salicylates and Nasal-Polyps

Aspirin-exacerbated respiratory disease (AERD) refers to the combination of asthma, chronic rhinosinusitis with nasal polyposis, and acute upper and lower respiratory tract reactions to the ingestion of aspirin (acetylsalicylic acid, ASA) and other cyclooxygenase-1 inhibiting non-steroidal anti-inflammatory drugs. AERD affects 0.3-0.9 % of the general population. AERD generally occurs due to abnormalities in mediators and expression of arachidonic acid biosynthesis. Local IgE responses to staphylococcal enterotoxins may also be responsible for eosinophilic activation in the nasal polyp tissues of AERD patients. Clinical features of AERD include the onset of nasal congestion with anosmia, progressing to chronic pansinusitis and nasal polyps that regrow rapidly after surgery. Aspirin desensitization, Leukotriene-modifying agents, biologic agents, management of asthma, chronic rhinosinusitis, and nasal polyposis are recommended as treatment modalities. Immunotherapy is prescribed only to those AERD patients who experience clear seasonal or perennial allergy symptoms in addition to the symptoms attributable to chronic nasal polyposis. There are also investigational and dietary therapies. In this review, the important aspects of AERD will be presented, along with a literature survey.

Topics: Algorithms; Anti-Allergic Agents; Anti-Inflammatory Agents, Non-Steroidal; Antibodies, Monoclonal, Humanized; Aspirin; Asthma; Desensitization, Immunologic; Diet; Humans; Immunotherapy; Leukotriene Antagonists; Nasal Polyps; Omalizumab; Rhinitis; Salicylates; Sinusitis

Aspirin-exacerbated respiratory disease (AERD) is characterized by eosinophilic rhinosinusitis, nasal polyposis, and bronchial asthma, along with the onset of respiratory reactions after the ingestion of nonsteroidal anti-inflammatory drugs (NSAIDs) or acetylsalicylic acid (ASA). In addition to the therapeutic routines and surgical options available, a low dietary intake of food salicylate has been suggested as adjunctive therapy for this condition. This study aimed to assess the influence of a short-term low salicylate diet on inflammatory markers in patients with AERD and whether that would result in symptomatic improvement.. Prospective study with randomization to either a high or low salicylate diet for 1 week, followed by cross-over to the other study arm. Participants were asked to record their dietary salicylate for each week of the study. Urinary creatinine, salicylate and leukotriene levels were measured at the time of recruitment, end of week one and end of week two and the SNOT-22 questionnaire was filled out at the same time points.. A total of seven participants completed the study. There was no statistical difference in the urinary salicylate and leukotriene levels between the two diets; nevertheless, participants on low salicylate diet reported improved SNOT-22 symptoms scores (p = 0.04), mainly in the rhinologic, ear/facial, and sleep dysfunction symptom domains. In addition, these last two domains outcomes were more significant than the minimal clinically important difference.. A short-term low salicylate diet may not result in biochemical outcomes changes but seems to provide significant symptomatic relief for patients with AERD.. NCT01778465 ( www.clinicaltrials.gov ).

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Asthma, Aspirin-Induced; Biomarkers; Cross-Over Studies; Female; Humans; Male; Middle Aged; Nasal Polyps; Salicylates; Sino-Nasal Outcome Test; Sinusitis

Aspirin exacerbated respiratory disease (AERD) is comprised of aspirin/acetylsalicylic acid (ASA) sensitivity, bronchial asthma, and nasal polyposis. Treatment of this condition is challenging and may include topical/systemic steroids, endoscopic sinus surgery, and/or aspirin desensitization.. A prospective crossover pilot study (n = 10) was conducted in which patients were randomized into either of 2 groups with 6 weeks of regular diet (R) or 6 weeks of a low salicylate diet (LS).. The study was conducted in a tertiary otolaryngology clinic.. Patients with AERD were enrolled in the study.. Subjective (Sino-nasal Outcome Test-22 [SNOT-22], Nasal Sinus Symptom Scale [NSSS], and the Asthma Control Questionnaire-7 [ACQ-7]) and objective outcome instruments (Peri-Operative Sinus Evaluation [POSE] and Lund-Kennedy Endoscopic Score [LKES]) were used to evaluate patients at baseline, 6 weeks (at crossover), and 12 weeks.. Wilcoxon rank sum tests demonstrated that patients on the low salicylate diet had improved scores compared to their regular diet when evaluated by 4 of the 5 outcome measures (SNOT-22 pLS = 0.0059, NSSS pLS = 0.0195, LKES pLS = 0.0039, POSE pLS = 0.005).. Results of the pilot study indicate that implementation of a low salicylate diet improves the nasal symptoms and nasal endoscopy findings of individuals with AERD. Further research is required to support these findings.

