scholarly journals IL13 May Play an Important Role in Developing Eosinophilic Chronic Rhinosinusitis and Eosinophilic Otitis Media with Severe Asthma

2021 ◽  
Vol 22 (20) ◽  
pp. 11209
Author(s):  
Hideyasu Shimizu ◽  
Masamichi Hayashi ◽  
Hisayuki Kato ◽  
Mitsuru Nakagawa ◽  
Kazuyoshi Imaizumi ◽  
...  
Keyword(s):  
Chronic Rhinosinusitis ◽  
Otitis Media ◽  
Good Control ◽  
Inflammatory Cells ◽  
Lung Parenchyma ◽  
Lavage Fluid ◽  
Chronic Eosinophilic Pneumonia ◽  
Patient Reported ◽  
Eosinophilic Chronic Rhinosinusitis

A woman in her 50s was a super responder to benralizumab administered for the treatment of severe bronchial asthma (BA) with eosinophilic chronic rhinosinusitis with nasal polyp (ECRS) and eosinophilic otitis media (EOM). She exhibited the gradual exacerbation of ECRS/EOM despite good control of BA approximately 1 year after benralizumab initiation. Therefore, the treatment was switched to dupilumab, and the condition of the paranasal sinuses and middle ear greatly improved with the best control of her asthma. The patient reported that her physical condition was the best of her life. However, she developed a pulmonary opacity on chest computed tomography after 6 months. Histological examination of the lung parenchyma and cell differentiation of the bronchoalveolar lavage fluid indicated atypical chronic eosinophilic pneumonia, and treatment was switched to mepolizumab. Similarly to the period of benralizumab treatment, exacerbation of ECRS/EOM reduced her quality of life approximately 10 months after the administration of mepolizumab. Dupilumab was again introduced as a replacement for mepolizumab. The clinical course and consideration of the interaction between inflammatory cells led us to speculate that interleukin-13 could play a key role in the development of ECRS/EOM with severe BA.

Clinical Traits Characterizing an Exacerbation-Prone Phenotype in Chronic Rhinosinusitis

2019 ◽  
Vol 161 (5) ◽  
pp. 890-896 ◽  
Author(s):  
Katie M. Phillips ◽  
Eric Barbarite ◽  
Lloyd P. Hoehle ◽  
David S. Caradonna ◽  
Stacey T. Gray ◽  
...  
Keyword(s):  
Chronic Rhinosinusitis ◽  
Disease Burden ◽  
Tertiary Care ◽  
Symptom Burden ◽  
Cross Sectional ◽  
Patient Reported ◽  
Oral Corticosteroids ◽  
Sinonasal Outcome Test ◽  
Snot 22

Objective Acute exacerbation of chronic rhinosinusitis (AECRS) is associated with significant quality-of-life decreases. We sought to determine characteristics associated with an exacerbation-prone phenotype in chronic rhinosinusitis (CRS). Study Design Cross-sectional. Setting Tertiary care rhinology clinic. Subjects Patients with CRS (N = 209). Methods Patient-reported number of sinus infections, CRS-related antibiotics, and CRS-related oral corticosteroids taken in the last 12 months were used as metrics for AECRS frequency. Sinonasal symptom burden was assessed with the 22-item Sinonasal Outcome Test (SNOT-22). Ninety patients reporting 0 for all AECRS metrics were considered to have had no AECRS in the prior 12 months. A total of 119 patients reported >3 on at least 1 AECRS metric and were considered as having an exacerbation-prone phenotype. Characteristics associated with patients with an exacerbation-prone phenotype were identified with exploratory regression analysis. Results An exacerbation-prone phenotype was positively associated with comorbid asthma (adjusted odds ratio [ORadj] = 3.68, 95% CI: 1.42-9.50, P = .007) and SNOT-22 (ORadj = 1.06, 95% CI: 1.04-1.09, P < .001). Polyps were negatively associated (ORadj = 0.27, 95% CI: 0.11-0.68, P = .005) with an exacerbation-prone phenotype. SNOT-22 score ≥24 identified patients with an exacerbation-prone phenotype with a sensitivity of 93.3% and a specificity of 57.8%. Having either a SNOT-22 score ≥24 with a nasal subdomain score ≥12 or a SNOT-22 score ≥24 with an ear/facial discomfort subdomain score ≥3 provided >80% sensitivity and specificity for detecting patients prone to exacerbation. Conclusions In total, these results point to a CRS exacerbation-prone phenotype characterized by high sinonasal disease burden with comorbid asthma but interestingly without polyps.

