Journal articles on the topic 'Asthma; airway inflammation; zinc levels in sputum'
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1
Gauvreau, Gail M., Mark D. Inman, Margaret Kelly, Richard M. Watson, Sandra C. Dorman, and Paul M. O’Byrne. "Increased Levels of Airway Neutrophils Reduces the Inhibitory Effects of Inhaled Glucocorticosteroids on Allergen-Induced Airway Eosinophils." Canadian Respiratory Journal 9, no. 1 (2002): 26–32. http://dx.doi.org/10.1155/2002/161969.
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BACKGROUND: Treatment with inhaled glucocorticosteroids attenuates allergen-induced airway inflammation but is less effective in people with asthma who have noneosinophilic airway inflammation.OBJECTIVE: Studies in which glucocorticosteroid treatment was used before allergen challenges were re-examined to determine whether the efficacy of steroid treatment could be predicted by baseline levels of sputum inflammatory cells.PATIENTS AND METHODS: Twenty-eight nonsmoking subjects with atopic asthma controlled by beta2-agonists participated in only one of three studies, each carried out with a double-blind, placebo controlled, randomized, crossover design. Subjects were treated with glucocorticosteroids or placebo for six to eight days and then underwent allergen inhalation challenge. Spirometry was measured for 7 h after allergen challenge, and then sputum inflammatory cells were measured. Sputum inflammatory cells were also measured before and after treatment, and 24 h after allergen challenge. The per cent inhibition of the allergen-induced airway responses by glucocorticosteroids was calculated.RESULTS: Inhaled gluticocorticosteroids significantly attenuated the early and late asthmatic responses, and the number of allergen-induced sputum eosinophils (P<0.05). There was a significant negative relationship between the number of sputum neutrophils at baseline, and the per cent inhibition of allergen-induced sputum eosinophils measured at 7 h (r=-0.61, P<0.001) and 24 h (r=-0.73, P<0.0001) after challenge, suggesting that glucocorticosteroids are less effective in attenuating allergen-induced airway inflammation in subjects with high levels of neutrophils. There was no correlation between the number of sputum eosinophils at baseline and the per cent inhibition of allergen-induced responses.CONCLUSIONS: Baseline airway neutrophils, not eosinophils, can be used to predict the efficacy of inhaled steroids on allergen-induced sputum eosinophils.
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Pospelova, S. N., S. A. Sobchenko, and V. Yu Kravtsov. "POSSIBILITIES OF CYTOLOGICAL AND IMMUNOCYTOCHEMICAL MARKERSOF INDUCED SPUTUM IN THE EVALUATION OF AIRWAY INFLAMMATION IN PATIENTSWITH DIFFERENT LEVELS OF ASTHMA CONTROL." HERALD of North-Western State Medical University named after I.I. Mechnikov 7, no. 2 (June 15, 2015): 68–73. http://dx.doi.org/10.17816/mechnikov20157268-73.
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Were analyzed cytological and immunocytochemical data of induced sputum 43 patients with dif- ferent levels of asthma controlResults of cytological research showed lack or presence of eosinophilic airway inflammation (rela- tive number of eosinophils> 3%), but were not helpful in distinguishing uncontrolled from partially controlled asthma, these data could not be used for determination of level of asthma control. Objective indicator of the severity of airway inflammation, significantly correlated with the levels of disease con- trol, is the ratio of IL-1Ra/IL-1 in AM.
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Parameswaran, Krishnan, Christopher J. Allen, Dennis Kamada, Ann Efthimiadis, Mehran Anvari, and Frederick E. Hargreave. "Sputum Cell Counts and Exhaled Nitric Oxide in Patients with Gastroesophageal Reflux, and Cough or Asthma." Canadian Respiratory Journal 8, no. 4 (2001): 239–44. http://dx.doi.org/10.1155/2001/418490.
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BACKGROUND: Gastroesophageal reflux (GER) is commonly associated with chronic cough and asthma, but there is little or no information on the nature of any associated airway inflammation.OBJECTIVE: To observe whether the association with GER worsens airway inflammation in patients with chronic cough or asthma.PATIENTS AND METHODS: The airway inflammatory indexes in induced sputum and exhaled air were examined in a cross-sectional study of 11 patients with cough and GER, nine patients with mildly symptomatic asthma and GER, nine patients with mildly symptomatic asthma without GER and nine normal, healthy control subjects. GER was shown objectively by 24 h ambulatory pH recording.RESULTS: The sputum total cell count, the proportion of neutrophils and macrophages, and the fibrinogen level were normal in all four groups, with no significant differences among the groups. The sputum eosinophil and metachromatic cell percentages, and eosinophil cationic protein levels were normal in patients with cough and GER. They were significantly increased in patients with asthma compared with healthy subjects (P<0.01) and patients with cough (P<0.01), but were not different between groups with and without GER. Exhaled nitric oxide levels showed similar results (P<0.01). The correlations between the number of episodes of reflux and the proportion of sputum eosinophils, neutrophils or exhaled nitric oxide were modest but not significant.CONCLUSIONS: GER, when associated with cough or mildly symptomatic asthma, does not cause or aggravate existing airway inflammation as measured by induced sputum cell counts and fibrinogen level, or by exhaled nitric oxide.
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Pizzichini, Marcia Margaret Menezes, Cristiane Cinara Rocha, Michelle Gonçalves de Souza Tavares, Leila John Marques Steidle, Rosemeri Maureci da Silva, Felipe dal Pizzol, Peter G. Gibson, and Emilio Pizzichini. "How does the GINA definition of control correlate with quality of life and sputum cellularity?" ERJ Open Research 5, no. 1 (February 2019): 00146–2018. http://dx.doi.org/10.1183/23120541.00146-2018.
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Since 2014, the Global Initiative for Asthma (GINA) has stated that asthma control should be measured using four questions concerning diurnal and nocturnal symptoms, activity limitation, and rescue medication use. We assessed how asthma control by this definition correlates with airway inflammation and quality of life.113 asthmatic subjects consecutively recruited from their routine clinical appointment underwent spirometry, sputum induction and answered the Standardised Asthma Quality of Life Questionnaire (AQLQ(S)) during a single visit.43 (38.1%), 37 (32.7%) and 33 (29.2%) subjects had controlled asthma, partly controlled asthma and uncontrolled asthma, respectively. The majority of subjects with controlled asthma (67.4%) had paucigranulocytic sputum. Eosinophilic sputum was present in all levels of asthma control. Although most subjects with controlled asthma (58.1%) achieved an AQLQ(S) score ≥6 (minimal or no impairment), the remaining patients (41.9%) had moderate/some impairment (AQLQ(S) score <6 and ≥3) due to activity impairment and environmental exposure.The present GINA definition of current symptom control reflects control of airway inflammation. However, quality of life impairment can be present even in these patients. Measuring quality of life may provide useful information when evaluating asthma control.
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Yang, Xu, Haining Li, Qianli Ma, Qiao Zhang, and Changzheng Wang. "Neutrophilic Asthma Is Associated with Increased Airway Bacterial Burden and Disordered Community Composition." BioMed Research International 2018 (July 9, 2018): 1–11. http://dx.doi.org/10.1155/2018/9230234.
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Neutrophilic asthma (NA) is an important asthma inflammatory phenotype associated with disease severity, airflow limitation, and steroid resistance, and its mechanism is still uncertain. Evidences suggest a potential role for bacteria in its pathogenesis, but, so far, this remains poorly understood. We sought to investigate airway bacterial burden, community composition, and inflammatory response in NA. Fifty-four stable asthmatics without infection were enrolled and separated into either NA group (n = 20) or non-NA group (n = 34). Subject demographics, Asthma Control Test (ACT) scores, medications, and pulmonary functions were documented. Sputum cytology, airway bacterial burden, microbial community composition, and inflammatory cytokines were assessed. The total airway bacterial burden was significantly increased in subjects with NA versus non-NA and was positively correlated with the sputum neutrophil percentage. Airway neutrophilia was associated with less airway bacterial community richness and diversity, along with a distinct community composition. In patients with NA, bacteria in phylum Proteobacteria, especially Haemophilus spp. and Moraxella spp., showed significant increases in both actual loads and relative abundances, while bacteria in phyla Firmicutes, Actinobacteria, and Saccharibacteria showed decreased relative abundances compared with non-NA. Patients with NA demonstrated higher levels of interleukin-1β (IL-1β), IL-6, IL-8, IL-12, IL-17A, and tumor necrosis factor-α (TNF-α) in sputum samples compared with non-NA. Increased bacterial burden and distinct microbiota composition were the key characters of neutrophilic phenotype in asthma, accompanied by excessive airway inflammation. Understanding the relationship between airway microbiota and neutrophilic inflammation may help in treatment and management of asthma, such as targeting airway microbiota.
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Issa, Hamdia Yousif, Ali A. Ramadhan, Abdulazeez S. Safo, and Omar A. M. Al Habib. "Relationship between pulmonary function tests, sputum eosinophilia and total serum IgE levels among asthmatic patients in Duhok, Iraq." International Journal of Research in Medical Sciences 8, no. 6 (May 26, 2020): 2033. http://dx.doi.org/10.18203/2320-6012.ijrms20202239.
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Background: Bronchial asthma is a disease characterized by reversible airway obstruction, airway inflammation; and hyper-responsiveness. The prevalence of asthma is high, and both its prevalence and burden have increased over the last several decades. The study of inflammatory markers has implications for the appropriate management of this disease. Inflammatory markers has implications for the appropriate management of this disease. Objective of the study is to determine the correlation between asthma severity using pulmonary function tests with sputum eosinophilia and total serum IgE levels.Methods: This case-control study was conducted from March 2017 to September 2018 in the respiratory unit of Azadi general teaching hospital. It included 42 asthmatic patients and 18 healthy subjects. They underwent pulmonary function tests and measurement of total serum IgE levels. Induced sputum was done for asthmatic patients.Results: The age of asthmatic patients ranged from 16-70 years (mean 42±19 years). The asthmatic patient’s female: male ratio was 1.8. Mild asthma was the most common severity group (N=18, 43%) followed by moderate asthma (N=14, 33%) then severe asthma (N=10, 24%). Abnormal sputum eosinophilia (≥3%) was detected in 90% of severe asthma (N=9) compared to 36% in moderate asthma (N=5) and 5.6% in mild asthma (N=1). There was significant statistical association between asthma severity and sputum eosinophilia (p=0.00004). The association between asthma severity and total serum IgE levels was highly significant (p<0.0000) with levels of total serum IgE increasing as the severity of asthma increases.Conclusions: Severe asthma is the least common severity group in this study. Both abnormal sputum eosinophilia and total serum IgE levels are associated with the severity of asthma.
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Papaioannou, Andriana I., Evangelia Fouka, Polyxeni Ntontsi, Grigoris Stratakos, and Spyridon Papiris. "Paucigranulocytic Asthma: Potential Pathogenetic Mechanisms, Clinical Features and Therapeutic Management." Journal of Personalized Medicine 12, no. 5 (May 23, 2022): 850. http://dx.doi.org/10.3390/jpm12050850.
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Asthma is a heterogeneous disease usually characterized by chronic airway inflammation, in which several phenotypes have been described, related to the age of onset, symptoms, inflammatory characteristics and treatment response. The identification of the inflammatory phenotype in asthma is very useful, since it allows for both the recognition of the asthmatic triggering factor as well as the optimization of treatment The paucigranulocytic phenotype of asthma (PGA) is characterized by sputum eosinophil levels <1–3% and sputum neutrophil levels < 60%. The precise characteristics and the pathobiology of PGA are not fully understood, and, in some cases, it seems to represent a previous eosinophilic phenotype with a good response to anti-inflammatory treatment. However, many patients with PGA remain uncontrolled and experience asthmatic symptoms and exacerbations, irrespective of the low grade of airway inflammation. This observation leads to the hypothesis that PGA might also be either a special phenotype driven by different kinds of cells, such as macrophages or mast cells, or a non-inflammatory phenotype with a low grade of eosinophilic inflammation. In this review, we aim to describe the special characteristics of PGA and the potential therapeutic interventions that could be offered to these patients.
