Cases Of Nonspecific Interstitial Pneumonia Research Articles

The efficacy and safety of modified transbronchial cryobiopsy in the diagnosis of interstitial lung disease.

The objective of this study is to investigate the efficacy and safety of flexible transbronchial cryobiopsy (TBCB) in the diagnosis of diffuse parenchymal lung disease (DPLD) in a routine bronchoscopy examination room under analgesia and sedation, using neither endotracheal intubation or rigid bronchoscope nor fluoroscopy or general anesthesia. The data from 50 DPLD patients with unknown etiology who were treated in the Affiliated Hospital of Guilin Medical College from May 2018 to September 2020 were collected, and 43 were eventually included. The specimens obtained from these 43 patients were subjected to pathological examination, pathogenic microorganism culture, etc, and were analyzed in the clinical-radiological-pathological diagnosis mode to confirm the efficacy of TBCB in diagnosing the cause of DPLD. Subsequently, the intraoperative and postoperative complications of TBCB and their severity were closely observed and recorded to comprehensively evaluate the safety of TBCB. For the 43 patients included, a total of 85 TBCB biopsies were performed (1.98 [1, 4] times/case), and 82 valid tissue specimens were obtained (1.91 [1, 4] pieces/case), accounting for 96.5% (82/85) of the total sample. The average specimen size was 12.41 (1, 30) mm2. Eventually, 38 cases were diagnosed, including 11 cases of idiopathic pulmonary fibrosis, 5 cases of connective tissue-related interstitial lung disease, 5 cases of nonspecific interstitial pneumonia, 4 cases of tuberculosis, 4 cases of occupational lung injury, 3 cases of interstitial pneumonia with autoimmune characteristics, 1 case of lung cancer, 2 cases of interstitial lung disease (unclassified interstitial lung disease), 1 case of hypersensitivity pneumonitis, 1 case of pulmonary alveolar proteinosis, and 1 case of fungal infection. The remaining 5 cases were unclarified. For infectious diseases, the overall etiological diagnosis rate was 88.4% (38/43). With respect to complications, pneumothorax occurred in 4 cases (9.3%, 4/43, including 1 mild case and 3 moderate cases), of which 3 cases (75%) were closed by thoracic drainage and 1 case (25%) was absorbed without treatment. In addition, 22 cases experienced no bleeding (51.2%) and 21 cases suffered bleeding to varying degrees based on different severity assessment methods. TBCB is a minimally invasive, rapid, economical, effective, and safe diagnostic technique.

Severity and Prevalence in Non-Specific Interstitial Pneumonia and COVID-19 Associated Pneumonia

Background: The non-specific clinical presentation and absence of definitive diagnostic markers further complicate the diagnosis of nterstitial lung diseases (ILD), particularly idiopathic interstitial pneumonia (IIP). This study aimed to investigate the clinical and epidemiological characteristics, along with imaging diagnostics, of patients with non-specific interstitial pneumonia (NsIP) in the Samarkand region from 2020 to 2023. Methods: A retrospective analysis of medical records was conducted for 262 patients diagnosed with ILD and hospitalized at the Samarkand State Medical Association (SamSMA). Using a multidisciplinary approach and adhering to the international classification of diseases (ICD-10) criteria, patients were categorized into two groups: those diagnosed with NsIP and a comparison group of patients with COVID-19-associated pneumonia (COVID-19 AP). The patients were further subdivided based on disease severity: moderate (IA) and severe (IB) for the NsIP group, and moderate (IIA) and severe (IIB) for the COVID-19 AP group. Results: The study found that 72.5% of ILD patients had NsIP, predominantly older males. Moderate disease severity was more common in NsIP patients, while severe cases were more prevalent in the COVID-19 AP group. The age groups 45-59 and 60-74 years represented 78% of the NsIP cases. Conclusion: The study found a higher prevalence of NsIP among men, with the majority of cases occurring in older age groups. Moderate disease severity was more common in NsIP patients, contrasting with COVID-19 AP patients, where severe cases were more prevalent.

Retinal Microvasculature in Systemic Sclerosis Patients and the Correlation between Nailfold Capillaroscopic Findings and Optical Coherence Angiography Results.