Efficacy of Endoscopic Posterior Nasal Neurectomy in Treating Eosinophilic Chronic Rhinosinusitis

ORL ◽  
2021 ◽  
pp. 1-5
Author(s):  
Manman Chen ◽  
Ming Xu ◽  
Xuefeng Lei ◽  
Bin Zhang
Keyword(s):  
Chronic Rhinosinusitis ◽  
Surgical Recurrence ◽  
Eosinophilic Chronic Rhinosinusitis ◽  
Group A ◽  
Sinonasal Outcome Test ◽  
Random Number Table ◽  
Group B

<b><i>Objectives:</i></b> Recent guidelines have revealed that eosinophilic chronic rhinosinusitis (ECRS) exhibits a strong tendency for recurrence after surgery and impairs quality of life. Neuropeptides play an important neuroimmunological role. The aim of this study was to determine the efficacy of posterior nasal neurectomy (PNN) for the treatment of ECRS by inhibiting type 2 cytokine expression. <b><i>Methods:</i></b> Forty-six patients were divided into group A and group B according to a random number table. Group A underwent conventional functional endoscopic sinusitis surgery (FESS) combined with PNN, and group B underwent conventional FESS alone. The subjective and objective symptoms included a 10-cm visual analog scale (VAS), 22-item SinoNasal Outcome Test (SNOT-22) score, nasal speculum Lund-Kennedy score, and paranasal sinus computed tomography (CT) Lund-Mackay score at the 1-year postoperative follow-up. <b><i>Results:</i></b> Postoperative VAS (10.33 ± 2.18 vs. 8.38 ± 2.11, <i>p</i> &#x3c; 0.01) and Lund-Kennedy score (1.95 ± 1.32 vs. 3.14 ± 1.35, <i>p</i> &#x3c; 0.01) were significantly improved. The rhinorrhea score (1.76 ± 0.83 vs. 2.90 ± 1.14, <i>p</i> &#x3c; 0.001) in the VAS and the discharge (0.43 ± 0.51, vs. 0.95 ± 0.67, <i>p</i> &#x3c; 0.01) and edema (0.57 ± 0.60 vs. 0.95 ± 0.59, <i>p</i> &#x3c; 0.05) scores in the Lund-Kennedy score were observed to have improved significantly in group A compared with those in group B. <b><i>Conclusions:</i></b> FESS combined with PNN suppresses edema symptoms, which might significantly decrease the surgical recurrence rate of ECRS in the long term.

International recognition of the Chronic Otitis Media Questionnaire 12

2017 ◽  
Vol 131 (6) ◽  
pp. 514-517 ◽  
Author(s):  
S I Kosyakov ◽  
J V Minavnina ◽  
J S Phillips ◽  
M W Yung
Keyword(s):  
Quality Of Life ◽  
Otitis Media ◽  
Chronic Otitis Media ◽  
Health Related Quality ◽  
Russian Version ◽  
Patient Reported ◽  
Related Quality ◽  
Health Related ◽  
The Uk

AbstractObjective:The Chronic Otitis Media Questionnaire 12 was developed initially in the UK to assess patient-reported health-related quality of life associated with chronic otitis media. This study aimed to determine whether this tool is applicable to the Russian population, which has a materially different healthcare system.Method:A total of 108 patients with different forms of chronic otitis media completed the Russian Chronic Otitis Media Questionnaire 12.Results:The average Russian Chronic Otitis Media Questionnaire 12 score was 19.4 (standard deviation = 8.3). The internal consistency of the Russian Chronic Otitis Media Questionnaire 12 was high, with a Cronbach's alpha value of 0.860.Conclusion:The Russian version of the Chronic Otitis Media Questionnaire 12 was found to be a reliable tool for the assessment of health-related quality of life in patients with chronic otitis media. This sets the scene for international collaboration, using this tool to assess the effectiveness of surgical treatments even amongst countries with different healthcare systems.

Dupilumab in the treatment of chronic rhinosinusitis with nasal polyposis

Immunotherapy ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 111-121 ◽  
Author(s):  
John V Boyle ◽  
Kent Lam ◽  
Joseph K Han
Keyword(s):  
Chronic Rhinosinusitis ◽  
Patient Reported Outcomes ◽  
Nasal Polyposis ◽  
Biologic Therapy ◽  
Patient Reported ◽  
The Us ◽  
Us Fda ◽  
Underlying Mechanisms ◽  
Novel Agent

Chronic rhinosinusitis with nasal polyposis (CRSwNP) imparts a significant healthcare challenge, resulting in diminished quality of life for patients and high costs with resource utilization for disease management. Understanding of CRSwNP pathophysiology has progressively evolved and the identification of various inflammatory biomarkers has led to the development of monoclonal antibodies that target the underlying mechanisms of inflammation. Dupilumab, which targets IL-4 and IL-13 signaling, serves as a novel agent for CRSwNP treatment. Three clinical trials, NCT01920893, SINUS-24 and SINUS-52, have shown that dupilumab improves both subjective patient-reported outcomes and objective physician-evaluated metrics for CRSwNP. The favorable findings have resulted in approval by the US FDA in June 2019 as the first biologic therapy for CRSwNP.