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Nuijsink, M., W. C. J. Hop, P. J. Sterk, E. J. Duiverman, P. S. Hiemstra, and J. C. de Jongste. "Urinary Eosinophil Protein X in Children with Atopic Asthma." Mediators of Inflammation 2007 (2007): 1–6. http://dx.doi.org/10.1155/2007/49240.
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The aim of this study was to investigate the relationship between urinary eosinophil protein X (uEPX) and asthma symptoms, lung function, and other markers of eosinophilic airway inflammation in asthmatic school children.Methods. A cross-sectional study was performed in 180 steroid dependent atopic children with stable moderately severe asthma, who were stable on 200 or 500μg of fluticasone per day. uEPX was measured in a single sample of urine and was normalized for creatinine concentration (uEPX/c). Symptom scores were kept on a diary card.FEV1andPD20methacholine were measured. Sputum induction was performed in 49 andFENOlevels measured in 24 children.Results. We found an inverse correlation between uEPX/c andFEV1(r=−.20,P=.01) and a borderline significant correlation between uEPX/c andPD20methacholine (r=−.15,P=.06). Symptom score,%eosinophils and ECP in induced sputum andFENOlevels did not correlate with uEPX/c.Conclusion. uEPX/c levels did not correlate with established markers of asthma severity and eosinophilic airway inflammation in atopic asthmatic children.
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Moraes-Ferreira, Renilson, Maysa Alves Rodrigues Brandao-Rangel, Thiago Gonçalves Gibson-Alves, Anamei Silva-Reis, Victor Hugo Souza-Palmeira, Helida Cristina Aquino-Santos, Claudio Ricardo Frison, Luis Vicente Franco Oliveira, Regiane Albertini, and Rodolfo P. Vieira. "Physical Training Reduces Chronic Airway Inflammation and Mediators of Remodeling in Asthma." Oxidative Medicine and Cellular Longevity 2022 (October 20, 2022): 1–13. http://dx.doi.org/10.1155/2022/5037553.
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Several benefits of aerobic training for asthmatic patients have been demonstrated. However, its effects on systemic inflammation and on airway remodeling mediators and lung mechanics are unknown. This prospective study included 21 intermittent and mild asthma patients, and as primary outcomes, the evaluation of pro- and anti-inflammatory and pro- and antifibrotic mediators in exhaled breath condensate (EBC) and blood were performed, beyond the cell counting in blood and in induced sputum. Aerobic training was performed for 3 months, 3 times per week. Aerobic training increased the levels of anti-inflammatory cytokines and of antifibrotic mediators in the breath condensate: IL-1ra ( p = 0.0488 ), IL-10 ( p = 0.0048 ), relaxin-3 ( p = 0.0019 ), and klotho ( p < 0.0043 ), respectively. Similarly, in plasma, increased levels of IL-1ra ( p = 0.0147 ), IL-10 ( p < 0.0001 ), relaxin-3 ( p = 0.004 ), and klotho ( p = 0.0023 ) were found. On contrary, reduced levels of proinflammatory cytokines in the breath condensate, IL-1β ( p = 0.0008 ), IL-4 ( p = 0.0481 ), IL-5 ( p < 0.0001 ), IL-6 ( p = 0.0032 ), IL-13 ( p = 0.0013 ), and TNF-α ( p = 0.0001 ) and profibrotic markers VEGF ( p = 0.0017 ) and TSLP ( p = 0.0056 ) were found. Similarly, in plasma, aerobic training significantly reduced the levels of proinflammatory cytokines IL-1β ( p = 0.0008 ), IL-4 ( p = 0.0104 ), IL-5 ( p = 0.0001 ), IL-6 ( p = 0.006 ), IL-13 ( p = 0.0341 ), and TNF-α ( p = 0.0003 ) and of profibrotic markers VEGF ( p = 0.0009 ) and TSLP ( p < 0.0076 ). Fractional exhaled nitric oxide (FeNO) was reduced after the intervention ( p = 0.0313 ). Regarding inflammatory cells in sputum, there was a reduction in total cells ( p = 0.008 ), eosinophils ( p = 0.009 ), and macrophages ( p = 0.020 ), as well as of blood eosinophils ( p = 0.0203 ) and lymphocytes ( p = 0.0198 ). Aerobic training positively modulates chronic airway inflammation and remodeling mediators, beyond to improve systemic inflammation in intermittent and mild asthmatic patients.
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Paplińska-Goryca, Magdalena, Paulina Misiukiewicz-Stępień, Katarzyna Górska, and Rafał Krenke. "Cilia proteins CFAP36 and sentan in induced sputum as possible new markers of epithelial damage in obstructive lung diseases: A preliminary study." Postępy Higieny i Medycyny Doświadczalnej 74 (October 15, 2020): 437–42. http://dx.doi.org/10.5604/01.3001.0014.4522.
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Background: Asthma and chronic obstructive pulmonary disease (COPD) are the most common chronic respiratory diseases characterized by inflammation in the lower airways and epithelium remodeling. Dysfunction of cilium is related to severe asthma and COPD, the role of cilium proteins in obstructive lung diseases is not known. The aim of the study was to evaluate the concentration of cilia associated proteins: sentan and CFAP36 in induced sputum (IS) of asthma and COPD patients. Materials/Methods: The study involved 15 patients with asthma, 12 patients with COPD and 17 control subjects (9 non-smoking, 8 smoking) who underwent lung function tests and sputum induction. Sentan, CFAP36, IL-6, IL-8, concentrations were measured in induced sputum supernatants by ELISA. Results: The level of CFAP36 in induced sputum was elevated in asthma patients and subjects with atopy. Cilium protein levels in sputum were not related to spirometric tests results. Both CFAP36 and sentan concentrations were positively correlated with age. The level of sentan was associated with airway neutrophilic inflammation and active smoking status. CFAP36 concentration was negatively related to cell viability, whereas sentan level was positively related, but only in COPD patients. Conclusions: The results of our study revealed CFAP36 and sentan as possible new markers of epithelial damage of different origin in obstructive lung diseases.
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Mo, Yuqing, Kan Zhang, Yuchen Feng, Lingling Yi, Yuxia Liang, Wenliang Wu, Jianping Zhao, et al. "Epithelial SERPINB10, a novel marker of airway eosinophilia in asthma, contributes to allergic airway inflammation." American Journal of Physiology-Lung Cellular and Molecular Physiology 316, no. 1 (January 1, 2019): L245—L254. http://dx.doi.org/10.1152/ajplung.00362.2017.
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Serine peptidase inhibitor, clade B, member 10 (SERPINB10) expression is increased in IL-13-stimulated human bronchial epithelial cells and in a murine model of allergic airway inflammation. However, the role of SERPINB10 in asthma remains unknown. We examined the association between epithelial SERPINB10 expression and airway eosinophilia in subjects with asthma and the role of Serpinb10 in allergic airway inflammation in an animal model. Epithelial SERPINB10 mRNA and protein expression were markedly increased in subjects with asthma ( n = 60) compared with healthy controls ( n = 25). Epithelial SERPINB10 mRNA levels were significantly correlated with airway hyperresponsiveness (AHR) and three parameters reflecting airway eosinophilia including the percentage of sputum eosinophils, the number of eosinophils in bronchial submucosa, and fraction of exhaled nitric oxide in subjects with asthma. Moreover, epithelial SERPINB10 expression was strongly correlated with the epithelial gene signature ( CLCA1, POSTN, and SERPINB2) for type 2 status. In normal human bronchial epithelial cells cultured at air-liquid interface, knockdown of SERPINB10 suppressed IL-13-stimulated periostin (encoded by POSTN) and CCL26 (eotaxin-3) expression by inhibiting the activation of p38 MAPK. Epithelial CCL26 mRNA levels were correlated with SERPINB10 expression in subjects with asthma. Airway knockdown of Serpinb10 alleviated AHR, airway eosinophilia and the expression of periostin and Ccl26 in a murine model of allergic airway disease. Taken together, epithelial SERPINB10 is a novel marker for airway eosinophilia in asthma. Epithelial SERPINB10 contributes to allergic airway eosinophilic inflammation, at least in part, by regulating the expression of periostin and CCL26.
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Nakayama, Toshinori, Kiyoshi Hirahara, and Masakatsu Yamasahita. "ROG, repressor of GATA, regulates Th2-driven allergic airway inflammation and airway hyperresponsiveness (79.8)." Journal of Immunology 182, no. 1_Supplement (April 1, 2009): 79.8. http://dx.doi.org/10.4049/jimmunol.182.supp.79.8.
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Abstract Studies of human asthma and of animal models of allergic inflammation/asthma highlight a crucial role for type 2 helper T (Th2) cells in the pathogenesis of allergic asthma. Repressor of GATA (ROG) is a POZ (BTB) domain-containing Kruppel type zinc finger family (or POK family) repressor. A repressive function to GATA3, a master transcription factor for Th2 cell differentiation is indicated. The aim of this study is to clarify the regulatory roles of ROG in the pathogenesis of Th2-driven allergic diseases, such as allergic asthma. We examined allergic airway inflammation and airway hyperresponsiveness in three different mouse models, which use either ROG-deficient (ROG-/-) mice, ROG transgenic mice or adoptive transfer of cells. In ROG-/- mice, Th2 cell differentiation, Th2 responses, eosinophilic airway inflammation and airway hyperresponsiveness were enhanced. In ROG transgenic mice, the levels of eosinophilic airway inflammation and airway hyperresponsiveness were dramatically reduced. Furthermore, adoptive transfer of Th2 cells with increased or decreased levels of ROG expression into the asthmatic mice resulted in reduced or enhanced airway inflammation, respectively. These results indicate that ROG regulates allergic airway inflammation and airway hyperresponsiveness in a negative manner, and thus ROG may represent another potential therapeutic target for the treatment of asthma patients.
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Patel, Kalpesh, Varun Patel, and Payal Gogdani. "Association of induced sputum eosinophil, absolute eosinophil count and serum immunoglobulin E level in assessment of the clinical severity in bronchial asthma." IP Indian Journal of Immunology and Respiratory Medicine 7, no. 2 (July 15, 2022): 65–68. http://dx.doi.org/10.18231/j.ijirm.2022.016.
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The study was done with the aim to determine the relationship between the severity of asthma in patient and the level of serum immunoglobulin E, peripheral eosinophil count and nature of sputum.Current research was conducted at the Department of Respiratory Medicine, GAIMS, Bhuj, India over one year. All subjects of Bronchial asthma distinct by Genetic Information Nondiscrimination Act (GINA) guidelines of age 17-61 year were registered. Severity of asthma was assessed by clinical features and by Forced expiratory volume in the first second (FEV1 in spirometry. Following evaluating the sternness of bronchial asthma all subjects undergo sputum examination for sputum eosinophil counts, blood sampling for absolute eosinophil counts and serum IgE levels. Elevated sputum eosinophil count (>3) was significantly elevated in additional subjects with severe persistent asthma even though extra than half of them had normal sputum eosinophil. An important association amid peripheral eosinophil count, sputum eosinophil count, and serum IgE with severe persistent asthma. Mean sputum eosinophil% augments considerably according to severity, demonstrates though affirmative association which was statistically important.The use of inexpensive and easy method with evaluation of AEC, sputum eosinophil count and evaluation of serum IgE level showed a straight measurement of inflammation of airway and allergic etiology of illness.
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Latorre, Manuela, Elena Bacci, Veronica Seccia, Maria Laura Bartoli, Cristina Cardini, Silvana Cianchetti, Ludovica Cristofani, et al. "Upper and lower airway inflammation in severe asthmatics: a guide for a precision biologic treatment." Therapeutic Advances in Respiratory Disease 14 (January 2020): 175346662096515. http://dx.doi.org/10.1177/1753466620965151.