Background: The comparison of retinal perfusion in the eyes of patients with systemic sclerosis (SSc) and in healthy controls using optical coherence tomography angiography (OCTA). The correlation between nailfold capillaroscopy results and OCTA findings among SSc. Methods: The study enrolled 31 patients with systemic sclerosis and 41 healthy controls. OCTA was performed in both groups to assess the retinal vasculature in the superficial (SCP) and deep (DCP) capillary plexuses and the foveal avascular zone (FAZ) area. Nailfold capillaroscopy (NC) was performed in SSc patients and compared to the FAZ area and the superficial and the deep vessel density. Results: In the SSc group, the parafoveal vessel density in DCP was significantly higher in relation to the mean value (p < 0.0001) and in each quadrant of the macula (p < 0.0001) compared to healthy subjects (p < 0.0001). The patients with early scleroderma patterns in capillaroscopy had a larger superficial and deep FAZ (p = 0.0104, p = 0.0076, respectively) than those with active and late patterns. There was a statistically significant difference in the FAZ when comparing early to active (p < 0.0001) and early to late scleroderma patterns (p < 0.0001). A statistically significant difference was found in the type of interstitial lung disease and the deep FAZ area (p = 0.0484). SSc patients with nonspecific interstitial pneumonia (NSIP) had a larger FAZ than those with usual interstitial pneumonia (UIP) (p = 0.0484). Moreover, NSIP cases had a higher parafoveal mean superficial vessel density than those with UIP (p = 0.0471). Conclusions: Our investigation showed that the peripheral microvascular system correlates with ocular microcirculatory impairment. The results indicate the important role of OCTA in the diagnosis, monitoring, and prognosis of microvascular changes in SSc.

Histopathological significance of connective tissue disease-associated interstitial lung disease in transbronchial lung cryobiopsy specimens

Differentiating between idiopathic interstitial pneumonia (IIP) and secondary interstitial pneumonia, particularly connective tissue disease-associated interstitial lung disease (CTD-ILD), can be challenging histopathologically, and there may be discrepancies among pathologists. While surgical lung biopsy has traditionally been considered the gold standard for diagnosing interstitial pneumonia, the usefulness of transbronchial lung cryobiopsy (TBLC) has been reported. If TBLC could effectively distinguish between primary and secondary diseases, it would provide a less invasive option for patients. The aim of this study was to identify specific pathologic findings in TBLC specimens that could assist in distinguishing CTD-ILD from IIP. A total of 93 underwent TBLC at Tenri Hospital between 2018 and 2022. We retrospectively reviewed cases of CTD-ILD exhibiting a nonspecific interstitial pneumonia (NSIP) pattern (CTD-NSIP) and cases of NSIP with an unknown etiology (NSIP-UE), as determined through multidisciplinary discussion. Nineteen patients with CTD-NSIP and 26 patients with NSIP-UE were included in the study for clinicopathological analysis. The CTD-NSIP group had a significantly higher proportion of female patients compared to the NSIP-UE group (79% vs. 31%; p = 0.002). The presence of both fresh and old intraluminal fibrosis within the same TBLC specimen was significantly more frequent in CTD-NSIP group than in the NSIP-UE group (p = 0.023). The presence of an NSIP pattern with co-existing fresh and old intraluminal fibrosis in TBLC specimens raised suspicion for CTD-ILD.

Surgical Treatment of Secondary Pneumothorax-Complicated Interstitial Lung Disease.

To investigate the feasibility of early surgical treatment and perioperative steroid use in patients with interstitial lung disease (ILD) complicated by pneumothorax. We retrospectively examined data, including patient characteristics, laboratory findings, surgical treatment details, postoperative complications, and deaths, of nine patients with ILD complicated by secondary pneumothorax. The patients had been treated at our hospital during the past 10 years. All nine patients were male (median age, 69.0 years). A total of nine patients had a histopathologic diagnosis of ILD after surgery. Of these, five were clinically diagnosed with ILD before surgery. Collagen disease was diagnosed in one case, drug-induced in one case, and idiopathic ILD (IILD) in three cases. All nine patients were diagnosed with postoperative ILD, including one case of collagen disease, one case of drug-induced, three cases of idiopathic pulmonary fibrosis (IPF)/cryptogenic fibrosing alveolitis, one case of nonspecific interstitial pneumonia (NSIP), and three cases of cryptogenic organizing pneumonia (COP). Regarding preoperative clinical characteristics, the performance status (PS) was 0 or 1 in all patients. Overall, three patients received oxygen (0-3 L/min), whereas steroids were administered to five patients. The mean drainage period was 23.5 days, and this was consistent with the time taken from pneumothorax occurrence to surgery. Video-assisted thoracic surgery (VATS) and thoracoscopic-assisted surgery were performed in seven and two patients, respectively. No postoperative recurrence or surgery-related deaths occurred. Early surgery for secondary pneumothorax complicated by ILD may be a viable option for patients in good preoperative condition. For patients who are preoperatively treated with steroids, continued use of steroids should be carefully considered.

Clinical behaviour and mortality in idiopathic vs secondary nonspecific interstitial pneumonia.

