Two Patterns of Changes in Nasal Nitric Oxide after Lysine Aspirin Nasal Challenge in Patients with Aspirin-exacerbated Respiratory Disease

2012 ◽  
Vol 26 (6) ◽  
pp. 428-432 ◽  
Author(s):  
Damian Tworek ◽  
Izabela Kuprys-Lipinska ◽  
Wioletta Pietruszewska ◽  
Piotr Kuna
Keyword(s):  
Nitric Oxide ◽  
Positive Result ◽  
Respiratory Disease ◽  
Nasal Polyps ◽  
Control Groups ◽  
Control Solution ◽  
Time Points ◽  
Nasal Nitric Oxide ◽  
Nasal Challenge ◽  
Aspirin Exacerbated Respiratory Disease

Background Nasal nitric oxide (nNO) levels after nasal lysine acetylsalicylic acid (lys-ASA) challenge have not been determined. This study was designed to determine a pattern of changes after lys-ASA challenge in aspirin-exacerbated respiratory disease (AERD) patients and to evaluate the usefulness of nNO measurements in the assessment of lys-ASA nasal challenge outcome. Methods Eighteen patients with aspirin hypersensitivity, nasal polyps, and asthma were included. Aspirin-tolerant control groups consisted of 10 healthy volunteers without asthma and nasal polyps and 10 patients with nasal polyps without asthma. All subjects underwent nasal challenge with lys-ASA. nNO was measured before and 1, 2, 4, and 24 hours after control solution and lys-ASA administration. Results A significant fall in nNO levels was noted in AERD patients with a positive result to challenges at time points 1 hour (p = 0.0033), 2 hours (p = 0.0033), and 3 hours (p = 0.026) after lys-ASA. A trend toward higher nNO concentrations was observed after lys-ASA challenge at the 2-hour (p = 0.018) and 4-hour (p = 0.018) time points compared with baseline in subjects with AERD and a clinically negative re to the challenge. No significant changes in nNO levels after the challenge were observed in control groups. The combined increase and decrease in nNO levels gave the sensitivity as 0.94 and specificity 1.00 at best. Conclusion nNO levels decrease after lys-ASA nasal challenge in subjects with AERD and a clinically positive result of the challenge. An unexpected trend toward an increase in nNO levels is observed in subjects with AERD and a clinically negative result of the challenge.

scholarly journals Aspirin Exacerbated Respiratory Disease and Nasal Polyps

2017 ◽  
Author(s):  
MB Cupic ◽  
S Savovic ◽  
S Hromis ◽  
SL Komazec ◽  
M Savic
Keyword(s):  
Respiratory Disease ◽  
Nasal Polyps ◽  
Aspirin Exacerbated Respiratory Disease

Predictive and Diagnostic Value of Nasal Nitric Oxide in Eosinophilic Chronic Rhinosinusitis with Nasal Polyps

2020 ◽  
Vol 181 (11) ◽  
pp. 853-861
Author(s):  
Hao Lv ◽  
Pei-Qiang Liu ◽  
Rong Xiang ◽  
Wei Zhang ◽  
Shi-Ming Chen ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Chronic Rhinosinusitis ◽  
Nasal Polyps ◽  
Upper Airway ◽  
Central China ◽  
Clinical Parameters ◽  
Total Ige ◽  
Nasal Nitric Oxide ◽  
Eosinophilic Chronic Rhinosinusitis ◽  
Plasma Cytokines

