Oral Sebetralstat for On-Demand Treatment of Hereditary Angioedema Attacks.

BACKGROUND: Approved on-demand treatments for hereditary angioedema attacks need to be administered parenterally, a route of administration that is associated with delays in treatment or withholding of therapy. METHODS: In this phase 3, double-blind, three-way crossover trial, we randomly assigned participants at least 12 years of age with type 1 or type 2 hereditary angioedema to take up to two oral doses of sebetralstat (300 mg or 600 mg) or placebo for an angioedema attack. The primary end point, assessed in a time-to-event analysis, was the beginning of symptom relief, defined as a rating of "a little better" on the Patient Global Impression of Change scale (ratings range from "much worse" to "much better") at two or more consecutive time points within 12 hours after the first administration of the trial agent. Key secondary end points, assessed in a time-to-event analysis, were a reduction in attack severity (an improved rating on the Patient Global Impression of Severity [PGI-S] scale, with ratings ranging from "none" to "very severe") at two or more consecutive time points within 12 hours and complete attack resolution (a rating of "none" on the PGI-S scale) within 24 hours. RESULTS: A total of 136 participants were assigned to one of six trial sequences, with 110 treating 264 attacks. The time to the beginning of symptom relief with the 300-mg dose and the 600-mg dose was faster than with placebo (P<0.001 and P = 0.001 for the two comparisons, respectively), with median times of 1.61 hours (interquartile range, 0.78 to 7.04), 1.79 hours (1.02 to 3.79), and 6.72 hours (1.34 to >12), respectively. The time to reduction in the attack severity with the 300-mg dose and the 600-mg dose was faster than with placebo (P = 0.004 and P = 0.003), with median times of 9.27 hours (interquartile range, 1.53 to >12), 7.75 hours (2.19 to >12), and more than 12 hours (6.23 to >12). The time to complete resolution was faster with the 300-mg and 600-mg doses than with placebo (P = 0.002 and P<0.001). The percentage of attacks with complete resolution within 24 hours was 42.5% with the 300-mg dose, 49.5% with the 600-mg dose, and 27.4% with placebo. Sebetralstat and placebo had similar safety profiles; no serious adverse events related to the trial agents were reported. CONCLUSIONS: Oral sebetralstat provided faster times to the beginning of symptom relief, reduction in attack severity, and complete attack resolution than placebo. (Funded by KalVista Pharmaceuticals; KONFIDENT ClinicalTrials.gov number, NCT05259917; EudraCT number, 2021-001226-21.).

Spirulina (Arthrospira platensis): Antiallergic Agent or Hidden Allergen? A Literature Review.

Presently, there has been an increase in the consumption of the blue-green microalga-spirulina (Arthrospira species), which dominates 99.5% of the total world production of microalgae. Primarily sold as a dietary supplement, it is also incorporated into snacks, pasta, cookies, and bread. Owing to its nutrient abundance, spirulina has a variety of potential applications. Extensive studies have been conducted on the health benefits of spirulina, but its safety in terms of allergy has received limited attention. Therefore, to bridge this knowledge deficit, this review aimed to evaluate the allergenic and antiallergic potential of spirulina. In the PubMed and Scopus databases using words related to allergy, we attempted to detect papers on hypersensitivity to spirulina. A total of 128 records were identified, of which 49 were screened. Ultimately, in this review, we analyzed four case studies, encompassing a total of five patients with allergies to spirulina. We assessed the severity of allergic reactions following World Allergy Organization (WAO) Anaphylaxis Guidance 2020, which varied from mild (grade 2) to severe (grade 4) based on the patient's symptoms. Additionally, our findings indicate that allergy to spirulina is not commonly reported or diagnosed. However, most of the described cases (four of five) regarding allergy to spirulina according to WAO Anaphylaxis Guidance 2020 were classified as anaphylaxis. Furthermore, it is noteworthy that spirulina also possesses antiallergic properties, as evidenced by research studies. Our article delves into both the allergic and antiallergic potential of spirulina.

Evaluation of respiratory allergies burden and management in primary care and comparative analysis of health care data from Romania, Poland, Czech Republic and Bulgaria - preliminary study.