Nonspecific interstitial pneumonia (NSIP) is a subtype of interstitial lung disease which can either be idiopathic or secondary to other conditions. Idiopathic NSIP is a relatively rare entity and diagnosis should be considered carefully as it is mainly a diagnosis of exclusion. The aim of this retrospective study was to evaluate a cohort of NSIP patients with a view to identifying any clinical and mortality differences between idiopathic and secondary varieties. We screened 700 patients from our interstitial lung disease database and identified 44 cases of NSIP retrospectively. Statistical analysis was conducted to evaluate if there was a difference in demographics such as gender and ethnicity, physiological parameters including forced vital capacity, diffusing capacity, average oxygen saturations, and immunology profile between two groups. Furthermore, a difference in mortality was evaluated between idiopathic and secondary NSIP. The data analysis showed that 63.6% (28 of 44) of patients had idiopathic NSIP versus 36.4% (16 of 44) of patients had secondary NSIP. Majority of the secondary NSIP patients had an underlying connective tissue disease. In the idiopathic variety, there was a male preponderance (64.2%, P = .02) which was statistically different compared to relatively equal gender divide in secondary NSIP which was statistically insignificant (male vs. female: 43.8% vs. 56.3%, respectively, P = .42). The mean age of the idiopathic group was 74 years compared to 64 years in the secondary group which was statistically different (P = .01). In both groups (idiopathic and secondary NSIP), more than two-thirds (68%) were of White British ethnicity. Immunology profile was similar across both groups with no statistical difference in IgM, IgG, or IgA levels. At the time of analysis, there were 17.9% deaths (5 of 28) in the idiopathic NSIP group versus 6.3% (1 of 16) in the secondary NSIP group but this was not statistically significant (P = .14). Similarly, there was no statistically significant difference in the forced vital capacity (P = .59), diffusing capacity (P = .88), and resting oxygen saturations (P = .28) between idiopathic and secondary NSIP varieties. Our analysis showed that there was a statistically significant difference in gender (male preponderance in idiopathic NSIP only) and mean age difference among both varieties. There were no statistically significant differences in the clinical features and outcomes including mortality, physiological, and immunological parameters between idiopathic and secondary NSIP. Idiopathic NSIP was more common than secondary NSIP and secondary NSIP is mostly due to underlying connective tissue disease.

Diagnostic value and safety of medical thoracoscopy under local anesthesia for unexplained diffuse interstitial lung disease: A retrospective study.

ObjectiveWe aimed to explore the safety and diagnostic value of medical thoracoscopic lung biopsy in patients with unexplained diffuse interstitial lung disease (ILD) in a single center pilot study.MethodWe retrospectively analyzed clinical and pathological diagnostic data from 52 patients with diffuse ILD undergoing medical thoracoscopic lung biopsy.ResultsForty-four cases of diffuse ILD were confirmed pathologically, giving a diagnostic rate of 84.6%. Among these 44 patients, 11 patients were diagnosed with cancer, including eight patients with lung adenocarcinoma, three patients with metastases; two from a gastrointestinal malignancy, and one from a granulosa cell tumor of the ovary. There were 17 cases of idiopathic interstitial pneumonia, including nine cases of usual interstitial pneumonia (UIP), four cases of non-specific interstitial pneumonia (NSIP), three cases of cryptogenic organizing pneumonia (COP), and one case of acute interstitial pneumonia (AIP). There were 12 cases of rare interstitial pneumonias, which included six cases of pulmonary alveolar proteinosis, one case each of pulmonary Langerhans cell histiocytosis (LCH) and pulmonary lymphangiomyomatosis, two cases of nodular sarcoidosis, and two cases of chronic eosinophilic pneumonia. We recorded various complications, including bleeding, infection, and pneumothorax. A total of 28 patients (53.8%) experienced at least one of the above complications, but there were no deaths associated with biopsy.ConclusionsMedical thoracoscopic lung biopsy appears a safe and effective method for diagnosing diffuse ILD of unknown cause but further prospective studies, with larger numbers, including comparison with other established techniques are required.

Content-based Image Retrieval by Using Deep Learning for Interstitial Lung Disease Diagnosis with Chest CT.

Background Evaluation of interstitial lung disease (ILD) at CT is a challenging task that requires experience and is subject to substantial interreader variability. Purpose To investigate whether a proposed content-based image retrieval (CBIR) of similar chest CT images by using deep learning can aid in the diagnosis of ILD by readers with different levels of experience. Materials and Methods This retrospective study included patients with confirmed ILD after multidisciplinary discussion and available CT images identified between January 2000 and December 2015. Database was composed of four disease classes: usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP), cryptogenic organizing pneumonia, and chronic hypersensitivity pneumonitis. Eighty patients were selected as queries from the database. The proposed CBIR retrieved the top three similar CT images with diagnosis from the database by comparing the extent and distribution of different regional disease patterns quantified by a deep learning algorithm. Eight readers with varying experience interpreted the query CT images and provided their most probable diagnosis in two reading sessions 2 weeks apart, before and after applying CBIR. Diagnostic accuracy was analyzed by using McNemar test and generalized estimating equation, and interreader agreement was analyzed by using Fleiss κ. Results A total of 288 patients were included (mean age, 58 years ± 11 [standard deviation]; 145 women). After applying CBIR, the overall diagnostic accuracy improved in all readers (before CBIR, 46.1% [95% CI: 37.1, 55.3]; after CBIR, 60.9% [95% CI: 51.8, 69.3]; P < .001). In terms of disease category, the diagnostic accuracy improved after applying CBIR in UIP (before vs after CBIR, 52.4% vs 72.8%, respectively; P < .001) and NSIP cases (before vs after CBIR, 42.9% vs 61.6%, respectively; P < .001). Interreader agreement improved after CBIR (before vs after CBIR Fleiss κ, 0.32 vs 0.47, respectively; P = .005). Conclusion The proposed content-based image retrieval system for chest CT images with deep learning improved the diagnostic accuracy of interstitial lung disease and interreader agreement in readers with different levels of experience. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Wielpütz in this issue.