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Background and aims: Severe asthma may require the prescription of one of the biologic drugs currently available, using surrogate markers of airway inflammation (serum IgE levels and allergic sensitization for anti-IgE, or blood eosinophils for anti-IL5/IL5R). Our objective: to assess upper and lower airway inflammation in severe asthmatics divided according to the eligibility criteria for one of the target biologic treatments. Methods: We selected 91 severe asthmatics, uncontrolled despite high-dose ICS-LABA, and followed for >6 months with optimization of asthma treatment. Patients underwent clinical, functional and biological assessment, including induced sputum and nasal cytology. They were then clustered according to the eligibility criteria for omalizumab or mepolizumab/benralizumab. Results: Four clusters were selected: A (eligible for omalizumab, n = 23), AB (both omalizumab and mepolizumab, n = 26), B (mepolizumab, n = 22) and C (non-eligible for both omalizumab and mepolizumab, n = 20). There was no difference among clusters for asthma control (Asthma Control Test and Asthma Control Questionnaire 7), pre-bronchodilator forced expiratory volume in 1 s, serum IgE and fractional exhaled nitric oxide levels. Sputum eosinophils were numerically higher in clusters AB and B, in agreement with the higher levels of blood eosinophils. Allergic rhinitis was more frequent in clusters A and AB, while chronic rhinosinusitis with nasal polyps prevalence increased progressively from A to C. Eosinophils in nasal cytology were higher in clusters AB, B and C. Conclusion: Eosinophilic upper and lower airway inflammation is present in the large majority of severe asthmatics, independently from the prescription criteria for the currently available biologics, and might suggest the use of anti-IL5/IL5R or anti IL4/13 also in patients without blood eosinophilia. The reviews of this paper are available via the supplemental material section.
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Gomez, Jose L., Xiting Yan, Carole T. Holm, Nicole Grant, Qing Liu, Lauren Cohn, Vera Nezgovorova, et al. "Characterisation of asthma subgroups associated with circulating YKL-40 levels." European Respiratory Journal 50, no. 4 (October 2017): 1700800. http://dx.doi.org/10.1183/13993003.00800-2017.
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The chitinase-like protein YKL-40 mediates airway inflammation and serum levels are associated with asthma severity. However, asthma phenotypes associated with YKL-40 levels have not been precisely defined.We conducted an unsupervised cluster analysis of asthma patients treated at the Yale Center for Asthma and Airways Disease (n=156) to identify subgroups according to YKL-40 level. The resulting YKL-40 clusters were cross-validated in cohorts from the Severe Asthma Research Programme (n=167) and the New York University/Bellevue Asthma Repository (n=341). A sputum transcriptome analysis revealed molecular pathways associated with YKL-40 subgroups.Four YKL-40 clusters (C1–C4) were identified. C3 and C4 had high serum YKL-40 levels compared with C1 and C2. C3 was associated with earlier onset and longer duration of disease, severe airflow obstruction, and near-fatal asthma exacerbations. C4 had the highest serum YKL-40 levels, adult onset and less airflow obstruction, but frequent exacerbations. An airway transcriptome analysis in C3 and C4 showed activation of non-type 2 inflammatory pathways.Elevated serum YKL-40 levels were associated with two distinct clinical asthma phenotypes: one with irreversible airway obstruction and another with severe exacerbations. The YKL-40 clusters are potentially useful for identification of individuals with severe or exacerbation-prone asthma.
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Miyamoto, Shintaro, Noboru Hattori, Tadashi Senoo, Yojiro Onari, Hiroshi Iwamoto, Masashi Kanehara, Nobuhisa Ishikawa, et al. "Intra-airway administration of small interfering RNA targeting plasminogen activator inhibitor-1 attenuates allergic asthma in mice." American Journal of Physiology-Lung Cellular and Molecular Physiology 301, no. 6 (December 2011): L908—L916. http://dx.doi.org/10.1152/ajplung.00115.2011.
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Recent studies suggest that plasminogen activator inhibitor-1 (PAI-1), a major inhibitor of the fibrinolytic system, may promote the development of asthma. To further investigate the significance of PAI-1 in the pathogenesis of asthma and determine the possibility that PAI-1 could be a therapeutic target for asthma, this study was conducted. First, PAI-1 levels in induced sputum (IS) from asthmatic subjects and healthy controls were measured. In asthmatic subjects, IS PAI-1 levels were elevated, compared with that of healthy controls, and were significantly higher in patients with long-duration asthma compared with short-duration asthma. PAI-1 levels were also found to correlate with IS transforming growth factor-β levels. Then, acute and chronic asthma models induced by ovalbumin were established in PAI-1-deficient mice and wild-type mice that received intra-airway administrations of small interfering RNA against PAI-1 (PAI-1-siRNA). We could demonstrate that eosinophilic airway inflammation and airway hyperresponsiveness were reduced in an acute asthma model, and airway remodeling was suppressed in a chronic asthma model in both PAI-1-deficient mice and wild-type mice that received intra-airway administration of PAI-1-siRNA. These results indicate that PAI-1 is strongly involved in the pathogenesis of asthma, and intra-airway administration of PAI-1-siRNA may be able to become a new therapeutic approach for asthma.
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Takahashi, Kentaro, Stelios Pavlidis, Francois Ng Kee Kwong, Uruj Hoda, Christos Rossios, Kai Sun, Matthew Loza, et al. "Sputum proteomics and airway cell transcripts of current and ex-smokers with severe asthma in U-BIOPRED: an exploratory analysis." European Respiratory Journal 51, no. 5 (April 12, 2018): 1702173. http://dx.doi.org/10.1183/13993003.02173-2017.
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Severe asthma patients with a significant smoking history have airflow obstruction with reported neutrophilia. We hypothesise that multi-omic analysis will enable the definition of smoking and ex-smoking severe asthma molecular phenotypes.The U-BIOPRED cohort of severe asthma patients, containing current-smokers (CSA), ex-smokers (ESA), nonsmokers and healthy nonsmokers was examined. Blood and sputum cell counts, fractional exhaled nitric oxide and spirometry were obtained. Exploratory proteomic analysis of sputum supernatants and transcriptomic analysis of bronchial brushings, biopsies and sputum cells was performed.Colony-stimulating factor (CSF)2 protein levels were increased in CSA sputum supernatants, with azurocidin 1, neutrophil elastase and CXCL8 upregulated in ESA. Phagocytosis and innate immune pathways were associated with neutrophilic inflammation in ESA. Gene set variation analysis of bronchial epithelial cell transcriptome from CSA showed enrichment of xenobiotic metabolism, oxidative stress and endoplasmic reticulum stress compared to other groups. CXCL5 and matrix metallopeptidase 12 genes were upregulated in ESA and the epithelial protective genes, mucin 2 and cystatin SN, were downregulated.Despite little difference in clinical characteristics, CSA were distinguishable from ESA subjects at the sputum proteomic level, with CSA patients having increased CSF2 expression and ESA patients showing sustained loss of epithelial barrier processes.
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Uzunay, Oznur, Serife Torun, and Turgut Teke. "The anti-inflammatory effects of inhaled steroids and β2-agonist added to inhaled steroids in the treatment of mild asthma." Medicine Science | International Medical Journal 11, no. 3 (2022): 1306. http://dx.doi.org/10.5455/medscience.2022.06.147.
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The use of inhaled corticosteroids (ICS) alone may be sufficient for asthma control in mild asthma. We investigated the effect of inhaled steroid and beta-2 agonist combination on airway function and inflammation in mild asthma.We randomized 20 mild persistent asthma patients treated with the 200μg budesonide (10 patients) or budesonide 200μg -formoterol 12μg (10 patients) twice daily for 4 weeks. We investigated the effects of treatment groups on pulmonary function tests by spirometry and eosinophil percentage and eosinophil cationic protein (ECP) levels in serum and induced sputum. We compared values before and after treatment within budesonide and budesonide-formoterol groups and after treatment between groups. We observed that eosinophil percentage and ECP levels in serum and induced sputum decreased significantly after treatment in both treatment groups. Only the decrease in serum eosinophil percentage level was not significant in the budesonide group. On the other that, there was no significant reduction of inflammatory markers between the two treatment groups. The spirometric measurements (FVC, FEV1, FEF25-75) showed a statistically significant increase within the budesonide-formoterol treatment group, but not in the budesonide group. These measurements were not statistically changed between the two treatment groups. In patients with mild asthma, budesonide and formoterol combination therapy did not add to the improvement of airway obstruction and inflammation more than budesonide therapy.
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Bilodeau, Lara, Marie-Eve Boulay, Philippe Prince, Pierre Boisvert, and Louis-Philippe Boulet. "Comparative clinical and airway inflammatory features of asthmatics with or without polyps." Rhinology journal 48, no. 4 (December 1, 2010): 420–25. http://dx.doi.org/10.4193/rhino09.095.
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BACKGROUND: Nasal polyposis (NP) is associated with a more severe and steroid-resistant asthma. OBJECTIVE: To compare clinical and airway inflammatory features of asthmatics with or without NP. METHODS: Two groups of asthmatic patients were studied: group 1; n=39, with NP; group 2; n=40, without NP. Asthma control was assessed according to the Asthma Control Scoring System (ACSS). Expiratory flows, induced sputum, and blood eosinophils were also measured. RESULTS: ACSS score was lower (poorer control) in group 1 (meanA+-SEM = 73A+-3%) compared with group 2 (82A+-2%, p=0.01). FEV1 (mean of predicted value A+- SEM) was 81A+-3 for group 1 and 96A+-3 for group 2 (p=0.001), and the FEV1/FVC ratio was lower in group 1 (70A+-2%) compared with group 2 (76A+-1%, p=0.01). Blood and induced sputum eosinophils, as well as fibronectin and eosinophil cationic protein levels, were higher in group 1. CONCLUSION: Asthmatic subjects with NP have increased airway obstruction, increased inflammatory cells and reduced asthma control compared to those without NP. This may suggest a contribution of nasal polyps to the severity of asthma or a common susceptibility to develop upper and lower airways mucosal inflammation.
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Ratnawati, Ratnawati, V. Nguyen, J. Morton, R. L. Henry, and P. S. Thomas. "Exhaled nitric oxide in acute exacerbation of pediatric asthma." Paediatrica Indonesiana 48, no. 2 (May 1, 2008): 64. http://dx.doi.org/10.14238/pi48.2.2008.64-70.
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Background Measurement of exhaled nitric oxide (eNO) is a non-invasive and easy method to monitor airway inflammation.Objectives To compare the levels of eNO during and after anexacerbation of asthma, to evaluate the effect of glucocor-ticosteroids (GCS) on the levels of eNO and to correlate eNOwith other markers of inflammation such as symptom scores, FEV 1and sputum eosinophils.Methods The observational study was performed over 24 monthsat a tertiary paediatric hospital. Subjects underwent eNOmeasurement, spirometry and sputum induction during an asthmaexacerbation and then two weeks later. A symptom score wasrecorded everyday for two weeks. All subjects were treated withß 2 -adrenergic agonists and an oral glucocorticosteroid (GCS).Results Fifteen subjects with acute asthma exacerbation aged 5and 16 years old participated in the study. The mean level ofeNO during the acute exacerbation was significantly higher thaneNO levels at the follow-up visit, 11.2 (95%CI 9.2;13.2) vs. 8.0(95%CI 5.0;11.1) ppb, P=0.03. In the acute exacerbation, eNOcorrelated with sputum eosinophils (P=0.04), but no correlationcould be found between eNO and the other markers ofinflammation during exacerbation or follow up.Conclusions eNO level increased during asthma exacerbation anddecreased after two weeks of glucocorticosteroid therapy.Measurement of eNO is a practical monitoring method inemergency management of asthmatic children.
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Hamzaoui, Agnès, Kamel Hamzaoui, Habib Salah, and Abdellatif Chabbou. "Lymphocytes Apoptosis in Patients with Acute Exacerbation of Asthma." Mediators of Inflammation 8, no. 4-5 (1999): 237–43. http://dx.doi.org/10.1080/09629359990405.
