RESUMEN
BACKGROUND: Nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD) is often characterized by a severe course of chronic rhinosinusitis with nasal polyps (CRSwNP), comorbid asthma, and NSAID hypersensitivity. The gold standard for N-ERD diagnosis is challenge with acetylsalicylic acid (ASA). In expert recommendations, the diagnosis of N-ERD is established based on a plausible positive history of NSAID hypersensitivity and CRSwNP with asthma. OBJECTIVE: The following review describes the performance of ASA challenges and their sensitivity and specificity. It also examines the extent to which a positive history of NSAID hypersensitivity correlates with ASA challenge results in clinical trials and when ASA challenges should be performed. RESULTS AND CONCLUSION: ASA challenges have high sensitivity and specificity. In clinical ASA challenge studies, there is a high concordance between a positive history of NSAID hypersensitivity obtained by rhinologists and the measured data of ASA challenge in patients with CRSwNP and comorbid asthma. Therefore, ASA challenge is primarily indicated in patients with an unclear history of NSAID hypersensitivity.
Asunto(s)
Antiinflamatorios no Esteroideos , Aspirina , Asma Inducida por Aspirina , Humanos , Aspirina/efectos adversos , Antiinflamatorios no Esteroideos/efectos adversos , Asma Inducida por Aspirina/diagnóstico , Sensibilidad y Especificidad , Sinusitis/inducido químicamente , Sinusitis/diagnóstico , Reproducibilidad de los Resultados , Hipersensibilidad a las Drogas/diagnóstico , Medicina Basada en la Evidencia , Rinitis/inducido químicamente , Rinitis/diagnóstico , Pruebas de Provocación Bronquial , Pruebas de Provocación Nasal/métodosRESUMEN
BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type2 inflammatory disease of the upper airways, with severe impairment of quality of life. Persons affected by NSAID-exacerbated respiratory disease (NERD) usually present with highly dynamic recurrence of polyps and disease despite prior treatment with sinus surgeries, oral corticosteroids, and aspirin desensitization (ATAD). Biologic therapy has fundamentally changed the choice of therapeutic concept; however, limited data exist on subgroups such as NERD patients. The aim of the current article is to report on a multicenter retrospective study on add-on therapy with dupilumab, omalizumab, and mepolizumab in patients with NERD. METHODS: This is a retrospective cohort study of patients (NERD+, status after ATAD) in three reference centers in Germany (Munich, Mainz, Berlin). Subjective and objective parameters were collected at 4, 8, and 12 months after biologic therapy initiation in accordance with current EPOS/EUFOREA (European Position Paper on Rhinosinusitis and Nasal Polyps/European Forum for Research and Education in Allergy and Airway Diseases) guidelines. Biologic agents were chosen depending on availability and patient characteristics. RESULTS: Treatment was commenced in 122 patients meeting the criteria for CRSwNP and NERD. The endoscopic polyp score, SNOT-22 questionnaire score, visual analogue scoring of total symptoms/severity of disease, and sense of smell (psychophysical testing with Sniffin'Sticks/Brief Smell Identification Test, BSIT; Sensonics, Inc., Haddon Heights, NJ, USA) improved significantly after 4 and 12 months of add-on therapy (pâ¯< 0.0001). All three biologic agents significantly improved one or more disease parameter. Adverse events were not life threatening but led to change of biologic agent in 4 cases. Patients rated biologic therapy significantly better than ATAD, with improved long-term disease control. CONCLUSION: Add-on biologic therapy is effective, safe, and widely accepted among CRSwNPâ¯+ NERD patients. Future studies might allow for personalized algorithms with sequential surgery, ATAD, and/or biologic therapy.
Asunto(s)
Antiinflamatorios no Esteroideos , Aspirina , Humanos , Femenino , Masculino , Persona de Mediana Edad , Antiinflamatorios no Esteroideos/efectos adversos , Antiinflamatorios no Esteroideos/uso terapéutico , Alemania , Estudios Retrospectivos , Aspirina/efectos adversos , Resultado del Tratamiento , Desensibilización Inmunológica/métodos , Sinusitis/inducido químicamente , Sinusitis/tratamiento farmacológico , Sinusitis/terapia , Adulto , Pólipos Nasales/tratamiento farmacológico , Asma Inducida por Aspirina/terapia , Asma Inducida por Aspirina/diagnóstico , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Terapia Biológica/métodos , Terapia Biológica/efectos adversos , Rinitis/inducido químicamente , Rinitis/terapia , Omalizumab/uso terapéutico , Omalizumab/efectos adversos , Estudios de Cohortes , Anciano , Enfermedad CrónicaRESUMEN
PURPOSE OF REVIEW: Aspirin-exacerbated respiratory disease (AERD) is a syndrome of high type 2 inflammation and is known to critically involve mast cell activation. The mast cell is an important cell in the baseline inflammatory processes in the upper and lower airway by maintaining and amplifying type 2 inflammation. But it also is prominent in the hypersensitivity reaction to COX-1 inhibition which defines this condition. RECENT FINDINGS: Recent work highlights the mast cell as a focal point in AERD pathogenesis. Using AERD as a specific model of both high type 2 asthma and chronic sinusitis, the role of mast cell activity can be better understood in other aspects of airway inflammation. Further dissecting out the mechanism of COX-1-mediated mast cell activation in AERD will be an important next phase in our understanding of NSAID-induced hypersensitivity as well as AERD pathophysiology.
