible for his symptoms, and the therapy targeted at the plasma cell clone-inducing pulmonary disease. This therapy included a novel successful treatment with an autologous stem cell transplantation. To date, it is among the first such documented successful bone marrow transplantations in treatment of isolated pulmonary light chain deposition disease.

Non-Infectious Granulomatous Lung Disease: Imaging Findings with Pathologic Correlation.

Non-infectious granulomatous lung disease represents a diverse group of disorders characterized by pulmonary opacities associated with granulomatous inflammation, a relatively nonspecific finding commonly encountered by pathologists. Some lesions may present a diagnostic challenge because of nonspecific imaging features; however, recognition of the various imaging manifestations of these disorders in conjunction with patients' clinical history, such as age, symptom onset and duration, immune status, and presence of asthma or cutaneous lesions, is imperative for narrowing the differential diagnosis and determining appropriate management of this rare group of disorders. In this pictorial review, we describe the pathologic findings of various non-infectious granulomatous lung diseases as well as the radiologic features and high-resolution computed tomography imaging features.

A comprehensive assessment of environmental exposures and the medical history guides multidisciplinary discussion in interstitial lung disease.

BACKGROUND: Multidisciplinary discussion (MDD) is widely recommended for patients with interstitial lung disease (ILD), but published primary data from MDD has been scarce, and factors influencing MDD other than chest computed tomography (CT) and lung histopathology interpretations have not been well-described. METHODS: Single institution MDD of 179 patients with ILD. RESULTS: MDD consensus clinical diagnoses included autoimmune-related ILD, chronic hypersensitivity pneumonitis, smoking-related ILD, idiopathic pulmonary fibrosis, medication-induced ILD, occupation-related ILD, unclassifiable ILD, and a few less common pulmonary disorders. In 168 of 179 patients, one or more environmental exposures or pertinent features of the medical history were identified, including recreational/avocational, residential, and occupational exposures, systemic autoimmune disease, malignancy, medication use, and family history. The MDD process demonstrated the importance of comprehensively assessing these exposures and features, beyond merely noting their presence, for rendering consensus clinical diagnoses. Precise, well-defined chest CT and lung histopathology interpretations were rendered at MDD, including usual interstitial pneumonia, nonspecific interstitial pneumonia, and organizing pneumonia, but these interpretations were associated with a variety of MDD consensus clinical diagnoses, demonstrating their nonspecific nature in many instances. In 77 patients in which MDD consensus diagnosis differed from referring diagnosis, assessment of environmental exposures and medical history was found retrospectively to be the most impactful factor. CONCLUSIONS: A comprehensive assessment of environmental exposures and pertinent features of the medical history guided MDD. In addition to rendering consensus clinical diagnoses, MDD presented clinicians with opportunities to initiate environmental remediation, behavior modification, or medication alteration likely to benefit individual patients with ILD.

Complex obstructive lung disease - A diagnostic and management conundrum.

Rheumatoid arthritis (RA) is a common autoimmune disease most well-known for its inflammatory, destructive polyarthropathy. Extraarticular manifestations of the disease may involve the respiratory system, including interstitial lung disease, pleural disease, pulmonary vascular abnormalities, and airways disease. Smoking is highly prevalent in the RA population, and may even have a synergistic effect in disease development and progression. In the diagnosis of pulmonary disease, this presents a unique diagnostic and therapeutic challenge. We present a case of a woman in her 50s who presented for evaluation of dyspnea and was found to have obstructive lung disease. In addition to RA, she had a significant smoking history and also owned pet birds, making definitive diagnosis difficult. Ultimately, chest imaging was crucial in identifying RA-related lung disease as the root cause of her symptoms, leading to successful treatment and symptom management.

Combined Pulmonary Fibrosis and Emphysema: Pulmonary Function Testing and a Pathophysiology Perspective.

