Aspirin-exacerbated respiratory disease (AERD) is an asthma phenotype characterized by nasal polyps, chronic hypertrophic eosinophilic sinusitis, asthma, and sensitivity to aspirin. Unawareness of this disease by pati...Aspirin-exacerbated respiratory disease (AERD) is an asthma phenotype characterized by nasal polyps, chronic hypertrophic eosinophilic sinusitis, asthma, and sensitivity to aspirin. Unawareness of this disease by patients and their physicians may have serious consequences because of the risk of near-fatal asthma. Its confirmative diagnosis can be established only by provocative aspirin challenge, which represents a potential risk for patient health. Purpose: Because CCL4 plays an important role in several pulmonary conditions, we tested its immunoreactivity in nasal lavages and sera from control subjects, and from aspirin-sensitive and non-aspirin-sensitive patients. Method: Immunoreactivity of CCL4 was measured in serum and nasal lavages from 30 healthy controls (HC), 23 patients with AERD, and 20 patients with aspirin-tolerant asthma (ATA). Additionally, a serum biobank contained sera from 90 HC, 83 patients with AERD, and 69 patients with ATA was employed. Results: The serum immunoreactivity of CCL4 could distinguish both types of asthma phenotypes. Conclusion: CCL4 may play an unexpected role in thephysiopathology of AERD.展开更多
Objective:To review and evaluate outcomes of patients with aspirin-exacerbated respiratory disease(AERD)following endoscopic sinus surgery and subsequent aspirin desensitization.Methods:Electronic searches of OVID MED...Objective:To review and evaluate outcomes of patients with aspirin-exacerbated respiratory disease(AERD)following endoscopic sinus surgery and subsequent aspirin desensitization.Methods:Electronic searches of OVID MEDLINE(1948 to September 10,2019),EMBASE(1980 to September 10,2019),and PubMed were performed on September 10,2019.A systematic review of the literature was performed using the 2009 PRISMA guidelines.Studies with both preoperative and postoperative data for patients with AERD who underwent sinus surgery and aspirin desensitization were considered appropriate for inclusion.Publications were written in English and included patients aged 18 years or older.Results:Six studies met inclusion criteria for this systematic review.The primary outcome measure was change in symptom profile measured by patient-reported quality of life scores.The results demonstrate statistically significant improvement in symptoms following endoscopic sinus surgery,with sustained improvement following aspirin desensitization.Revision surgery rates were significantly lower in patients maintained on aspirin therapy.Conclusion:This review suggests that surgery followed by aspirin desensitization results in improvement in both subjective and objective outcome measures.The adjunctive use of aspirin desensitization allows for long-term stability in symptom scores.Recurrence of polyps and worsening symptoms requiring revision surgery occurs when aspirin maintenance therapy is inter-rupted.展开更多
Patients with aspirin exacerbated respiratory disease(AERD)experience a severe and recalcitrant form of chronic rhinosinusitis with nasal polyposis(CRSwNP)and asthma,which are exacerbated by aspirin/NSAID ingestion.As...Patients with aspirin exacerbated respiratory disease(AERD)experience a severe and recalcitrant form of chronic rhinosinusitis with nasal polyposis(CRSwNP)and asthma,which are exacerbated by aspirin/NSAID ingestion.As compared with aspirin-tolerant CRSwNP,patients with AERD experience more severe olfactory dysfunction,which is one of the key contributors to the observed decrease in quality of life(QOL)in this disease.The objective of this paper is to review the published olfactory outcomes observed with various treatment modalities.展开更多
Background:Aspirin-exacerbated respiratory disease(AERD)is an aggressive inflammatory disorder of the upper and lower respiratory tract.Corticosteroids,leukotriene modifiers,endoscopic sinus surgery(ESS),aspirin(ASA)d...Background:Aspirin-exacerbated respiratory disease(AERD)is an aggressive inflammatory disorder of the upper and lower respiratory tract.Corticosteroids,leukotriene modifiers,endoscopic sinus surgery(ESS),aspirin(ASA)desensitization,and biological immu-nomodulators are currently used to treat the disorder.Objective:The objective of this study was to determine the psychosocial impact of ESS and ASA desensitization on AERD patients.Methods:All AERD patients who underwent complete ESS were divided into two cohorts based on ASA desensitization status.The psychosocial metrics of the SNOT-22 were collected and analyzed at the following time points:pre-operative,1-month,3-month,6-month,and 12-month after ESS.Results:One hundred and eighty-four AERD patients underwent ESS from November 2009 to November 2018.From this group,130 patients underwent ASA desensitization(AD cohort)and 54 patients remained non-desensitized(ND cohort).AD patients showed a significantly greater reduction in total SNOT-22 scores over the study period compared to ND patients(p=0.0446).Analysis of SNOT-22 psychosocial metrics showed a significantly greater improvement in patient productivity in the AD cohort when compared to the ND cohort(p=0.0214).Further,a sub-group analysis accounting for subject attrition showed a significantly greater improvement in both productivity and concentration in AD patients when compared to the ND cohort(productivity:p=0.0068;concentration:p=0.0428).Conclusions:ESS followed by ASA desensitization decreases the overall psychosocial burden in AERD patients with a significant improvement in perceived productivity and concentration.This has significant implications given the psychosocial impact of chronic diseases.展开更多
