Fleischner Society: Glossary of Terms for Thoracic Imaging.

Members of the Fleischner Society have compiled a glossary of terms for thoracic imaging that replaces previous glossaries published in 1984, 1996, and 2008, respectively. The impetus to update the previous version arose from multiple considerations. These include an awareness that new terms and concepts have emerged, others have become obsolete, and the usage of some terms has either changed or become inconsistent to a degree that warranted a new definition. This latest glossary is focused on terms of clinical importance and on those whose meaning may be perceived as vague or ambiguous. As with previous versions, the aim of the present glossary is to establish standardization of terminology for thoracic radiology and, thereby, to facilitate communications between radiologists and clinicians. Moreover, the present glossary aims to contribute to a more stringent use of terminology, increasingly required for structured reporting and accurate searches in large databases. Compared with the previous version, the number of images (chest radiography and CT) in the current version has substantially increased. The authors hope that this will enhance its educational and practical value. All definitions and images are hyperlinked throughout the text. Click on each figure callout to view corresponding image. © RSNA, 2024 Supplemental material is available for this article. See also the editorials by Bhalla and Powell in this issue.

European Respiratory Society guidelines on transbronchial lung cryobiopsy in the diagnosis of interstitial lung diseases.

BACKGROUND: In patients with interstitial lung diseases (ILD), histopathological input is often required to obtain a diagnosis. Surgical lung biopsy (SLB) is considered the reference standard, but many patients are clinically unfit to undergo this invasive procedure, and adverse events, length of hospitalisation and costs are considerable. This European Respiratory Society (ERS) guideline provides evidence-based clinical practice recommendations for the role of transbronchial lung cryobiopsy (TBLC) in obtaining tissue-based diagnosis in patients with undiagnosed ILD. METHODS: The ERS Task Force consisted of clinical experts in the field of ILD and/or TBLC and methodological experts. Four PICO (Patient, Intervention, Comparator, Outcomes) questions and two narrative questions were formulated. Systematic literature searches were performed in MEDLINE and Embase (up to June 2021). GRADE (Grading, Recommendation, Assessment, Development and Evaluation) methodology was applied. RESULTS: In patients with undiagnosed ILD and an indication to obtain histopathological data: 1) TBLC is suggested as a replacement test in patients considered eligible to undergo SLB, 2) TBLC is suggested in patients not considered eligible to undergo SLB, 3) SLB is suggested as an add-on test in patients with a non-informative TBLC, 4) no recommendation is made for or against a second TBLC in patients with a non-informative TBLC and 5) TBLC operators should undergo training, but no recommendation is made for the type of training required. CONCLUSIONS: TBLC provides important diagnostic information in patients with undiagnosed ILD. Diagnostic yield is lower compared to SLB, at reduced serious adverse events and length of hospitalisation. Certainty of the evidence is mostly "very low".

Radiological findings in low-dose CT for COVID-19 pneumonia in 182 patients: Correlation of signs and severity with patient outcome.

ABSTRACT: To characterize computed tomography (CT) findings of coronavirus disease 2019 (COVID-19) pneumonia and their value in outcome prediction.Chest CTs of 182 patients with a confirmed diagnosis of COVID-19 infection by real-time reverse transcription polymerase chain reaction were evaluated for the presence of CT-abnormalities and their frequency. Regarding the patient outcome each patient was categorized in 5 progressive stages and the duration of hospitalization was determined. Regression analysis was performed to find which CT findings are predictive for patient outcome and to assess prognostic factors for the hospitalization duration.Multivariate statistical analysis confirmed a higher age (OR = 1.023, P  =  .025), a higher total visual severity score (OR = 1.038, P  =  .002) and the presence of crazy paving (OR = 2.160, P  =  .034) as predictive parameters for patient outcome. A higher total visual severity score (+0.134 days; P  =  .012) and the presence of pleural effusion (+13.985 days, P  =  0.005) were predictive parameters for a longer hospitalization duration. Moreover, a higher sensitivity of chest CT (false negatives 10.4%; true positives 78.6%) in comparison to real-time reverse transcription polymerase chain reaction was obtained.An increasing percentage of lung opacity as well as the presence of crazy paving and a higher age are associated with a worse patient outcome. The presence of a higher total visual severity score and pleural effusion are significant predictors for a longer hospitalization duration. These results are underscoring the value of chest CT as a diagnostic and prognostic tool in the pandemic outbreak of COVID-19, to facilitate fast detection and to preserve the limited (intensive) care capacity only for the most vulnerable patients.