Topics: Adult; Aged; Aspirin; Asthma; Cross-Over Studies; Desensitization, Immunologic; Drug Hypersensitivity; Female; Humans; Male; Middle Aged; Nasal Polyps; Pilot Projects; Prospective Studies; Respiratory Tract Diseases; Rhinitis; Salicylates; Single-Blind Method; Sinusitis

Pharmacological salicylates are known to trigger respiratory exacerbations in patients with Non-Steroidal Exacerbated Respiratory Disease (N-ERD), a specific phenotype of Chronic Rhinosinusitis (CRS) and asthma. The impact of dietary sources of salicylates across subgroups of CRS is not well understood. The hypothesis is that in patients with nasal polyps present, there is likely to be a higher incidence of symptom exacerbation due to dietary salicylates regardless of any known response to pharmacological salicylate.. The Chronic Rhinosinusitis Epidemiology Study (CRES) was a questionnaire-based case-control study which sought to characterise the UK CRS population in terms of sociological, economic and medical factors. Using specific questions to examine participant responses relating to symptom exacerbation from food groups thought to be high in salicylate content, this analysis of the CRES database sought to compare an estimate of the prevalence of dietary sensitivity due to food with higher potential salicylate content across patients with CRS with (CRSwNPs) and without nasal polyposis (CRSsNPs) and with allergic fungal rhinosinusitis (AFRS).. The CRSwNPs group were significantly more likely than controls to report symptom exacerbation due to ingestion of food groups with higher potential dietary salicylate content. The same trend was observed amongst CRSsNPs participants to a lesser degree. Reported response to the individual specific food groups wine, nuts, spicy foods, fruit and vegetables demonstrated that a statistically significant proportion of CRSwNPs and AFRS participants reported sensitivity to wine.. This analysis suggests that there is an association between symptom exacerbation in response to food products with higher potential salicylate content, specifically wine, in CRS patients both with and without nasal polyposis when compared to controls, but especially in the CRSwNPs and AFRS phenotypes. Further studies are needed to detail if this relationship represents a causal relationship to dietary salicylate. The data present the possibility that a wider group of CRS patients may elicit salicylate sensitivity than those with known N-ERD.

Topics: Case-Control Studies; Chronic Disease; Diet; Epidemiologic Studies; Humans; Nasal Polyps; Rhinitis; Salicylates; Sinusitis; United Kingdom

A clear association between allergy and nasal polyposis (NP) is not determined and the role of food intolerance in patients with NP is not investigated by oral food challenge (OFC).. To investigate the relation of salicylate food intolerance and atopy in patients with NP according to recurrence and aspirin sensitivity.. A cross sectional multicenter study was done in two tertiary centers for allergy in Iran. Adult patients with NP were selected for the study that had been referred to allergy clinics. The oral aspirin challenge (OAC) test was performed to identify aspirin exacerbated respiratory disease (AERD) and the OFC test was used to investigate food intolerance. Atopic evaluation was performed by skin-prick tests, nasal smear and blood eosinophil count as well as serum total IgE.. One hundred and nineteen Iranian patients (female to male ratio 1.05) with NP were enrolled (mean age, 38 ± 11 years). Recurrence of nasal polyposis was 64.7%. OAC was performed in all cases; 43.79% cases had aspirin hypersensitivity. In addition, OFC tests determined that 69.9% of patients had salicylate food allergy. Salicylate food intolerance was significantly higher in NP cases with AERD than in aspirin tolerant patients (p<0.05). Yet, positive skin prick test was not associated with NP recurrence and AERD.. Atopy and NSAID exacerbated respiratory disease; therefore, they can both be considered as predictors of NP recurrence. Our study also showed that salicylate food intolerance was associated with AERD in nasal polyposis.

Topics: Adult; Allergens; Aspirin; Cross-Sectional Studies; Drug Hypersensitivity; Female; Food Hypersensitivity; Humans; Iran; Male; Middle Aged; Nasal Polyps; Prognosis; Salicylates; Skin Tests

Channel activators (potentiators) of cystic fibrosis (CF) transmembrane conductance regulator (CFTR), can be used for the treatment of the small subset of CF patients that carry plasma membrane-resident CFTR mutants. However, approximately 90% of CF patients carry the misfolded ΔF508-CFTR and are poorly responsive to potentiators, because ΔF508-CFTR is intrinsically unstable at the plasma membrane (PM) even if rescued by pharmacological correctors. We have demonstrated that human and mouse CF airways are autophagy deficient due to functional sequestration of BECN1 and that the tissue transglutaminase-2 inhibitor, cystamine, or antioxidants restore BECN1-dependent autophagy and reduce SQSTM1/p62 levels, thus favoring ΔF508-CFTR trafficking to the epithelial surface. Here, we investigated whether these treatments could facilitate the beneficial action of potentiators on ΔF508-CFTR homozygous airways. Cystamine or the superoxide dismutase (SOD)/catalase-mimetic EUK-134 stabilized ΔF508-CFTR at the plasma membrane of airway epithelial cells and sustained the expression of CFTR at the epithelial surface well beyond drug withdrawal, overexpressing BECN1 and depleting SQSTM1. This facilitates the beneficial action of potentiators in controlling inflammation in ex vivo ΔF508-CFTR homozygous human nasal biopsies and in vivo in mouse ΔF508-CFTR lungs. Direct depletion of Sqstm1 by shRNAs in vivo in ΔF508-CFTR mice synergized with potentiators in sustaining surface CFTR expression and suppressing inflammation. Cystamine pre-treatment restored ΔF508-CFTR response to the CFTR potentiators genistein, Vrx-532 or Vrx-770 in freshly isolated brushed nasal epithelial cells from ΔF508-CFTR homozygous patients. These findings delineate a novel therapeutic strategy for the treatment of CF patients with the ΔF508-CFTR mutation in which patients are first treated with cystamine and subsequently pulsed with CFTR potentiators.