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Asma Inducida por Aspirina , Pólipos Nasales , Sinusitis , Humanos , Mastocitos/patología , Sinusitis/inducido químicamente , Sinusitis/patología , Inflamación/patología , Aspirina/efectos adversosRESUMEN
BACKGROUND: Chronic rhinosinusitis (CRS) is a prevalent inflammatory disease. No medications are Food and Drug Administration-approved for the most common form, CRS without nasal polyps (also called "chronic sinusitis"). Novel biomechanics of the exhalation delivery system deliver fluticasone (EDS-FLU; XHANCE) to sinonasal areas above the inferior turbinate, especially sinus drainage pathways not reached by standard-delivery nasal sprays. OBJECTIVE: Assess EDS-FLU efficacy for CRS (irrespective of nasal polyps). METHODS: Two randomized, EDS-placebo-controlled trials in adults with CRS irrespective of polyps (ReOpen1) or exclusively without polyps (ReOpen2) were conducted at 120 sites in 13 countries. Patients received EDS-FLU 1 or 2 sprays/nostril, or EDS-placebo, twice daily for 24 weeks. Coprimary measures were composite symptom score through week 4 and ethmoid/maxillary sinus percent opacification by computed tomography at week 24. RESULTS: ReOpen1 (N = 332) composite symptom score least-squares mean change for EDS-FLU 1 or 2 sprays/nostril versus EDS-placebo was -1.58 and -1.60 versus -0.62 (P < .001, P < .001); ReOpen2 (N = 223), -1.54 and -1.74 versus -0.81 (P = .011, P = .001). In ReOpen1, sinus opacification least-squares mean change for EDS-FLU 1 or 2 sprays/nostril versus EDS-placebo was -5.58 and -6.20 versus -1.60 (P = .045, P = .018), and in ReOpen2, -7.00 and -5.14 versus +1.19 (P < .001, P = .009). Acute disease exacerbations were reduced by 56% to 66% with EDS-FLU versus EDS-placebo (P = .001). There were significant, and similar magnitude, symptom reductions in patients using standard-delivery nasal steroid products just before entering the study (P < .001). Adverse events were similar to standard-delivery intranasal steroids. CONCLUSIONS: EDS-FLU is the first nonsurgical treatment demonstrated to reduce symptoms, intrasinus opacification, and exacerbations in replicate randomized clinical trials in CRS, regardless of polyp status.
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Pólipos Nasales , Rinitis , Rinosinusitis , Sinusitis , Adulto , Humanos , Enfermedad Crónica , Fluticasona/uso terapéutico , Pólipos Nasales/tratamiento farmacológico , Pólipos Nasales/inducido químicamente , Ensayos Clínicos Controlados Aleatorios como Asunto , Rinitis/tratamiento farmacológico , Rinitis/inducido químicamente , Sinusitis/tratamiento farmacológico , Sinusitis/inducido químicamente , Esteroides/uso terapéuticoRESUMEN
BACKGROUND: Budesonide irrigations (BIs) are commonly used to control inflammation in chronic rhinosinusitis (CRS). In 2016 we reported an analysis of long-term BI with regard to hypothalamic-pituitary-adrenal axis function. We present a follow-up analysis in a larger cohort of patients with longer follow-up. METHODS: Patients were candidates for stimulated cortisol testing after regularly performing BI for CRS at least daily for ≥6 months. We retrospectively evaluated all patients who received stimulated cortisol testing at our center between 2012 and 2022. We correlated cortisol levels with the use of BI and other forms of corticosteroids. RESULTS: We analyzed 401 cortisol test results in 285 patients. The mean duration of use was 34 months. Overall, 21.8% of patients were hypocortisolemic (<18 ug/dL) at first test. In patients who used only BI, the rate of hypocortisolemia was 7.5%, whereas in patients who also used concurrent oral and inhaled corticosteroids, the rate was 40% to 50%. Lower cortisol levels were associated with male sex (p < 0.0001) and concomitant use of oral and inhaled steroids (p < 0.0001). Duration of BI use was not significantly associated with lower cortisol levels (p = 0.701), nor was greater dosing frequency (p = 0.289). CONCLUSION: Prolonged use of BI alone is not likely to cause hypocortisolemia in the majority of patients. However, concomitant use of inhaled and oral steroids and male sex may be associated with hypocortisolemia. Surveillance of cortisol levels may be considered in vulnerable populations who use BI regularly, particularly in patients using other forms of corticosteroids with known systemic absorption.
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Rinosinusitis , Sinusitis , Humanos , Masculino , Budesonida/efectos adversos , Hidrocortisona , Sistema Hipotálamo-Hipofisario , Incidencia , Estudios Retrospectivos , Sistema Hipófiso-Suprarrenal , Corticoesteroides/efectos adversos , Sinusitis/tratamiento farmacológico , Sinusitis/epidemiología , Sinusitis/inducido químicamente , Administración por InhalaciónRESUMEN
Aspirin-exacerbated respiratory disease (AERD) is a subtype of chronic rhinosinusitis with polyps (CRSwNP) and asthma with higher recurrence of nasal polyps after surgery and severe asthma. Patients with CRSwNP and asthma should be screened for AERD by detailed history of aspirin/nonsteroidal anti-inflammatory drug reactions and review of medications that may mask aspirin reaction or directly by aspirin challenge. Treatment of AERD may require more intensive therapy, including endoscopic sinus surgery, daily aspirin therapy, leukotriene modifiers, or biologics.
