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23 pages, 2184 KB  
Review
Role of Inflammatory Mediators in Chronic Obstructive Pulmonary Disease Pathogenesis: Updates and Perspectives
by Pankush, Khushboo Bharti, Rohit Pandey, Namita Srivastava, Shashank Kashyap, Deepak Kumar, Lokender Kumar, Sunil K. Suman and Sanjay K. S. Patel
Immuno 2025, 5(2), 13; https://doi.org/10.3390/immuno5020013 - 15 Apr 2025
Viewed by 5834
Abstract
Chronic obstructive pulmonary disease (COPD) is a chronic, debilitating condition that affects the lungs and airways. It is characterized by persistent bronchitis, a condition exemplified by the inflammation of the bronchial tubes, the hypersecretion of mucus, emphysema, and the destruction of the airway [...] Read more.
Chronic obstructive pulmonary disease (COPD) is a chronic, debilitating condition that affects the lungs and airways. It is characterized by persistent bronchitis, a condition exemplified by the inflammation of the bronchial tubes, the hypersecretion of mucus, emphysema, and the destruction of the airway parenchyma. The combination of these conditions leads to persistent tissue damage, pulmonary fibrosis, and ongoing inflammation of the airways. The inflammatory response in COPD is a complex process that is orchestrated by a wide range of immune cells. These include lung epithelial cells, monocytes, macrophages, neutrophils, eosinophils, and T and B lymphocytes, among others. These cells work together to produce a wide range of inflammatory biomarkers that are involved in the pathogenesis of COPD. Some of the key inflammatory biomarkers that have been identified in COPD include a variety of cytokines, the C-reactive protein/serum albumin ratio, fibrinogen, soluble receptor for advanced glycation endproducts, club/clara cells in the lungs with a molecular weight of 16 kDa, surfactant protein D, adiponectin, reactive oxygen species, and proteases. This review aims to provide a comprehensive overview of the role of immune cells and key inflammatory biomarkers in the development and progression of COPD. It will delve into the intricacies of the inflammatory response in COPD, exploring the various cell types and biomarkers that are involved in this process. By understanding the underlying mechanisms that drive COPD, we can better develop targeted treatments that can help to alleviate the symptoms of COPD. Full article
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22 pages, 273 KB  
Article
Retrospective Study of Chronic Coughing in Dogs in a Referral Centre in the UK: 329 Cases (2012–2021)
by Carla Asorey Blazquez, Ico Jolly Frahija, Arran Smith, Rachel Miller, Mayank Seth, Edgar Garcia Manzanilla and Ferran Valls Sanchez
Animals 2025, 15(2), 254; https://doi.org/10.3390/ani15020254 - 17 Jan 2025
Cited by 1 | Viewed by 2457
Abstract
Chronic coughing is a common complaint in small animal medicine and it has an extensive differential diagnosis with very different treatment and prognosis. Coughing is considered chronic when it lasts at least 8 weeks. This retrospective study aimed to describe the most common [...] Read more.