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Asthma is characterized by airway inflammation, which can be now assessed by the analysis of induced sputum . Ten patients with asthma were investigated during acute exacerbation for the quantification of apoptosis, for Bcl-2 and Fas expression, in induced sputum lymphocytes. They were compared to 12 patients with chronic obstructive pulmonary disease (COPD), and 10 healthy controls. Spontaneous apoptosis was determined by staining nuclei with propidium iodide, and analyzed with a FACScan. Bcl-2 was measured by Western blotting, and results were obtained by densitometric scanning, done by the gel proanalyser. The investigation of Fas was performed using the streptavidin-biotin preroxidase-complex method. Patients with asthma and patients with COPD exhibited a significant increase of cellularity, percentage of neutrophils, eosinophils and lymphocytes when compared to healthy controls. Apoptosis in induced sputum mononuclear cells was found decreased in patients with asthma compared to COPD patients and healthy controls. The quantification of apoptosis was measured after exposure to anticytokine antibodies. Anti-TNF-α antibody blocked the apoptosis in both patients groups and healthy controls, suggesting that TNF-α acted as an inducer of apoptosis. Anti-IL-10 blocked apoptosis completely exclusively in patients with asthma. Bcl-2 expression was found to be increased in induced sputum mononuclear cells from patients with asthma, compared to healthy controls and patients with COPD. Expression of Fas could be detected in patients with asthma, at a lower level than COPD patients and healthy controls. Distinct mechanisms of apoptosis were found in patients with asthma and patients with COPD, characterized by different levels of Bcl-2 and Fas expression. Induction of apoptosis should be a beneficial process in allergic inflammation traduced in induced sputum mononuclear cells. The apoptosis process is assumed by two different mechanisms in asthma and COPD. Our findings indicated that in asthmatic patients, activated lymphocytes accumulate in the bronchi; because of their prolonged survival that maintains inflammation.
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Rijavec, Matija, Tomaž Krumpestar, Sabina Škrgat, Izidor Kern, and Peter Korošec. "T2-high Asthma, Classified by Sputum mRNA Expression of IL4, IL5, and IL13, is Characterized by Eosinophilia and Severe Phenotype." Life 11, no. 2 (January 27, 2021): 92. http://dx.doi.org/10.3390/life11020092.
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Asthma is a common chronic disease, with different underlying inflammatory mechanisms. Identification of asthma endotypes, which reflect a variable response to different treatments, is important for more precise asthma management. T2 asthma is characterized by airway inflammation driven by T2 cytokines including interleukins IL-4, IL-5, and IL-13. This study aimed to determine whether induced sputum samples can be used for gene expression profiling of T2-high asthma classified by IL4, IL5, and IL13 expression. Induced sputum samples were obtained from 44 subjects, among them 36 asthmatic patients and eight controls, and mRNA expression levels of IL4, IL5, and IL13 were quantified by RT-qPCR. Overall, gene expression levels of IL4, IL5, and IL13 were significantly increased in asthmatic patients’ samples compared to controls and there was a high positive correlation between expressions of all three genes. T2 gene mean was calculated by combining the expression levels of all three genes (IL4, IL5, and IL13) and according to T2 gene mean expression in controls, we set a T2-high/T2-low cutoff value. Twenty-four (67%) asthmatic patients had T2-high endotype and those patients had significantly higher eosinophil blood and sputum counts. Furthermore, T2-high endotype was characterized as a more severe, difficult-to-treat asthma, and often uncontrolled despite the use of inhaled and/or oral corticosteroids. Therefore, the majority of those patients (15 [63%] of 24) needed adjunct biological therapy to control their asthma symptoms/exacerbations. In conclusion, we found that interleukins IL4, IL5, and IL13 transcripts could be effectively detected in sputum from asthmatic patients. Implementation of T2 gene mean can be used as sputum molecular biomarker to categorize patients into T2-high endotype, characterized by eosinophilia and severe, difficult-to-treat asthma, and often with a need for biological treatment.
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Perelman, Juliy M., Aleksey B. Pirogov, Anna G. Prikhodko, and Victor P. Kolosov. "Bronchial inflammatory profile in interferon-gamma-mediated immune response in asthma patients during airway response to cold stimulus." Frigid Zone Medicine 2, no. 4 (December 1, 2022): 244–50. http://dx.doi.org/10.2478/fzm-2022-0031.
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Abstract Objective To evaluate the inflammatory pattern and the interferon (IFN)-γ in the bronchial secretion of asthma patients in response to acute cold bronchoprovocation. Material and methods We enrolled 42 patients with asthma. We assessed asthma by Asthma Control Test, the lung function by spirometry before and after the bronchodilator test, followed by collecting induced sputum. The next day, we collected exhaled breath condensate (EBC) and conducted a 3-minute isocapnic hyperventilation with cold air (IHCA), followed by collecting spontaneously produced sputum. Results Group 1 included 20 patients with cold airway hyperresponsiveness (CAHR), and group 2 included 22 patients without CAHR. In both groups, a high level of neutrophils in bronchial secretion was observed before and after IHCA. In response to IHCA, the number of epitheliocytes in the sputum decreased to a greater extent in patients of group 1. The baseline epitheliocytes and the concentration of IFN-γ after IHCA had an inverse relationship (r = −0.60; P = 0.017). The baseline IFN-γ in EBC before and after IHCA was lower in group 1. Airway response to cold exposure directly correlated with IFN-γ levels after IHCA (Rs = 0.42; P = 0.014). Conclusion In asthma patients with CAHR, there is a relationship between the persistence of mixed inflammation and the level of IFN-γ in the bronchi. IFN-γ in response to IHCA is decreased with increased cytokine utilization during cold bronchospasm, which is accompanied by the mobilization of neutrophils and the shift in the cytokine spectrum of the respiratory tract towards the T helper cells (Th) 1 immune response.
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Nejman-Gryz, Patrycja, Katarzyna Górska, Magdalena Paplińska-Goryca, Małgorzata Proboszcz, and Rafał Krenke. "Periostin and Thymic Stromal Lymphopoietin—Potential Crosstalk in Obstructive Airway Diseases." Journal of Clinical Medicine 9, no. 11 (November 15, 2020): 3667. http://dx.doi.org/10.3390/jcm9113667.
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Periostin and thymic stromal lymphopoietin (TSLP) are newly described markers of obstructive airway diseases and the mechanism by which both markers participate in immune response remains poorly understood. The aim of our study was to determine periostin and TSLP concentration in serum and induced sputum (IS) in patients with atopic asthma, chronic obstructive pulmonary disease (COPD), and controls, as well as to evaluate the potential link between periostin, TSLP, and Th2 immune response. Serum and IS levels of periostin, TSLP, IL-4, and IL-13 were determined in 12 atopic asthmatics, 16 COPD sufferers, and 10 controls. We noticed a significantly higher IS periostin and TSLP concentration at protein and mRNA level in asthmatics compared to the two other groups; additionally, periostin and TSLP were correlated positively with IS eosinophil count. A strong positive correlation between IS periostin and TSLP protein levels (r = 0.96) as well as mRNA expression level (r = 0.95) was found in patients with asthma. The results of our study show that periostin and TSLP are associated with eosinophilic airway inflammation and seem to be important drivers of atopic asthma but not COPD pathobiology. Very strong correlations between local periostin, TSLP, eosinophils, and IL-4 in asthma point to the link between periostin–TSLP and Th2 response.
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Shaw, Dominick E., Ana R. Sousa, Stephen J. Fowler, Louise J. Fleming, Graham Roberts, Julie Corfield, Ioannis Pandis, et al. "Clinical and inflammatory characteristics of the European U-BIOPRED adult severe asthma cohort." European Respiratory Journal 46, no. 5 (September 10, 2015): 1308–21. http://dx.doi.org/10.1183/13993003.00779-2015.
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U-BIOPRED is a European Union consortium of 20 academic institutions, 11 pharmaceutical companies and six patient organisations with the objective of improving the understanding of asthma disease mechanisms using a systems biology approach.This cross-sectional assessment of adults with severe asthma, mild/moderate asthma and healthy controls from 11 European countries consisted of analyses of patient-reported outcomes, lung function, blood and airway inflammatory measurements.Patients with severe asthma (nonsmokers, n=311; smokers/ex-smokers, n=110) had more symptoms and exacerbations compared to patients with mild/moderate disease (n=88) (2.5 exacerbations versus 0.4 in the preceding 12 months; p<0.001), with worse quality of life, and higher levels of anxiety and depression. They also had a higher incidence of nasal polyps and gastro-oesophageal reflux with lower lung function. Sputum eosinophil count was higher in severe asthma compared to mild/moderate asthma (median count 2.99% versus 1.05%; p=0.004) despite treatment with higher doses of inhaled and/or oral corticosteroids.Consistent with other severe asthma cohorts, U-BIOPRED is characterised by poor symptom control, increased comorbidity and airway inflammation, despite high levels of treatment. It is well suited to identify asthma phenotypes using the array of “omic” datasets that are at the core of this systems medicine approach.
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Syabbalo, Nightingale. "Mechanisms, diagnosis and management of eosinophilic asthma." Journal of Lung, Pulmonary & Respiratory Research 7, no. 2 (April 2, 2020): 28–37. http://dx.doi.org/10.15406/jlprr.2020.07.00225.
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Asthma is a common chronic airway disease affecting about 334 million people worldwide, and up to 10% of asthma patients have severe asthma, which may be uncontrolled despite high doses of the standard treatment modifiers and may require the use of chronic oral corticosteroids. It is the most common chronic disease in children in the developed countries. Asthmamanifests as reversible airflow obstruction, due to airway inflammation, bronchial smooth muscle contraction, increased mucus secretion, vascular engorgement, mucosal oedema, and airway hyper responsiveness, which leads to airflow obstruction and symptoms of asthma. Eosinophilic asthma is a phenotype of asthma that is usually very severe and persistent, with frequent exacerbations. It is usually observed in adult asthmatic patients, although it may occur in children. It is characterized by the presence of high levels of eosinophils, and CD+4 Th2 cells in the lungs and airways, which can be demonstrated by a raised eosinophil count in blood, and induced sputum or bronchial biopsy. It is managed in a similar stepwise treatment for childhood-onset asthma, but some of the patients with eosinophilic asthma do not respond to this standard treatment including inhaled or oral corticosteroids. The logical approach to treat corticosteroid-refractory asthma is to target the eosinophilic interleukins which cause airway inflammation using monoclonal antibodies to block their activity on the eosinophils, and Th2 cells. Currently, the following monoclonal antibodies are used in the treatment of eosinophilic asthma: IgE antibody such as omalizumab, or interleukin receptor 5, or 4, and 13 antagonists, such mepolizumab, reslizumab, and dupilumab. These novel agents have proved to be very useful in relieving the symptoms, and in improving the forced expired volume in one second (FEV1), and in reducing exacerbations. They are also steroid-sparing agents, and improve the quality of lifein this debilitating phenotype of asthma.
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Lang, Carol, Chiara Murgia, Mary Leong, Lor-Wai Tan, Giuditta Perozzi, Darryl Knight, Richard Ruffin, and Peter Zalewski. "Anti-inflammatory effects of zinc and alterations in zinc transporter mRNA in mouse models of allergic inflammation." American Journal of Physiology-Lung Cellular and Molecular Physiology 292, no. 2 (February 2007): L577—L584. http://dx.doi.org/10.1152/ajplung.00280.2006.