Combined pulmonary fibrosis and emphysema (CPFE) has been increasingly recognized over the past 10-15 years as a clinical entity characterized by rather severe imaging and gas exchange abnormalities, but often only mild impairment in spirometric and lung volume indices. In this review, we explore the gas exchange and mechanical pathophysiologic abnormalities of pulmonary emphysema, pulmonary fibrosis, and combined emphysema and fibrosis with the goal of understanding how individual pathophysiologic observations in emphysema and fibrosis alone may impact clinical observations on pulmonary function testing (PFT) patterns in patients with CPFE. Lung elastance and lung compliance in patients with CPFE are likely intermediate between those of patients with emphysema and fibrosis alone, suggesting a counter-balancing effect of each individual process. The outcome of combined emphysema and fibrosis results in higher lung volumes overall on PFTs compared to patients with pulmonary fibrosis alone, and the forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) ratio in CPFE patients is generally preserved despite the presence of emphysema on chest computed tomography (CT) imaging. Conversely, there appears to be an additive deleterious effect on gas exchange properties of the lungs, reflecting a loss of normally functioning alveolar capillary units and effective surface area available for gas exchange, and manifested by a uniformly observed severe reduction in the diffusing capacity for carbon monoxide (DLCO). Despite normal or only mildly impaired spirometric and lung volume indices, patients with CPFE are often severely functionally impaired with an overall rather poor prognosis. As chest CT imaging continues to be a frequent imaging modality in patients with cardiopulmonary disease, we expect that patients with a combination of pulmonary emphysema and pulmonary fibrosis will continue to be observed. Understanding the pathophysiology of this combined process and the abnormalities that manifest on PFT testing will likely be helpful to clinicians involved with the care of patients with CPFE.

Interstitial Lung Disease and Pulmonary Fibrosis: A Practical Approach for General Medicine Physicians with Focus on the Medical History.

Interstitial lung disease (ILD) and pulmonary fibrosis comprise a wide array of inflammatory and fibrotic lung diseases which are often confusing to general medicine and pulmonary physicians alike. In addition to the myriad of clinical and radiologic nomenclature used in ILD, histopathologic descriptors may be particularly confusing, and are often extrapolated to radiologic imaging patterns which may further add to the confusion. We propose that rather than focusing on precise histologic findings, focus should be on identifying an accurate etiology of ILD through a comprehensive and detailed medical history. Histopathologic patterns from lung biopsy should not be dismissed, but are often nonspecific, and overall treatment strategy and prognosis are likely to be determined more by the specific etiology of ILD rather than any particular histologic pattern. In this review, we outline a practical approach to common ILDs, highlight important aspects in obtaining an exposure history, clarify terminology and nomenclature, and discuss six common subgroups of ILD likely to be encountered by general medicine physicians in the inpatient or outpatient setting: Smoking-related, hypersensitivity pneumonitis, connective tissue disease-related, occupation-related, medication-induced, and idiopathic pulmonary fibrosis. Accurate diagnosis of these forms of ILD does require supplementing the medical history with results of the physical examination, autoimmune serologic testing, and chest radiographic imaging, but the importance of a comprehensive environmental, avocational, occupational, and medication-use history cannot be overstated and is likely the single most important factor responsible for achieving the best possible outcomes for patients.

Radiologist Performance in the Detection of Pulmonary Embolism: Features that Favor Correct Interpretation and Risk Factors for Errors.

PURPOSE: This study aimed to assess the factors contributing toward accurate detection and erroneous interpretation of pulmonary embolism (PE). MATERIALS AND METHODS: Over 13 months, all computed tomography pulmonary angiography studies were retrospectively rereviewed by a chest radiologist. Two additional chest radiologists assessed cases with disagreement between the first interpretation and rereview. The number, extent, and location of PE and specialty training, experience, time of study, kV, resident prelim, use of iterative reconstruction, signal to noise ratio (SNR), and reports describing the study as "limited" were recorded. Parametric and nonparametric statistical testing was performed (significance P<0.05). RESULTS: Of 2555 computed tomography pulmonary angiography cases assessed, there were 230 true positive (170 multiple, 60 single PE), 2271 true negative, 35 false-negative (15 multiple and 20 single PE), and 19 false-positive studies. The overall sensitivity, specificity, positive predictive value, negative predictive value and accuracy of radiologists was 86.8%, 99.2%, 92.4%, 98.5%, and 97.9%. Sensitivity for the detection of multiple and central PE was significantly higher than the detection of single and peripheral PE, respectively (P<0.01 for both). The sensitivity of thoracic radiologists (91.7%) was higher than nonthoracic (82.8%) and reached significance for single PE (89.2% vs. 61.4%, P<0.02). Errors were more likely in cases with lower SNR (P=0.04) and those described as limited (P<0.001). Misses occurred more frequently in the upper lobe posterior and lower lobe lateral segments and subsegments (P=0.038). CONCLUSIONS: The accuracy for PE detection is high, but errors are more likely in studies with single PE interpreted by nonthoracic radiologists, especially when located in certain segments and in cases with low SNR or described as limited.