BACKGROUND: Respiratory allergies mostly allergic rhinitis and asthma represent an important and increasing public health problem and one of the priorities for the European health systems. There is an increasing public concern regarding the persistence and severity of allergic diseases and many difficulties of health systems in providing prompt specialized medical assistance. Our study aims to highlight the main results of the Alliance 4Life project focused on the evaluation of the burden and management of respiratory allergies in primary care from Romania and comparative health-related data from four Central and Eastern European countries. METHOD: We developed a questionnaire focused on patients with allergic rhinitis and asthma directly addressed to general practitioner (GP) specialists from Romania who attended the annual national conference in Bucharest. RESULTS: The main results showed that patients with respiratory allergies are frequently encountered in primary care practice, only a few patients are evaluated by allergists and there is a clear need for education in this field. CONCLUSIONS: This preliminary study confirms that respiratory allergies represent a considerable burden in primary care and the questionnaire may be a useful tool in further studies considering the experience of other healthcare systems. More advanced studies integrating epidemiology with data on air pollution and environmental conditions should be envisaged.

Challenges in Local Allergic Rhinitis Diagnosis, Management, and Research: Current Concepts and Future Perspectives.

Local allergic rhinitis (LAR) is diagnosed based on the presence of clinical symptoms such as rhinorrhea, sneezing, and nasal itching using negative skin prick testing and serum IgE assessment. Several novel studies have shown that it is possible to use the assessment of nasal sIgE (specific immunoglobulin E) secretion as an additional diagnostic criterion for local allergic rhinitis. Additionally, allergen immunotherapy is a promising-albeit still not fully assessed and evaluated-future method of managing patients with LAR. In this review, the historical background, epidemiology, and main pathophysiological mechanisms of LAR shall be presented. Additionally, we address the current state of knowledge based on selected articles regarding the assessment of the local mucosal IgE presence in response to exposure to such allergens as mites, pollen, molds, and others. The impact of LAR on quality of life as well as the possible options of management (including allergen immunotherapy (AIT), which showed promising results) will then be presented.

Chronic Urticaria Treatment with Omalizumab-Verification of NLR, PLR, SIRI and SII as Biomarkers and Predictors of Treatment Efficacy.

Biomarkers that are able to predict the response to omalizumab (OMA) in chronic spontaneous urticaria (CSU) are highly valued. The aim of our study was to evaluate the UAS7 (urticaria activity score assessed for 7 days), DLQI (dermatology life quality index), SII (systemic immune-inflammation index), SIRI (systemic inflammation response index), PLR (platelet/lymphocyte ratio) and NLR (neutrophil/lymphocyte ratio) in a group of 46 CSU a patients treated for 24 weeks with OMA (300 mg every 4 weeks). There were no statistically significant differences observed at the start nor at the end of the treatment between the two groups (responders vs. non-responders) and SII, SIRI, PLR and NLR. However, a statistically significant correlation was observed between severity of urticaria expressed in UAS7 scores and the quality of life (evaluated by DLQI). Furthermore, at week 24, both groups demonstrated significant improvement in quality of life. Our single center study did not confirm the usefulness of SII, SIRI, NLR or PLR as predictors of the response to OMA in CSU. However, it is of importance that even patients who did not respond to the treatment presented a significant improvement in quality of life. Additionally, we also observed that the efficacy of treatment was unchanged amongst patients who underwent a second series of treatment in cases of relapse.

Physical exercise, immune response, and susceptibility to infections-current knowledge and growing research areas.

This review presents state-of-the-art knowledge and identifies knowledge gaps for future research in the area of exercise-associated modifications of infection susceptibility. Regular moderate-intensity exercise is believed to have beneficial effects on immune health through lowering inflammation intensity and reducing susceptibility to respiratory infections. However, strenuous exercise, as performed by professional athletes, may promote infection: in about half of athletes presenting respiratory symptoms, no causative pathogen can be identified. Acute bouts of exercise enhance the release of pro-inflammatory mediators, which may induce infection-like respiratory symptoms. Relatively few studies have assessed the influence of regularly repeated exercise on the immune response and systemic inflammation compared to the effects of acute exercise. Additionally, ambient and environmental conditions may modify the systemic inflammatory response and infection susceptibility, particularly in outdoor athletes. Both acute and chronic regular exercise influence humoral and cellular immune response mechanisms, resulting in decreased specific and non-specific response in competitive athletes. The most promising areas of further research in exercise immunology include detailed immunological characterization of infection-prone and infection-resistant athletes, examining the efficacy of nutritional and pharmaceutical interventions as countermeasures to infection symptoms, and determining the influence of various exercise loads on susceptibility to infections with respiratory viruses, including SARS-CoV-2. By establishing a uniform definition of an "elite athlete," it will be possible to make a comparable and straightforward interpretation of data from different studies and settings.