Aspirin-exacerbated respiratory disease(AERD)patients with CRSwNP suffer from reduced quality of life,reduced economic productivity,and higher risk of depression and sleep dysfunction.These patients often require freq...Aspirin-exacerbated respiratory disease(AERD)patients with CRSwNP suffer from reduced quality of life,reduced economic productivity,and higher risk of depression and sleep dysfunction.These patients often require frequent medical and surgical therapy,including functional endoscopic sinus surgery for recalcitrant disease.Given this severity,anti-type 2 biologic treatments are being investigated for use in this subgroup of patients with CRSwNP,including Omalizumab and Dupilumab.Preliminary data suggests that SNOT-22 related quality of life improvements following treatment with biologies are comparable to the current standard of care in the short term,but there is a lack of long-term data and standardized regimen that makes direct comparison difficult.Biologic therapies additionally require continuous use to avoid recurrence,and currently cost many times more than existing medical or surgical therapies.展开更多
It is well-established that following ingestion of aspirin or any other inhibitor of cyclooxygenase-1, patients with Samter’s disease, or aspirin-exacerbated respiratory disease (AERD) develop the sudden onset of wor...It is well-established that following ingestion of aspirin or any other inhibitor of cyclooxygenase-1, patients with Samter’s disease, or aspirin-exacerbated respiratory disease (AERD) develop the sudden onset of worsening respiratory clinical symptoms, which usually in-volves nasal congestion, rhinorrhea, wheezing and bronchospasm. Gastrointestinal distress, nausea, a pruritic rash and angioedema can also occasionally develop. However, the underlying pathologic mechanism that drives these clinical reactions remains elusive. Pretreatment with medications that inhibit the leukotriene pathway decreases the severity of clinical reactions, which points to the involvement of cysteinyl leukotrienes (cysLTs) in the pathogenesis of these aspirin-induced reactions. Furthermore, studies of aspirin challenges in carefully-phenotyped patients with AERD have confirmed that both proinflammatory lipid mediators, predominantly cysLTs and prostaglandin (PG) D 2, and the influx of effector cells to the respiratory tissue, contribute to symptom development during aspirin-induced reactions. Mast cells, which have been identified as the major cellular source of cysLTs and PGD 2, are likely to be major participants in the acute reactions, and are an attractive target for future pharmacotherapies in AERD. Although several recent studies support the role of platelets as inflammatory effector cells and as a source of cysLT overproduction in AERD, it is not yet clear whether platelet activation plays a direct role in the development of the aspirin-induced reactions. To further our understanding of the pathogenesis of aspirin-induced reactions in AERD, and to broaden the pharmacotherapeutic options available to these patients, additional investigations with targeted clinical trials will be required.展开更多
Backgroud:Aspirin-exacerbated respiratory disease(AERD)is a difficult-to-treat syndrome where timely diagnosis and initiation of disease-specific therapies are pertinent to improved patient outcomes.Objective:To chara...Backgroud:Aspirin-exacerbated respiratory disease(AERD)is a difficult-to-treat syndrome where timely diagnosis and initiation of disease-specific therapies are pertinent to improved patient outcomes.Objective:To characterize the most common timeline for development of the clinical triad[asthma,nasal polyposis,and reactions to nonsteroidal anti-inflammatory drugs(NSAIDs)],identify barriers to prompt diagnosis of AERD,and describe indications for an aspirin challenge to facilitate accurate diagnosis.Methods:Six hundred ninety-seven patients with diagnosed AERD and history of at least one sinus surgery to remove nasal polyps were identified in the Brigham and Women’s Hospital AERD registry.Patient reported age at disease onset of asthma,nasal polyposis,and age of first NSAID reaction were obtained from 2013 to 2019 at enrollment.Results:Of the 697 patients identified,diagnosis of asthma preceded diagnosis of nasal polyposis and first NSAID reaction,although there was considerable variability between patients.Conclusions:Prompt diagnosis of AERD is important for patient and provider education and improved care of this difficult-to-treat population of patients.Consider diagnostic aspirin challenge in patients without historical reactions to NSAIDs who have an otherwise compatible clinical history,specifically in patients who take daily low-dose aspirin,leukotriene modifiers,avoid NSAIDs,or who are severely symptomatic at baseline where it would be difficult to identify an acute worsening of symptoms.展开更多
