Centrilobular Emphysema Research Articles

RARE BACTERIAL EMPYEMA AFTER A BLUNT TRAUMA

TOPIC: Disorders of the Pleura TYPE: Medical Student/Resident Case Reports INTRODUCTION: Pleural effusion (PE) is an accumulation of excess fluid in the pleural space. PE is classified as transudative or exudative. Transudative pleural effusion can result from: increased hydrostatic pressure, decreased oncotic forces or increased negative intrapleural pressure. On the other hand, exudative pleural effusion result from increased capillary permeability and impaired lymphatic drainage caused by inflammatory processes. Parapneumonic effusions such as empyema are related to pneumonia in 20-40%. ß hemolytic Lancefield group A streptococcus pyogenes (GAS) is a common cause of upper respiratory tract and cutaneous infections which commonly is related to streptococcal toxic shock syndrome. GAS is an uncommon pathogen with 1.14 per 100,000 habitants associated to bacterial pneumonia, however the prevalence of GAS associated to empyema is only 0.7%. CASE PRESENTATION: Case of 46-year-old man with history of IVDA who arrived to urgency room due to shortness of breath, dry cough and left pleuritic chest pain of 3 weeks of evolution. He had a chest trauma as a pedestrian 2 weeks prior arrival. He denied fever, night sweats, hemoptysis, palpitations, or weight changes. Vitals signs were remarkable for tachycardia, tachypnea and decreased peripheral oxygen saturation. Physical examination was remarkable for bilateral decreased breath sounds and left side dullness to percussion. ABG's with oxygen supplementation revealed hypercapnia 57.3 mmHg with elevated A-a gradient 66.3 mmHg. CBC showed leukocytosis with left shifting. Chemistry panel was remarkable for metabolic alkalosis 31 mmol/L and lactate dehydrogenase was elevated 615 IU/L. Chest X-Ray showed left sided white lung, followed by a chest CT with bilateral pleuro-parenchyma fibrotic changes, bullae formation, centrilobular emphysema, patchy ground glass appearance at both lung fields and decreased right lung volume with ipsilateral displacement of the heart and mediastinal structures with large, multiloculated left pleural effusion with increased density. Left side thoracentesis performed collecting 120ml of purulent fluid, elevated WBC 150,000 with PMN 65% and gram stain positive. Chest tube was placed and drain 1400ml of brown-yellow purulent fluid and pleural culture showed growth of streptococcus pyogenes group A. Patient started on directed IV antibiotic therapy. DISCUSSION: Empyema is an accumulation of excess pus in pleural space. The M protein, the major virulence factor, is a macromolecule incorporated in fimbriae present on the cell membrane projecting on the bacterial cell wall. It is the primary cause of antigenic shift and antigenic drift among GAS. CONCLUSIONS: We expect to contribute awareness and knowledge to the medical field to always include empyema in the working diagnosis of all patients with progressive dyspnea after blunt trauma. REFERENCE #1: Sakai T, Taniyama D, Takahashi S, Nakamura M, Takahashi T. Pleural empyema and streptococcal toxic shock syndrome due to Streptococcus pyogenes in a healthy Spanish traveler in Japan. IDCases. 2017;9:85-88. Published 2017 Jun 27. doi:10.1016/j.idcr.2017.06.006 REFERENCE #2: Shebl E, Paul M. Parapneumonic Pleural Effusions And Empyema Thoracis. [Updated 2020 Aug 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK534297/ REFERENCE #3: Tamayo E, Montes M, Vicente D, Pérez-Trallero E. Streptococcus pyogenes Pneumonia in Adults: Clinical Presentation and Molecular Characterization of Isolates 2006-2015. PLoS One. 2016;11(3):e0152640. Published 2016 Mar 30. doi:10.1371/journal.pone.0152640 DISCLOSURES: No relevant relationships by Maria Betancourt, source=Web Response No relevant relationships by Marlene Farinacci Vilaro, source=Web Response No relevant relationships by Kyomara Hernandez-Moya, source=Web Response No relevant relationships by Arnaldo Nieves-Ortiz, source=Web Response No relevant relationships by Ivanisse Ortiz Velez, source=Web Response No relevant relationships by Neshma Roman-Velez, source=Web Response