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There is clinical evidence linking asthma with the trace element, zinc (Zn). Using a mouse model of allergic inflammation, we have previously shown that labile Zn decreases in inflamed airway epithelium (Truong-Tran AQ, Ruffin RE, Foster PS, Koskinen AM, Coyle P, Philcox JC, Rofe AM, Zalewski PD. Am J Respir Cell Mol Biol 27: 286–296, 2002). Moreover, mild nutritional Zn deficiency worsens lung function. Recently, a number of proteins belonging to the Solute Carrier Family 39 (ZIP) and Solute Carrier Family 30 (ZnT) have been identified that bind Zn and regulate Zn homeostasis. Mice were sensitized, and subsequently aerochallenged, with ovalbumin to induce acute and chronic airway inflammation. Mice received 0, 54, or 100 μg of Zn intraperitoneally. Tissues were analyzed for Zn content and histopathology. Inflammatory cells were counted in bronchoalveolar lavage fluid. Cytokine and Zn transporter mRNA levels were determined by cDNA gene array and/or real-time PCR. Zn supplementation decreased bronchoalveolar lavage fluid eosinophils by 40 and 80%, and lymphocytes by 55 and 66%, in the acute and chronic models, respectively. Alterations in Zn transporter expression were observed during acute inflammation, including increases in ZIP1 and ZIP14 and decreases in ZIP4 and ZnT4. Zn supplementation normalized ZIP1 and ZIP14, but it did not affect mRNA levels of cytokines or their receptors. Our results indicate that inflammation-induced alterations in Zn transporter gene expression are directed toward increasing Zn uptake. Increases in Zn uptake may be needed to counteract the local loss of Zn in the airway and to meet an increased demand for Zn-dependent proteins. The reduction of inflammatory cells by Zn in the airways provides support for Zn supplementation trials in human asthmatic individuals.
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Zajac, Dominika. "Mineral Micronutrients in Asthma." Nutrients 13, no. 11 (November 10, 2021): 4001. http://dx.doi.org/10.3390/nu13114001.
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Asthma represents one of the most common medical issues in the modern world. It is a chronic inflammatory disease characterized by persistent inflammation of the airways and disturbances in redox status, leading to hyperresponsiveness of bronchi and airway obstruction. Apart from classical risk factors such as air pollution, family history, allergies, or obesity, disturbances of the levels of micronutrients lead to impairments in the defense mechanisms of the affected organism against oxidative stress and proinflammatory stimuli. In the present review, the impact of micronutrients on the prevalence, severity, and possible risk factors of asthma is discussed. Although the influence of classical micronutrients such as selenium, copper, or zinc are well known, the effects of those such as iodine or manganese are only rarely mentioned. As a consequence, the aim of this paper is to demonstrate how disturbances in the levels of micronutrients and their supplementation might affect the course of asthma.
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Quoc, Quang Luu, Youngwoo Choi, Tra Cao Thi Bich, Eun-Mi Yang, Yoo Seob Shin, and Hae-Sim Park. "S100A9 in adult asthmatic patients: a biomarker for neutrophilic asthma." Experimental & Molecular Medicine 53, no. 7 (July 2021): 1170–79. http://dx.doi.org/10.1038/s12276-021-00652-5.
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AbstractThe biomarkers and therapeutic targets of neutrophilic asthma (NA) are poorly understood. Although S100 calcium-binding protein A9 (S100A9) has been shown to correlate with neutrophil activation, its role in asthma pathogenesis has not been clarified. This study investigated the mechanism by which S100A9 is involved in neutrophil activation, neutrophil extracellular trap (NET)-induced airway inflammation, and macrophage polarization in NA. The S100A9 levels (by ELISA) in sera/culture supernatant of peripheral blood neutrophils (PBNs) and M0 macrophages from asthmatic patients were measured and compared to those of healthy controls (HCs). The function of S100A9 was evaluated using airway epithelial cells (AECs) and PBNs/M0 macrophages from asthmatic patients, as well as a mouse asthma model. The serum levels of S100A9 were higher in NA patients than in non-NA patients, and there was a positive correlation between serum S100A9 levels and sputum neutrophil counts (r = 0.340, P = 0.005). Asthmatic patients with higher S100A9 levels had lower PC20 methacholine values and a higher prevalence of severe asthma (SA) (P < .050). PBNs/M0 macrophages from SA released more S100A9 than those from non-SA patients. PBNs from asthmatic patients induced S100A9 production by AECs, which further activated AECs via the extracellular signal-regulated kinase (ERK) pathway, stimulated NET formation, and induced M1 macrophage polarization. Higher S100A9 levels in sera, bronchoalveolar lavage fluid, and lung tissues were observed in the mouse model of NA but not in the other mouse models. These results suggest that S100A9 is a potential serum biomarker and therapeutic target for NA.
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Espada-Sánchez, Marta, Rocío Sáenz de Santa María, María del Carmen Martín-Astorga, Clara Lebrón-Martín, María Jesús Delgado, Ibón Eguiluz-Gracia, Carmen Rondón, et al. "Diagnosis and Treatment in Asthma and Allergic Rhinitis: Past, Present, and Future." Applied Sciences 13, no. 3 (January 18, 2023): 1273. http://dx.doi.org/10.3390/app13031273.
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Respiratory diseases are pathological conditions that affect airways, hampering breathing and causing high mortality. In particular, asthma and allergic rhinitis (AR) are two of the most common airway diseases that affect millions of people and have a high prevalence in childhood and adulthood. Asthma is a heterogeneous chronic inflammatory disease characterized by wheezing, chest tightness, shortness of breath, and cough. AR occurs with rhinorrhea, nasal congestion, and sneezing. Indeed, these pathologies share common physiopathological mechanisms such as airway hyperresponsiveness and similar immunopathology such as tissue eosinophilia and T-helper type 2 inflammation. Moreover, AR can be an important risk factor for suffering asthma. Thus, early diagnosis and effective treatment are crucial to improving the health and quality of life of these patients. Classical drugs such as corticosteroids have been used; however, in the last decades, efforts to improve treatments have increased, focusing on biological agents and specific allergen immunotherapy development. Moreover, more precise diagnostic tools have been elaborated, besides classical methods (medical history, physical examination, and pulmonary function tests), such as basophil activation test, and specific cellular and molecular biomarkers (microRNAs, sputum/blood eosinophils, IgE serum, and periostin levels). Therefore, in this review, we compile all these important issues for managing asthma and AR.
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Doyle, Alfred D., Manali Mukherjee, William E. LeSuer, Tyler B. Bittner, Saif M. Pasha, Justin J. Frere, Joseph L. Neely, et al. "Eosinophil-derived IL-13 promotes emphysema." European Respiratory Journal 53, no. 5 (February 6, 2019): 1801291. http://dx.doi.org/10.1183/13993003.01291-2018.
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The inflammatory responses in chronic airway diseases leading to emphysema are not fully defined. We hypothesised that lung eosinophilia contributes to airspace enlargement in a mouse model and to emphysema in patients with chronic obstructive pulmonary disease (COPD).A transgenic mouse model of chronic type 2 pulmonary inflammation (I5/hE2) was used to examine eosinophil-dependent mechanisms leading to airspace enlargement. Human sputum samples were collected for translational studies examining eosinophilia and matrix metalloprotease (MMP)-12 levels in patients with chronic airways disease.Airspace enlargement was identified in I5/hE2 mice and was dependent on eosinophils. Examination of I5/hE2 bronchoalveolar lavage identified elevated MMP-12, a mediator of emphysema. We showed, in vitro, that eosinophil-derived interleukin (IL)-13 promoted alveolar macrophage MMP-12 production. Airspace enlargement in I5/hE2 mice was dependent on MMP-12 and eosinophil-derived IL-4/13. Consistent with this, MMP-12 was elevated in patients with sputum eosinophilia and computed tomography evidence of emphysema, and also negatively correlated with forced expiratory volume in 1 s.A mouse model of chronic type 2 pulmonary inflammation exhibited airspace enlargement dependent on MMP-12 and eosinophil-derived IL-4/13. In chronic airways disease patients, lung eosinophilia was associated with elevated MMP-12 levels, which was a predictor of emphysema. These findings suggest an underappreciated mechanism by which eosinophils contribute to the pathologies associated with asthma and COPD.
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Mehra, Divya, David I. Sternberg, Yuxia Jia, Stephen Canfield, Vincent Lemaitre, Takwi Nkyimbeng, Julie Wilder, Joshua Sonett, and Jeanine D'Armiento. "Altered lymphocyte trafficking and diminished airway reactivity in transgenic mice expressing human MMP-9 in a mouse model of asthma." American Journal of Physiology-Lung Cellular and Molecular Physiology 298, no. 2 (February 2010): L189—L196. http://dx.doi.org/10.1152/ajplung.00042.2009.
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Matrix metalloproteinase-9 (MMP-9) is hypothesized to facilitate leukocyte extravasation and extracellular remodeling in asthmatic airways. Careful descriptive studies have shown that MMP-9 levels are higher in the sputum of asthmatics; however, the consequence of increased MMP-9 activity has not been determined in this disease. We induced asthma in transgenic mice that express human MMP-9 in the murine lung tissue macrophage to determine the direct effect of human MMP-9 expression on airway inflammation. Transgenic (TG) and wild-type (WT) mice were immunized and challenged with ovalbumin. Forty-eight hours after the ovalbumin challenge, airway hyperresponsiveness (AHR) was measured, and inflammatory cell infiltration was evaluated in bronchoalveolar lavage fluid (BALF) and lung tissue. Baseline levels of inflammation were similar in the TG and WT groups of mice, and pulmonary eosinophilia was established in both groups by sensitization and challenge with ovalbumin. There was a significant reduction in AHR in sensitized and challenged trangenics compared with WT controls. Although total BALF cell counts were similar in both groups, the lymphocyte number in the lavage of the TG group was significantly diminished compared with the WT group (0.25 ± 0.08 vs. 0.89 ± 0.53; P = 0.0032). In addition, the draining lymphocytes were found to be larger in the TG animals compared with the WT mice. Equal numbers of macrophages, eosinophils, and neutrophils were seen in both groups. IL-13 levels were found to be lower in the sensitized TG compared with the WT mice. These results demonstrate an inverse relationship between human MMP-9 and AHR and suggest that MMP-9 expression alters leukocyte extravasation by reducing lymphocyte accumulation in the walls of asthmatic airways.
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De Raeve, H. R., F. B. Thunnissen, F. T. Kaneko, F. H. Guo, M. Lewis, M. S. Kavuru, M. Secic, M. J. Thomassen, and S. C. Erzurum. "Decreased Cu,Zn-SOD activity in asthmatic airway epithelium: correction by inhaled corticosteroid in vivo." American Journal of Physiology-Lung Cellular and Molecular Physiology 272, no. 1 (January 1, 1997): L148—L154. http://dx.doi.org/10.1152/ajplung.1997.272.1.l148.
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To investigate the antioxidant response of respiratory epithelium to the chronic airway inflammation in asthma, the major intracellular antioxidants [copper and zinc-containing superoxide dismutase (Cu,Zn-SOD) and manganese-containing SOD (Mn-SOD), catalase, and glutathione peroxidase] were quantitated in bronchial epithelial cells of healthy control and asthmatic individuals. Although catalase and glutathione peroxidase in bronchial epithelium of asthmatics were similar to control SOD activity in asthmatics not on inhaled corticosteroid (-CS) was lower than asthmatics on inhaled corticosteroid (+CS) and controls. Investigation of Mn-SOD and Cu,Zn-SOD activities revealed that the lower SOD activity in asthmatics -CS was because of decreased Cu,Zn-SOD activity. However, Mn-SOD and Cu,Zn-SOD mRNA and protein levels were similar among asthmatics -CS, asthmatics +CS, and controls. Importantly, Cu,Zn-SOD specific activity in asthmatics -CS was decreased in comparison with control and asthmatics +CS. Furthermore, in paired comparisons of asthmatics -CS and +CS, inhaled corticosteroids resulted in normalization of bronchial epithelial Cu,Zn-SOD specific activity. These findings suggest loss of Cu,Zn-SOD activity in asthma is related to inflammation, perhaps through oxidant inactivation of Cu,Zn-SOD protein.
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Kniajeskaia, N. P., E. Kh Anaev, A. A. Kameleva, E. V. Safoshkina, and N. D. Kirichenko. "Targeted therapy in bronchial asthma. Benralizumab: focus on patients using systemic glucocorticosteroids." Meditsinskiy sovet = Medical Council, no. 17 (November 22, 2020): 9–16. http://dx.doi.org/10.21518/2079-701x-2020-17-9-16.