文摘Aspirin-exacerbated respiratory disease (AERD) is an asthma phenotype characterized by nasal polyps, chronic hypertrophic eosinophilic sinusitis, asthma, and sensitivity to aspirin. Unawareness of this disease by patients and their physicians may have serious consequences because of the risk of near-fatal asthma. Its confirmative diagnosis can be established only by provocative aspirin challenge, which represents a potential risk for patient health. Purpose: Because CCL4 plays an important role in several pulmonary conditions, we tested its immunoreactivity in nasal lavages and sera from control subjects, and from aspirin-sensitive and non-aspirin-sensitive patients. Method: Immunoreactivity of CCL4 was measured in serum and nasal lavages from 30 healthy controls (HC), 23 patients with AERD, and 20 patients with aspirin-tolerant asthma (ATA). Additionally, a serum biobank contained sera from 90 HC, 83 patients with AERD, and 69 patients with ATA was employed. Results: The serum immunoreactivity of CCL4 could distinguish both types of asthma phenotypes. Conclusion: CCL4 may play an unexpected role in thephysiopathology of AERD.
文摘Objective:To review and evaluate outcomes of patients with aspirin-exacerbated respiratory disease(AERD)following endoscopic sinus surgery and subsequent aspirin desensitization.Methods:Electronic searches of OVID MEDLINE(1948 to September 10,2019),EMBASE(1980 to September 10,2019),and PubMed were performed on September 10,2019.A systematic review of the literature was performed using the 2009 PRISMA guidelines.Studies with both preoperative and postoperative data for patients with AERD who underwent sinus surgery and aspirin desensitization were considered appropriate for inclusion.Publications were written in English and included patients aged 18 years or older.Results:Six studies met inclusion criteria for this systematic review.The primary outcome measure was change in symptom profile measured by patient-reported quality of life scores.The results demonstrate statistically significant improvement in symptoms following endoscopic sinus surgery,with sustained improvement following aspirin desensitization.Revision surgery rates were significantly lower in patients maintained on aspirin therapy.Conclusion:This review suggests that surgery followed by aspirin desensitization results in improvement in both subjective and objective outcome measures.The adjunctive use of aspirin desensitization allows for long-term stability in symptom scores.Recurrence of polyps and worsening symptoms requiring revision surgery occurs when aspirin maintenance therapy is inter-rupted.
文摘Patients with aspirin exacerbated respiratory disease(AERD)experience a severe and recalcitrant form of chronic rhinosinusitis with nasal polyposis(CRSwNP)and asthma,which are exacerbated by aspirin/NSAID ingestion.As compared with aspirin-tolerant CRSwNP,patients with AERD experience more severe olfactory dysfunction,which is one of the key contributors to the observed decrease in quality of life(QOL)in this disease.The objective of this paper is to review the published olfactory outcomes observed with various treatment modalities.
文摘Background:Aspirin-exacerbated respiratory disease(AERD)is an aggressive inflammatory disorder of the upper and lower respiratory tract.Corticosteroids,leukotriene modifiers,endoscopic sinus surgery(ESS),aspirin(ASA)desensitization,and biological immu-nomodulators are currently used to treat the disorder.Objective:The objective of this study was to determine the psychosocial impact of ESS and ASA desensitization on AERD patients.Methods:All AERD patients who underwent complete ESS were divided into two cohorts based on ASA desensitization status.The psychosocial metrics of the SNOT-22 were collected and analyzed at the following time points:pre-operative,1-month,3-month,6-month,and 12-month after ESS.Results:One hundred and eighty-four AERD patients underwent ESS from November 2009 to November 2018.From this group,130 patients underwent ASA desensitization(AD cohort)and 54 patients remained non-desensitized(ND cohort).AD patients showed a significantly greater reduction in total SNOT-22 scores over the study period compared to ND patients(p=0.0446).Analysis of SNOT-22 psychosocial metrics showed a significantly greater improvement in patient productivity in the AD cohort when compared to the ND cohort(p=0.0214).Further,a sub-group analysis accounting for subject attrition showed a significantly greater improvement in both productivity and concentration in AD patients when compared to the ND cohort(productivity:p=0.0068;concentration:p=0.0428).Conclusions:ESS followed by ASA desensitization decreases the overall psychosocial burden in AERD patients with a significant improvement in perceived productivity and concentration.This has significant implications given the psychosocial impact of chronic diseases.