Health effects of exposure to chlorination by-products in swimming pools.

Concerns have been raised regarding the potential negative effects on human health of water disinfectants used in swimming pools. Among the disinfection options, the approaches using chlorine-based products have been typically preferred. Chlorine readily reacts with natural organic matter that are introduced in the water mainly through the bathers, leading to the formation of potentially harmful chlorination by-products (CBPs). The formation of CBPs is of particular concern since some have been epidemiologically associated with the development of various clinical manifestations. The higher the concentration of volatile CBPs in the water, the higher their concentration in the air above the pool, and different routes of exposure to chemicals in swimming pools (water ingestion, skin absorption, and inhalation) contribute to the individual exposome. Some CBPs may affect the respiratory and skin health of those who stay indoor for long periods, such as swimming instructors, pool staff, and competitive swimmers. Whether those who use chlorinated pools as customers, particularly children, may also be affected has been a matter of debate. In this article, we discuss the current evidence regarding the health effects of both acute and chronic exposures in different populations (work-related exposures, intensive sports, and recreational attendance) and identify the main recommendations and unmet needs for research in this area.

Prevalence and early-life risk factors of school-age allergic multimorbidity: The EuroPrevall-iFAAM birth cohort.

BACKGROUND: Coexistence of childhood asthma, eczema and allergic rhinitis is higher than can be expected by chance, suggesting a common mechanism. Data on allergic multimorbidity from a pan-European, population-based birth cohort study have been lacking. This study compares the prevalence and early-life risk factors of these diseases in European primary school children. METHODS: In the prospective multicentre observational EuroPrevall-iFAAM birth cohort study, we used standardized questionnaires on sociodemographics, medical history, parental allergies and lifestyle, and environmental exposures at birth, 12 and 24 months. At primary school age, parents answered ISAAC-based questions on current asthma, rhinitis and eczema. Allergic multimorbidity was defined as the coexistence of at least two of these. RESULTS: From 10,563 children recruited at birth in 8 study centres, we included data from 5,572 children (mean age 8.2 years; 51.8% boys). Prevalence estimates were as follows: asthma, 8.1%; allergic rhinitis, 13.3%; and eczema, 12.0%. Allergic multimorbidity was seen in 7.0% of the whole cohort, ranging from 1.2% (Athens, Greece) to 10.9% (Madrid, Spain). Risk factors for allergic multimorbidity, identified with AICc, included family-allergy-score, odds ratio (OR) 1.50 (95% CI 1.32-1.70) per standard deviation; early-life allergy symptoms, OR 2.72 (2.34-3.16) for each symptom; and caesarean birth, OR 1.35 (1.04-1.76). Female gender, OR 0.72 (0.58-0.90); older siblings, OR 0.79 (0.63-0.99); and day care, OR 0.81 (0.63-1.06) were protective factors. CONCLUSION: Allergic multimorbidity should be regarded as an important chronic childhood disease in Europe. Some of the associated early-life factors are modifiable and may be considered for prevention strategies.

Frequency of food allergy in school-aged children in eight European countries-The EuroPrevall-iFAAM birth cohort.

BACKGROUND: The prevalence of food allergy (FA) among European school children is poorly defined. Estimates have commonly been based on parent-reported symptoms. We aimed to estimate the frequency of FA and sensitization against food allergens in primary school children in eight European countries. METHODS: A follow-up assessment at age 6-10 years of a multicentre European birth cohort based was undertaken using an online parental questionnaire, clinical visits including structured interviews and skin prick tests (SPT). Children with suspected FA were scheduled for double-blind, placebo-controlled oral food challenges (DBPCFC). RESULTS: A total of 6105 children participated in this school-age follow-up (57.8% of 10 563 recruited at birth). For 982 of 6069 children (16.2%), parents reported adverse reactions after food consumption in the online questionnaire. Of 2288 children with parental face-to-face interviews and/or skin prick testing, 238 (10.4%) were eligible for a DBPCFC. Sixty-three foods were challenge-tested in 46 children. Twenty food challenges were positive in 17 children, including seven to hazelnut and three to peanut. Another seventy-one children were estimated to suffer FA among those who were eligible but refused DBPCFC. This yielded prevalence estimates for FA in school age between 1.4% (88 related to all 6105 participants of this follow-up) and 3.8% (88 related to 2289 with completed eligibility assessment). INTERPRETATION: In primary school children in eight European countries, the prevalence of FA was lower than expected even though parents of this cohort have become especially aware of allergic reactions to food. There was moderate variation between centres hampering valid regional comparisons.