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Asma Inducida por Aspirina , Asma , Pólipos Nasales , Rinitis , Sinusitis , Humanos , Rinitis/inducido químicamente , Rinitis/terapia , Asma Inducida por Aspirina/diagnóstico , Asma Inducida por Aspirina/terapia , Aspirina/efectos adversos , Antiinflamatorios no Esteroideos/efectos adversos , Pólipos Nasales/terapia , Sinusitis/inducido químicamente , Sinusitis/terapia , Enfermedad CrónicaRESUMEN
Importance: Environmental and occupational toxicants have been shown to be associated with an increased prevalence of chronic rhinosinusitis (CRS). However, few to no studies have evaluated patients for CRS using objective testing and workup protocols that fulfill guidelines for CRS diagnostic criteria. Furthermore, no study, to our knowledge, has investigated the risks of CRS in the context of residential exposure through proximity to a commercial pesticide application site. Objectives: To evaluate associations of residential proximity to a commercial pesticide application site and the prevalence of CRS with nasal polyps (CRSwNP) and without nasal polyps (CRSwoNP). Design, Setting, and Participants: This was a retrospective cohort study of patients who presented to a tertiary care institution for rhinology evaluation between March 1, 2018, and December 31, 2022. Main Outcomes and Measures: The outcome variable was the clinical diagnosis of CRS (CRSwNP, CRSwoNP, or non-CRS control). Patients' residential addresses were utilized to determine pesticide exposure status based on a validated computational geographic information algorithm based on data from the California Pesticide Use Report System. The dichotomous independent variable of exposure status (exposed or non-exposed) was determined by assessing reports of any pesticide applications within 2000 m of each participant's residence in 2017. Multivariable logistic regressions assessing CRS status and CRS subtypes were conducted with pesticide exposure as the primary covariate of interest. The primary study outcome and measurements as well as study hypothesis were all formulated before data collection. Results: Among a total of 310 patients (90 CRSwNP, 90 CRSwoNP, and 130 control), the mean (SD) age was 50 (17) years; 164 (53%) were female. Race and ethnicity information was not considered. Controlling for patient demographic information, smoking history, county of residence, and medical comorbidities, pesticide exposure was associated with an approximately 2.5-fold increase in odds of CRS (adjusted odds ratio, 2.41; 95% CI, 1.49-3.90). Pesticide exposure was associated with similar risks for CRSwNP (adjusted relative risk ratio [aRRR], 2.34; 95% CI, 1.31-4.18) and CRSwoNP (aRRR, 2.42; 95% CI, 1.37-4.30). Conclusions and Relevance: The findings of this retrospective cohort study and analysis revealed that residential exposure to commercial pesticide application within a 2000-m buffer was independently associated with an approximately 2.5-fold increase in odds of being diagnosed with CRS. If validated by additional research, this association would have substantial implications for public health.
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Pólipos Nasales , Rinitis , Sinusitis , Humanos , Femenino , Persona de Mediana Edad , Masculino , Rinitis/inducido químicamente , Rinitis/epidemiología , Rinitis/complicaciones , Estudios Retrospectivos , Pólipos Nasales/complicaciones , Sinusitis/inducido químicamente , Sinusitis/epidemiología , Sinusitis/complicaciones , Enfermedad Crónica , Modelos LogísticosRESUMEN
Chronic rhinosinusitis (CRS) is a chronic inflammatory condition affecting the nasal and paranasal sinuses of approximately 11.5% of the United States adult population. Oral corticosteroids are effective in controlling sinonasal inflammation in CRS, but the associated adverse effects limit their clinical use. Topical budesonide has demonstrated clinical efficacy in patients with CRS. Herein, we investigated the systemic delivery of liposomes tethered with poly(ethylene glycol) (PEG) and loaded with budesonide in a murine model of CRS. PEGylated liposomes encapsulated with budesonide phosphate (L-BudP) were administered via tail vein injection, and the feasibility of L-BudP to reduce sinonasal inflammation was compared to that of free budesonide phosphate (F-BudP) and topical budesonide phosphate (T-BudP) treatment over a 14-day study period. Compared to a single injection of F-BudP and repeat T-BudP administration, a single injection of L-BudP demonstrated increased and prolonged efficacy, resulting in the significant improvement of sinonasal tissue histopathological scores (p < 0.05) with decreased immune cell infiltration (p < 0.05). Toxicities associated with L-BudP and T-BudP treatment, assessed via body and organ weight, as well as peripheral blood liver enzyme and differential white blood cell analyses, were transient and comparable. These data suggest that systemic liposomal budesonide treatment results in improved efficacy over topical treatment.