Role of Drug-Gene Interactions and Pharmacogenetics in Simvastatin-Associated Pulmonary Toxicity.

IntroductionSimvastatin has previously been associated with drug-induced interstitial lung disease. In this retrospective observational study, cases with non-specific interstitial pneumonia (NSIP) or idiopathic pulmonary fibrosis (IPF) with simvastatin-associated pulmonary toxicity (n = 34) were evaluated.ObjectiveTo identify whether variations in genes encoding cytochrome P450 (CYP) enzymes or in the SLCO1B1 gene (Solute Carrier Organic anion transporting polypeptide 1B1 gene, encoding the organic anion transporting polypeptide 1B1 [OATP1B1] drug transporter enzyme), and/or characteristics of concomitantly used drugs, predispose patients to simvastatin-associated pulmonary toxicity.MethodsCharacteristics of concomitantly used drugs and/or variations in the CYP or SLCO1B1 genes and drug–gene interactions were assessed. The outcome after withdrawal of simvastatin and/or switch to another statin was assessed after 6 months.ResultsMultiple drug use involving either substrates and/or inhibitors of CYP3A4 and/or three or more drugs with the potential to cause acidosis explained the simvastatin-associated toxicity in 70.5% (n = 24) of cases. Cases did not differ significantly from controls regarding CYP3A4, CYP2C9, or OATP1B1 phenotypes, and genetic variation explained only 20.6% (n = 7) of cases. Withdrawal of simvastatin without switching to another statin or with a switch to a hydrophilic statin led to improvement or stabilization in all NSIP cases, whereas all cases who were switched to the lipophilic atorvastatin progressed.ConclusionSimvastatin-associated pulmonary toxicity is multifactorial. For patients with this drug-induced pulmonary toxicity who need to continue taking a statin, switching to a hydrophilic statin should be considered.ClinicalTrials.gov identifierNCT00267800, registered in 2005.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40264-021-01105-8.

Concordance of Bronchoalveolar Lavage Cytology with Transbronchial Lung Biopsies in Non-neoplastic Pulmonary Diseases

Introduction: In many pulmonary diseases, despite radiological &amp; clinical investigations, laboratory tests and function studies, the diagnosis becomes difficult. Bronchoalveolar Lavage (BAL) is a minimally invasive method in which cells are collected from bronchial and alveolar spaces for cytology. This is facilitated by using a flexible bronchoscope with which a biopsy is taken following BAL. Bronchoscopy with BAL when used appropriately can offer correct diagnosis which in turn aids in proper management of the patient. Aim: To find the concordance of BAL findings with the histopathological features of Transbronchial Lung Biopsy (TBLB) in non-neoplastic lung diseases. Materials and Methods: It was a retrospective study conducted in Kempegowda Institute of Medical Sciences, Bengaluru, Karnataka. A total of 40 patients presenting with clinico-radiological findings, suggesting a non-neoplastic lung disease in the year 2019, undergoing bronchoscopy with BAL and concurrent TBLB were chosen. The BAL fluid was processed and differential count of cells was done to classify according to the American Thoracic Society Guidelines. Concordance was checked between the diagnoses made on TBLB and BAL analysis. Results: In the present study, a total of 40 cases were included of which 13 (32.5%) cases showed neutrophilic, 16 (40%) cases showed lymphocytic, 5 (12.5%) cases showed eosinophilic and 6 (15%) cases showed normal cellular distribution on BAL cytology. Diagnoses on studying TBLB included nine cases of Nonspecific Interstitial Pneumonia, seven cases of Usual Interstitial Pneumonia, six cases of Bronchiolitis Obliterans Organising Pneumonia, three cases of Bronchiolitis, two cases each of pulmonary tuberculosis and granulomatous inflammation. There was one case each of actinomycosis, sarcoidosis, lung abscess and mucor mycosis. Normal histology was noted in seven cases. The sensitivity of BAL fluid analysis was found to be 84.84% and the concordance was 80%. The Kappa value obtained was 0.71 indicating good agreement/concordance between BAL cytology and TBLB. Conclusion: The data from the current study suggest that differential cell counts in BAL provide diagnostic information of fundamental importance in frequently occurring non-neoplastic lung diseases in the community.