Chronic coughing is a common complaint in small animal medicine and it has an extensive differential diagnosis with very different treatment and prognosis. Coughing is considered chronic when it lasts at least 8 weeks. This retrospective study aimed to describe the most common causes of chronic coughing in a population of dogs that presented to a referral hospital in England between January 2012 and December 2021. In addition, we aimed to evaluate if an association with signalment, weight, coughing characteristics, and/or concomitant clinical signs could be identified. A total of 329 dogs met the inclusion criteria. The most frequent diagnoses were airway collapse (102/329, 30.7%), chronic bronchitis (80/329, 24.3%), neoplasia (62/329, 18.8%), and infectious bronchopneumonia (54/329, 16.4%). Other diagnoses were also identified in a lower number of cases. Pomeranian, Chihuahua, and Yorkshire Terrier were over-represented breeds for airway collapse. No predictive factors were identified for chronic bronchitis. Lower body weight (odds ratio [OR] 0.92, 95% confidence interval [CI]: 0.90–0.95), non-productive (OR 14.3 CI 3.44–50) paroxysmal coughing (OR 4.9, 95%, CI: 2.2–11.0), and exercise intolerance (OR 3.3, 95%, CI: 1.7–6.3) increased the odds of airway collapse. Older dogs (OR 1.025, 95%, CI: 1.014–1.036), higher body weight (OR 1.048, 95%, CI: 1.018–1.080), lethargy (OR 5.1, 95%, CI: 1.5–17.7), haemoptysis (OR 8.6, 95%, CI: 1.9–38.4), weight loss (OR 4.0, 95%, CI: 1.1–15.3), and inappetence (OR 6.5, 95%, CI: 1.9–22.1) increased the odds of neoplasia. Productive coughing (OR 3.0, 95%, CI: 1.5–6) and nasal discharge (OR 4.1, 95%, CI: 1.4–11.9) were predictive factors of infectious bronchopneumonia. Younger age (OR 0.96, 95%, CI: 1.061–1.150), higher body weight (OR 1.097, 95%, CI: 1.037–1.161), and haemoptysis (OR 11.8, 95%, CI: 1.8–78.5), increased the odds of airway foreign body. Higher body weight (OR 1.105, 95%, CI: 1.061–1.150), older age (OR 1.041, 95%, CI: 1.022–1.061), and regurgitation were predictive factors of laryngeal paralysis. Epiglottic retroversion was associated with younger age (OR 0.969, 95%, CI: 0.943–0.994), dysphagia (OR 42.5, 95%, CI: 4.7–382.7), and regurgitation (OR 11.6, 95%, CI: 1.2–113.1). All the aforementioned findings are valuable for prioritising differential diagnoses and consequently increasing the efficacy of the diagnostic plan and prioritising tests, which becomes even more important in cases where financial constraints are present. Finally, an appropriate selection of diagnostics tools helps optimise veterinary resources. Full article
(This article belongs to the Section Veterinary Clinical Studies)
15 pages, 1663 KB  
Article
Long-Term Eosinophil Depletion: A Real-World Perspective on the Safety and Durability of Benralizumab Treatment in Severe Eosinophilic Asthma
by Francesco Menzella, Mariarita Marchi, Marco Caminati, Micaela Romagnoli, Claudio Micheletto, Matteo Bonato, Giuseppe Idotta, Manuele Nizzetto, Giuseppina D’Alba, Massimiliano Cavenaghi, Michela Bortoli, Bianca Beghè, Laura Pini, Roberto Benoni, Gianluca Casoni, Rodolfo Muzzolon, Lucio Michieletto, Annamaria Bosi, Andrea Mastrototaro, Adela Diamandi, Mara Nalin and Gianenrico Sennaadd Show full author list remove Hide full author list
J. Clin. Med. 2025, 14(1), 191; https://doi.org/10.3390/jcm14010191 - 31 Dec 2024
Cited by 4 | Viewed by 3264
Abstract
Background/Objectives: Benralizumab is an anti-IL-5 receptor alpha monoclonal antibody that induces the near-complete depletion of eosinophils. This study aimed to evaluate the long-term safety and effectiveness of benralizumab in patients with severe eosinophilic asthma (SEA) over an extended 48-month follow-up period, offering one [...] Read more.