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Rinitis , Sinusitis , Adulto , Humanos , Animales , Ratones , Budesonida/uso terapéutico , Liposomas/uso terapéutico , Rinitis/tratamiento farmacológico , Rinitis/inducido químicamente , Sinusitis/tratamiento farmacológico , Sinusitis/inducido químicamente , Inflamación/tratamiento farmacológico , Enfermedad Crónica , Polietilenglicoles/uso terapéuticoRESUMEN
PURPOSE: Dupilumab represents an innovative and effective therapy for refractory/recurrent severe chronic rhinosinusitis with nasal polyps (CRSwNP). Intranasal corticosteroids should be used during treatment with biological agents. However, adherence to nasal therapy may not be complete. The aim of this study was to evaluate the role of intranasal corticosteroids in patients with CRSwNP who underwent treatment with dupilumab. MATERIALS AND METHODS: Fifty-two patients treated with dupilumab for CRSwNP were enrolled. Clinical parameters (age, sex, comorbidities, blood eosinophils, Nasal Polyp Score - NPS, Visual Analogue Scale - VAS - for smell loss, Asthma Control Test - ACT), quality of life (Sino Nasal Outcome Test 22 - SNOT-22 questionnaire), nasal cytology, and adherence to regular administration of intranasal corticosteroids were recorded before treatment (T0), and after 3 (T1), 6 (T2), and 12 months (T3). RESULTS: NPS, VAS for smell, ACT and SNOT-22 total score and subscores improved during treatment (p < 0.05). Blood eosinophils reached a peak at T1-T2 and then decreased toward baseline at T3. Adherence to regular treatment with intranasal steroids was 61.5 %. No statistically significant differences in all the clinical outcomes were observed between patients who regularly used intranasal steroids and other subjects (p > 0.05). Nasal cytology showed a decrease of eosinophils and an increase of neutrophils during treatment. CONCLUSIONS: Dupilumab is still effective in patients who are using topical nasal steroids with variable adherence (real world settings).
Asunto(s)
Pólipos Nasales , Rinitis , Sinusitis , Humanos , Pólipos Nasales/complicaciones , Pólipos Nasales/tratamiento farmacológico , Calidad de Vida , Rinitis/complicaciones , Rinitis/tratamiento farmacológico , Rinitis/inducido químicamente , Corticoesteroides , Esteroides , Sinusitis/complicaciones , Sinusitis/tratamiento farmacológico , Sinusitis/inducido químicamente , Enfermedad CrónicaRESUMEN
BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is the triad of asthma, nasal polyposis, and respiratory reactions to COX-1 inhibitors. Overproduction of cysteinyl leukotrienes and underproduction of prostaglandin E2 (PGE2) are hallmarks of AERD. A mouse model predicted a key role for the thromboxane-prostanoid (TP) receptor in AERD. OBJECTIVE: Our aim was to determine whether ifetroban, a TP receptor antagonist, attenuates aspirin-induced respiratory symptoms in patients with AERD. METHODS: A total of 35 patients with AERD completed a 4-week double-blinded, placebo-controlled trial of ifetroban and underwent an oral aspirin challenge. The primary outcome was change in the provocative dose of aspirin that caused a 2-point increase in Total Nasal Symptom Score. Changes in lung function, eicosanoid levels, and platelet and mast cell activation were assessed. Cultured human nasal fibroblasts were stimulated with or without the TP agonist U46619 and assayed for prostanoid production. RESULTS: Ifetroban was well tolerated in AERD and did not change the mean 2-point increase in Total Nasal Symptom Score (P = .763). Participants taking ifetroban had greater aspirin-induced nasal symptoms and a greater decline in FEV1 value than did participants receiving placebo (-18.8% ± 3.6% with ifetroban vs -8.4% ± 2.1% with placebo [P = .017]). Four weeks of ifetroban significantly increased urinary leukotriene E4 levels and decreased nasal PGE2 levels compared with placebo. Peak aspirin-induced urinary thromboxane levels correlated with peak urinary leukotriene E4 and prostaglandin D2 metabolite levels in participants taking ifetroban. U46119 significantly potentiated the production of PGE2 by cultured nasal fibroblasts from subjects with AERD but not by cultured nasal fibroblasts from controls without polypoid sinusitis. CONCLUSION: Contrary to our hypothesis, TP receptor blockade worsened aspirin-induced reactions in AERD, possibly by exacerbating dysregulation of the eicosanoid system. TP signaling on stromal cells may be critical to maintaining PGE2 production when COX-2 function is low.
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Asma Inducida por Aspirina , Sinusitis , Animales , Ratones , Humanos , Prostaglandinas , Tromboxanos/uso terapéutico , Leucotrieno E4 , Receptores de Tromboxanos/uso terapéutico , Asma Inducida por Aspirina/tratamiento farmacológico , Asma Inducida por Aspirina/diagnóstico , Aspirina/efectos adversos , Eicosanoides , Dinoprostona , Homeostasis , Sinusitis/inducido químicamenteRESUMEN
OBJECTIVE: The study aimed to investigate the feasibility of establishing rhinosinusitis model in rats combinated with Lipopolysaccharide (LPS) and merocel sponge. METHODS: SD (Sprague Dawley) rats that underwent nasal obstruction using Merocel sponge packing, rats with LPS instillation alone, and rats with both nasal obstruction and LPS instillation were used to establish rat models of rhinosinusitis. After the models were established, the nasal symptoms of rats were recorded, the histopathological examination and Transmission Electron Microscopy (TME) of the sinus tissue were performed and the levels of Tumor Necrosis Factor-α (TNF-α), Interleukin-6 (IL-6) in the blood were also analyzed. The expressions of Aquaporin-5 (AQP5), Occludin, Toll-Like Receptor-4 (TLR4), Medullary differentiation factor 88 (MyD88) and phosphorylated (p)-p65 protein were detected by Western blot to evaluate the effect and mechanism of the experimental models. RESULTS: We found that compared with the control group and LPS group, the sinusitis symptom scores in the Merocel sponge combined with LPS group were significantly increased; the respiratory epithelia of the maxillary sinus were degenerated, cilia were detached, and even inflammatory cell infiltration occurred; the levels of TNF-α and IL-6 were increased; the expression of AQP5 and Occludin protein was decreased; and the expressions of TLR4, MyD88, and p-p65 protein were increased. CONCLUSION: For the first time, we successfully established a rat rhinosinusitis model using Merocel sponge with LPS and explored the possible mechanism of LPS action.