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A severe course of bronchial asthma develops in 5–20% of patients with bronchial asthma. The use of key disease-modifying agents for the treatment of severe bronchial asthma (SBA) is not always effective due to the possible uncontrolled course of the disease and persistence of signs of eosinophilic airway inflammation. Therefore, the isolation of phenotypes/ endotypes is important for an individual approach to the treatment of such patients. This method permits to get better control over the disease and reduces the risks of exacerbations, airway remodelling and unwanted adverse reactions to the therapy particularly with systemic glucocorticosteroids. The use of biological therapy among other drugs can greatly contribute to the achievement of good control over management of patients with uncontrolled severe asthma. There are currently 5 registered immunobiological drugs in Russia that belong to the group of SBA phenotype-based treatment modalities: anti-IgE therapy, anti-IL-4/13 therapy, anti-IL-5 therapy and anti-IL5Rα therapy. Depending on the disease history, clinical features of bronchial asthma course, the presence of hypersensitivity to one of the year-round allergens and the levels of laboratory markers, the medical professional establishes the exact diagnosis indicating a disease phenotype (allergic BA, eosinophilic or non-allergic BA) and addresses an issue of an appropriate drug for a patient with BA. Benralizumab (Fazenra), a humanized monoclonal antibody, generates considerable interest. Benralizumab has a slightly different principle of action: it blocks not interleukin-5 itself, but the alpha subunit of the interleukin-5 receptor (IL-5Rα), triggers active apoptosis of eosinophils, reducing their level in sputum and blood. The results of clinical studies showed the efficacy of the drug, which resulted in the significant reduction of bronchial asthma exacerbations and a dose of systemic glucocorticosteroids.
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Boulet, Louis-Philippe, Gail M. Gauvreau, Donald W. Cockcroft, Beth Davis, Luc Vachon, Yvon Cormier, and Paul M. O’Byrne. "Effects of Asm-024, A Modulator of Acetylcholine Receptor Function, On Airway Responsiveness and Allergen-Induced Responses in Patients with Mild Asthma." Canadian Respiratory Journal 22, no. 4 (2015): 230–34. http://dx.doi.org/10.1155/2015/832865.
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OBJECTIVES: To evaluate the safety, tolerability and clinical activity of ASM-024, a new cholinergic compound with dual nicotinic and muscarinic activity, in mild allergic asthma.METHODS: The present study involved 24 stable, mild allergic asthmatic subjects. In a cross-over design, ASM-024 (50 mg or 200 mg) or placebo were administered once daily by nebulization over three periods of nine consecutive days separated by a three-week washout. The effect of each treatment on the forced expiratory volume in 1 s (FEV1), provocative concentration of methacholine causing a 20% decline in FEV1 (PC20), early and late asthmatic responses, and allergen-induced inflammation were measured.RESULTS: Seventeen subjects completed the study. During treatment with ASM-024 at 50 mg or 200 mg, the PC20 value increased respectively from a mean (± SD) 2.56±3.86 mg/mL to 4.11 mg/mL (P=0.007), and from 3.12±4.37 mg/mL to 5.23 mg/mL (P=0.005) (no change with placebo). On day 7 (day preceding allergen challenge), postdosing FEV1 increased by 2.0% with 50 mg (P=0.005) and 1.9% with 200 mg (P=0.008) (placebo −1.1%). ASM-24 had no inhibitory effect on early and late asthmatic responses, nor on sputum eosinophil or neutrophil levels. ASM-024 induced no serious adverse events, but caused cough in 22% and 48% of the subjects with 50 mg and 200 mg, respectively, compared with 10% who were on placebo.CONCLUSIONS: ASM-024 did not inhibit allergen-induced asthmatic response and related airway inflammation, but reduced methacholine airway responsiveness and slightly improved lung function. The mechanism by which ASM-024 improves these outcomes requires further study.
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Vezir, Emine, Ersoy Civelek, Emine Dibek Misirlioglu, Muge Toyran, Murat Capanoglu, Esra Karakus, Tamer Kahraman, et al. "Effects of Obesity on Airway and Systemic Inflammation in Asthmatic Children." International Archives of Allergy and Immunology, March 22, 2021, 1–11. http://dx.doi.org/10.1159/000513809.
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Background: Obese asthma is a complex syndrome with certain phenotypes that differ in children and adults. There is no clear evidence regarding the presence of additive or synergistic pathological interaction between obesity and asthma in children. Objectives: Our aim was to demonstrate the interaction of obesity and asthma in children in terms of airway and systemic inflammation by a controlled observational study. Methods: Four groups were formed: asthma obese (AO), asthma nonobese (ANO), non-AO (NAO), nonasthma nonobese (NANO). Spirometry test, fractional exhaled nitric oxide (FeNO) test, skin prick test, serum inflammatory biomarkers (C-reactive protein, C3, C4, adiponectin, leptin, resistin, periostin, YKL-40, Type 1, and Type 2 cytokines) were conducted and evaluated in all participants. Sputum inflammatory cells (sputum eosinophils and neutrophils) were evaluated in patients who could produce induced sputum and obesity-asthma interactions were determined. Results: A total of 153 participants aged 6–18 years were included in the study, including the AO group (n = 46), the ANO group (n = 45), the NAO group (n = 30), and the NANO group (n = 32). IL-4 (p < 0.001), IL-5 (p < 0.001), IL-13 (p < 0.001), resistin (p < 0.001), and YKL-40 (p < 0.001) levels were higher in patients with asthma independent of obesity. The lowest adiponectin level was found in the AO group and obesity-asthma interaction was detected (p < 0.001). Sputum eosinophilia (p < 0.01), sputum neutrophilia (p < 0.01), and FeNO levels (p = 0.07) were higher in asthmatic patients independent of obesity. In the group with paucigranulocytic inflammation, resistin and YKL-40 levels were significantly lower than in the group without paucigranulocytic inflammation (p < 0.01). Conclusion: No interaction was found between obesity and asthma in terms of airway inflammation. Interaction between obesity and asthma was shown in terms of adiponectin level and resistin/adiponectin and leptin/adiponectin ratios. It was found that serum YKL-40 and resistin levels could be associated with airway inflammation.
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Du, Lijuan, Changyi Xu, Zhimin Zeng, Fengjia Chen, Kun Tang, Yuxia Liang, and Yubiao Guo. "Exploration of induced sputum BIRC3 levels and clinical implications in asthma." BMC Pulmonary Medicine 22, no. 1 (March 14, 2022). http://dx.doi.org/10.1186/s12890-022-01887-2.
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Abstract Background Baculoviral IAP repeat-containing 3 (BIRC3) which encodes a member of the IAP family of proteins upregulated in the asthma expression profile dataset. However, there was few research on studying the clinical implication of BIRC3 in asthma. Objective To validate BIRC3 expression and its clinical implications in induced sputum of asthma. Methods Based on the GSE76262 (118 asthma cases and 21 healthy controls) dataset, differentially expressed genes were screened using R software. Subsequently, BIRC3 mRNA and protein were clinically verified in induced sputum samples through quantitative real‐time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). Besides, the correlations between BIRC3 expression and asthmatic eosinophilic/allergic inflammation indicators (FeNO, IgE, and EOS%), pulmonary function (FEV1, FEV1% pred, FVC% pred, and FEV1/FVC), and inflammatory cytokines (IL-4, IL-5, IL-13, IL-25, IL-10, IL-33, and TSLP) were analyzed. Finally, BIRC3 mRNA was detected in human primary bronchial epithelial cells stimulated by cytokines (IL-4 or IL-13). Results BIRC3 was screened as a candidate gene in the GSE76262, which was highly expressed in asthma. Highly expressed BIRC3 was positively correlated with eosinophilic and allergic indicators, including FeNO, blood eosinophil, and serum IgE. Moreover, BIRC3 protein was positively associated with inflammation cytokines, like IL-4, IL-5, IL-13, IL-25, IL-10, IL-33, and TSLP, while negatively correlated with FEV1, FEV1%pred, FVC% pred, and FEV1/FVC. Furthermore, the expression of BIRC3 could be induced in primary bronchial epithelial cells treated by cytokines IL-4 or IL-13. Conclusions BIRC3 significantly increased in induced sputum of asthma and positively correlated with airway eosinophilic and peripheral blood allergic inflammation, type 2 cytokines, and airway obstruction. Increased BIRC3 might be involved in the pathogenesis of asthma by affecting the eosinophilic and allergic inflammation.
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Bora, Mine, Aylin Ozgen Alpaydin, Arzu Yorgancioglu, Gizem Akkas, Aydın Isisag, Aysın Sakar Coskun, and Pınar Celik. "Does asthma control as assessed by the asthma control test reflect airway inflammation?" Multidisciplinary Respiratory Medicine 6 (December 11, 2019). http://dx.doi.org/10.4081/mrm.2011.453.
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Background and aims: The treatment of asthmatic patients is particularly focused on the control of symptoms as well as functional and inflammatory parameters. In our study, we investigated the relationship between the asthma control test (ACT) which evaluates symptoms and airway inflammation and functional parameters.
Materials and methods: Stable asthmatic patients admitted to our pulmonary outpatient clinic were enrolled in the study consecutively and underwent the ACT, pulmonary function tests and methacholine bronchial provocation test (MBPT). Additionally, fractional exhaled nitric oxide level (FeNO) and induced sputum cell distribution were assessed. All these parameters were re-evaluated at the third month after adjusting medications of the patients according to baseline ACT scores.
Results: Of the 101 patients screened, we analyzed 83 who proceeded to the follow up visit. At the baseline visit, 8 were totally controlled, 36 partially controlled and 39 uncontrolled according to ACT. At the follow up visit, 10 were totally controlled, 39 partially controlled and 34 uncontrolled. Comparison of the two visits in terms of all parameters revealed significant reductions only in the percentages of patients with MBPT positivity (p = 0.029) and FeNO levels > 20 ppb (p = 0.025) at follow up. The percentages of patients with FeNO > 20 ppb, MBPT positivity, induced sputum eosinophilia or induced sputum neutrophilia did not show significant differences between totally controlled, partially controlled and uncontrolled groups at both baseline and follow up visits.
Conclusion: Although the ACT scores did not show significant correlations with the airway inflammation parameters tested in this study, a marked reduction in the percentage of patients with MBPT positivity and FeNO > 20 ppb at follow up may suggest the importance of the control concept in the management of asthma.
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Qaiser, Shanawer. "Frequency of Raised Total Serum Ig E, Sputum Eosinophilia and Blood Eosinophil Count in Patients with Severe Persistent Asthma." Proceedings of Shaikh Zayed Medical Complex Lahore 35, no. 1 (January 15, 2021). http://dx.doi.org/10.47489/p000s351z7791-4mc.
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Introduction: Asthma is a chronic inflammatory airway disorder that has several inflammatory phenotypes. Serum immunoglobulin E (IgE) and eosinophils are airway inflammation markers in asthmatic patients. In this research, we assessed the asthma severity with various inflammatory markers. Aims & Objectives: To find the frequency of raised total serum immunoglobulin E, sputum eosinophilia, and absolute blood eosinophil count in patients with severe persistent asthma. Place and duration of study: This study was conducted in Department of Pulmonology, Shaikh Zayed FPGMI, Lahore from 1st October 2018 to 1st April 2019. Material & Methods: A Cross-sectional study in which total of 125 patients were enrolled after fulfilling the inclusion criteria. Blood samples were taken with aseptic measures for total serum immunoglobulin E and absolute blood eosinophils count. Sputum was collected in the sterile jar and dispensed properly to the histopathology lab. Results: Of 125 patients, 44.8% were males, and 55.2% were females. The mean patient's age was 49.37 years, and the mean duration of symptoms was 25.49 years. Raised serum immunoglobulin E levels were seen in 74.4% patients, sputum eosinophilia was seen in 25.6% patients, and increased peripheral eosinophil count was seen in 55.2%. Age was significantly associated with sputum eosinophilia; however, no such association was seen between the other effect modifiers and inflammatory markers. Conclusion: Inflammatory markers immunoglobulin E, sputum and blood eosinophil levels were significantly raised in asthma patients. These can be used in the detection of asthma as their detection is easy, simple, and non-invasive, and they are directly linked to the inflammation.