Redistribution of pulmonary EC-SOD after exposure to asbestos

2004 ◽  
Vol 97 (5) ◽  
pp. 2006-2013 ◽  
Author(s):  
Roderick J. Tan ◽  
Cheryl L. Fattman ◽  
Simon C. Watkins ◽  
Tim D. Oury
Keyword(s):  
Extracellular Matrix ◽  
Lung Injury ◽  
Asbestos Exposure ◽  
Intratracheal Instillation ◽  
Inflammatory Cells ◽  
Lung Parenchyma ◽  
Lavage Fluid ◽  
Binding Domain ◽  
Heparin Binding ◽  
Heparin Binding Domain

Inhalation of asbestos fibers leads to interstitial lung disease (asbestosis) characterized by inflammation and fibrosis. The pathogenesis of asbestosis is not fully understood, but reactive oxygen species are thought to play a central role. Extracellular superoxide dismutase (EC-SOD) is an antioxidant enzyme that protects the lung in a bleomycin-induced pulmonary fibrosis model, but its role has not been studied in asbestos-mediated disease. EC-SOD is found in high levels in the extracellular matrix of lung alveoli because of its positively charged heparin-binding domain. Proteolytic removal of this domain results in clearance of EC-SOD from the matrix of tissues. We treated wild-type C57BL/6 mice with 0.1 mg of crocidolite asbestos by intratracheal instillation and euthanized them 24 h later. Compared with saline- or titanium dioxide-treated control mice, bronchoalveolar lavage fluid (BALF) from asbestos-treated mice contained significantly higher total protein levels and increased numbers of inflammatory cells, predominantly neutrophils, indicating acute lung injury in response to asbestos. Decreased EC-SOD protein and activity were found in the lungs of asbestos-treated mice, whereas more EC-SOD was found in the BALF of these mice. The EC-SOD in the BALF was predominantly in the proteolyzed form, which lacks the heparin-binding domain. This redistribution of EC-SOD correlated with development of fibrosis 14 days after asbestos exposure. These data suggest that asbestos injury leads to enhanced proteolysis and clearance of EC-SOD from lung parenchyma into the air spaces. The depletion of EC-SOD from the extracellular matrix may increase susceptibility of the lung to oxidative stress during asbestos-mediated lung injury.

scholarly journals Sequential expression of IGF-IB followed by active TGF-β1 induces synergistic pulmonary fibroproliferation in vivo

2012 ◽  
Vol 303 (9) ◽  
pp. L788-L798 ◽  
Author(s):  
Graciela Andonegui ◽  
Ai Ni ◽  
Caroline Léger ◽  
Margaret M. Kelly ◽  
Josée F. Wong ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Ex Vivo ◽  
Smooth Muscle Actin ◽  
Wild Type Mouse ◽  
Inflammatory Cells ◽  
Lung Parenchyma ◽  
Lavage Fluid ◽  
Igf I ◽  
Tgf Β1

Pulmonary fibrosis, the end stage of a variety of fibroproliferative lung diseases, is usually induced after repetitive or chronic lung injury or inflammation. The mechanisms of fibroproliferation are poorly understood. Insulin-like growth factor-I (IGF-I) is significantly elevated in patients with pulmonary fibrosis and fibroproliferative acute respiratory distress syndrome. However, we showed that IGF-I overexpression alone in wild-type mouse lungs does not cause fibroproliferation. We therefore questioned whether IGF-I, acting together with active TGF-β1, a known profibrotic cytokine, enhances pulmonary fibroproliferation caused by active TGF-β1. A unique sequential adenoviral transgene mouse model was used expressing AdEmpty/AdTGF-β1 or AdhIGF-IB/AdTGF-β1 transgenes. IGF-IB plus active TGF-β1 transgene expression synergistically increased collagen deposition in the lung parenchyma compared with active TGF-β1 expression alone. The enhanced fibrosis was accompanied by an increased recruitment of macrophages and lymphocytes into the bronchoalveolar lavage fluid (BALF) and inflammatory cells in the lungs. α-Smooth muscle actin expression, a marker of myofibroblast proliferation and differentiation, was also increased. Finally, fibroblasts exposed ex vivo to BALF isolated from AdhIGF-IB/AdTGF-β1-transduced mice showed synergistic collagen induction compared with BALF from AdEmpty/AdTGF-β1-transduced mice. This study provides the first direct evidence that IGF-I is able to synergistically enhance pulmonary fibroproliferation in cooperation with TGF-β1.