Background/Objectives: Benralizumab is an anti-IL-5 receptor alpha monoclonal antibody that induces the near-complete depletion of eosinophils. This study aimed to evaluate the long-term safety and effectiveness of benralizumab in patients with severe eosinophilic asthma (SEA) over an extended 48-month follow-up period, offering one of the longest real-world perspectives available. Methods: This was a single-arm, retrospective, observational, multicenter study involving 123 SEA patients treated with benralizumab at a dosage of 30 mg every 4 weeks for the first 3 doses and then every 8 weeks. The safety endpoints focused on the frequency and nature of adverse events and the likelihood that they were induced by benralizumab. The efficacy endpoints focused on lung function, asthma exacerbations and control, and oral corticosteroid use. Results: Benralizumab, consistent with its mechanism of action, led to the rapid and nearly complete depletion of eosinophils. In total, 26 adverse events (21.1%) were observed, with 1.6% related to the treatment and 0.8% categorized as serious (vagal hypotension). Bronchitis was the most common unrelated adverse event (15.4%), occurring between months 36 and 38. Importantly, benralizumab effectiveness and safety were maintained consistently across the 48-month duration, resulting in significant improvements in lung function and reductions in oral corticosteroid use and exacerbation frequency. Conclusions: Benralizumab demonstrated a favorable safety profile, comparable to previously published studies, with perdurable effectiveness in controlling SEA and reducing oral corticosteroid use. Finally, this study provides evidence that near-complete eosinophil depletion does not increase long-term safety risks and supports benralizumab as a reliable treatment option for SEA patients. Full article
(This article belongs to the Special Issue Advances in Asthma: 2nd Edition)
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14 pages, 2667 KB  
Article
Machine-Learning-Based Classification Model to Address Diagnostic Challenges in Transbronchial Lung Biopsy
by Hisao Sano, Ethan N. Okoshi, Yuri Tachibana, Tomonori Tanaka, Kris Lami, Wataru Uegami, Yoshio Ohta, Luka Brcic, Andrey Bychkov and Junya Fukuoka
Cancers 2024, 16(4), 731; https://doi.org/10.3390/cancers16040731 - 9 Feb 2024
Cited by 2 | Viewed by 2119
Abstract
Background: When obtaining specimens from pulmonary nodules in TBLB, distinguishing between benign samples and mis-sampling from a tumor presents a challenge. Our objective is to develop a machine-learning-based classifier for TBLB specimens. Methods: Three pathologists assessed six pathological findings, including interface bronchitis/bronchiolitis (IB/B), [...] Read more.
Background: When obtaining specimens from pulmonary nodules in TBLB, distinguishing between benign samples and mis-sampling from a tumor presents a challenge. Our objective is to develop a machine-learning-based classifier for TBLB specimens. Methods: Three pathologists assessed six pathological findings, including interface bronchitis/bronchiolitis (IB/B), plasma cell infiltration (PLC), eosinophil infiltration (Eo), lymphoid aggregation (Ly), fibroelastosis (FE), and organizing pneumonia (OP), as potential histologic markers to distinguish between benign and malignant conditions. A total of 251 TBLB cases with defined benign and malignant outcomes based on clinical follow-up were collected and a gradient-boosted decision-tree-based machine learning model (XGBoost) was trained and tested on randomly split training and test sets. Results: Five pathological changes showed independent, mild-to-moderate associations (AUC ranging from 0.58 to 0.75) with benign conditions, with IB/B being the strongest predictor. On the other hand, FE emerged to be the sole indicator of malignant conditions with a mild association (AUC = 0.66). Our model was trained on 200 cases and tested on 51 cases, achieving an AUC of 0.78 for the binary classification of benign vs. malignant on the test set. Conclusion: The machine-learning model developed has the potential to distinguish between benign and malignant conditions in TBLB samples excluding the presence or absence of tumor cells, thereby improving diagnostic accuracy and reducing the burden of repeated sampling procedures for patients. Full article
(This article belongs to the Special Issue Advanced Research in Cancer Initiation and Early Detection)
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13 pages, 290 KB  
Article
Serum Allergen-Specific Immunoglobulin E in Cats with Inflammatory Bronchial Disease
by Lina Hörner-Schmid, Jelena Palić, Ralf S. Mueller and Bianka Schulz
Animals 2023, 13(20), 3226; https://doi.org/10.3390/ani13203226 - 15 Oct 2023
Cited by 2 | Viewed by 3189
Abstract
The etiology of feline inflammatory bronchial disease is poorly understood. This study compares the degree of allergen-specific serum IgE responses between cats with feline asthma, chronic bronchitis, mixed inflammation, and clinically healthy cats (HCs). The retrospective case–control study used serum from eighteen cats [...] Read more.