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Refaat, M. M., E. E. Ahmed, H. M. Elsayed, and A. H. Elbanna. "Sputum periostin in patients with different asthma phenotypes." QJM: An International Journal of Medicine 113, Supplement_1 (March 1, 2020). http://dx.doi.org/10.1093/qjmed/hcaa052.045.
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Abstract Background Asthma is a common respiratory condition causing symptoms such as cough, chest tightness and wheezing that are triggered by factors as exercise, allergens and viral infection. Asthma is characterized by airflow limitation, airway hyper-responsiveness and bronchial inflammation. Aim of the work to identify the different phenotypes in a group of asthmatic patients; and to evaluate the role of periostin in bronchial asthma and its different cellular phenotypes and its correlation asthma severity. Subjects and Methods This observational cross-sectional study was conducted on 96 adult asthmatic patients. They were classified into two groups: group (A) 48 patients with severe asthma (persistent airflow limitation), group (B) 48 patients with mild to moderate asthma according to (GINA 2016) criteria attending the Allergy and Clinical Immunology outpatient clinic, Ain Shams University Hospitals. The study also included 10 healthy controls of matched age and sex group. Results sputum periostin levels in asthmatic patients are higher than its levels in healthy controls. Sputum eosinophil percentage in asthmatic patients is higher than those in healthy controls. Sputum periostin levels in patients with severe asthma were found to be higher than sputum periostin levels in patients with mild to moderate asthma. There is high positive correlation between sputum periostin and asthma severity and age and there is negative but significant correlation between sputum periostin and (FEV1) and it is found to be correlated with duration of asthma and pattern of (PFT) abnormality (higher in mixed pattern) and sputum eosinophilia. Conclusion Sputum periostin is correlated with asthma severity and eosinophilic asthma. Periostin is considered to be an important biomarker for severe asthma and eosinophilic phenotype of asthma.
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Huang, Xiaolin, Xiaoyu Tan, Yue Liang, Changchun Hou, Dongming Qu, Mengze Li, and Qinghua Huang. "Differential DAMP release was observed in the sputum of COPD, asthma and asthma-COPD overlap (ACO) patients." Scientific Reports 9, no. 1 (December 2019). http://dx.doi.org/10.1038/s41598-019-55502-2.
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AbstractAsthma-COPD overlap (ACO) has been under intensive focus; however, the levels of damage-associated molecular patterns (DAMPs) that can activate the innate and adaptive immune responses of ACO are unknown. The present study aimed to examine the levels of some DAMPs in asthma, COPD, and ACO and to identify the associations between clinical characteristics and DAMPs in ACO. Sputum from subjects with asthma (n = 87) or COPD (n = 73) and ACO (n = 68) or from smokers (n = 62) and never-smokers (n = 62) was analyzed for high mobility group protein B1 (HMGB1), heat shock protein 70 (HSP70), LL-37, S100A8, and galectin-3 (Gal-3). The concentration of HMGB1, HSP70, LL-37, and S100A8 proteins in sputum from ACO patients was significantly elevated, whereas that of Gal-3 was reduced, compared to that of smokers and never-smokers. The levels of HMGB1 and Gal-3 proteins in ACO patients were elevated compared to those in asthma patients. The sputum from ACO patients showed an increase in the levels of LL-37 and S100A8 proteins compared to that of asthma patients, whereas the levels decreased compared to those of COPD patients. The concentrations of HMGB1, HSP70, LL-37, and S100A8 proteins in the sputum of 352 participants were negatively correlated, whereas the levels of Gal-3 were positively correlated, with FEV1, FEV1%pred, and FEV1/FVC. Sputum HMGB1 had a high AUC of the ROC curve while distinguishing ACO patients from asthma patients. Meanwhile, sputum LL-37 had a high AUC of the ROC curve in differentiating asthma and COPD. The release of sputum DAMPs in ACO may be involved in chronic airway inflammation in ACO; the sputum HMGB1 level might serve as a valuable biomarker for distinguishing ACO from asthma, and the sputum LL-37 level might be a biomarker for differentiating asthma and COPD.
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Refaat, Maged Mohammed, Dina Sayed Sheha, Riham Hazem Raaft, Maged Mohamed Refaat, Heba Eid Farhat Abo Alia, Marwa mohammed EL-Begermy, Marwa Abd ElRasoul El-Ashry, and Dina Sayed Sheha. "Identifying the Clinical Pattern of Eosinophilic and Non-Eosinophilic Asthma subtype in adult patients with Bronchial Asthma." QJM: An International Journal of Medicine 114, Supplement_1 (October 1, 2021). http://dx.doi.org/10.1093/qjmed/hcab100.063.
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Abstract Background Context:- Asthma is a heterogenous disease with various phenotypes, it is the most common chronic disease characterized by airway limitation due to bronchospasm and airway inflammation associated with excessive mucus secretion from agitated mucus gland that occur due to air way hyper responiveness. Purpose of the study Comparison between eosinophilic and non-eosinophilic asthma patients. Patients and Methods 100 bronchial asthma patients of age ≥ 18 years old divided into2 groups according to blood eosinophilia. All patients were subjected to: history. Total Asthma Control Test. Spirometry. Sputum eosinophil count. IgE levels 6-Skin prick testing (SPT). Nasal endoscopy. Results the mean age of all patients was (35.4 ± 12.8) years, majority (61%) of patients were males,; the mean ACT score was (18.7 ± 2); 39% of cases have obstructive pattern by spirometry, 39% of cases had abnormal nasal endoscopy, SPT had significant relation with asthma, there is significant correlation between total IGE,sputum eosinophilia with eosinophilic asthma. Conclusion Blood eosinophils had the highest accuracy in the identification of sputum eosinophilia in asthma. Total IgE values and sutum eosinophilia were markedly increased in patients with eosinophilic asthma more than patients with non-eosinophilic asthma.
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Shi, Bingqing, Yuqiu Hao, Wei Li, Hongna Dong, Mengting Xu, and Peng Gao. "TIPE2 May Target the Nrf2/HO-1 Pathway to Inhibit M1 Macrophage–Related Neutrophilic Inflammation in Asthma." Frontiers in Immunology 13 (April 28, 2022). http://dx.doi.org/10.3389/fimmu.2022.883885.
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PurposeAlthough recent studies have highlighted the link of TIPE2 and asthma airway inflammation, its roles and molecular mechanisms in different asthma inflammatory phenotypes remain largely unknown. We evaluated sputum TIPE2 expression level and its correlation with different asthma phenotypes. Additionally, we explored the roles and mechanism of TIPE2 in M1 polarization of macrophages.MethodsA total of 102 asthma patients who underwent sputum induction were enrolled to evaluate the expression level of TIPE2 and its association with different asthma phenotypes. To explore the roles and mechanism of TIPE2 in M1 polarization of macrophages, THP-1 monocytes stimulated with phorbol-12-myristate-13-acetate, were used as a model of undifferentiated (M0) macrophages, and M0 macrophages were treated with lipopolysaccharide to induce M1 macrophages.ResultsThe sputum TIPE2 level was significantly lower in patients with neutrophilic asthma (NA) and higher in patients with eosinophilic asthma (EA) compared with patients with paucigranulocytic asthma. The levels of IL-1β, TNF-α and IL-6 were highest in NA compared with other groups. TIPE2 levels in sputum negatively correlated with IL-1β and TNF-α levels but positively correlated with IL-4, IL-5, IL-13, and IL-10 levels (P < 0.05). In vitro, TIPE2 enhanced Nrf2/HO-1 pathway activation in macrophages and inhibited LPS-induced M1 macrophage differentiation and related cytokine release. Further analysis showed that the Nrf2 inhibitor ML385 weakened TIPE2-induced activation of the Nrf2/HO-1 pathway, as well as TIPE2-induced suppression in M1 polarization of macrophage and inflammatory cytokines secretion.ConclusionsTIPE2 expression level was highly down-regulated in NA and was negatively correlated with inflammatory factors (IL-1β and TNF-α). Aberrant expression of TIPE2 may target the Nrf2/HO-1 pathway to inhibit M1 macrophage–related neutrophilic inflammation in asthma.
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Burgess, Janette K., Marnix R. Jonker, Marijn Berg, Nick T. H. ten Hacken, Kerstin B. Meyer, Maarten van den Berge, Martijn C. Nawijn, and Irene H. Heijink. "Periostin: contributor to abnormal airway epithelial function in asthma?" European Respiratory Journal, September 9, 2020, 2001286. http://dx.doi.org/10.1183/13993003.01286-2020.
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Periostin may serve as a biomarker for type-2-mediated eosinophilic airway inflammation in asthma. We hypothesised that type-2 cytokine IL-13 induces airway epithelial expression of periostin, which in turn contributes to epithelial changes observed in asthma.We studied the effect of IL-13 on periostin expression in BEAS-2B and air-liquid interface (ALI)-differentiated primary bronchial epithelial cells (PBECs). Additionally, effects of recombinant human periostin on epithelial-to-mesenchymal transition (EMT) markers and mucin genes were assessed. In bronchial biopsies and induced sputum from asthma patients and healthy controls, we analysed periostin single cell gene expression and protein levels.IL-13 increased POSTN expression in both cell types, which was accompanied by EMT-related features in BEAS-2B. In ALI-differentiated PBECs, IL-13 increased periostin basolateral and apical release. Apical administration of periostin increased the expression of MMP9, MUC5B and MUC5AC. In bronchial biopsies, POSTN expression was mainly confined to basal epithelial cells, ionocytes, endothelial cells and fibroblasts, showing higher expression in basal epithelial cells from asthma patients versus controls. Higher protein levels of periostin, expressed in epithelial and subepithelial layers, was confirmed in bronchial biopsies from asthma patients compared to healthy controls. Although sputum periostin levels were not higher in asthma, levels correlated with eosinophil numbers and coughing up mucus.Periostin expression is increased by IL-13 in bronchial epithelial cells and higher in bronchial biopsies from asthma patients. This may have important consequences, as administration of periostin increased epithelial expression of mucin genes, supporting the relationship of periostin with type-2 mediated asthma and mucus secretion.
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Du, Lijuan, Changyi Xu, Jia Shi, Lu Tang, Lisha Xiao, Chengcheng Lei, Huicong Liu, Yuxia Liang, Yubiao Guo, and Kun Tang. "Elevated CXCL14 in Induced Sputum Was Associated with Eosinophilic Inflammation and Airway Obstruction in Patients with Asthma." International Archives of Allergy and Immunology, September 5, 2022, 1–10. http://dx.doi.org/10.1159/000526367.
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<b><i>Introduction:</i></b> CXCL14 involved in inflammatory processes was upregulated in the asthma expression profile datasets in our pilot study. However, the expression of CXCL14 in induced sputum and its potential clinical role in asthma were poorly reported. <b><i>Objective:</i></b> We sought to detect CXCL14 expression in airway epithelium and induced sputum cells of asthma and explore its potential clinical implications. <b><i>Methods:</i></b> The expression of CXCL14 in asthma was analyzed using R software based on multiple microarray datasets, including GSE43696, GSE63142, GSE67940, and GSE76262. Subsequent verification of the CXCL14 expression pattern in induced sputum and bronchial epithelium cells was performed by qRT-PCR and ELISA. Besides, the correlations between CXCL14 and eosinophilic inflammation indicators (FeNO, EOS#, and IgE), Th2 signature genes (SERPINB2, POSTN, and CLCA1), inflammatory cytokines (IL-4, IL-5, IL-10, IL-13, IL-25, IL-33, TSLP, IL-8, IL-17A, IFN-γ, and IL-2), and airway obstruction indicators (pulmonary function and mucin secretion) were further explored. <b><i>Results:</i></b> The expression of CXCL14 in epithelium and sputum cells was upregulated in asthma and positively correlated with clinical eosinophilic indicators. The protein levels of CXCL14 were positively associated with Th2 signature genes (SERPINB2, POSTN, and CLCA1) and Th2 cytokines (IL-4, IL-5, IL-10, IL-13, IL-25, IL-33, and TSLP). Increased expression of CXCL14 was also observed in BEAS-2B cells stimulated by the cytokine IL-4. Furthermore, the expression of CXCL14 was positively correlated with MUC5AC secretion and negatively associated with pulmonary function. <b><i>Conclusions:</i></b> Upregulated CXCL14 in asthma was positively correlated with inflammatory indicators and negatively correlated with pulmonary function, which indicated that upregulated CXCL14 might act as a pathogenic gene through involvement in Th2 inflammation in asthma.