Lung Microenvironments and Disease Progression in Fibrotic Hypersensitivity Pneumonitis.

Rationale: Fibrotic hypersensitivity pneumonitis (fHP) is an interstitial lung disease caused by sensitization to an inhaled allergen. Objectives: To identify the molecular determinants associated with progression of fibrosis. Methods: Nine fHP explant lungs and six unused donor lungs (as controls) were systematically sampled (4 samples/lung). According to microcomputed tomography measures, fHP cores were clustered into mild, moderate, and severe fibrosis groups. Gene expression profiles were assessed using weighted gene co-expression network analysis, xCell, gene ontology, and structure enrichment analysis. Gene expression of the prevailing molecular traits was also compared with idiopathic pulmonary fibrosis (IPF). The explant lung findings were evaluated in separate clinical fHP cohorts using tissue, BAL samples, and computed tomography scans. Measurements and Main Results: We found six molecular traits that associated with differential lung involvement. In fHP, extracellular matrix and antigen presentation/sensitization transcriptomic signatures characterized lung zones with only mild structural and histological changes, whereas signatures involved in honeycombing and B cells dominated the transcriptome in the most severely affected lung zones. With increasing disease severity, endothelial function was progressively lost, and progressive disruption in normal cellular homeostatic processes emerged. All six were also found in IPF, with largely similar associations with disease microenvironments. The molecular traits correlated with in vivo disease behavior in a separate clinical fHP cohort. Conclusions: We identified six molecular traits that characterize the morphological progression of fHP and associate with in vivo clinical behavior. Comparing IPF with fHP, the transcriptome landscape was determined considerably by local disease extent rather than by diagnosis alone.

Effects of Corticosteroid Treatment and Antigen Avoidance in a Large Hypersensitivity Pneumonitis Cohort: A Single-Centre Cohort Study.

BACKGROUND: Although the third most frequent interstitial lung disease, hypersensitivity pneumonitis (HP) remains an enigmatic disease without clear diagnostic and therapeutic guidelines. We assessed the effect of the commonly used therapeutic interventions (i.e. exposure avoidance and corticosteroid treatment) in an HP cohort. METHODS: We collected clinical data of all HP patients followed at our centre between January 1, 2005, and December 31, 2016. HP patients were stratified according to the presence of fibrosis on chest CT. Survival was analysed using the multivariate Cox proportional hazards model. Forced vital capacity (percent predicted, FVC%) and diffusing capacity of the lung for carbon monoxide (percent predicted, DLCO%) evolution were analysed using linear mixed-effect models. RESULTS: Two hundred and two HP patients were identified: 93 non-fibrotic HP (nfHP) and 109 fibrotic HP (fHP), experiencing a monthly FVC% decline before treatment of 0.93% and 0.56%, respectively. While nfHP had an excellent survival, fHP patients experienced a median survival of 9.2 years. Corticosteroid treatment and exposure avoidance did not result in survival differences. Although nfHP patients showed FVC% and DLCO% increase after corticosteroid initiation, no therapeutic effect was seen in fHP patients. FVC% and DLCO% increased in nfHP patients after exposure avoidance, while a positive numerical trend was seen for FVC% after exposure avoidance in fHP patients (p = 0.15). CONCLUSIONS: nfHP patients experienced an excellent survival with good therapeutic effect on pulmonary function tests with both corticosteroid initiation as well as antigen avoidance. In contrast, fHP patients experienced a dismal prognosis (median survival of 9.2 years) without any therapeutic effect of corticosteroid treatment. Whether antigen avoidance is useful in fHP patients is still unclear.

Clinical behaviour of patients exposed to organic dust and diagnosed with idiopathic pulmonary fibrosis.

BACKGROUND AND OBJECTIVE: Although idiopathic pulmonary fibrosis (IPF) patients experience a worse survival compared with chronic hypersensitivity pneumonitis (CHP), organic dust exposure is a known risk factor for both IPF and CHP. METHODS: We divided patients diagnosed with IPF, based on their exposure to moulds/birds (absent: group A; present: group B). We retrospectively compared pulmonary function and survival between groups A and B, and a separate CHP cohort (group C). RESULTS: A total of 293 patients were included (group A: n = 171, group B: n = 73, group C: n = 49). Demographics and baseline pulmonary function did not differ between groups A and B, but significant differences were seen between groups B and C. Median survival of group B was 84 months, which was longer than group A (43 months, P = 0.002), but lower than group C (157 months, P = 0.04), in both univariate and multivariate analyses. Antifibrotic treatment resulted in a better outcome in group A (hazard ratio (HR): 0.44) and group B (HR: 0.12) without interaction between exposure and antifibrotic use (P = 0.20). Forced vital capacity (FVC) decline was not associated with mould/bird exposure in this cohort. CONCLUSION: Group B patients experienced a better outcome compared with (non-exposed) IPF patients, although worse compared with CHP patients. Antifibrotic treatment in group B resulted in a similar beneficial effect compared with group A. Further research is needed to ascertain the diagnostic designation in this exposed usual interstitial pneumonia (UIP) patient group without other CHP features.