<b><i>Background:</i></b> A hallmark of eosinophilic chronic rhinosinusitis with nasal polyps (eCRSwNP) is mucosal eosinophil-predominant inflammation. Nasal nitric oxide (nNO) is a known biomarker of eosinophilic inflammation in the upper airway. However, the utility of nNO measurement in the upper airway remains controversial. The present study aimed to compare the use of other clinical parameters with nNO to prediagnose patients with eCRSwNP from Central China. <b><i>Methods:</i></b> From June 2019 to December 2019, 70 patients with CRSwNP undergoing endoscopic sinus surgery and 30 healthy subjects were enrolled. nNO measurements were performed in all of these subjects. Computed tomography scans, full blood count with differential analysis, and determination of total immunoglobulin E (total IgE) and plasma cytokines were performed before surgery. Receiver operating characteristic curves and logistic regression analysis were used to assess the predictive potential of the clinical parameters. <b><i>Results:</i></b> We recruited 24 patients with eCRSwNP and 46 with noneosinophilic CRSwNP (non-eCRSwNP). In patients with eCRSwNP, nNO levels were significantly higher than those in patients with non-eCRSwNP (<i>p</i> &#x3c; 0.0001). Blood eosinophil percentages and counts, total IgE, and CT-derived ethmoid sinus and maxillary sinus ratio (E/M ratio) were all significantly higher compared with those in patients with non-eCRSwNP (<i>p</i> &#x3c; 0.05). To diagnose eCRSwNP, the highest area under the curve (0.803) was determined for nNO. At a cutoff of &#x3e;329 parts per billion (ppb), the sensitivity was 83.30% and the specificity was 71.70%. However, the levels of plasma cytokines Th1/Th2 were not significantly different between the histological types of CRSwNP (<i>p</i> &#x3e; 0.05). <b><i>Conclusion:</i></b> Measurement of nNO is useful for the early diagnosis of eCRSwNP.

scholarly journals Cysteinyl leukotriene overproduction in aspirin-exacerbated respiratory disease is driven by platelet-adherent leukocytes

Blood ◽  
2012 ◽  
Vol 119 (16) ◽  
pp. 3790-3798 ◽  
Author(s):  
Tanya M. Laidlaw ◽  
Molly S. Kidder ◽  
Neil Bhattacharyya ◽  
Wei Xing ◽  
Shiliang Shen ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Respiratory Disease ◽  
Peripheral Blood ◽  
Nasal Polyps ◽  
Tissue Inflammation ◽  
Cysteinyl Leukotriene ◽  
Aspirin Exacerbated Respiratory Disease ◽  
Platelet Adherence ◽  
Adherent Leukocytes ◽  
Respiratory Tissue

Abstract Cysteinyl leukotriene (cysLT) overproduction is a hallmark of aspirin-exacerbated respiratory disease (AERD), but its mechanism is poorly understood. Because adherent platelets can convert the leukocyte-derived precursor leukotriene (LT)A4 to LTC4, the parent cysLT, through the terminal enzyme LTC4 synthase, we investigated the contribution of platelet-dependent transcellular cysLT production in AERD. Nasal polyps from subjects with AERD contained many extravascular platelets that colocalized with leukocytes, and the percentages of circulating neutrophils, eosinophils, and monocytes with adherent platelets were markedly higher in the blood of subjects with AERD than in aspirin-tolerant controls. Platelet-adherent subsets of leukocytes had higher expression of several adhesion markers than did platelet nonadherent subsets. Adherent platelets contributed more than half of the total LTC4 synthase activity of peripheral blood granulocytes, and they accounted for the higher level of LTC4 generation by activated granulocytes from subjects with AERD compared with aspirin-tolerant controls. Urinary LTE4 levels, a measure of systemic cysLT production, correlated strongly with percentages of circulating platelet-adherent granulocytes. Because platelet adherence to leukocytes allows for both firm adhesion to endothelial cells and augmented transcellular conversion of leukotrienes, a disturbance in platelet-leukocyte interactions may be partly responsible for the respiratory tissue inflammation and the overproduction of cysLTs that characterize AERD.

scholarly journals IL-5Rα marks nasal polyp IgG4 and IgE-secreting cells in aspirin-exacerbated respiratory disease