Circulating MicroRNAs and T-Cell Cytokine Expression Are Associated With the Characteristics of Asthma Exacerbation.

PURPOSE: Immunological mechanisms underlying asthma exacerbation have not been elucidated. The aim of this study was to assess the associations of various asthma exacerbation traits with selected serum microRNA (miRNA) expression and T-cell subpopulations. METHODS: Twenty-one asthmatics were studied during asthma exacerbation (exacerbation visit [EV] and the follow-up visit [FV] at 6 weeks). At both visits, spirometry was performed, fractional exhaled nitric oxide (FeNO) was measured, and nasopharyngeal and blood samples were collected. In nasopharyngeal samples, respiratory viruses were assayed by multiplex polymerase chain reaction (PCR), and bacterial cultures were performed. Serum miRNAs were assayed with real-time PCR. T-cell surface markers, eosinophil progenitors and intracellular cytokines were assessed by flow cytometry. RESULTS: Two-thirds of patients had moderate or severe exacerbation and the FV, overall improvement in asthma control was observed. The mean expression of serum miRNA-126a, miRNA-16 and miRNA-21 was significantly lower at the EV than at the FV. At EV, miRNA-29b correlated with FeNO (r = 0.44, P < 0.05), and 5 of 7 miRNA tested correlated with pulmonary function tests. The number of cluster of differentiation (CD)45+CD4+interleukin (IL)4+ cells was significantly higher at the EV than at the FV, and positive correlations of T-regulatory cells and eosinophil progenitors with asthma control was found. At the EV, serum miRNAs negatively correlated with the number of T cells expressing IL-4, IL-17, IL-22 and interferon gamma, while at the FV both positive and negative correlations with T-cell subsets were observed. No association of detected pathogen (viruses and bacteria) in nasopharyngeal fluid with clinical, functional and immunological parameters was found. CONCLUSIONS: Epigenetic dysregulation during asthma exacerbation could be related to respiratory function, airway inflammation and T-cell cytokine expression.

Parainfluenza virus infection enhances NSAIDs-induced inhibition of PGE2 generation and COX-2 expression in human airway epithelial cells.

PURPOSE: Respiratory viral infection and nonsteroidal anti-inflammatory drugs (NSAIDs) may affect arachidonic acid (AA) metabolism in the airway epithelium, however their joint effect has not been studied. We hypothesized, that alternations of AA metabolism in human airway epithelial cells (ECs) - induced by Parainfluenza virus type 3 (PIV3) - may be modified by concomitant treatment with NSAIDs. MATERIALS AND METHODS: Nasal (RPMI 2650) and bronchial (BEAS-2B) epithelial cells were cultured into confluence and then infected with PIV3. Prostaglandin E2 (PGE2) and 15-hydroxyeicosatetraenoic acid (15-HETE) levels in cell supernatants were measured by ELISA and expression of cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LO) and 15-lipoxygenase (15-LO) mRNA in cells was evaluated after reverse transcription with real-time polymerase chain reactions. RESULTS: PGE2 generation was decreased by PIV3 infection in the upper airway epithelial cells, and increased in the lower airway epithelial cells. Both naproxen and celecoxib induced significant reduction in PGE2 release in both infected and non-infected upper and lower airway epithelial cells. However, in PIV3-infected epithelial cells celecoxib inhibited PGE2 release and COX-2 expression to significantly higher degree as compared to non-infected cells. 15-HETE generation or COX-1, 5-LO and 15-LO expression were not affected by the virus infection or by NSAIDs. CONCLUSION: Virus infection in airway epithelial cells enhances inhibitory effect of NSAIDs on prostaglandin E2 generation.

Asthma and exercise-induced respiratory disorders in athletes. The position paper of the Polish Society of Allergology and Polish Society of Sports Medicine.

Exercise-induced respiratory symptoms describe acute airway narrowing that occurs as a result of exercise. It includes exercise-induced bronchoconstriction (EIB) and exercise-induced asthma (EIA) issues. To provide clinicians with practical guidelines, a multidisciplinary panel of stakeholders was convened to review the pathogenesis of EIB/EIA and to develop evidence-based guidelines for the diagnosis and treatment. Recommendations for the diagnosis and treatment of EIB were developed. High-intensity exercise in polluted environment (cold air, humidity, contamination, allergens) may increase the risk of EIB and asthma symptoms in athletes. Diagnostic procedures should include history taking, physical examination, atopy assessment and functional tests of the respiratory system. A strong recommendation was made for regular use of inhaled glucocorticosteroids and avoidance of short-acting ß2-agonists as the only treatment. The treatment of asthma in athletes should always take into account current anti-doping regulations. This position paper reflects the currently available evidence.