NEUROFIBROMATOSIS-ASSOCIATED LUNG DISEASE: A CASE REPORT

TOPIC: Genetic and Developmental Disorders TYPE: Fellow Case Reports INTRODUCTION: Neurofibromatosis type I (NF-1) is a rare disorder that affects multiple organs, with cutaneous findings being the most well-known. It is an autosomal dominant disease caused by dysplasia of ectoderm and mesoderm with variable expression[1]. NF is characterized by a collection of neurofibromas, café au lait spots, and Lisch nodules. Neurofibromatosis is a rare disease and only 10-20% of the cases have associated diffuse lung disease (NF-DLD). Thus, many of the specific characteristics have yet to be elucidated[2]. CASE PRESENTATION: A 50-year-old white man with NF-1 diagnosed by skin biopsy 2 years ago was seen by his PCP due to worsening shortness of breath associated with a productive cough. Levofloxacin was ordered, but 5 days later symptoms persisted so he was referred to the ED.He reported a prior tube thoracostomy after spontaneous right-sided pneumothorax.Family history was remarkable for neurofibromatosis in his mother and spontaneous pneumothorax in his brother. However, his brother does not have any of the cutaneous findings consistent with NF.He is a former smoker with a 20 pack-year history, quitting a month before admission. He works in a furniture company with exposure to wood dust and chemical fumes for more than 30 years.He denies any fever, chills, chest pain, or weight change. Denies any sick contacts.Physical examination demonstrated no respiratory distress. He had mild bibasilar crackles and multiple neurofibromas throughout his body, more so on his back. SARS-CoV-2, influenza A, influenza B, RSV PCR were all negative. Chest x-ray demonstrated peripheral interstitial opacities. He was started on empiric antibiotic coverage for community-acquired pneumonia. Chest CT showed evidence of upper lobe predominant cystic disease and pulmonary reticular abnormalities in the lower lobes consistent with neurofibromatosis associated diffuse lung disease. Centrilobular emphysema and mild bronchiectatic changes were also noted. He was started on bronchodilators with a 5-day course of prednisone. Respiratory status returned to baseline and he was discharged with a LABA+LAMA inhaler and follow-up with the pulmonary clinic. DISCUSSION: The exact prevalence of NF-DLD is unknown. Based on the limited case reports, NF-DLD is more predominant in men, occurring during the third or fourth decade of life with dyspnea being the more common presenting symptom. Whether smoking plays a role in NF-DLD is still unknown. The typical HRCT finding in NF-DLD is upper-lobe cystic and bullous disease with basilar interstitial lung disease. HRCT results demonstrate bibasilar reticular opacities 50%, bullae 50%, ground-glass opacities 37%, cysts, and emphysema 25%[3]. CONCLUSIONS: NF-DLD is considered one of the rare etiologies of cystic lung disease characterized by upper lobe cystic and bullous disease and lower lobe interstitial changes. REFERENCE #1: V. M. Riccardi, "Von Recklinghausen Neurofibromatosis," https://doi.org/10.1056/NEJM198112313052704, Jan. 19, 2010. https://www.nejm.org/doi/pdf/10.1056/NEJM198112313052704 REFERENCE #2: J. H. Ryu, J. G. Parambil, P. S. McGrann, and G. L. Aughenbaugh, "Lack of Evidence for an Association Between Neurofibromatosis and Pulmonary Fibrosis," Chest, vol. 128, no. 4, pp. 2381–2386, Oct. 2005, doi: 10.1378/chest.128.4.2381. REFERENCE #3: A. C. Zamora, H. R. Collard, P. J. Wolters, W. R. Webb, and T. E. King, "Neurofibromatosis-associated lung disease: a case series and literature review," European Respiratory Journal, vol. 29, no. 1, pp. 210–214, Jan. 2007, doi: 10.1183/09031936.06.00044006. DISCLOSURES: No relevant relationships by Susanti Ie, source=Web Response No relevant relationships by seyed pourshahid, source=Web Response No relevant relationships by Seyedmohammad Pourshahid, source=Web Response No relevant relationships by Edmundo Rubio, source=Web Response

EOSINOPHILS LEAD THE WAY

TOPIC: Lung Pathology TYPE: Medical Student/Resident Case Reports INTRODUCTION: Hypereosinophilic Syndrome (HES) is a rare condition characterized by sustained eosinophil counts greater than 1.5x103/uL with pathologic confirmation of tissue hypereosinophilia (HE). It usually affects multiple organs in the absence of clonal or other secondary causes of eosinophilia. The most common organs affected are the lungs, skin, heart, gastrointestinal tract, and brain. CASE PRESENTATION: This is an 81-year-old male patient with history of alcohol abuse, hypertension, and atrial fibrillation, who presented with diffuse skin itching and burning sensation for three days after working with polyvinyl chloride (PVC) tubing material. He referred having associated generalized weakness, anorexia, and dry cough. Labs were remarkable for having eosinophilia of 17x10^3/uL, mild transaminitis (SGPT:54 U/L, SGOT:45 U/L), elevated high sensitive troponins of 41-43 without delta and worsening renal function with serum creatinine increasing from 0.9 to 1.9 mg/dL. Immunoglobulin E was found to be elevated in 774.8, however Strongyloides IgG antibody and Schistosoma antibody were negative, ruling out endemic parasite involvement. Chest CT scan without contrast revealed moderate centrilobular emphysema, mild areas of ground glass opacities and tree-in-bud opacities bilaterally, for which it was decided to undergo bronchoscopy examination to exclude other etiologies, including malignancy or pneumoconiosis. This procedure revealed no lesions or masses, with bronchoalveolar lavage reporting no malignant cells, as well as negative acid-fast bacilli or fungal organisms. To rule out myelodysplastic syndrome a bone marrow biopsy was performed revealing hypercellular marrow with 48 percent of eosinophils, however flow cytometry showed no clonal cells or blasts, as well as negative BCL/ABL and PDGFR alpha. These findings were consistent with Idiopathic Hypereosinophilic Syndrome, for which he was started on prednisone 40 mg PO daily. DISCUSSION: HE can be confirmed by bone marrow biopsy of more than 20 percent of eosinophils. Most of these patients tolerate and respond well to glucocorticoid therapy, however in refractory cases the tyrosine kinase inhibitor imatinib has shown to improve the patient's outcome. CONCLUSIONS: It is essential to rule out secondary causes of hypereosinophilia, which may be seen in parasitic infections, pneumoconiosis, or malignancy, to prevent delay in diagnosis and prompt adequate therapy. REFERENCE #1: Roufosse, F.E., et al. Hypereosinophilic syndromes. Orphanet J Rare Dis 2, 37 (2007) DISCLOSURES: No relevant relationships by Christina Arraut-Hernandez, source=Web Response No relevant relationships by Jose Gutierrez-Nunez, source=Web Response No relevant relationships by Francisco Tirado-Polo, source=Web Response