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Obstrucción Nasal , Sinusitis , Ratas , Animales , Ratas Sprague-Dawley , Lipopolisacáridos/farmacología , Transducción de Señal , Receptor Toll-Like 4/metabolismo , Interleucina-6 , Factor de Necrosis Tumoral alfa , Factor 88 de Diferenciación Mieloide/metabolismo , Factor 88 de Diferenciación Mieloide/farmacología , Ocludina/metabolismo , Ocludina/farmacología , Sinusitis/inducido químicamenteRESUMEN
BACKGROUND: The impact of delayed hypersensitivity to Dermatophagoides pteronyssinus (DP) on comorbidities of allergic rhinitis (AR) is unknown. OBJECTIVE: The primary end point was to test the hypothesis that DP-induced AR could be divided into 2 subendotypes on the basis of presence or absence of a delayed-type mite sensitization detected by the positive result of atopy patch test for DP (DP-APT). The second end point was to evaluate differences in the long-term risk of respiratory comorbidities and nasal airway response to mite exposure. METHODS: In a prospective observational study, we included 472 patients with DP-induced AR. A total of 343 patients had positive results of skin prick test/serum specific IgE and DP-APT and were assigned to a subendotype with both IgE- and T-cell-mediated mite sensitization (BMSS). The remaining 129 patients without delayed-type mite sensitization were included in the subendotype with only IgE-mediated mite sensitization. Nasal allergen provocation test with active anterior rhinomanometry, paranasal sinuses computed tomography scan, nasal endoscopy, and spirometry were performed. RESULTS: At baseline, BMSS showed a larger increase in nasal airway resistance, total nasal score, and visual analogue scale score to mite exposure. During a 15-year follow-up, 56 patients developed chronic rhinosinusitis with nasal polyps, with higher incidence in BMSS than in the subendotype with only IgE-mediated mite sensitization (50 patients, 14.6% vs 6 patients, 12.4%; P < .001). BMSS also showed a higher incidence of conjunctivitis (25.7% vs 12.4%; P < .01). The rate of adult-onset asthma did not differ between groups, but patients with BMSS showed a more frequent link to chronic rhinosinusitis with nasal polyps (6 of 29 patients, 20.7% vs 0 of 10 patients, 0%). DP-APT independently predicted chronic rhinosinusitis with nasal polyps and conjunctivitis. CONCLUSIONS: Two subendotypes with significantly different clinical outcome can be identified among patients with DP-induced AR according to the presence of delayed-type mite sensitization detected by positive DP-APT result.
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Conjuntivitis , Pólipos Nasales , Rinitis Alérgica Perenne , Rinitis Alérgica , Rinitis , Sinusitis , Adulto , Animales , Humanos , Dermatophagoides pteronyssinus , Rinitis/epidemiología , Rinitis/inducido químicamente , Pólipos Nasales/epidemiología , Pólipos Nasales/inducido químicamente , Rinitis Alérgica/epidemiología , Alérgenos , Pruebas Cutáneas , Sinusitis/inducido químicamente , Enfermedad Crónica , Inmunoglobulina E , Antígenos DermatofagoidesRESUMEN
Aspirin-exacerbated respiratory disease (AERD) is characterized by abnormal arachidonic acid metabolism leading to chronic rhinosinusitis with nasal polyposis (CRSwNP), asthma, and upper and/or lower respiratory symptoms after ingestion of cyclooxygenase-1 inhibiting nonsteroidal antiinflammatory drugs. Diagnosis is clinical and may involve an aspirin challenge. Inflammatory biomarkers may be useful for diagnosis and treatment monitoring. Conventional medical management for asthma and CRSwNP is often inadequate. Endoscopic sinus surgery followed by continued medical management with or without aspirin desensitization frequently improves symptoms and objective disease measures. Biological agents targeting eosinophilic inflammation are promising alternatives to conventional management.
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Asma Inducida por Aspirina , Asma , Pólipos Nasales , Rinitis , Sinusitis , Humanos , Rinitis/inducido químicamente , Rinitis/diagnóstico , Rinitis/terapia , Asma Inducida por Aspirina/diagnóstico , Asma Inducida por Aspirina/terapia , Sinusitis/inducido químicamente , Sinusitis/terapia , Sinusitis/diagnóstico , Pólipos Nasales/inducido químicamente , Pólipos Nasales/terapia , Aspirina/efectos adversos , Antiinflamatorios no Esteroideos/efectos adversos , Enfermedad CrónicaRESUMEN
OBJECTIVE: To evaluate the clinical efficacy and safety of cefetamet pivoxil for the treatment of acute bacterial rhinosinusitis in Korean patients compared to treatment with cefdinir. METHODS: A prospective, multicenter, randomized double-blind, comparative study was conducted by the Departments of Otorhinolaryngology-Head and Neck Surgery at 17 hospitals or universities in the Republic of Korea from March 2017 to April 2019. A total of 309 patients were screened and 249 patients participated in the study. RESULTS: Treatment with cefetamet pivoxil for 2 weeks showed 82.4% clinical cure and improvement rates in patients with acute bacterial rhinosinusitis compared to 84.68% in those taking cefdinir for 2 weeks, showing that cefetamet pivoxil administered twice a day for 2 weeks was as effective as cefdinir 3 times a day for 2 weeks for the treatment of acute bacterial rhinosinusitis. The overall adverse reaction rates of both drugs were 10.56% in the cefetamet pivoxil group and 15.49% in the cefdinir group, without serious adverse events or drug reactions. CONCLUSIONS: Cefetamet pivoxil twice a day was as efficacious and safe as cefdinir 3 times a day for the treatment of acute bacterial rhinosinusitis, which suggested that cefetamet pivoxil may be a suitable alternative to cefdinir.