Transcriptomic evidence of immune activation in macroscopically normal-appearing and scarred lung tissues in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease manifested by overtly scarred peripheral and basilar regions and more normal-appearing central lung areas. Lung tissues from macroscopically normal-appearing (IPFn) and scarred (IPFs) areas of explanted IPF lungs were analyzed by RNASeq and compared with healthy control (HC) lung tissues. There were profound transcriptomic changes in IPFn compared with HC tissues, which included elevated expression of numerous immune-, inflammation-, and extracellular matrix-related mRNAs, and these changes were similar to those observed with IPFs compared to HC. Comparing IPFn directly to IPFs, elevated expression of epithelial mucociliary mRNAs was observed in the IPFs tissues. Thus, despite the known geographic tissue heterogeneity in IPF, the entire lung is actively involved in the disease process, and demonstrates pronounced elevated expression of numerous immune-related genes. Differences between normal-appearing and scarred tissues may thus be driven by deranged epithelial homeostasis or possibly non-transcriptomic factors.

Diagnostic criteria for idiopathic pulmonary fibrosis: a Fleischner Society White Paper.

This Review provides an updated approach to the diagnosis of idiopathic pulmonary fibrosis (IPF), based on a systematic search of the medical literature and the expert opinion of members of the Fleischner Society. A checklist is provided for the clinical evaluation of patients with suspected usual interstitial pneumonia (UIP). The role of CT is expanded to permit diagnosis of IPF without surgical lung biopsy in select cases when CT shows a probable UIP pattern. Additional investigations, including surgical lung biopsy, should be considered in patients with either clinical or CT findings that are indeterminate for IPF. A multidisciplinary approach is particularly important when deciding to perform additional diagnostic assessments, integrating biopsy results with clinical and CT features, and establishing a working diagnosis of IPF if lung tissue is not available. A working diagnosis of IPF should be reviewed at regular intervals since the diagnosis might change. Criteria are presented to establish confident and working diagnoses of IPF.

Clinical-Radiologic-Pathologic Correlation of Smoking-Related Diffuse Parenchymal Lung Disease.

The direct toxicity of cigarette smoke and the body's subsequent response to this lung injury leads to a wide array of pathologic manifestations and disease states that lead to both reversible and irreversible injury to the large airways, small airways, alveolar walls, and alveolar spaces. These include emphysema, bronchitis, bronchiolitis, acute eosinophilic pneumonia, pulmonary Langerhans cell histiocytosis, respiratory bronchiolitis, desquamative interstitial pneumonia, and pulmonary fibrosis. Although these various forms of injury have different pathologic and imaging manifestations, they are all part of the spectrum of smoking-related diffuse parenchymal lung disease.

Castleman Disease of the Thorax: Clinical, Radiologic, and Pathologic Correlation: From the Radiologic Pathology Archives.

Castleman disease is a complex lymphoproliferative disease pathologically divided into two subtypes, the hyaline vascular variant (HVV) and the plasma cell variant (PCV). The HVV is the most common, is thought to represent a benign neoplasm of lymph node stromal cells, and is treated with surgical resection. It is most commonly found in the mediastinum, where it classically appears as a unicentric, avidly enhancing mass at computed tomography (CT) and magnetic resonance imaging. This appearance can mimic other avidly enhancing mediastinal masses, and location, clinical history, laboratory data, and nuclear medicine single photon emission CT (SPECT) and positron emission tomography (PET) studies can help narrow the differential diagnosis. Multicentric Castleman disease (MCD), which in the majority of cases is composed of the PCV, is an aggressive lymphoproliferative disorder associated with human herpesvirus infection, interleukin 6 dysregulation, and other systemic disorders. While it can be difficult to differentiate MCD from lymphoma, the presence of avidly enhancing lymph nodes can suggest the diagnosis. The purpose of this article is to review the clinical, immunologic, and pathologic findings associated with both unicentric Castleman disease and MCD and discuss how the imaging findings correlate with the pathophysiology of the disease.

Primary Extranodal Lymphoma of the Thorax.

Primary pulmonary lymphomas represent a pathologically heterogeneous group of disorders that often share imaging features, which include peribronchovascular nodules and masses or areas of nonresolving consolidation. Primary mediastinal B-cell lymphoma is an extranodal non-Hodgkin lymphoma seen in younger patients that has imaging and pathologic features that demonstrate some degree of overlap with Hodgkin lymphoma. Primary lymphomas of the pleural space are rare and associated with concomitant viral infections.