English

The differential diagnosis of the cystic lung disease is extensive, ranging from an isolated incidental lung cyst to multiple diffuse lung cysts with other varied associated lung abnormalities. High resolution computed tomography (HRCT) thorax is the imaging modality of choice in the evaluation of these diseases, by improving the characterisation of the lung cysts (number, size, shape, distribution, wall thickness and regularity), and associated pulmonary and extrapulmonary abnormalities (like ground glass densities, nodules, interstitial fibrosis, mediastinal lymphadenopathy). After differentiating from the common cyst mimickers (cavity, centrilobular emphysema and cystic bronchiectasis), they should be grouped by location into subpleural cysts (paraseptal emphysema, bulla and honeycombing) and intraparenchymal cysts. Intraparenchymal cysts are in turn categorised into solitary / localised cysts (incidental cyst, congenital pulmonary airway malformations, intrapulmonary bronchogenic cyst and hydatid cyst) and multiple diffuse cysts. The next step will be the categorisation of these multiple diffuse cysts into those without other lung abnormalities (lymphangioleiomyomatosis and Birt-Hogg-Dube syndrome) and those with other lung abnormalities such as predominant ground glass densities (Pneumocystis jirovecii pneumonia, desquamative interstitial pneumonia, lymphoid interstitial pneumonia, subacute hypersensitivity pneumonitis and pneumatoceles) or predominant nodules (pulmonary Langerhans cell histiocytosis, amyloidosis, light chain deposition disease, follicular bronchiolitis, recurrent respiratory papillomatosis, cystic tuberculosis, cystic lung metastasis, sarcoidosis, and pulmonary mesenchymal cystic hamartomas). We conclude that this orderly radiologic approach in a given HRCT chest study of a cystic lung disease (in addition to correlation with clinical and laboratory findings), can lead us to a specific diagnosis in majority of instances, thereby optimising their treatment management, without the need of an invasive biopsy. KEY WORDS HRCT Thorax, Lung Cysts, Ground Glass Densities, Lung Nodules

Computed tomography-based visual assessment of chronic obstructive pulmonary disease: comparison with pulmonary function test and quantitative computed tomography.

BackgroundChronic obstructive pulmonary disease (COPD) has variable subtypes involving mixture of large airway inflammation, small airway disease, and emphysema. This study evaluated the relationship between visually assessed computed tomography (CT) subtypes and clinical/imaging characteristics.MethodsIn total, 452 participants were enrolled in this study between 2012 and 2017. Seven subtypes were defined by visual evaluation of CT images using Fleischner Society classification: normal, paraseptal emphysema (PSE), bronchial disease, and centrilobular emphysema (trace, mild, moderate and confluent/advanced destructive). The differences in several variables, including clinical, laboratory, spirometric, and quantitative CT features among CT-based visual subtypes, were compared using the chi-square tests and one-way analysis of variance.ResultsSubjects who had PSE had better forced expiratory volume in 1 second (FEV1) (P=0.03) percentage and higher lung density (P<0.05) than those with moderate to confluent/advanced destructive centrilobular emphysema. As the visual grade of centrilobular emphysema worsened, pulmonary function declined and modified Medical Research Council, COPD assessment test (CAT) score, and quantitative assessment (emphysema index and air trapping) increased. The bronchial subtype was associated with higher body mass index (BMI), better lung function and higher lung density. Participants with trace emphysema showed a rapid increase in functional small airway diseaseConclusionsClassifying subtypes using visual CT imaging features can reflect heterogeneity and pathological processes of COPD.

Improving clinical disease subtyping and future events prediction through a chest CT-based deep learning approach.

PurposeTo develop and evaluate a deep learning (DL) approach to extract rich information from high‐resolution computed tomography (HRCT) of patients with chronic obstructive pulmonary disease (COPD).MethodsWe develop a DL‐based model to learn a compact representation of a subject, which is predictive of COPD physiologic severity and other outcomes. Our DL model learned: (a) to extract informative regional image features from HRCT; (b) to adaptively weight these features and form an aggregate patient representation; and finally, (c) to predict several COPD outcomes. The adaptive weights correspond to the regional lung contribution to the disease. We evaluate the model on 10 300 participants from the COPDGene cohort.ResultsOur model was strongly predictive of spirometric obstruction (r2 = 0.67) and grouped 65.4% of subjects correctly and 89.1% within one stage of their GOLD severity stage. Our model achieved an accuracy of 41.7% and 52.8% in stratifying the population‐based on centrilobular (5‐grade) and paraseptal (3‐grade) emphysema severity score, respectively. For predicting future exacerbation, combining subjects’ representations from our model with their past exacerbation histories achieved an accuracy of 80.8% (area under the ROC curve of 0.73). For all‐cause mortality, in Cox regression analysis, we outperformed the BODE index improving the concordance metric (ours: 0.61 vs BODE: 0.56).ConclusionsOur model independently predicted spirometric obstruction, emphysema severity, exacerbation risk, and mortality from CT imaging alone. This method has potential applicability in both research and clinical practice.