Diagnostic Ability of a Dynamic Multidisciplinary Discussion in Interstitial Lung Diseases: A Retrospective Observational Study of 938 Cases.

BACKGROUND: The advice of a dynamic multidisciplinary discussion (MDD) is believed to be important in the diagnosis of interstitial lung diseases (ILDs). However, to what extent MDD diagnoses differ from the preliminary diagnoses before formal workup and MDD (preMDD diagnoses) is still insufficiently studied. METHODS: We compared preMDD and MDD diagnoses in patients discussed at the Leuven University Hospitals MDDs between January 2005 and December 2015. RESULTS: Of 938 consecutive patients discussed in an MDD, 755 (80.5%) received a specific diagnosis. From the 183 patients with unclassifiable ILD, 150 patients (16.0%) received suggestions concerning further investigations to establish a definite diagnosis. In 191 patients (41.9% of patients with a preMDD diagnosis), the MDD changed the diagnosis. In 384 patients (79.5% of patients without preMDD diagnosis), MDD provided a diagnosis when the referring physician did not. MDD diagnosis showed a trend toward better prognostic discrimination between idiopathic pulmonary fibrosis and other ILDs compared with preMDD diagnosis (Harrell C-index, 0.666 vs 0.631; P = .08), which was particularly clear in patients with discordant MDD and preMDD diagnoses (hazard ratio, 2.68 vs 0.84; P = .012 vs .768). CONCLUSIONS: The MDD provided a definite diagnosis in 80.5% of presented cases, suggesting further investigations in almost all others. Given the high number of patients without preMDD diagnosis, the rate of change in preMDD diagnoses (41.9% of patients with a preMDD diagnosis) probably is an underestimation. The better prognostic discrimination among ILDs by using MDD indicates the added value of MDD in ILD.

Thin-Section CT Features of Idiopathic Pulmonary Fibrosis Correlated with Micro-CT and Histologic Analysis.

Purpose To elucidate the underlying lung changes responsible for the computed tomographic (CT) features of idiopathic pulmonary fibrosis (IPF) and to gain insight into the way IPF proceeds through the lungs and progresses over time. Materials and Methods Micro-CT studies of tissue cores obtained from explant lungs were examined and were correlated 1:1 with a CT study obtained immediately before transplantation. Samples for histologic analysis were obtained from selected cores. Results In areas with no or minimal abnormalities on CT images, small areas of increased attenuation located in or near the interlobular septa can be seen on micro-CT studies. In more involved lung areas, the number of opacities increases and opacities enlarge and approach each other along the interlobular septa, causing a fine reticular pattern on CT images. Simultaneously, air-containing structures in and around these opacities arise, corresponding with small cysts on CT images. Honeycombing is caused by a progressive increase in the number and size of these cystic structures and tissue opacities that gradually extend toward the centrilobular region and finally replace the entire lobule. At histologic analysis, the small islands of increased attenuation very likely correspond with fibroblastic foci. Near these fibroblastic foci, an abnormal adjacency of alveolar walls was seen, suggesting alveolar collapse. In later stages, normal lung tissue is replaced by a large amount of young collagen, as seen in patients with advanced fibrosis. Conclusion Fibrosis and cyst formation in patients with IPF seem to start at the periphery of the pulmonary lobule and progressively extend toward the core of this anatomic lung unit. Evidence was found that alveolar collapse might already be present in an early stage when there is only little pulmonary fibrosis. © RSNA, 2016.

Restrictive allograft syndrome after lung transplantation: new radiological insights.