Toll-Like Receptor Agonists Modulate Wound Regeneration in Airway Epithelial Cells.

BACKGROUND: Impaired regeneration of airway epithelium may lead to persistence of inflammation and remodelling. Regeneration of injured epithelium is a complex phenomenon and the role of toll-like receptors (TLRs) in the stimulation of respiratory virus products in this process has not been established. OBJECTIVE: This study was undertaken to test the hypothesis that the wound repair process in airway epithelium is modulated by microbial products via toll-like receptors. METHODS: Injured and not-injured bronchial epithelial cells (ECs) (BEAS-2B line) were incubated with the TLR agonists poly(I:C), lipopolisacharide (LPS), allergen Der p1, and supernatants from virus-infected epithelial cells, either alone or in combination with TLR inhibitors. Regeneration and immune response in injured and not-injured cells were studied. RESULTS: Addition of either poly(I:C) or LPS to ECs induced a marked inhibition of wound repair. Supernatants from RV1b-infected cells also decreased regeneration. Preincubation of injured and not-injured ECs with TLR inhibitors decreased LPS and poly(I:C)-induced repair inhibition. TGF-ß and RANTES mRNA expression was higher in injured ECs and IFN-α, IFN-ß, IL-8, and VEGF mRNA expression was lower in damaged epithelium as compared to not-injured. Stimulation with poly(I:C) increased IFN-α and IFN-ß mRNA expression in injured cells, and LPS stimulation decreased interferons mRNA expression both in not-injured and injured ECs. CONCLUSION: Regeneration of the airway epithelium is modulated by microbial products via toll-like receptors.

Winter ambient training conditions are associated with increased bronchial hyperreactivity and with shifts in serum innate immunity proteins in young competitive speed skaters.

INTRODUCTION: Regular training modulates airway inflammation and modifies susceptibility to respiratory infections. The impact of exercise and ambient conditions on airway hyperreactivity and innate immunity has not been well studied. We aimed to assess exercise-related symptoms, lung function, airway hyperresponsiveness and innate immunity proteins in relation to meteorological conditions and exercise load in competitive athletes. MATERIAL AND METHODS: Thirty-six speed skaters were assessed during winter (WTP) and summer (STP) periods. The control group comprised 22 non-exercising subjects. An allergy questionnaire for athletes (AQUA) and IPAQ (International Physical Activity Questionnaire) were used to assess symptoms and exercise. Meteorological parameters were acquired from World Meteorological Organization resources. Serum innate immunity proteins were measured by ELISA. RESULTS: Exercise-associated respiratory symptoms were reported by 79.4% of skaters. Despite similar exercise load and lung parameters during both periods, positive methacholine challenge was more frequent during winter (p = 0.04). Heat shock protein HSPA1 and IL-1RA were significantly decreased during STP compared to WTP and controls. During WTP, IL-1RA was elevated in skaters reporting exercise-induced symptoms (p = 0.007). sCD14 was elevated in athletes versus controls in both periods (p < 0.05). HSPA1 was significantly higher in WTP compared to STP irrespective of presence of respiratory tract infections (RTIs). IL-1RA in WTP was elevated versus STP (p = 0.004) only in RTI-negative athletes. Serum IL-1RA negatively correlated with most meteorological parameters during WTP. CONCLUSIONS: Ambient training conditions, but not training load, influence bronchial hyperreactivity and the innate immune response in competitive athletes assessed during winter. The protective effect of regular exercise against respiratory infections is associated with a shift in serum innate immunity proteins.

Serum but not exhaled breath condensate periostin level is increased in competitive athletes.