Structural alteration of lung parenchyma in patients with NF1: a phenotyping study using multidetector computed tomography (MDCT)

BackgroundDiffuse interstitial lung disease have been described in Neurofibromatosis type 1 (NF1), but its diversity and prevalence remain unknown. The aim of this study was to assess the prevalence and characteristics of (NF1)-associated lung manifestations in a large single-center study using multidetector computed tomography (MDCT) and to evaluate the smoking history, patients’ age, genetics, and the presence of malignant peripheral nerve sheath tumors (MPNST) as potential influencing factors for lung pathologies.MethodsIn this retrospective study, 71 patients with NF1 were evaluated for the presence of distinctive lung manifestations like reticulations, consolidations, type of emphysema, pulmonary nodules and cysts. All patients underwent F-18-FDG PET/CT scans, which were reviewed by two experienced radiologists in consensus. Patients’ subgroups were formed based on their smoking history (current smokers/previous smokers/never smokers), age (< 12 years, 12–18 years, > 18 years), and presence of MPNST (MPNST/no MPNST). In 57 patients (80%), genetic analysis of sequences coding for the neurofibromin on chromosome 17 was performed, which was correlated with different lung pathologies.ResultsAmong all NF1 patients (33 ± 14 years, 56% females), 17 patients (24%) were current smokers and 62 patients (87%) were > 18 years old. Pulmonary cysts, nodules, and paraseptal emphysema were the most common pulmonary findings (35%, 32%, 30%). The presence of pulmonary metastases, MPNST and centrilobular emphysema was associated with smoking. Cysts were observed only in adults, whereas no significant correlation between age and all other pulmonary findings was found (p > 0.05). Presence of MPNST was accompanied by higher rates of intrapulmonary nodules and pulmonary metastasis. Neither the presence nor absence of any of the specific gene mutations was associated with any particular lung pathology (p > 0.05).ConclusionsAll pulmonary findings in NF1 patients occurred independently from specific mutation subtypes, suggesting that many NF1 mutations can cause various pulmonary pathologies. The presence of pulmonary metastases, MPNST and centrilobular emphysema was associated with smoking, indicating the value of smoking secession or the advice not to start smoking in NF1 patients as preventive strategy for clinicians. For screening of pulmonary manifestations in NF1 patients, an MDCT besides medical history and physical examination is mandatory in clinical routine.

Disproportionally Impaired Diffusion Capacity Relative to Airflow Limitation in COPD

Forced expiratory volume in 1 s (FEV1) is a standard physiological index of chronic obstructive pulmonary disease (COPD), but reflects emphysema and vascular abnormalities less sensitively than diffusion capacity for carbon monoxide (DLCO). This study tested whether a disproportionally impaired DLCO relative to FEV1 (FEV1 z-score>-3 and DLCO z-score≤-3) is a common functional COPD phenotype associated with distinct clinical and structural features and the prognosis of two cohorts. The cross-sectional analyses of the Korea COPD Subgroup Study (KOCOSS) cohort (multicenter study in Korea) included 743 males with COPD whose DLCO was available. The cross-sectional and longitudinal analyses of the Kyoto University Cohort (single-center study in Japan) included 195 males with COPD who were prospectively followed for 10 years. A disproportionally impaired DLCO relative to FEV1 was observed in 29% and 31% of patients in the KOCOSS and Kyoto University cohorts, respectively. In the multivariable analysis, the disproportionally impaired DLCO was associated with worse symptoms, shorter 6-minute walking distance, paraseptal and centrilobular emphysema on computed tomography, and reduced arterial oxygen and carbon dioxide pressures compared to the reference (FEV1 z-score>-3 and DLCO z-score>-3). In the multivariable Cox proportional hazard model, a higher long-term mortality was observed in the disproportionally impaired DLCO group than in the reference group (hazard ratio [95% confidence interval] = 3.09 [1.52–6.29]) and similar to the DLCO z-score≤-3 and FEV1 z-score≤-3 group. The disproportionally impaired DLCO relative to FEV1 is common and associated with increased symptoms, emphysema, arterial blood gas abnormalities, and increased long-term mortality in patients with COPD.

The Role of Granzyme B Containing Cells in the Progression of Chronic Obstructive Pulmonary Disease.

BackgroundLung inflammation plays a vital role in the pathogenesis of chronic obstructive pulmonary disease (COPD), but the characteristics of the inflammatory process remain unclear. There is growing interest in the role of granzyme B (GzmB) because CD8+ T cells can induce apoptosis of target cells by releasing GzmB, which in turn may cause tissue injury and remodeling. However, GzmB is also expressed by regulatory cells, which are able to suppress CD8+ T cell. The role of GzmB+ cells needs to be defined in COPD.MethodsGzmB+ and CD8+ cells on alveolar wall of surgically resected lungs of microscopically classified 12 nonsmoking control, 12 panlobular emphysema (PLE) and 30 centrilobular emphysema (CLE) subjects were localized by immunohistochemical method. Positively stained cells on alveolar wall were counted and length of corresponding alveolar wall was measured. The results were expressed as mean number of positively stained cells per mm of alveolar wall in each subject.ResultsThe number of GzmB+ and CD8+ cells on alveolar wall of CLE was greater than that of control or PLE subjects (p<0.05 and p<0.001, respectively). There was a positive relationship between the number of alveolar GzmB+ cells and forced expiratory volume in 1 second (FEV1) (r=0.610, p=0.003) in CLE subjects. The number of alveolar GzmB+ cells progressively decreased with decline of FEV1.ConclusionOur finding that number of alveolar GzmB+ cells was associated with FEV1 suggests that GzmB+ cells might have protective role in the progression of lung destruction and airflow limitation in CLE, which is the predominant emphysema subtype of COPD.