OBJECTIVES: To describe the CT changes in patients with restrictive allograft syndrome (RAS) after lung transplantation, before and after clinical diagnosis. METHODS: This retrospective study included 22 patients with clinical diagnosis of RAS. Diagnosis was based on a combination of forced expiratory volume (FEV1) decline (≥20 %) and total lung capacity (TLC) decline (≥10 %). All available CT scans after transplantation were analyzed for the appearance and evolution of lung abnormalities. RESULTS: In 14 patients, non-regressing nodules and reticulations predominantly affecting the upper lobes developed an average of 13.9 months prior to the diagnosis of RAS. Median graft survival after onset of non-regressing abnormalities was 33.5 months, with most patients in follow-up (9/14). In eight patients, a sudden appearance of diffuse consolidations mainly affecting both upper and lower lobes was seen an average of 2.8 months prior to the diagnosis of RAS. Median graft survival was 6.4 months after first onset of non-regressing abnormalities, with graft loss in most patients (6/8). CONCLUSIONS: RAS has been previously described as a homogenous group. However, our study shows two different groups of RAS-patients: one with slow progression and one with fast progression. The two groups show different onset and progression patterns of CT abnormalities. KEY POINTS: • RAS is the newest discovered form of chronic lung allograft dysfunction (CLAD). • RAS is not a homogenous group, as survival varies greatly between patients. • In this study, we see two different CT onset and progression patterns. • These two different CT patterns also correlate with a different survival rate.

Is there an added value of cardiopulmonary exercise testing in sarcoidosis patients?

BACKGROUND: Cardiopulmonary exercise testing (CPET) with blood gas analysis may be helpful when there is a discrepancy between clinical findings and physiologic tests at rest. The aim of this study was to examine the added value of CPET compared to the measurement of the diffusing capacity of the lung for carbon monoxide (DLCO) in detecting impaired pulmonary gas exchange in sarcoidosis patients. METHODS: The clinical records of 160 (age = 41.3 ± 10.0 years; number of females = 63) sarcoidosis patients referred to the former MUMC ild care center were retrospectively reviewed. Patients performed a symptom-limited incremental exercise test with blood gas analysis on a bicycle ergometer. DLCO was measured by the single-breath method. RESULTS: DLCO (mean = 83.2 ± 18.0 %) below 80 % of predicted was demonstrated by 38 % of the sarcoidosis patients in our sample. Of the patients with normal DLCO (n = 99, 61.9 %), the P(A-a)O(2) at maximal exercise [P(A-a)O(2)max] was moderately increased (>2.5 kPa) in 69.7 % and excessively increased (>4.7 kPa) in 18.2 %. Pulmonary gas exchange impairment (PGEI) was more obvious in patients with lower DLCO values. A DLCO value below 60 % of predicted indicated substantial gas exchange impairment. PaO(2) at rest, DLCO, and FVC as a percentage of predicted and radiographic staging predicted 40 % of the PGEI at maximal exercise. CONCLUSION: A substantial number of the symptomatic sarcoidosis patients with normal DLCO appeared to have PGEI at maximal exercise, suggesting that normal DLCO at rest is an inappropriate predictor of abnormal pulmonary gas exchange during exercise. CPET appeared to offer added value in detecting impaired gas exchange during exercise in sarcoidosis patients with unexplained disabling symptoms.

The pathogenesis of pulmonary fibrosis: a moving target.

Pulmonary fibrosis is the end stage of many diffuse parenchymal lung diseases. It is characterised by excessive matrix formation leading to destruction of the normal lung architecture and finally death. Despite an exponential increase in our understanding of potentially important mediators and mechanisms, the delineation of primary pathways has proven to be elusive. In this review susceptibility and injurious agents, such as viruses and gastro-oesophageal reflux, and their probable role in initiating disease will be discussed. Further topics that are elaborated are candidate ancillary pathways, including immune mechanisms, oxidative and endoplasmic reticulum stress, activation of the coagulation cascade and the potential role of stem cells. This review will try to provide the reader with an integrated view on the current knowledge and attempts to provide a road map for future research. It is important to explore robust models of overall pathogenesis, reconciling a large number of clinical and scientific observations. We believe that the integration of current data into a "big picture" overview of fibrogenesis is essential for the development of effective antifibrotic strategies. The latter will probably consist of a combination of agents targeting a number of key pathways.

Severity of pulmonary involvement and (18)F-FDG PET activity in sarcoidosis.