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Ceftizoxima , Sinusitis , Humanos , Cefdinir , Estudios Prospectivos , Ceftizoxima/efectos adversos , Sinusitis/tratamiento farmacológico , Sinusitis/inducido químicamente , BacteriasRESUMEN
The present study conducted a systematic review and Meta-analysis on the efficacy and safety of Biyuan Tongqiao Granules in the treatment of chronic sinusitis. CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, EMbase, and Web of Science were searched for randomized controlled trials(RCTs) of Biyuan Tongqiao Granules in the treatment of chronic sinusitis. The quality of the included RCTs was assessed according to the Cochrane risk-of-bias assessment tool and the final included trials underwent Meta-analysis with RevMan 5.4.1. Fifty-four RCTs were included, with a total sample size of 7 278 cases. The results of Meta-analysis showed that the clinical efficacy of Biyuan Tongqiao Granules alone or in combination in the experimental group in the treatment of chronic sinusitis was superior to that in the control group with conventional western medicine, Chinese medicinal preparations, or surgery only(RR=1.19, 95%CI[1.15, 1.24], P<0.000 01). The combined use of Biyuan Tongqiao Granules on the basis of the control group was superior to the control group in improving the main symptoms and signs of chronic sinusitis [RR_(nasal congestion)=1.33, 95%CI[1.21, 1.45], P<0.000 01, RR_(runny nose)=1.28, 95%CI[1.18, 1.40], P<0.000 01, RR_(turbinate congestion or swelling)=1.28, 95%CI[1.16, 1.41], P<0.000 01]. Biyuan Tongqiao Granules alone or in combination could effectively reduce the Snot-20 score, which was superior to the control group(MD=-2.94, 95%CI[-3.60,-2.28], P<0.000 01). Biyuan Tongqiao Granules alone and in combination could effectively reduce the VAS score, which was superior to the control group(MD_(total score)=-4.44, 95%CI[-6.05,-2.82], P<0.000 01; MD_(nasal congestion VAS score)=-0.99, 95%CI[-1.38,-0.60], P<0.000 01; MD_(runny nose VAS score)=-1.19, 95%CI[-1.62,-0.76], P<0.000 01; MD_(dysosmia VAS score)=-0.96, 95%CI[-1.26,-0.65], P<0.000 01; MD_(head and face pain VAS score)=-0.73, 95%CI[-0.98,-0.47], P<0.000 01). The combined use of Biyuan Tongqiao Granules could effectively reduce the sinus CT score and the Lund-Mackey score of the endoscopic mucosal morphology(MD_(sinus CT score)=-3.68, 95%CI[-5.47,-1.88], P<0.000 1, MD_(endoscopic mucosal morphology score)=-3.06, 95%CI[-5.53,-0.59], P=0.02). Compared with the control group with conventional western medicine, Chinese medicinal preparations, or surgery only, combined use of Biyuan Tongqiao Granules did not increase the occurrence of adverse reactions(RR=0.68, 95%CI[0.26, 1.77], P=0.43). As demonstrated by the existing evidence, Biyuan Tongqiao Granules can improve the clinical efficacy of chronic sinusitis, relieve the clinical symptoms and signs, and reduce the Snot-20 score, VAS score, and Lund-Mackey score, without inducing serious adverse reactions, indicating that Biyuan Tongqiao Granules alone or in combination are more effective and safe in the treatment of chronic sinusitis than conventional western medicine, Chinese medicinal preparations, or surgical treatment. Since the quality of the included trials was generally low, large-scale, high-quality, rigorous, multi-center, and blinded-designed RCTs that meet international standards should be adopted in the future to increase the strength and level of evidence.