scholarly journals Creatine Supply Attenuates Ischemia-Reperfusion Injury in Lung Transplantation in Rats

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2765
Author(s):  
Francine M. Almeida ◽  
Angela S. Battochio ◽  
João P. Napoli ◽  
Katiusa A. Alves ◽  
Grace S. Balbin ◽  
...  
Keyword(s):  
Lung Transplantation ◽  
Reperfusion Injury ◽  
Inflammatory Responses ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Left Lung ◽  
Inflammatory Cells ◽  
Lung Parenchyma ◽  
Lavage Fluid ◽  
Immune System Activation

Ischemia-reperfusion injury (IRI) is one of the factors limiting the success of lung transplantation (LTx). IRI increases death risk after transplantation through innate immune system activation and inflammation induction. Some studies have shown that creatine (Cr) protects tissues from ischemic damage by its antioxidant action. We evaluated the effects of Cr supplementation on IRI after unilateral LTx in rats. Sixty-four rats were divided into four groups: water + 90 min of ischemia; Cr + 90 min of ischemia; water + 180 min of ischemia; and Cr + 180 min of ischemia. Donor animals received oral Cr supplementation (0.5 g/kg/day) or vehicle (water) for five days prior to LTx. The left lung was exposed to cold ischemia for 90 or 180 min, followed by reperfusion for 2 h. We evaluated the ventilatory mechanics and inflammatory responses of the graft. Cr-treated animals showed a significant decrease in exhaled nitric oxide levels and inflammatory cells in blood, bronchoalveolar lavage fluid and lung tissue. Moreover, edema, cell proliferation and apoptosis in lung parenchyma were reduced in Cr groups. Finally, TLR-4, IL-6 and CINC-1 levels were lower in Cr-treated animals. We concluded that Cr caused a significant decrease in the majority of inflammation parameters evaluated and had a protective effect on the IRI after LTx in rats.

Medical Therapy Versus Balloon Sinus Dilation in Adults With Chronic Rhinosinusitis (MERLOT): 12-Month Follow-up

2018 ◽  
Vol 32 (4) ◽  
pp. 294-302 ◽  
Author(s):  
J. Pablo Stolovitzky ◽  
Neelesh Mehendale ◽  
Keith E. Matheny ◽  
William J. Brown ◽  
Anthony A. Rieder ◽  
...  
Keyword(s):  
Chronic Rhinosinusitis ◽  
Medical Therapy ◽  
Final Analysis ◽  
The United States ◽  
Primary Objective ◽  
Medication Usage ◽  
Serious Adverse Events ◽  
Patient Reported

Background Chronic rhinosinusitis (CRS) is a devastating disease affecting nearly 30 million people in the United States. An interim analysis of data from the present study suggested that, in patients who had previously failed medical therapy, balloon sinus dilation (BSD) plus medical management (MM) provides a significant improvement in the quality of life (QOL) at 24 weeks postprocedure compared to MM alone. Objective The primary objective of this final analysis was to evaluate the durability of treatment effects through the 52-week follow-up. Methods Adults aged 19 and older with CRS who had failed MM elected either BSD plus MM or continued MM. Patients were evaluated at 2 (BSD arm only), 12, 24, and 52 weeks posttreatment. Balloon dilations were performed either as an office-based procedure under local anesthesia or in the operating room per physicians’ and patients’ discretion. The primary end point was change in patient-reported QOL as measured by Chronic Sinusitis Survey (CSS) total score from baseline to the 24-week follow-up. Secondary outcomes including changes in CSS, Rhinosinusitis Disability Index (RSDI), and Sino-Nasal Outcome Test (SNOT) total and subscores, sinus medication usage, missed days of work/school, number of medical care visits, and sinus infections from baseline to the 52-week follow-up are reported here within. Results BSD led to sustained greater improvements in self-reported QOL using the CSS and RSDI total scores with a trend toward improvement in the SNOT-20 total score from baseline to the 52-week follow-up compared to continued MM. There were no changes in medication usage apart from nasal steroid usage for which the MM cohort had an increase in usage. There were no device-related serious adverse events. Conclusion The current analysis highlights the safety, effectiveness, and durability of BSD in CRS patients aged 19 and older who had previously failed MM.

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