CT Assessment of Subtypes of Pulmonary Emphysema in Mongolian Miners

Objectives: To determine the incidence of subtypes of pulmonary emphysema identified by LDCT imaging and the relationship between emphysema subtypes with smoking and pulmonary function in miners. Methods: We reviewed 329 miners (245 men and 84 women). Each miner had a low dose (LD) chest CT. Among them 75 miners had a standard chest CT. The images were reconstructed using contemporary iterative reconstruction. Lung volumes and emphysema severity was calculated using automated densitometry segmentation software and qualitative visual analyses.There were two subtypes of pulmonary emphysema found: centrilobular emphysema (CLE) and paraseptal emphysema (PSE). Based on these subtypes, CLE was divided into the following five categories: trace, mild, moderate, confluent, and advanced CLE. PSE was divided into the following two catergories: mild and substantial PSE. Results: Pulmonary emphysema was found in 89 (27.1%) of 329 miners. According to the survey, 73 (82.0%) miners had centrilobulor emphysema, and 17 (18.0%) had a paraseptal emphysema. The emphysema group was a lower Gensler index than thenon-emphysema group. The smoker group had higher emphysematous changes than the non-smoker groups (p &lt; 0.05). Conclusions: Dose reduced CT isauseful study for the assessment of emphysema.

Serine Protease Imbalance in the Small Airways and Development of Centrilobular Emphysema in Chronic Obstructive Pulmonary Disease.

Epithelial dysfunction in the small airways may cause the development of emphysema in chronic obstructive pulmonary disease. C/EBPα (CCAAT/enhancer binding protein-α), a transcription factor, is required for lung maturation during development, and is also important for lung homeostasis after birth, including the maintenance of serine protease/antiprotease balance in the bronchiolar epithelium. This study aimed to show the roles of C/EBPα in the distal airway during chronic cigarette smoke exposure in mice and in the small airways in smokers. In a model of chronic smoke exposure using epithelial cell-specific C/EBPα-knockout mice, significant pathological phenotypes, such as higher protease activity, impaired ciliated cell regeneration, epithelial cell barrier dysfunction via reduced zonula occludens-1 (Zo-1), and decreased alveolar attachments, were found in C/EBPα-knockout mice compared with control mice. We found that Spink5 (serine protease inhibitor kazal-type 5) gene (encoding lymphoepithelial Kazal-type-related inhibitor [LEKTI], an anti-serine protease) expression in the small airways is a key regulator of protease activity in this model. Finally, we showed that daily antiprotease treatment counteracted the phenotypes of C/EBPα-knockout mice. In human studies, CEBPA (CCAAT/enhancer binding protein-α) gene expression in the lung was downregulated in patients with emphysema, and six smokers with centrilobular emphysema (CLE) showed a significant reduction in LEKTI in the small airways compared with 22 smokers without CLE. LEKTI downregulation in the small airways was associated with disease development during murine small airway injury and CLE in humans, suggesting that LEKTI might be a key factor linking small airway injury to the development of emphysema.

Exploring the Association Between Emphysema Phenotypes and Low Bone Mineral Density in Smokers with and without COPD.

RationaleEmphysema and osteoporosis are tobacco-related diseases. Many studies have shown that emphysema is a strong and independent predictor of low bone mineral density (BMD) in smokers; however, none of them explored its association with different emphysema subtypes.ObjectiveTo explore the association between the different emphysema subtypes and the presence of low bone mineral density in a population of active or former smokers with and without chronic obstructive pulmonary disease (COPD).MethodsOne hundred and fifty-three active and former smokers from a pulmonary clinic completed clinical questionnaires, pulmonary function tests, a low-dose chest computed tomography (LDCT) and a dual-energy absorptiometry (DXA) scans. Subjects were classified as having normal BMD or low BMD (osteopenia or osteoporosis). Emphysema was classified visually for its subtype and severity. Logistic regression analysis explored the relationship between the different emphysema subtypes and the presence of low BMD adjusting for other important factors.ResultsSeventy-five percent of the patients had low BMD (78 had osteopenia and 37 had osteoporosis). Emphysema was more frequent (66.1 vs 26.3%, p=<0.001) and severe in those with low BMD. Multivariable analysis adjusting for other significant cofactors (age, sex, FEV1, and severity of emphysema) showed that BMI (OR=0.91, 95% CI: 0.76–0.92) and centrilobular emphysema (OR=26.19, 95% CI: 1.71 to 399.44) were associated with low BMD.ConclusionLow BMD is highly prevalent in current and former smokers. BMI and centrilobular emphysema are strong and independent predictors of its presence, which suggests that they should be considered when evaluating smokers at risk for low BMD.