Asunto(s)
Medicamentos Herbarios Chinos , Sinusitis , Enfermedad Crónica , Medicamentos Herbarios Chinos/efectos adversos , Humanos , Rinorrea , Sinusitis/inducido químicamente , Sinusitis/tratamiento farmacológico , Resultado del TratamientoRESUMEN
PURPOSE: Nasal polyps (NPs) develop in 20% to 30% of patients with chronic rhinosinusitis. Severe forms of chronic rhinosinusitis with nasal polyposis (CRSwNP) may be treated with systemic corticosteroids (SCSs), which increase the risk for adverse clinical outcomes. This study compared the incidence of SCS-related adverse outcomes and health care resource utilization and costs between patients with CRSwNP who had SCS exposure and those who did not have SCS exposure. METHODS: This retrospective cohort study used health care claims data from adult patients with CRSwNP identified in the IBMâ MarketScanâ Databases between January 2003 and June 2019. The first SCS prescription date in SCS users or a matched date in SCS nonusers (controls) represented the index date. Enrollment for ≥1 year before and after the index date was required. SCS-related adverse outcomes and costs were compared between all SCS users and controls, and among subgroups of patients who had claims for 1-3 and ≥4 SCS prescriptions in the 12-month postindex period. Comparisons were also made among SCS users and controls who previously had and did not have NP surgery, and those with and without comorbid asthma. Inverse probability of treatment weights was applied to all comparisons, which were evaluated for a variable-length follow-up period. FINDINGS: SCS users (nâ¯=â¯37,740) had a greater risk for any adverse outcome than controls (nâ¯=â¯7032) (incidence rate ratio [IRR]â¯=â¯1.10; 95% CI, 1.05-1.16). The risk for adverse outcomes was highest in the subgroups that did not have NP surgery and that had ≥4 SCS claims (nâ¯=â¯2993) versus controls who did not have NP surgery (nâ¯=â¯5078) (IRRâ¯=â¯1.30; 95% CI, 1.18-1.44). Similarly, patients with asthma and ≥4 SCS claims (nâ¯=â¯4195) had a greater risk for SCS-related outcomes versus controls with asthma (nâ¯=â¯1226) (IRRâ¯=â¯1.36; 95% CI, 1.19-1.55). SCS users incurred 60% higher all-cause costs versus non-SCS users (P < 0.001). IMPLICATIONS: In patients with CRSwNP, SCS use was associated with a higher risk for adverse outcomes and with increased health care costs compared with controls without SCS exposure. Alternative treatment strategies that avoid and/or reduce SCS use may decrease health care costs and the risk for adverse outcomes among patients with CRSwNP.
Asunto(s)
Asma , Pólipos Nasales , Sinusitis , Corticoesteroides/efectos adversos , Adulto , Asma/tratamiento farmacológico , Asma/epidemiología , Enfermedad Crónica , Humanos , Pólipos Nasales/complicaciones , Pólipos Nasales/tratamiento farmacológico , Pólipos Nasales/epidemiología , Aceptación de la Atención de Salud , Estudios Retrospectivos , Sinusitis/inducido químicamente , Sinusitis/tratamiento farmacológico , Sinusitis/epidemiologíaRESUMEN
BACKGROUND: Dupilumab, a mAb targeting IL-4Rα, improves upper and lower airway symptoms in patients with aspirin-exacerbated respiratory disease (AERD), but the mechanisms leading to clinical improvement are not fully elucidated. OBJECTIVE: Our aim was to identify the mechanistic basis of clinical improvement in patients with AERD treated with dupilumab. METHODS: A total of 22 patients with AERD were treated with dupilumab for 3 months for severe asthma and/or chronic rhinosinusitis with nasal polyps. Clinical outcomes were assessed at baseline and at 1 and 3 months after initiation of dupilumab. Nasal fluid, urine, blood, and inferior turbinate scrapings were collected at the 3 time points for determination of mediator levels, cellular assays, and RNA sequencing. RESULTS: Participants had rapid improvement in clinical measures, including sense of smell, sinonasal symptoms, and lung function after 1 month of treatment with dupilumab; the improvements were sustained after 3 months of dupilumab. Baseline severity of smell loss was correlated with lower nasal prostaglandin E2 levels. Dupilumab increased nasal prostaglandin E2 level and decreased levels of nasal albumin, nasal and urinary leukotriene E4, and serum and nasal IgE. Transcripts related to epithelial dysfunction and leukocyte activation and migration were downregulated in inferior turbinate tissue after treatment with dupilumab. There were no dupilumab-induced changes in nasal eosinophilia. CONCLUSION: Inhibition of IL-4Rα in AERD led to rapid improvement in respiratory symptoms and smell, with a concomitant improvement in epithelial barrier function, a decrease in inflammatory eicosanoid levels, and an increase in the anti-inflammatory eicosanoid prostaglandin E2 level. The therapeutic effects of dupilumab are likely due to decreased IL-4Rα signaling on respiratory tissue granulocytes, epithelial cells, and B cells.
Asunto(s)
Asma Inducida por Aspirina , Pólipos Nasales , Rinitis , Sinusitis , Aspirina/efectos adversos , Asma Inducida por Aspirina/diagnóstico , Enfermedad Crónica , Eicosanoides , Humanos , Pólipos Nasales/inducido químicamente , Pólipos Nasales/tratamiento farmacológico , Prostaglandinas , Rinitis/inducido químicamente , Rinitis/tratamiento farmacológico , Sinusitis/inducido químicamente , Sinusitis/tratamiento farmacológicoRESUMEN
BACKGROUND: Patients with aspirin-exacerbated respiratory disease (AERD) are among the most challenging rhinologic patients to treat. AERD has a complex inflammatory milieu of lipid mediators and cytokines. In this study we evaluated cytokine differences in the complex AERD environment at the mucus, epithelial, and tissue levels. METHODS: Samples were acquired at the time of sinus surgery from 21 patients (seven steroid-treated, 14 untreated) with aspirin challenge-confirmed AERD. Three methods (sponge adsorption, epithelial brushing, tissue biopsy) were used to acquire samples from the respective sinus sampling sites (mucus, polyp epithelium, and full-thickness polyp) of each patient. We measured and compared 16 cytokine concentrations in AERD patients with or without prednisone treatment using the Luminex platform. RESULTS: In most sampling sites, IL-5, IL-6, IL-10, IL-13, IL-33, CCL20, and TNF-α were detected at higher concentrations than IFN-γ, IL-1ß, IL-17A, IL-4, IL-22, IL-17E/IL25, and GM-CSF. Each sampling site had a different pattern of cytokine levels, and except for IL-5 and IL-25 there was no correlation among sampling methods for each cytokine tested. The most notable and significant decreases in cytokines from those treated with prednisone were observed in the epithelium for IL-5, IL-10, IL-33, and IFN-γ. CONCLUSIONS: In the epithelial samples, type 2-associated cytokines IL-5 and IL-33, the anti-inflammatory cytokine IL-10, and IFN-γ were lower in AERD patients treated with prednisone. This work serves as a basis to assess therapeutic-induced mucosal cytokine responses in AERD and indicates that the site of cytokine measurement is an important consideration when assessing results.