文摘Aspirin-exacerbated respiratory disease(AERD)patients with CRSwNP suffer from reduced quality of life,reduced economic productivity,and higher risk of depression and sleep dysfunction.These patients often require frequent medical and surgical therapy,including functional endoscopic sinus surgery for recalcitrant disease.Given this severity,anti-type 2 biologic treatments are being investigated for use in this subgroup of patients with CRSwNP,including Omalizumab and Dupilumab.Preliminary data suggests that SNOT-22 related quality of life improvements following treatment with biologies are comparable to the current standard of care in the short term,but there is a lack of long-term data and standardized regimen that makes direct comparison difficult.Biologic therapies additionally require continuous use to avoid recurrence,and currently cost many times more than existing medical or surgical therapies.
基金This work was supported by the National Institutes of Health(NIH grant#K23HL111113 and#R01HL128241)by generous contributions from the Vinik and Kaye Families.
文摘It is well-established that following ingestion of aspirin or any other inhibitor of cyclooxygenase-1, patients with Samter’s disease, or aspirin-exacerbated respiratory disease (AERD) develop the sudden onset of worsening respiratory clinical symptoms, which usually in-volves nasal congestion, rhinorrhea, wheezing and bronchospasm. Gastrointestinal distress, nausea, a pruritic rash and angioedema can also occasionally develop. However, the underlying pathologic mechanism that drives these clinical reactions remains elusive. Pretreatment with medications that inhibit the leukotriene pathway decreases the severity of clinical reactions, which points to the involvement of cysteinyl leukotrienes (cysLTs) in the pathogenesis of these aspirin-induced reactions. Furthermore, studies of aspirin challenges in carefully-phenotyped patients with AERD have confirmed that both proinflammatory lipid mediators, predominantly cysLTs and prostaglandin (PG) D 2, and the influx of effector cells to the respiratory tissue, contribute to symptom development during aspirin-induced reactions. Mast cells, which have been identified as the major cellular source of cysLTs and PGD 2, are likely to be major participants in the acute reactions, and are an attractive target for future pharmacotherapies in AERD. Although several recent studies support the role of platelets as inflammatory effector cells and as a source of cysLT overproduction in AERD, it is not yet clear whether platelet activation plays a direct role in the development of the aspirin-induced reactions. To further our understanding of the pathogenesis of aspirin-induced reactions in AERD, and to broaden the pharmacotherapeutic options available to these patients, additional investigations with targeted clinical trials will be required.
基金This work was supported by the National Institutes of Health(NIH grant nos U19AI095219,K23AI139352,R01HL128241)and by generous contributions from the Vinik and Kaye Families.
文摘Backgroud:Aspirin-exacerbated respiratory disease(AERD)is a difficult-to-treat syndrome where timely diagnosis and initiation of disease-specific therapies are pertinent to improved patient outcomes.Objective:To characterize the most common timeline for development of the clinical triad[asthma,nasal polyposis,and reactions to nonsteroidal anti-inflammatory drugs(NSAIDs)],identify barriers to prompt diagnosis of AERD,and describe indications for an aspirin challenge to facilitate accurate diagnosis.Methods:Six hundred ninety-seven patients with diagnosed AERD and history of at least one sinus surgery to remove nasal polyps were identified in the Brigham and Women’s Hospital AERD registry.Patient reported age at disease onset of asthma,nasal polyposis,and age of first NSAID reaction were obtained from 2013 to 2019 at enrollment.Results:Of the 697 patients identified,diagnosis of asthma preceded diagnosis of nasal polyposis and first NSAID reaction,although there was considerable variability between patients.Conclusions:Prompt diagnosis of AERD is important for patient and provider education and improved care of this difficult-to-treat population of patients.Consider diagnostic aspirin challenge in patients without historical reactions to NSAIDs who have an otherwise compatible clinical history,specifically in patients who take daily low-dose aspirin,leukotriene modifiers,avoid NSAIDs,or who are severely symptomatic at baseline where it would be difficult to identify an acute worsening of symptoms.