The etiology of feline inflammatory bronchial disease is poorly understood. This study compares the degree of allergen-specific serum IgE responses between cats with feline asthma, chronic bronchitis, mixed inflammation, and clinically healthy cats (HCs). The retrospective case–control study used serum from eighteen cats with eosinophilic inflammation (EI), ten with neutrophilic inflammation (NI), six with mixed inflammation (MI), and fourteen HCs. Affected cats were categorized into groups based on bronchoalveolar lavage cytology. The measurement of IgE for 34 different allergens including fungal organisms, weeds, grasses, trees, mites, and insects was performed using an indirect ELISA. Positive reactions to allergens were detected in the serum of 17/18 cats with EI, 8/10 with NI, 6/6 with MI, and 11/14 HCs (p = 0.364). When overall positive reactions were compared between groups, cats with MI (p = <0.01) had significantly more positive reactions against mite allergens than HCs. Blood eosinophils inversely correlated with the absolute amount of allergen-specific serum IgE expressed in ELISA absorbance units (EAs) (p = 0.014). Sensitization against dust mites seems to be more prevalent in cats with MI. However, positive IgE reactions can be observed in healthy and diseased cats, and, therefore, need to be interpreted in the light of clinical findings and environmental conditions of individual patients. Full article
(This article belongs to the Special Issue New Advances in Canine and Feline Diagnostics—2nd Edition)
11 pages, 2183 KB  
Article
Cough Characteristics and Their Association Patterns According to Cough Etiology: A Network Analysis
by Jieun Kang, Ji-Yong Moon, Deog Kyeom Kim, Jin Woo Kim, Seung Hun Jang and Hyeon-Kyoung Koo
J. Clin. Med. 2023, 12(16), 5383; https://doi.org/10.3390/jcm12165383 - 18 Aug 2023
Cited by 5 | Viewed by 2505
Abstract
Although cough is a common respiratory symptom, determining its cause is challenging. We aimed to explore how cough severity and characteristics vary with different etiologies, while investigating their interrelations with demographic features. Adult patients (n = 220) with chronic cough and completed [...] Read more.
Although cough is a common respiratory symptom, determining its cause is challenging. We aimed to explore how cough severity and characteristics vary with different etiologies, while investigating their interrelations with demographic features. Adult patients (n = 220) with chronic cough and completed diagnostic work-up and the COugh Assessment Test were enrolled. A correlation network analysis was used to examine the associations between the demographic features and cough severity/characteristics across various etiologies such as upper airway cough syndrome, asthma, eosinophilic bronchitis, gastroesophageal reflux disease (GERD), and idiopathic cough. Demographic features like age and sex showed complex associations with cough characteristics and severity. Cough severity decreased with age, especially in cases of eosinophilic bronchitis and GERD. Women with eosinophilic bronchitis reported more severe cough, while men with idiopathic cough reported more severe cough. Asthma was significantly linked to more sleep disturbance and fatigue, independent of age and sex, whereas GERD showed less sleep disturbance and fatigue. Network analysis revealed overall close associations between cough characteristics, though hypersensitivity in asthma and sleep disturbance in GERD were not linked with other cough traits. In conclusion, the demographic features and cough characteristics were interrelated, exhibiting distinct patterns based on the etiology. Full article
(This article belongs to the Section Respiratory Medicine)
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6 pages, 306 KB  
Article
The Role of Bronchoscopy in Diagnosis of Chronic Cough in Adults: A Retrospective Single-Center Study
by Patryk A. Sobczak, Justyna M. Sobczak, Sebastian Majewski, Joanna Miłkowska-Dymanowska, Zofia Kurmanowska, Karolina Szewczyk, Ewa Tyczkowska-Sieroń, Adam J. Białas, Adam Antczak, Paweł Górski and Wojciech J. Piotrowski
Adv. Respir. Med. 2020, 88(5), 406-411; https://doi.org/10.5603/ARM.a2020.0140 - 24 Oct 2020
Cited by 5 | Viewed by 1148
Abstract
Introduction: Cough is one of the most frequent symptoms reported to pulmonologists. The role of bronchoscopy in the diagnostic work-up of chronic cough is not clearly defined. The aim of this study was to evaluate the utility of fiberoptic bronchoscopy (FOB) and additional [...] Read more.