Chest High-resolution Computed Tomography Imaging Features of Lung Involvement in Rheumatoid Arthritis

Objective To explore the chest high-resolution computed tomography (HRCT) features in patients with rheumatoid arthritis (RA) complicated with pulmonary involvement. Methods Totally 161 patients with RA with lung involvement were collected from June 2014 to May 2018. The chest HRCT findings were retrospectively analyzed. According to the imaging features as well as the results of history taking,pulmonary function test,pathology,and bronchoalveolar lavage fluid test,RA-related lung diseases (RA-LD) were classified and their clinical characteristics were compared. Results These 161 RA-LD patients (56 males and 105 females) whose mean age at diagnosis was (60.7±12.8) years (14-85 years) included 87 cases of usual interstitial pneumonia (UIP) (including 16 cases of possible UIP),44 cases of non-specific interstitial pneumonia (NSIP),10 cases of organizing pneumonia,7 cases of lymphocytic interstitial pneumonia,9 cases of small airway disease (SAD) (including 8 cases of bronchiolitis obliterans and 1 case of follicular bronchiolitis),and 4 other lung manifestations (including 3 cases of diffuse alveolar hemorrhage and 1 case of rheumatoid nodules). The UIP group had the oldest average age [(63.3±12.1) years old] and the highest smoking rate (41.4%). The SAD group had the youngest average age [(54.7±15.1) years old] and there was no smoking history. There were significant differences between these two groups (P=0.020,P<0.001). Seventy patients (43.5%) with RA-LD were complicated with pleural lesions. Conclusions RA involving the lung is common and has varied imaging manifestations,with interstitial lung diseases (mainly UIP and NSIP) being the most important manifestations. RA patients should undergo lung HRCT as early as possible to identify the lung involvement and related types.

Clinical Case of Idiopathic Interstitial Pneumonia: Expert Approaches

The article describes the criteria for the examination of temporary disability and the establishment of a disability group for idiopathic interstitial pneumonia on the example of a clinical case of nonspecific interstitial pneumonia with a view to a uniform interpretation by clinical physicians and expert doctors of the criteria for persistent functional impairments in the case of respiratory organs and the timeliness of referring to medical and social examination of people suffering from it patients. Temporary disability is caused by the appearance of shortness of breath in patients, which is steadily progressing and leads to a decrease in exercise tolerance. The presence of an unfavorable prognosis in some forms of interstitial pneumonia predetermines the maximum period of temporary disability for 4 months with the subsequent registration of patients for medical and social examination. Restrictive dysfunction of external respiration is not singled out in quantitative criteria of functional persistent disorders of the body to establish the group of disability in the Order of the Ministry of Labor of Russia dated December 17, 2015 No. 1024н, which causes difficulties during the examination. A key sign of persistent respiratory function disorders is respiratory failure, the severity of which is put in its quantitative gradation for recognizing a citizen as disabled. Pulse oximetry is currently available as a verification method for the diagnosis of respiratory failure, which is used for medical and social expertise. The morphological variant of interstitial pneumonia, if histological diagnosis was performed, or the presumptive nosological form diagnosed on the basis of a complex of clinical and radiological data, do not have a direct impact on the result of the examination; just as the volume of drug therapy and the response to it are not taken into account in order to establish the fact of disability.

Computer-Aided Diagnosis of Pulmonary Fibrosis Using Deep Learning and CT Images.

ObjectivesThe objective of this study is to assess the performance of a computer-aided diagnosis (CAD) system (INTACT system) for the automatic classification of high-resolution computed tomography images into 4 radiological diagnostic categories and to compare this with the performance of radiologists on the same task.Materials and MethodsFor the comparison, a total of 105 cases of pulmonary fibrosis were studied (54 cases of nonspecific interstitial pneumonia and 51 cases of usual interstitial pneumonia). All diagnoses were interstitial lung disease board consensus diagnoses (radiologically or histologically proven cases) and were retrospectively selected from our database. Two subspecialized chest radiologists made a consensual ground truth radiological diagnosis, according to the Fleischner Society recommendations. A comparison analysis was performed between the INTACT system and 2 other radiologists with different years of experience (readers 1 and 2). The INTACT system consists of a sequential pipeline in which first the anatomical structures of the lung are segmented, then the various types of pathological lung tissue are identified and characterized, and this information is then fed to a random forest classifier able to recommend a radiological diagnosis.ResultsReader 1, reader 2, and INTACT achieved similar accuracy for classifying pulmonary fibrosis into the original 4 categories: 0.6, 0.54, and 0.56, respectively, with P > 0.45. The INTACT system achieved an F-score (harmonic mean for precision and recall) of 0.56, whereas the 2 readers, on average, achieved 0.57 (P = 0.991). For the pooled classification (2 groups, with and without the need for biopsy), reader 1, reader 2, and CAD had similar accuracies of 0.81, 0.70, and 0.81, respectively. The F-score was again similar for the CAD system and the radiologists. The CAD system and the average reader reached F-scores of 0.80 and 0.79 (P = 0.898).ConclusionsWe found that a computer-aided detection algorithm based on machine learning was able to classify idiopathic pulmonary fibrosis with similar accuracy to a human reader.