Asunto(s)
Asma Inducida por Aspirina , Pólipos Nasales , Sinusitis , Aspirina/efectos adversos , Asma Inducida por Aspirina/tratamiento farmacológico , Citocinas , Factor Estimulante de Colonias de Granulocitos y Macrófagos , Humanos , Interleucina-10 , Interleucina-13 , Interleucina-17 , Interleucina-33 , Interleucina-4 , Interleucina-5 , Interleucina-6 , Lípidos , Pólipos Nasales/tratamiento farmacológico , Prednisona/uso terapéutico , Sinusitis/inducido químicamente , Factor de Necrosis Tumoral alfaRESUMEN
BACKGROUND: Pathophysiology-targeting treatments exist for aspirin-exacerbated respiratory disease (AERD) through aspirin desensitization and biologics, such as dupilumab. With increasing attention paid to these treatments, which may be associated with significant side effects and/or cost, there is little description of chronic rhinosinusitis with nasal polyps (CRSwNP) response to treatment with intranasal corticosteroids and saline irrigations in AERD. OBJECTIVE: To determine the effect of intranasal budesonide irrigations for the treatment of CRSwNP in AERD. METHODS: This is an observational study of 14 AERD patients presenting to a rhinology clinic for CRS who were treated with twice daily high volume, low pressure irrigations with 240 mL of saline to which a 0.5 mg/2 mL respule of budesonide was added. All participants completed a 22-item Sinonasal Outcome Test (SNOT-22) at enrollment and at follow up 1 to 6 months later. Polyp scores were also calculated at each time point. RESULTS: SNOT-22 scores ranged from 26 to 98 (median: 40.5) at enrollment and 3 to 85 (median: 38.5) at follow-up. Polyp scores ranged from 2 to 6 (median: 4) at enrollment at 0 to 6 (median: 2) at follow-up. Over the treatment period, change in SNOT-22 score ranged from -38 to 16 (median: -18) and change in polyp score ranged from -2 to 0 (median: -0.5). Approximately 57% of participants experienced at least 1 minimal clinically important difference in SNOT-22 score and 21% of participants had a SNOT-22 score <20 at follow-up. CONCLUSION: Medical management with intranasal corticosteroids and saline irrigations alone leads to significant improvement in sinonasal symptomatology in a subset of AERD.
Asunto(s)
Asma Inducida por Aspirina , Pólipos Nasales , Rinitis , Sinusitis , Corticoesteroides/uso terapéutico , Aspirina/efectos adversos , Asma Inducida por Aspirina/terapia , Budesonida/efectos adversos , Enfermedad Crónica , Humanos , Pólipos Nasales/complicaciones , Pólipos Nasales/tratamiento farmacológico , Rinitis/inducido químicamente , Rinitis/complicaciones , Rinitis/tratamiento farmacológico , Sinusitis/inducido químicamente , Sinusitis/complicaciones , Sinusitis/tratamiento farmacológicoRESUMEN
Intranasal corticosteroid drugs are widely used in chronic rhinosinusitis with nasal polyps (CRSwNP). In contrast to classical delivery with nasal pump sprays, pulsating aerosols can deliver significant doses into superior and posterior sinonasal spaces. A case-control study was designed to assess the efficacy of corticosteroid transnasal nebulization on short-term mucosal recovery and quality of life (QoL) following endoscopic sinus surgery in CRSwNP. Thirty patients were prospectively enrolled to receive either 1-month budesonide nasal pump spray or 1-month budesonide 100-Hz acoustic pulsating nebulization at the first postoperative visit (day 8). Patients were evaluated with Lund-Kennedy endoscopic score at day 8 (D8) and 1 month later (M1). CRS-related QoL questionnaires (SNOT22 and RhinoQOL) were fulfilled at M1. The Lund-Kennedy endoscopic scores compared between D8 and M1 were suggestively improved in the group treated with budesonide nebulization (mean difference between groups, - 18.28 units; 95%CI, - 31.29 to - 5.28 units, p = 0.014). QoL measurements were comparable at M1 between the groups of patients. No unexpected adverse event was described with both budesonide delivery protocols. In the early postoperative period, patients with CRswNP may benefit from pulsating nebulization. Large studies should be conducted to confirm the results. Safety profile related to systemic steroid absorption and bioavailability in chronic respiratory diseases also need to be addressed for further use.