BACKGROUND: Assessing inflammatory activity is useful in the management of persistent symptomatic sarcoidosis patients. (18)F-FDG PET (PET) has been shown to be a sensitive technique to assess inflammatory activity in sarcoidosis. The aim of this study was to evaluate whether the severity of pulmonary involvement is associated with PET activity in persistent symptomatic sarcoidosis patients. METHODS: Over a 5-year period, relevant clinical data including laboratory and lung function test results were gathered from the medical records of 95 sarcoidosis patients with persistent disabling symptoms who underwent both a PET and HRCT. HRCT scans were classified using a semiquantitative scoring system and PET findings as positive or negative, respectively. RESULTS: PET was positive in 77/95 patients, of whom 56 demonstrated pulmonary PET-positivity. HRCT scores were high (7.1 ± 3.6) in patients with positive pulmonary PET findings (n = 56) compared to patients with negative pulmonary PET findings (n = 39; 3.0 ± 2.9; p < 0.001). DLCO (65 ± 20% predicted) and FVC (85 ± 24% predicted) were low in patients with pulmonary PET-positivity versus those with negative pulmonary PET findings (79 ± 16% predicted; p = 0.001 and 96 ± 22% predicted; p = 0.044, respectively). Interestingly, out of the 26 patients with fibrotic changes, 22 (85%) had positive pulmonary PET findings, of whom 18/22 (82%) showed extrathoracic PET-positive lesions and 16/22 (73%) showed signs of serological inflammation. CONCLUSIONS: The severity of the pulmonary involvement, assessed by HRCT features and lung function parameters, appeared to be associated with PET activity in sarcoidosis. The majority of patients with fibrotic changes demonstrated inflammatory activity at pulmonary and extrathoracic sites.

Diffuse alveolar hemorrhage in coumarin users: a fibrosing interstitial pneumonia trigger?

BACKGROUND: Fibrosing interstitial pneumonias (IPs) include idiopathic pulmonary fibrosis (IPF) and nonspecific interstitial pneumonia (NSIP). It has been suggested that oxidative damage plays a role in the pathophysiology of idiopathic interstitial pneumonias. Diffuse alveolar hemorrhage (DAH) can cause oxidative stress. Accordingly, we hypothesized that episodes of DAH might trigger fibrosing IP development. METHODS: Patients using coumarins with confirmed DAH were retrospectively gathered during a 9 year period and reviewed for the development of IPF or fibrosing NSIP. RESULTS: A total of 65 patients with DAH could finally be included, 31 (48 %) of whom subsequently developed a fibrosing IP. The majority of these 31 patients developed the fibrosing IP within 3 years after DAH confirmation. A total of 41 (63 %) patients died within 3.0 ± 0.9 (range 1.3-4.7) years after the DAH diagnosis had been confirmed. Twenty-two of the deceased (54 %) had finally developed fibrosing IP. CONCLUSIONS: Almost half of the patients with established episodes of DAH developed fibrosing IP; therefore it seems that DAH might be a trigger for the development of fibrosing IP. This observation warrants prospective studies to further evaluate the clinical impact of these findings.

A predictive tool for an effective use of (18)F-FDG PET in assessing activity of sarcoidosis.

BACKGROUND: (18)F-FDG PET/CT (PET) is useful in assessing inflammatory activity in sarcoidosis. However, no appropriate indications are available. The aim of this study was to develop a prediction rule that can be used to identify symptomatic sarcoidosis patients who have a high probability of PET-positivity. METHODS: We retrospectively analyzed a cohort of sarcoidosis patients with non organ specific persistent disabling symptoms (n = 95). Results of soluble interleukin-2 receptor (sIL-2R) assessment and high-resolution computed tomography (HRCT) were included in the predefined model. HRCT scans were classified using a semi-quantitative scoring system and PET findings as positive or negative, respectively. A prediction model was derived based on logistic regression analysis. We quantified the model's performance using measures of discrimination and calibration. Finally, we constructed a prediction rule that should be easily applicable in clinical practice. RESULTS: The prediction rule showed good calibration and good overall performance (goodness-of-fit test, p = 0.78, Brier score 20.1%) and discriminated between patients with positive and negative PET findings (area under the receiver-operating characteristic curve, 0.83). If a positive predictive value for the presence of inflammatory activity of ≥90% is considered acceptable for clinical decision-making without referral to PET, PET would be indicated in only 29.5% of the patients. Using a positive predictive value of 98%, about half of the patients (46.3%) would require referral to PET. CONCLUSIONS: The derived and internally validated clinical prediction rule, based on sIL-2R levels and HRCT scoring results, appeared to be useful to identify sarcoidosis patients with a high probability of inflammatory activity. Using this rule may enable a more effective use of PET scan for assessment of inflammatory activity in sarcoidosis.