PULMONARY EMPHYSEMA ANALYSIS USING SHEARLET BASED TEXTURES AND RADIAL BASIS FUNCTION NETWORK

The emergence of High Resolution Computed Tomography (HRCT) images of the lungs clearly shows the parenchymal lung architecture and thus the quantification of obstructive lung disease becomes most accurate. In this study, an automated system to diagnose obstructive lung disease called emphysema is presented using HRCT images of the lungs. The kind of texture information that ideally can be extracted from HRCT images depends on the multi-resolution representation system. The proposed Pulmonary Emphysema Analysis (PEA) system employs Shearlets as it can extracts more texture information than wavelets in different directions and levels. Radial Basis Function Network (RBFN) is employed for the classification of HRCT images into three categories; Normal Tissue (NT), Paraseptal Emphysema (PSE) and Centrilobular Emphysema (CLE). Results prove that a confident diagnosis of pulmonary emphysema is established to help clinicians which will also increase the precision of diagnosis.

VANISHING LUNG SYNDROME OR GIANT BULLOUS EMPHYSEMA

TYPE: Abstract Publication TOPIC: Obstructive Lung Diseases PURPOSE: We report a case of Giant Bullous Emphysema (Vanishing Lung Syndrome) that presented with pneumothorax in a smoker/COPD case. METHODS: A 40 years old female, current smoker, presented with pleuritic chest pain and dyspnoea. A chest x-ray showed a large right pneumothorax that was managed with a chest drain. However, pneumothorax recurred post-discharge and required another chest drain. Due to recurrence, a CT chest was performed, that showed bilateral giant bullae that occupied more than one-third of the lungs, located predominantly in upper lobes. The remaining lung parenchyma appeared normal except minor/early centrilobular emphysema. Alpha 1-antitrypsin levels were normal. RESULTS: CT Chest findings were consistent with giant bullous emphysema. She successfully managed to quit smoking and had a right-sided thoracoscopic bullectomy with resolution in her symptoms. CONCLUSIONS: A major complication of giant bullous emphysema is pneumothorax, that may pose a diagnostic challenge on a chest -x-ray in the presence of a giant bulla. A CT thorax remains an important tool to define the extent/distribution of bullous disease, pneumothorax, associated emphysema, and to assist immediate (chest drain) and long-term management (pre-operative planning). Smoking cessation and surgical resection of giant bullae (if occupy >1/3rd of lung) remain an effective strategy with improvement in dyspnoea, lung functions and exercise capacity. CLINICAL IMPLICATIONS: Vanishing Lung Syndrome is a rare clinical entity, that tends to be progressive, however, there appear to be no guidelines on its management or follow-up. The role of new interventions such as endoscopic lung volume reduction (ELVRS) remains undefined in the management of Giant Bullous Emphysema. DISCLOSURE: No significant relationships. KEYWORDS: Emphysema, Giant Bullae, Vanishing Lung

Imaging-Based Surrogate Markers of Epidermal Growth Factor Receptor Mutation in Lung Adenocarcinoma: A Local Perspective.

To identify computed tomography (CT) features of epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma in Canadian population and whether imaging-based surrogate markers of EGFR mutation in our population were similar to those found in the Asian population. Pretreatment CT scans of 223 patients with adenocarcinoma of the lung (112 with EGFR mutation and 111 without mutation) were retrospectively assessed for 20 specific CT features by 2 radiologists, who were blinded to the status of EGFR mutation. Univariate and multivariate logistic regression analyses as well as areas under the receiver operating characteristic curve were performed to discriminate characteristics of EGFR-activating mutation features. Epidermal growth factor receptor mutation-positive adenocarcinomas were more frequently found in female (P < .03), less than 20 pack-year smoking history (P < .001), smaller tumor (P < .01), spiculated margins (P < .05), without centrilobular emphysema (P < .001), and without lymphadenopathy (P < .05), similarly to the Asian population. Multivariate logistic regression analyses of combined clinical and radiological features identified less than 20 pack-year smoking history, smaller tumor diameter, fine or coarse spiculations, noncentral location of the tumor, and lack of centrilobular emphysema and pleural attachment as the strongest independent prognostic factors for the presence of an EGFR mutation. These combined features improved prognostic ability area under the curve to 0.879, compared to 0.788 for clinical features only. Several CT findings may help predict the presence of an activating mutation in EGFR in lung adenocarcinomas in our Canadian population. Combining clinical and radiological features improves prognostic ability to determine the EGFR mutation status compared to clinical features alone.

The Technome - A Predictive Internal Calibration Approach for Quantitative Imaging Biomarker Research

The goal of radiomics is to convert medical images into a minable data space by extraction of quantitative imaging features for clinically relevant analyses, e.g. survival time prediction of a patient. One problem of radiomics from computed tomography is the impact of technical variation such as reconstruction kernel variation within a study. Additionally, what is often neglected is the impact of inter-patient technical variation, resulting from patient characteristics, even when scan and reconstruction parameters are constant. In our approach, measurements within 3D regions-of-interests (ROI) are calibrated by further ROIs such as air, adipose tissue, liver, etc. that are used as control regions (CR). Our goal is to derive general rules for an automated internal calibration that enhance prediction, based on the analysed features and a set of CRs. We define qualification criteria motivated by status-quo radiomics stability analysis techniques to only collect information from the CRs which is relevant given a respective task. These criteria are used in an optimisation to automatically derive a suitable internal calibration for prediction tasks based on the CRs. Our calibration enhanced the performance for centrilobular emphysema prediction in a COPD study and prediction of patients’ one-year-survival in an oncological study.