Multidisciplinary approach to the diagnosis of nonspecific interstitial pneumonia (a case report)

Nonspecific interstitial pneumonia (NSIP) is one of idiopathic interstitial pneumonias. NSIP is characterized by non-specific clinical, radiologic, and morphological patterns; thereby, multidisciplinary approach is most reasonable to diagnose NSIP. A clinical case of NSIP is reported in the article. The case demonstrated that the multi-slice computed tomography of the lungs is more valuable to diagnose NSIP compared to the lung tissue biopsy, as typical morphological signs are absent. The multidisciplinary approach was also very useful in this case.

Comprehensive gene expression profiling identifies distinct and overlapping transcriptional profiles in non-specific interstitial pneumonia and idiopathic pulmonary fibrosis

BackgroundThe clinical-radiographic distinction between idiopathic pulmonary fibrosis (IPF) and non-specific interstitial pneumonia (NSIP) is challenging. We sought to investigate the gene expression profiles of IPF and NSIP vs. normal controls.MethodsGene expression from explanted lungs of patients with IPF (n = 22), NSIP (n = 10) and from normal controls (n = 11) was assessed. Microarray analysis included Significance Analysis of Microarray (SAM), Ingenuity Pathway, Gene-Set Enrichment and unsupervised hierarchical clustering analyses. Immunohistochemistry and serology of proteins of interest were conducted.ResultsNSIP cases were significantly enriched for genes related to mechanisms of immune reaction, such as T-cell response and recruitment of leukocytes into the lung compartment. In IPF, in contrast, these involved senescence, epithelial-to-mesenchymal transition, myofibroblast differentiation and collagen deposition. Unlike the IPF group, NSIP cases exhibited a strikingly homogenous gene signature. Clustering analysis identified a subgroup of IPF patients with intermediate and ambiguous expression of SAM-selected genes, with the interesting upregulation of both NSIP-specific and senescence-related genes. Immunohistochemistry for p16, a senescence marker, on fibroblasts differentiated most IPF cases from NSIP. Serial serum levels of periostin, a senescence effector, predicted clinical progression in a cohort of patients with IPF.ConclusionsComprehensive gene expression profiling in explanted lungs identifies distinct transcriptional profiles and differentially expressed genes in IPF and NSIP, supporting the notion of NSIP as a standalone condition. Potential gene and protein markers to discriminate IPF from NSIP were identified, with a prominent role of senescence in IPF. The finding of a subgroup of IPF patients with transcriptional features of both NSIP and senescence raises the hypothesis that “senescent” NSIP may represent a risk factor to develop superimposed IPF.

Transbronchial Cryobiopsies: Evidence Moving at Glacial Speed?