Introduction: Cough is one of the most frequent symptoms reported to pulmonologists. The role of bronchoscopy in the diagnostic work-up of chronic cough is not clearly defined. The aim of this study was to evaluate the utility of fiberoptic bronchoscopy (FOB) and additional testing of samples collected during FOB in the differential diagnosis of chronic cough in adults. Material and methods: This was a single-center retrospective study. Out of 7115 conventional white light FOB examinations, we finally selected 198 with cough as the only indication. Results: In 40.9% of bronchoscopic examinations, no visible cause of cough was found. Visual signs of chronic bronchitis (CB) were detected in 57.6% of reports. Only in 3 cases (1.5%) bronchoscopy revealed a potential cause of chronic cough other than CB. Mycobacterium tuberculosis or other mycobacteria were spotted in none of the samples. In 91.1% of bronchoalveolar lavage (BAL) cytologic examinations, at least one cell count abnormality was detected, but only in case of increased percentage of eosinophils, it might be considered clinically relevant. In 53% of bacteriological culture results, at least one potentially pathogenic bacterium was isolated. Conclusions: The present study results strengthen the evidence that FOB combined with additional testing of airway specimens obtained during FOB is not a powerful tool in the differential diagnosis of chronic cough, and FOB as a diagnostic tool may be overused. The appropriate timing and decision regarding referral for FOB and additional testing of achieved material requires careful clinical consideration. Full article
13 pages, 756 KB  
Article
Biomarkers of Oxidative Stress and Inflammation in Chronic Airway Diseases
by Liliya Chamitava, Lucia Cazzoletti, Marcello Ferrari, Vanessa Garcia-Larsen, Aneza Jalil, Paolo Degan, Alessandro G. Fois, Elisabetta Zinellu, Sara S. Fois, Anna Maria Fratta Pasini, Morena Nicolis, Mario Olivieri, Angelo Corsico, Roberto Bono, Pietro Pirina and Maria Elisabetta Zanolin
Int. J. Mol. Sci. 2020, 21(12), 4339; https://doi.org/10.3390/ijms21124339 - 18 Jun 2020
Cited by 43 | Viewed by 4629
Abstract
Introduction: The global burden of chronic airway diseases represents an important public health concern. The role of oxidative stress and inflammation in the pathogenesis of these diseases is well known. The aim of this study is to evaluate the behavior of both inflammatory [...] Read more.
Introduction: The global burden of chronic airway diseases represents an important public health concern. The role of oxidative stress and inflammation in the pathogenesis of these diseases is well known. The aim of this study is to evaluate the behavior of both inflammatory and oxidative stress biomarkers in patients with chronic bronchitis, current asthma and past asthma in the frame of a population-based study. Methods: For this purpose, data collected from the Gene Environment Interactions in Respiratory Diseases (GEIRD) Study, an Italian multicentre, multicase-control study, was evaluated. Cases and controls were identified through a two-stage screening process of individuals aged 20-65 years from the general population. Out of 16,569 subjects selected from the general population in the first stage of the survey, 2259 participated in the clinical evaluation. Oxidative stress biomarkers such as 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG), 8-isoprostane and glutathione and inflammatory biomarkers such as Fractional Exhaled Nitric Oxide (FENO) and white blood cells were evaluated in 1878 subjects. Results: Current asthmatics presented higher levels of FENO (23.05 ppm), leucocytes (6770 n/µL), basophils (30.75 n/µL) and eosinophils (177.80 n/µL), while subjects with chronic bronchitis showed higher levels of GSH (0.29 mg/mL) and lymphocytes (2101.6 n/µL). The multivariable multinomial logistic regression confirmed high levels of leucocytes (RRR = 1.33), basophils (RRR = 1.48), eosinophils (RRR = 2.39), lymphocytes (RRR = 1.26) and FENO (RRR = 1.42) in subjects with current asthma. Subjects with past asthma had a statistically significant higher level of eosinophils (RRR = 1.78) with respect to controls. Subjects with chronic bronchitis were characterized by increased levels of eosinophils (RRR = 2.15), lymphocytes (RRR = 1.58), GSH (RRR = 2.23) and 8-isoprostane (RRR = 1.23). Conclusion: In our study, current asthmatics show a greater expression of the inflammatory profile compared to subjects who have had asthma in the past and chronic bronchitis. On the other hand, chronic bronchitis subjects showed a higher rate of expression of oxidative stress biomarkers compared to asthmatic subjects. In particular, inflammatory markers such as circulating inflammatory cells and FENO seem to be more specific for current asthma, while oxidative stress biomarkers such as glutathione and 8-isoprostane appear to be more specific and applicable to patients with chronic bronchitis. Full article
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8 pages, 125 KB  
Article
The Usefulness of Induced Sputum Examination in the Diagnostic Evaluation of Selected Chronic Inflammatory Diseases of the Respiratory Tract
by Ewa Sozańska, Adam Barczyk, Marta Biedroń-Machura and Władysław Pierzchała
Adv. Respir. Med. 2009, 77(4), 349-356; https://doi.org/10.5603/ARM.27786 - 26 Jun 2009
Viewed by 685
Abstract
Introduction: Based on the normal values for inflammatory cell counts in induced sputum produced by healthy individuals living in the region of Silesia, Poland, we assessed the usefulness of cytological examination of induced sputum in the diagnostic evaluation of asthma, chronic obstructive pulmonary [...] Read more.