P1829 A middle aged man with pericardial cyst

Abstract Introduction Pericardial cysts are rare benign congenital anomaly that are usually accidentally discovered as a mass obliterating the costophrenic angle. The reported incidence is one to 100,000 with males are equally affected as females. They are usually asymptomatic; however, they can cause chest pain, shortness of breath and dry cough. Case report We present a 62 years old gentleman who presented with increasing shortness of breath. He was a heavy smoker and was known to have COPD. He was also known to have chronic heart failure with an EF of 40% and had a previous history of pericardial cyst that was initially discovered when he was investigated for shortness of breath. The patient had a one-month history of feeling more dyspneic than usual. His chest auscultation revealed scattered rhonchi and no murmurs were heard on auscultation of the heart. His ECG showed no new abnormality and his chest x-ray showed abnormal right cardio mediastinal silhouette with large opaque area adjacent to the right heart border and the size of the opacity the same compared to his previous x rays. An Echocardiography was done and this showed moderate to severe impairment of left ventricular systolic function with an EF of 30-35%, mild to moderate mitral regurgitation and showed a cystic lesion anterior to the right ventricle. A CT chest was done for evaluation of the pericardial cyst and showed centrilobular emphysema and a mass in the rt lung abutting the right border of the heart with a maximum diameter of 8.7 cm. The patient was non-compliant to his medications and repeatedly missed his follow up appointments. He also continued to smoke despite progression of his COPD. The cause of his shortness of breath was likely due to progression of heart failure and COPD with the pericardial cyst probably has no or minimal rule. Conclusion Pericardial cysts are rarely symptomatic and usually has a benign course. We aimed at increasing awareness of this rare benign animally. Abstract P1829 Figure.

Pulmonary emphysema not combined with lung fibrosis in systemic sclerosis.

Interstitial Lung Disease (ILD) is a common finding of Systemic Sclerosis (SSc) mainly presenting in the form of Nonspecific Interstitial Pneumonia (NSIP) and deeply affecting patients' prognosis. Beside NSIP, other types of ILD have been reported. The most recently described pattern is the so-called Combined-pulmonary emphysema and lung fibrosis, characterized by the coexistence of both upper lobes centrilobular and paraseptal emphysema and lower lobes ILD. We presented three cases of patients with SSc, in which High Resolution Computed Tomography examinations showed emphysema with atypical distribution and radiological presentation, without or with mild signs of fibrosing lung disease, that stabilized after immunosuppressive treatment.

AUTOIMMUNITY TRIGGERED BY IMMUNOTHERAPY: A CASE OF AUTOIMMUNE HEPATITIS-INDUCED BY NINTEDANIB TREATMENT FOR IPF

SESSION TITLE: Wednesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease characterized by progressive loss of lung function, dyspnea and impairment in quality of life.1 Nintedanib is a tyrosine kinase inhibitor approved for treatment of IPF which can reduce the annual rate of decline in forced vital capacity.2 Nintedanib’s adverse effects are managed symptomatically, by dose reduction or treatment interruption.3 We present a case of drug induced autoimmune hepatitis associated with Nintedanib. CASE PRESENTATION: A 59-year-old male with 19 pack year smoking history, COPD GOLD group B, GERD and CAD who initially presented to his PCP 2 years prior with dyspnea. Patient underwent CABG and bio-prosthetic aortic valve replacement, but dyspnea persisted. PFTs showed a restrictive pattern and reduced DLCO. Chest CT showed mild centrilobular emphysema, coarse interstitial markings and bilateral pleural-parenchymal scarring with early honeycombing in the lung bases, highly suggestive of pulmonary fibrosis. Workup for secondary causes of fibrotic lung disease including connective tissue diseases and barium swallow test were negative. He was diagnosed with IPF and was started on Nintedanib within a month. Pretreatment liver function tests (LFTs) were normal. Three months into treatment, Nintedanib was discontinued due severe nausea, vomiting and diarrhea. LFTs at this time were significant for ALP 471, AST 139 and ALT 189. Liver ultrasound showed fatty infiltration and chronic liver disease workup was negative except for gamma-globulin elevation. Repeat LFTs 4 weeks after stopping Nintedanib were persistently elevated while liver biopsy showed active lobular, portal hepatitis and mild focal fibrosis. Patient was diagnosed with drug-induced autoimmune hepatitis and started on Prednisone which led to normalization of liver enzymes. Liver panel worsened when prednisone was tapered, and therefore Azathioprine was started as a steroid sparing agent. Patient continues to be on Prednisone and Azathioprine and is undergoing workup for lung transplant. LFTs improved to normal limits on current treatment. DISCUSSION: Hepatitis is a potential complication associated with Nintedanib use 4. Mechanism of hepatocellular injury remains unclear but is thought to be due to epidemiologic variances in tolerability.5 Current recommendations are to monitor LFTs every 3 months while on Nintedanib. CONCLUSIONS: A literature review did not yield other cases of Nintedanib causing drug induced autoimmune hepatitis. Nintedanib’s adverse events are still not well known, making the documentation of cases such as this one important to aid in the monitoring of patients undergoing therapy. Reference #1: Raghu G, Collard HR, Egan JJ, et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med 2011;183:788–824.https://doi.org/10.1164/rccm.2009-040G. Reference #2: Richeldi L , Cottin V , du Bois RM , et al . Nintedanib in patients with idiopathic pulmonary fibrosis: Combined evidence from the TOMORROW and INPULSIS(®) trials. Respir Med 2016;:74–9.https://doi.org/10.1016/j.rmed.2016.02.001 Reference #3: Richeldi L , du Bois RM , Raghu G , et al . Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med 2014 2071;370 82:2071–82.https://doi.org/10.1056/NEJMoa1402584 DISCLOSURES: Speaker/Speaker's Bureau relationship with boehringer ingleheim Please note: $20001 - $100000 Added 03/13/2019 by Tariq Cheema, source=Web Response, value=Honoraria No relevant relationships by Muhammad Asad Faruqi, source=Web Response No relevant relationships by Ayla Gordon, source=Web Response No relevant relationships by Melissa Mosley, source=Web Response No relevant relationships by Erica Rabold, source=Web Response