2019 ◽  
Author(s):  
Kathleen M. Buchheit ◽  
Daniel F. Dwyer ◽  
Jose Ordovas-Montanes ◽  
Howard R. Katz ◽  
Erin Lewis ◽  
...  
Keyword(s):  
Chronic Rhinosinusitis ◽  
Respiratory Disease ◽  
Disease Severity ◽  
Nasal Polyp ◽  
Nasal Polyps ◽  
Mrna Levels ◽  
Aspirin Exacerbated Respiratory Disease ◽  
Polyp Tissue ◽  
Antibody Levels ◽  
Antibody Secreting Cells

AbstractBackgroundThe cause of nasal polyposis in aspirin-exacerbated respiratory disease (AERD) is unknown. Elevated antibody levels have been associated with disease severity in nasal polyps, but the upstream drivers and cellular mechanisms of local antibody production in AERD remain to be investigated.ObjectiveWe sought to identify the upstream drivers and phenotypic properties of local antibody-secreting cells in nasal polyps and to understand their clinical relevance in AERD.MethodsSinus tissue was obtained from subjects with AERD, aspirin-tolerant chronic rhinosinusitis with nasal polyps (CRSwNP), aspirin-tolerant chronic rhinosinusitis without nasal polyps (CRSsNP), and healthy controls. Tissue antibody levels were quantified via ELISA and immunohistochemistry, and were correlated with clinical markers of disease severity. Tissue cytokine mRNA levels were measured with quantitative PCR (qPCR). Antibody-secreting cells were profiled with a combination of single-cell RNA-sequencing (scRNA-seq), flow cytometry and immunofluorescence.ResultsTissue IgE and IgG4 were elevated in AERD compared to controls (p<0.01 for IgE and p<0.001 for IgG4, vs. CRSwNP). Total IgG and IgG4 positively correlated with the number of polyp surgeries per subject (r=0.48, p=0.011 and r=0.58, p=0.0003, respectively). Polyp IL-10 mRNA expression was higher in AERD vs. CRSwNP (p<0.05), but there were no differences in mRNA expression of type 2 cytokines. ScRNA-seq revealed increased IL5RA, IGHG4, and IGHE in the antibody-associated cells of subjects with AERD compared to CRSwNP. Total plasma cells and IL-5Rα+ plasma cell numbers in the polyp tissue from AERD exceeded those in polyps from CRSwNP (p=0.0051 and p=0.026, respectively) by flow cytometry. With immunofluorescence, we determined that IL-5Rα and IgG4 are co-expressed in antibody-secreting cells in AERD.ConclusionsOur study identifies unique clusters of antibody-secreting cells in AERD defined by enrichment of transcripts encoding IL5RA, IGHG4 and IGHE. We confirm surface expression of IL-5Rα on these cells, and identify T cells as a unique transcriptional source of IL-5. Tissue antibody levels are elevated in AERD and correlate with disease severity. Our findings suggest a role for IL-5 in facilitating local antibody production that may drive features of severe sinus disease.Key MessagesIgG4 and IgE levels are markedly increased in nasal polyp tissue from subjects with AERD compared to aspirin-tolerant CRSwNP.Tissue IgG4 levels positively correlate with disease recurrence.IL-10 mRNA levels are significantly higher in AERD polyp tissue compared to CRSwNP tissue, but differences were not noted for type 2 cytokines or cytokines involved in class switch recombination.IL-5Rα transcript and protein surface expression is elevated in antibody-secreting cells from subjects with AERD and may play a role in facilitating class switching and/or survival of antibody-secreting cells.Capsule SummarySingle-cell RNA-sequencing (scRNA-seq) of whole nasal polyp tissue identified increased IL5RA, IGHE, and IGHG4 expression in the antibody-secreting cell compartment of subjects with aspirin-exacerbated respiratory disease (AERD) compared to aspirin-tolerant chronic rhinosinusitis with nasal polyps (CRSwNP). IgE and IgG4 levels are elevated in nasal polyp tissue from subjects with AERD compared to CRSwNP and correlate with disease recurrence.

Sign in / Sign up

Export Citation Format

Share Document