Topics: Adaptor Proteins, Signal Transducing; Adolescent; Animals; Antioxidants; Apoptosis Regulatory Proteins; Autophagy; Beclin-1; Cell Membrane; Child; Cystamine; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Epithelial Cells; Epithelium; Female; Genistein; Heat-Shock Proteins; Humans; Inflammation; Lipopolysaccharides; Lung; Male; Membrane Proteins; Mice; Molecular Targeted Therapy; Nasal Mucosa; Nasal Polyps; Organometallic Compounds; Protein Glutamine gamma Glutamyltransferase 2; Salicylates; Sequestosome-1 Protein

Accumulation of unwanted/misfolded proteins in aggregates has been observed in airways of patients with cystic fibrosis (CF), a life-threatening genetic disorder caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). Here we show how the defective CFTR results in defective autophagy and decreases the clearance of aggresomes. Defective CFTR-induced upregulation of reactive oxygen species (ROS) and tissue transglutaminase (TG2) drive the crosslinking of beclin 1, leading to sequestration of phosphatidylinositol-3-kinase (PI(3)K) complex III and accumulation of p62, which regulates aggresome formation. Both CFTR knockdown and the overexpression of green fluorescent protein (GFP)-tagged-CFTR(F508del) induce beclin 1 downregulation and defective autophagy in non-CF airway epithelia through the ROS-TG2 pathway. Restoration of beclin 1 and autophagy by either beclin 1 overexpression, cystamine or antioxidants rescues the localization of the beclin 1 interactome to the endoplasmic reticulum and reverts the CF airway phenotype in vitro, in vivo in Scnn1b-transgenic and Cftr(F508del) homozygous mice, and in human CF nasal biopsies. Restoring beclin 1 or knocking down p62 rescued the trafficking of CFTR(F508del) to the cell surface. These data link the CFTR defect to autophagy deficiency, leading to the accumulation of protein aggregates and to lung inflammation.

Topics: Acetylcysteine; Adaptor Proteins, Signal Transducing; Adolescent; Adult; Animals; Antioxidants; Apoptosis Regulatory Proteins; Autophagy; Beclin-1; Cell Line; Cystamine; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Epithelial Sodium Channels; GTP-Binding Proteins; Heat-Shock Proteins; Humans; Inflammation; Membrane Proteins; Mice; Mice, Inbred CFTR; Mice, Inbred Strains; Mice, Transgenic; Microtubule-Associated Proteins; Models, Biological; Nasal Polyps; Organometallic Compounds; Phosphatidylinositol 3-Kinases; Phosphoinositide-3 Kinase Inhibitors; Protein Binding; Protein Glutamine gamma Glutamyltransferase 2; Protein Transport; Reactive Oxygen Species; Respiratory Mucosa; Salicylates; Sequestosome-1 Protein; Small Ubiquitin-Related Modifier Proteins; Transglutaminases; Young Adult

A woman experienced exacerbations of bronchial asthma after taking aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) for rheumatoid arthritis. On oral challenges, she developed an urticarial reaction after tartrazine; urticarial and bronchospastic reactions after salicylsalicylic acid; and urticarial and bronchospastic reactions after choline magnesium trisalicylate. Non-acetylated salicylates have been recommended for use in aspirin- and/or tartrazine-sensitive patients. The results of sensitivity studies of our patient indicates that such patients may also be sensitive to non-acetylated salicylates.

Topics: Albuterol; Arthritis, Rheumatoid; Asthma; Bronchial Spasm; Choline; Drug Combinations; Drug Hypersensitivity; Female; Humans; Middle Aged; Nasal Polyps; Salicylates; Tartrazine; Urticaria

Topics: Amino Acids; Animals; Aspirin; Asthma; Binding Sites; Cystic Fibrosis; Drug Hypersensitivity; Heterozygote; Humans; Immunoglobulins; Karyotyping; Nasal Polyps; Protein Binding; Rabbits; Salicylates; Saliva; Serum Globulins; Sweat; Time Factors; Tryptophan