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Loewenthal, Lola, and Andrew Menzies-Gow. "FeNO in Asthma." Seminars in Respiratory and Critical Care Medicine, March 4, 2022. http://dx.doi.org/10.1055/s-0042-1743290.
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AbstractAsthma is a common disease affecting 350 million people worldwide, which is characterized by airways inflammation and hyperreactivity. Historically diagnosis and treatment have been mainly based on symptoms, which have the potential to result in misdiagnosis and inappropriate treatment. Nitric oxide (NO) is exhaled in human breath and is a marker of airways inflammation. Levels of NO are increased in the exhaled breath of patients with type 2 asthma and fractional exhaled nitric oxide (FeNO) provides an objective biomarker of airway inflammation. FeNO testing is an accessible, noninvasive, and easy-to-use test. Cut-off values have been established by the American Thoracic Society (ATS), the Global Initiative for Asthma (GINA), and the National Institute for Health and Care Excellence (NICE) but vary between guidance. FeNO levels have been shown to be predictive of blood and sputum eosinophil levels but should not be used in isolation and current guidance emphasizes the importance of incorporating clinical symptoms and testing when utilizing FeNO results. The inclusion of FeNO testing can increase diagnostic accuracy of asthma, while high levels in asthmatic patients can help predict response to inhaled corticosteroids (ICS) and suppression of levels with ICS to monitor adherence. FeNO levels are also a predictor of asthma risk with increased exacerbation rates and accelerated decline in lung function associated with high levels as well as having an emerging role in predicting response to some biologic therapies in severe asthma. FeNO testing is cost-effective and has been shown, when combined with clinical assessment, to improve asthma management.
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Godwin, Matthew S., MaryJane Jones, Jonathan P. Blackburn, Zhihong Yu, Sadis Matalon, Annette T. Hastie, Deborah A. Meyers, and Chad Steele. "The chemokine CX3CL1/fractalkine regulates immunopathogenesis during fungal-associated allergic airway inflammation." American Journal of Physiology-Lung Cellular and Molecular Physiology, December 16, 2020. http://dx.doi.org/10.1152/ajplung.00376.2020.
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Individuals that present with difficult-to-control asthma and sensitivity to one or more fungal species are categorized as a subset of severe asthma patients belonging to a group herein referred to as severe asthma with fungal sensitization (SAFS). We have previously reported the identification of numerous cytokines and chemokines that were elevated in human asthmatics that were sensitized to fungi vs. non-fungal sensitized asthmatics. Here, we show that the unique chemokine CX3CL1 (fractalkine) is elevated in both bronchoalveolar lavage fluid and sputum from human asthmatics sensitized to fungi, implicating an association with CX3CL1 in fungal asthma severity. In an experimental model of fungal-associated allergic airway inflammation, we demonstrate that the absence of CX3CR1 signaling unexpectedly resulted in a profound impairment in lung function. Histological assessment of lung tissue revealed an unrestricted inflammatory response that was subsequently characterized by enhanced levels of neutrophils, eosinophils and inflammatory monocytes. Neutrophilic inflammation correlated with elevated IL-17A, proinflammatory cytokines (TNF-α, IL-1α IL-1β), neutrophil survival factors (G-CSF) and neutrophil-targeting chemokines (CCL3, CCL4). Eosinophilia correlated with elevated type 2 responses (IL-5, IL-13) whereas inflammatory monocyte levels correlated with elevated type 1 responses (IFN-γ, CXCL9) and survival factors (M-CSF). Despite enhanced inflammatory responses, the immunoregulatory cytokine IL-10 and the natural inhibitor of IL-1 signaling, IL-1RA, were significantly elevated rather than impaired. Regulatory T cell levels were unchanged, as were levels of the anti-inflammatory cytokines IL-35 and IL-38. Taken together, the CX3CL1/CX3CR1 axis preserves lung function during fungal-associated allergic airway inflammation through a non-classical immunoregulatory mechanism.
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Allam, Venkata Sita Rama Raju, Stelios Pavlidis, Gang Liu, Nazanin Zounemat Kermani, Jennifer Simpson, Joyce To, Sheila Donnelly, et al. "Macrophage migration inhibitory factor promotes glucocorticoid resistance of neutrophilic inflammation in a murine model of severe asthma." Thorax, November 7, 2022, thoraxjnl—2021–218555. http://dx.doi.org/10.1136/thorax-2021-218555.
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BackgroundSevere neutrophilic asthma is resistant to treatment with glucocorticoids. The immunomodulatory protein macrophage migration inhibitory factor (MIF) promotes neutrophil recruitment to the lung and antagonises responses to glucocorticoids. We hypothesised that MIF promotes glucocorticoid resistance of neutrophilic inflammation in severe asthma.MethodsWe examined whether sputum MIF protein correlated with clinical and molecular characteristics of severe neutrophilic asthma in the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) cohort. We also investigated whether MIF regulates neutrophilic inflammation and glucocorticoid responsiveness in a murine model of severe asthma in vivo.ResultsMIF protein levels positively correlated with the number of exacerbations in the previous year, sputum neutrophils and oral corticosteroid use across all U-BIOPRED subjects. Further analysis of MIF protein expression according to U-BIOPRED-defined transcriptomic-associated clusters (TACs) revealed increased MIF protein and a corresponding decrease in annexin-A1 protein in TAC2, which is most closely associated with airway neutrophilia and NLRP3 inflammasome activation. In a murine model of severe asthma, treatment with the MIF antagonist ISO-1 significantly inhibited neutrophilic inflammation and increased glucocorticoid responsiveness. Coimmunoprecipitation studies using lung tissue lysates demonstrated that MIF directly interacts with and cleaves annexin-A1, potentially reducing its biological activity.ConclusionOur data suggest that MIF promotes glucocorticoid-resistance of neutrophilic inflammation by reducing the biological activity of annexin-A1, a potent glucocorticoid-regulated protein that inhibits neutrophil accumulation at sites of inflammation. This represents a previously unrecognised role for MIF in the regulation of inflammation and points to MIF as a potential therapeutic target for the management of severe neutrophilic asthma.
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Huang, Kai, Fangyuan Li, Xuechen Wang, Bing Yan, Ming Wang, Shuling Li, Wenling Yu, et al. "Clinical and cytokine patterns of uncontrolled asthma with and without comorbid chronic rhinosinusitis: a cross-sectional study." Respiratory Research 23, no. 1 (May 11, 2022). http://dx.doi.org/10.1186/s12931-022-02028-3.
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Abstract Background Asthma is significantly related to chronic rhinosinusitis (CRS) both in prevalence and severity. However, the clinical patterns of uncontrolled asthma with and without comorbid CRS are still unclear. This study aimed to explore the clinical characteristics and cytokine patterns of patients with uncontrolled asthma, with and without comorbid CRS. Methods 22 parameters associated with demographic characteristics, CRS comorbidity, severity of airflow obstruction and airway inflammation, and inflammation type of asthma were collected and assessed in 143 patients with uncontrolled asthma. Different clusters were explored using two-step cluster analysis. Sputum samples were collected for assessment of Th1/Th2/Th17 and epithelium-derived cytokines. Results Comorbid CRS was identified as the most important variable for prediction of different clusters, followed by pulmonary function parameters and blood eosinophil level. Three clusters of patients were determined: Cluster 1 (n = 46) characterized by non-atopic patients with non-eosinophilic asthma without CRS, demonstrating moderate airflow limitation; Cluster 2 (n = 54) characterized by asthma patients with mild airflow limitation and CRS, demonstrating higher levels of blood eosinophils and immunoglobulin E (IgE) than cluster 1; Cluster 3 (n = 43) characterized by eosinophilic asthma patients with severe airflow limitation and CRS (46.5% with nasal polyps), demonstrating worst lung function, lowest partial pressure of oxygen (PaO2), and highest levels of eosinophils, fraction of exhaled nitric oxide (FeNO) and IgE. Sputum samples from Cluster 3 showed significantly higher levels of Interleukin (IL)-5, IL-13, IL-33, and tumor necrosis factor (TNF)-α than the other two clusters; and remarkably elevated IL-4, IL-17 and interferon (IFN)-γ compared with cluster 2. The levels of IL-10 and IL-25 were not significantly different among the three clusters. Conclusions Uncontrolled asthma may be endotyped into three clusters characterized by CRS comorbidity and inflammatory cytokine patterns. Furthermore, a united-airways approach may be especially necessary for management of asthma patients with Type 2 features.
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Zong, Weifeng, Yuqing Mo, and Yuxia Liang. "Correlation between Increased Monocyte Chemotactic Protein 1 Level and Lung Function in Patients with Asthma." International Archives of Allergy and Immunology, February 23, 2022, 1–9. http://dx.doi.org/10.1159/000521946.
Full textAbstract:
<b><i>Background:</i></b> The altered expression of monocyte chemotactic protein 1 (MCP1) in bronchoalveolar fluid was observed in patients and animal models of allergic asthma. However, the correlation between induced sputum MCP1 level and asthma clinical features remains poorly understood. <b><i>Objective:</i></b> This study aims to explore the relationship of MCP1 protein expression in induced sputum with Th2 inflammation and asthma clinical features. <b><i>Methods:</i></b> MCP1 protein expression in induced sputum and serum was detected by ELISA in patients with asthma, and its correlation with Th2 inflammation and lung function was analyzed. The effect of inhaled corticosteroids (ICSs) on MCP1 expression was also evaluated. <b><i>Results:</i></b> The MCP1 level in induced sputum (<i>p</i> = 0.0006) and serum (<i>p</i> = 0.0035) was markedly increased and negatively correlated with forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC)% (<i>r</i> = −0.3674, <i>p</i> = 0.0001) and PC-20 (<i>r</i> = −0.5746, <i>p</i> < 0.0001) in patients with asthma. The area under the curve (AUC) of MCP1 level receiver operating characteristic curve in induced sputum and serum was 0.7134 (<i>p</i> = 0.0007) and 0.7589 (<i>p</i> = 0.0042), respectively. The patients with asthma were grouped into four according to their induced sputum MCP1 level and Th2 signature categories (Th2<sup>Hi</sup> MCP1<sup>Hi</sup>, Th2<sup>Hi</sup> MCP1<sup>Low</sup>, Th2<sup>Low</sup> MCP1<sup>Hi</sup>, and Th2<sup>Low</sup> MCP1<sup>Low</sup>). The Th2<sup>Low</sup> MCP1<sup>Hi</sup> subgroup had the lowest FEV1/FVC% and histamine concentration required to cause a 20% decline in FEV1. After 4 weeks of ICS treatment, the MCP1 levels in induced sputum and serum were significantly reduced. <b><i>Conclusions:</i></b> The MCP1 level in induced sputum and serum increased in patients with asthma but decreased after ICS treatment. The Th2<sup>Low</sup> MCP1<sup>Hi</sup> subgroup had the worst lung function and highest airway hyperresponsiveness. The combination of MCP1 level in induced sputum and Th2 inflammation defines a new phenotype that can be used to predict lung function and treatment response in patients with asthma.