INVASIVE PULMONARY ASPERGILLOSIS SUPERINFECTION IN A CRITICALLY ILL PATIENT WITH INFLUENZA A AND LIMITED CORTICOSTEROID EXPOSURE

SESSION TITLE: Monday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: It is our aim to highlight less well-recognized risk factors for invasive pulmonary aspergillosis(IPA). Early recognition of risk factors can raise clinical suspicion for Aspergillus superinfection so that appropriate and prompt therapy can be initiated potentially reducing morbidity and mortality. CASE PRESENTATION: A 69 year old female with a history of diabetes mellitus type 2, pancreatic cancer in remission status post remote Whipple procedure and COPD presented with dyspnea, wheezing and non-productive cough. She quickly deteriorated and was admitted to the ICU with hypoxic respiratory failure. One week prior to admission, she had completed a five day corticosteroid steroid burst for COPD exacerbation. CT chest demonstrated bilateral ground glass alveolar opacities on a background of stable centrilobular emphysema. Influenza A molecular assay was positive and Oseltamivir therapy was initiated. Despite receiving broad spectrum antibiotics and oseltamivir she remained febrile, required more oxygen and declined. Repeat thoracic imaging demonstrated worsening of the infiltrates and bronchoalveolar lavage specimens isolated Aspergillus fumigatus prompting immediate voriconazole therapy. DISCUSSION: Classically, IPA has been regarded as an ailment of those with weakened host immune systems such as in hematological malignancy, solid organ transplant and neutropenia. Influenza A is known to lay the framework for bacterial superinfections, but predisposing patients to invasive fungal organisms has only garnered significant attention within the last decade. Abbott et al. documented a case of invasive aspergillosis plaguing a previously immunocompetent individual acutely infected with Influenza in 1952, but it was not until 2018 that Schauwvlieghe et al identified Influenza as an independent risk factor for IPA in patients admitted to the ICU with pneumonia. Further, those receiving prolonged, high-dose glucocorticoid therapy have also been shown to be at greater risk for development of IPA, but the threshold of glucocorticoid exposure remains unclear. In 2012, Wauters et al demonstrated that steroid administration within seven days of presentation was a significant risk factor for development of Aspergillus; however, no corticosteroid dose risk relationship could be identified. Both corticosteroid exposure and Influenza A infection predispose patients to Aspergillus superinfection, on their own, but additional investigation is necessary to determine the threshold of corticosteroid exposure as well as the concurrent additive risk of Aspergillus infection when these two factors are combined. CONCLUSIONS: Knowledge of risk factors and thus the ability to identify patients at increased risk for Aspergillus superinfection, earlier in the course of hospitalization, may lead to a better determination of who warrants empiric antifungal coverage with the end result being improved morbidity and mortality. Reference #1: Schauwvlieghe AFAD, Rijnders BJA, Philips N, Verwijs R, Vanderbeke L, Van Tienen C, Lagrou K, Verweij PE, Van de Veerdonk FL, Gommers D, Spronk P, Bergmans DCJJ, Hoedemaekers A, Andrinopoulou ER, van den Berg CHSB, Juffermans NP, Hodiamont CJ, Vonk AG, Depuydt P, Boelens J, Wauters J; Dutch-Belgian Mycosis study group. "Invasive aspergillosis in patients admitted to the intensive care unit with severe influenza: a retrospective cohort study". Lancet Respir Med. 2018 Oct;6(10):782-792. Reference #2: Lewis R, Kontoyiannis, D. "Invasive aspergillosis in glucocorticoid-treated patients". Medical Mycology, Volume 47, Issue Supplement 1, 1 January 2009, Pages S271–S281 Reference #3: Wauters J, Baar I, Meersseman P, Meersseman W, Dams K, De Paep R, Lagrou K, Wilmer A, Jorens P, Hermans G. "Invasive pulmonary aspergillosis is a frequent complication of critically ill H1N1 patients: a retrospective study". Intensive Care Med. 2012 Nov;38(11):1761-8. DISCLOSURES: No relevant relationships by Median Ali, source=Web Response No relevant relationships by James Gleason, source=Web Response No relevant relationships by Aleksandra Kozlova, source=Web Response No relevant relationships by Shawn Marein, source=Web Response No relevant relationships by Avneek Singh Sandhu, source=Web Response