SESSION TITLE: Interventional Pulmonology Posters IISESSION TYPE: Original Investigation PosterPRESENTED ON: Wednesday, October 28, 2015 at 01:30 PM - 02:30 PMPURPOSE: We reviewed our experience at a quaternary-care academic medical center with transbronchial cryobiopsies to highlight varying methodology, potential complications, and question the superiority of this format over standard transbronchial forceps biopsies.METHODS: We performed a retrospective review of our experience in obtaining transbronchial cryobiopsies in 25 patients. All procedures were performed under general anesthesia with a therapeutic flexible bronchoscope (Olympus, BF-1T180 or BF-1T160), via laryngeal mask airway (LMA) or endotracheal tube. Both 1.9 mm and 2.4 mm cryoprobes (Erbokryo CA) were used. Freeze times (2-4 seconds) and probe position in the airway varied, depending on the proceduralist's assessment of the parenchymal abnormalities noted on imaging.RESULTS: Twenty-five patients underwent transbronchial cryobiopsies. In 12 of these cases, standard forceps transbronchial biopsies were also performed, and were sent separately from cryobiopsy specimens in 8 of the 12 cases. Of the 8 cases in which specimens were sent separately, the final diagnosis on transbronchial cryobiopsy was identical to that obtained with transbronchial forceps biopsies. One case of non-specific interstitial pneumonia (NSIP) was diagnosed on cryobiopsy alone. There were no other diagnoses of NSIP, usual interstitial pneumonia (UIP), or hypersensitivity pneumonitis (HP). Pneumothorax occurred in 2 patients. Significant bleeding was reported in 4 patients, including one massive bleed, prompting a voluntary moratorium on transbronchial cryobiopsies at our institution.CONCLUSIONS: Methodology studies demonstrating best practices in utilizing transbronchial cryobiopsy technology are lacking, and potential complications demand additional study in this area.CLINICAL IMPLICATIONS: The small size of transbronchial biopsies obtained with standard flexible forceps has long been considered inadequate for the diagnosis of interstitial lung disease. Prior studies have suggested that transbronchial cryobiopsies obtain larger parenchymal tissue samples with preserved architecture capable of diagnosing interstitial lung disease, or, in cases of malignancy, to ensure adequate tissue for molecular studies. Our experience highlights the need for evidence-based methodology in obtaining parenchymal cryobiopsies. Factors that currently vary widely include probe size, probe airway position, freeze time, and airway management. Direct, randomized comparison to standard forceps transbronchial biopsies in human subjects has yet to be investigated.DISCLOSURE: The following authors have nothing to disclose: Jamie Bessich, Laura Frye, Edmund Moon, Anthony Lanfranco, Andrew Haas, Anil Vachani, Daniel StermanNo Product/Research Disclosure Information SESSION TITLE: Interventional Pulmonology Posters II SESSION TYPE: Original Investigation Poster PRESENTED ON: Wednesday, October 28, 2015 at 01:30 PM - 02:30 PM PURPOSE: We reviewed our experience at a quaternary-care academic medical center with transbronchial cryobiopsies to highlight varying methodology, potential complications, and question the superiority of this format over standard transbronchial forceps biopsies. METHODS: We performed a retrospective review of our experience in obtaining transbronchial cryobiopsies in 25 patients. All procedures were performed under general anesthesia with a therapeutic flexible bronchoscope (Olympus, BF-1T180 or BF-1T160), via laryngeal mask airway (LMA) or endotracheal tube. Both 1.9 mm and 2.4 mm cryoprobes (Erbokryo CA) were used. Freeze times (2-4 seconds) and probe position in the airway varied, depending on the proceduralist's assessment of the parenchymal abnormalities noted on imaging. RESULTS: Twenty-five patients underwent transbronchial cryobiopsies. In 12 of these cases, standard forceps transbronchial biopsies were also performed, and were sent separately from cryobiopsy specimens in 8 of the 12 cases. Of the 8 cases in which specimens were sent separately, the final diagnosis on transbronchial cryobiopsy was identical to that obtained with transbronchial forceps biopsies. One case of non-specific interstitial pneumonia (NSIP) was diagnosed on cryobiopsy alone. There were no other diagnoses of NSIP, usual interstitial pneumonia (UIP), or hypersensitivity pneumonitis (HP). Pneumothorax occurred in 2 patients. Significant bleeding was reported in 4 patients, including one massive bleed, prompting a voluntary moratorium on transbronchial cryobiopsies at our institution. CONCLUSIONS: Methodology studies demonstrating best practices in utilizing transbronchial cryobiopsy technology are lacking, and potential complications demand additional study in this area. CLINICAL IMPLICATIONS: The small size of transbronchial biopsies obtained with standard flexible forceps has long been considered inadequate for the diagnosis of interstitial lung disease. Prior studies have suggested that transbronchial cryobiopsies obtain larger parenchymal tissue samples with preserved architecture capable of diagnosing interstitial lung disease, or, in cases of malignancy, to ensure adequate tissue for molecular studies. Our experience highlights the need for evidence-based methodology in obtaining parenchymal cryobiopsies. Factors that currently vary widely include probe size, probe airway position, freeze time, and airway management. Direct, randomized comparison to standard forceps transbronchial biopsies in human subjects has yet to be investigated. DISCLOSURE: The following authors have nothing to disclose: Jamie Bessich, Laura Frye, Edmund Moon, Anthony Lanfranco, Andrew Haas, Anil Vachani, Daniel Sterman No Product/Research Disclosure Information

Organizing pneumonia components in non-specific interstitial pneumonia (NSIP): a clinicopathological study of 33 NSIP cases.

To review the clinical, radiological and pathological features of non-specific interstitial pneumonia (NSIP), mainly to characterize organizing pneumonia (OP) components in NSIP. Lung biopsy samples from 33 NSIP patients were collected over a period of 10years. Microscopic analysis revealed that 13 cases showed a cellular pattern and 20 showed a mixed/fibrosing pattern. OP components were detected in 26 cases (13 with a cellular pattern; 13 with a mixed/fibrosing pattern), and were found to constitute a median proportion of 9% (range, 1-40%) of the affected tissues. In nine cellular and four mixed/fibrosing NSIP cases, the OP components accounted for ≥10%. A proportion of ≥20% was found in only five cellular pattern cases. Twenty-nine patients were followed up: 17 showed improvements, five were stabilized, and seven showed progression. OP components are common basic lesions in NSIP cases, although their proportion in cellular and mixed/fibrosing pattern cases varies substantially between patients. OP components do not impact on prognosis, even when they constitute ≥20% of the affected tissue. Thus, a high level of OP components does not exclude a diagnosis of NSIP in cases that otherwise show pathological and radiological findings characteristic of NSIP.