Introduction: Based on the normal values for inflammatory cell counts in induced sputum produced by healthy individuals living in the region of Silesia, Poland, we assessed the usefulness of cytological examination of induced sputum in the diagnostic evaluation of asthma, chronic obstructive pulmonary disease (COPD) and chronic bronchitis. Material and methods: We analyzed the results of examinations performed in 96 healthy individuals (controls), 42 patients with asthma, 49 with COPD and 30 with chronic bronchitis. We performed spirometry with salbutamol reversibility testing and examination of induced sputum in all the subjects. Those without contraindications underwent methacholine challenge testing. Results: We found a significantly elevated percentage of eosinophils in all the patient groups compared to the controls (p < 0.00001). Median values were 10.3% for asthma, 1.5% for COPD, 1.6% for chronic bronchitis and 0.3% for the controls. We found statistically significant differences in the mean neutrophil percentages in induced sputum between healthy individuals and asthma patients, COPD patients and chronic bronchitis patients (p < 0.05). The median values were 45.75%, 38.1%, 77.5% and 58.1%, respectively. The percentage of subjects with positive eosinophil counts (>2.8%) in the sputum of patients with asthma, COPD, chronic bronchitis and in the controls was 85%, 38%, 20% and 6%, respectively. Conclusions: 1. Cytological examination of induced sputum is a good test supporting the diagnostic evaluation of chronic inflammatory diseases of the respiratory tract. 2. The percentage of eosinophils in induced sputum exceeding 2.8% is a very good indicator of asthma. Full article
5 pages, 155 KB  
Review
Patogeneza i klinika nieastmatycznego eozynofilowego zapalenia oskrzeli
by Anna Dor-Wojnarowska and Bernard Panaszek
Adv. Respir. Med. 2007, 75(4), 389-393; https://doi.org/10.5603/ARM.27966 - 10 Nov 2007
Viewed by 618
Abstract
The introduction of induced sputum, as the diagnostic and research tool allowed to define nonasthmatic eosinophilic bronchitis characterized as a chronic cough in patients with no symptoms or objective evidence of variable airflow obstruction, with normal airway hyperresponsiveness and sputum eosinophilia. Eosinophilic bronchitis [...] Read more.
The introduction of induced sputum, as the diagnostic and research tool allowed to define nonasthmatic eosinophilic bronchitis characterized as a chronic cough in patients with no symptoms or objective evidence of variable airflow obstruction, with normal airway hyperresponsiveness and sputum eosinophilia. Eosinophilic bronchitis is an important cause of chronic cough. Studies in which the assessment of airway inflammation has been undertaken in chronic cough patients have shown that nonasthmatic eosinophilic bronchitis accounts for 10 to 30% of cases referred for specialist investigation. Eosinophilic bronchitis, like asthma, is characterized by eosinophilic airway inflammation, but unlike asthma, there is no airway hyperresponsiveness or bronchoconstriction. The airway immunopathology of asthma and eosinophilic bronchitis are almost identical. An obvious question is why an apparently similar pattern of airway inflammation is associated with different functional abnormalities in patients with nonasthmatic eosinophilic bronchitis and asthma. The differences in functional association may be related to differences in the localization of mast cells within the airway wall, with airway smooth muscle infiltration occurring in patients with asthma, and epithelial infiltration in patients with nonasthmatic eosinophilic bronchitis. Full article
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