Nonspecific interstitial pneumonia and usual interstitial pneumonia: comparison of the clinicopathologic features and prognosis.

Nonspecific interstitial pneumonia (NSIP) has recently been proposed as a histologic type of idiopathic interstitial pneumonia (IIP), but its broad spectrum of clinicopathologic findings and variable prognosis are poorly understood. It is particularly unclear how NSIP and usual interstitial pneumonia (UIP) are related. The present study investigated the clinicopathologic features and prognosis of NSIP, and its differential diagnosis from UIP. The clinicopathologic findings and prognosis in 21 NSIP and 18 UIP patients who underwent surgical or video-assisted thoracoscopic lung biopsy were reviewed. NSIP was more frequent in women and showed nonspecific clinical manifestations. High-resolution computed tomography (HRCT) demonstrated ground-glass, net-like, and patchy attenuation in both lungs. Semiquantitative HRCT showed a median fibrosis score of 3 (range, 0 to 7) in NSIP patients and 5 (range, 2 to 7) in UIP patients (P<0.01). On histopathologic examination, NSIP cases were heterogeneous and the findings could be categorized into cellular and fibrosing patterns. The mean age of the NSIP and UIP patients was 48 and 60 years, respectively. The frequencies of fibroblast foci, myogelosis, honeycomb lesions, and pulmonary structural destruction in NSIP and UIP patients were 16.7% and 100% (P<0.001), 22.2% and 85.7% (P<0.05), 16.7% and 92.9% (P<0.001), and 27.8% and 100% (P<0.05), respectively. The responses to glucocorticoid treatment and the prognosis were significantly greater in NSIP than those in UIP. NSIP was difficult to be differentiated from UIP by general clinical manifestations, but HRCT can be helpful for this purpose. Definitive diagnosis depends on the results of surgical lung biopsy.

Airspace enlargement with fibrosis shows characteristic histology and immunohistology different from usual interstitial pneumonia, nonspecific interstitial pneumonia and centrilobular emphysema

The histologic characteristics of air space enlargement with fibrosis (AEF) are compared with usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP) and centrilobular emphysema (CLE) to determine similarities and differences. Lung specimens from 39 patients were studied; 9 with AEF, 13 with UIP and 5 with CLE identified in lobectomy specimens for cancer and 12 NSIP cases identified on surgical lung biopsies. We determined the characteristics of cystic structures (i.e. abnormal airspace), degree of inflammation and severity of pneumocyte injury semi-quantitatively. In AEF, the wall thickness of the cystic lesions (0.8 mm) was thinner than in UIP (2.1 mm) and thicker than in CLE (0.07 mm). The degree of inflammation and granulation tissue were milder in AEF than in UIP and NSIP and CLE showed milder inflammatory cells than AEF. As for pneumocyte injury, AEF had fewer erosions (0.1/case) and fewer ubiquitin-positive pneumocytes than UIP (4.8 cells/slide) and NSIP (9.8 cells/slide). Our data suggested that the histological characteristics of AEF differed significantly from UIP, NSIP and CLE.

Histological features of nonspecific interstitial pneumonia

Nonspecific interstitial pneumonia is a type of idiopathic interstitial pneumonia. By definition, the cases of nonspecific interstitial pneumonia are those which cannot be classified as any other type of interstitial pneumonia. The Material of the investigation included 12 transbronchial biopsy lung samples. The quantity, structure and distribution of specific cellular elements were determined semiquantitatively, recognizing three levels of the lesions' intensity: mild/ poor, moderate, and intense/abundant. The interalveolar septa were most frequently moderately thickened (50% of the cases) due to the presence of inflammatory cells and multiplied connective. Of the inflammatory cells, lymphocytes were most common and greatest in quantity (abundant, moderate and poor in 4, 5, and 3 cases respectively), followed by plasma cells and macrophages. The septal connective was moderately and mildly multiplied in 2 and 4 cases respectively. The lumen of the alveoli was infiltrated by lymphocytes and macrophages, while poor peribronchial and perivascular lymphocyte infiltrates were most commonly found. The interalveolar septa were most frequently moderately thickened due to the presence of chronic inflammatory cells, predominantly lymphocytes, as well as to mildly-to-moderately multiplied connective. The lymphocytes usually permeated the septa diffusely. Bronchiolar and blood vessel findings were nonspecific.