INTRODUCTION: Periostin is a matricellular protein expressed by many tissues. Its release may be enhanced, among others, through mechanical stimulation of muscles and bones as well as by cytokines of allergic inflammation. OBJECTIVES: Our aim was to assess periostin levels in serum and exhaled breath condensate (EBC) of professional athletes, asthmatics and healthy controls. We also sought to determine whether acute treadmill exercise influences serum and EBC periostin. METHODS: Study groups included 9 competitive swimmers, 10 mild-to-moderate asthmatics and 7 healthy controls. Athletes were assessed twice (in- and off-training period) while asthmatics and controls in one time-point. Data on demographics, allergy symptoms and exercise load were acquired through Allergy Questionnaire for Athletes (AQUA) and International Physical Activity Questionnaire (IPAQ). Serum and EBC were collected before and after treadmill exercise challenge. RESULTS: Baseline serum periostin in swimmers during training period was significantly higher (5- to 7-fold) than in asthmatics (P = .01) and controls (P < .05). In EBC, lowest periostin levels were seen in athletes in-training as compared with off-training period (P < .01) and with asthmatics (P < .03). Acute bout of exercise did not induce significant changes neither in serum nor in EBC periostin in any group. CONCLUSION: Increased serum, but not EBC, periostin levels in competitive athletes are probably because of permanently increased exercise load leading to stimulation, injury and regeneration of musculoskeletal tissues. Periostin may be considered marker of long-term exercise overload after confirmation in larger groups.

A similar pro/anti-inflammatory cytokine balance is present in the airways of competitive athletes and non-exercising asthmatics.

PURPOSE: Intensive exercise modifies airway inflammation and infection susceptibility. We aimed to determine the effect of exercise on pro- and anti-inflammatory cytokine (TNF-α, IL-1ra, IL-10) and innate immunity protein (HSPA1, sCD14) levels in exhaled breath condensate (EBC) and nasal secretions of competitive athletes, non-exercising asthmatics and healthy controls (HC). MATERIAL AND METHODS: The study group consisted of 15 competitive athletes (five speed skaters and ten swimmers) aged 15-25. The control groups comprised 10 mild-to-moderate asthmatics (AC) and seven HC. Athletes were assessed in- and off-training while asthmatics and controls at one time point. Nasal lavages and EBC were collected before and after a treadmill exercise challenge. Protein levels were assessed using ELISA. RESULTS: TNF-α levels in EBC were significantly higher in athletes than HC, but similar to asthmatic patients. In contrast, IL-1ra EBC concentrations were significantly lower in athletes than in HC, but again similar to asthmatics. Significant positive correlations were seen between baseline concentrations of TNF-α in EBC and fall in FEV1 following exercise challenge in athletes during training period (R=0.74, p<0.01) and in asthmatics (R=0.64, p<0.05). In nasal secretions, baseline IL-1ra levels were significantly higher in athletes and asthmatics than in HC. Exercise caused a slight, yet significant, increase in EBC HSPA1 in athletes (p=0.02). The exercise challenge did not considerably influence TNF-α, IL-1ra, HSPA1 and sCD14 in EBC or nasal secretions. CONCLUSIONS: Dysregulation of the TNF-α/IL-1ra balance in EBC and nasal secretions from athletes may reflect the presence of airway inflammation induced by repeated strenuous exercise.

Periostin in Exhaled Breath Condensate and in Serum of Asthmatic Patients: Relationship to Upper and Lower Airway Disease.

PURPOSE: Periostin is considered a biomarker for eosinophilic airway inflammation and have been associated with NSAID-Exacerbated Respiratory Disease (NERD) and chronic rhinosinusitis (CRS). In this study, we aimed to evaluate periostin in exhaled breath condensate (EBC) and in serum of patients with various asthma phenotypes. METHODS: The study included 40 asthmatic patients (22 with NERD) and 17 healthy controls. All the procedures (questionnaire, spirometry, FeNO, nasal swabs, EBC collecting, and blood sampling) were performed on the same day. Periostin concentrations were measured using an ELISA kit. RESULTS: Periostin was detected in EBC from 37 of 40 asthmatics and in 16 from 17 of controls. The concentration of periostin in EBC did not differ between the study groups and was not associated with NERD or asthma severity. However, the EBC periostin was significantly higher in asthmatics with CRS as compared to those without (3.1 vs 2 ng/mL, P=0.046). Patients with positive bacterial culture from nasal swabs had higher EBC periostin concentrations than those without (3.2 vs 2.1 ng/mL; P=0.046). The mean serum periostin level was higher in asthmatics with a 1-year history of exacerbation than in those without (3.2 vs 2.3 ng/mL, P=0.045). Asthmatics with skin manifestation of NSAIDs hypersensitivity had higher serum periostin levels as compared to those without (3.5 vs 2.3 ng/mL; P=0.03). CONCLUSIONS: EBC periostin levels seem to reflect intensity of upper airway disease in asthmatics, while serum levels of periostin are associated with asthma activity (exacerbations or FeNO) or NERD subphenotypes.

Clinical benefits of aspirin desensitization in patients with nonsteroidal anti-inflammatory drug exacerbated respiratory disease are not related to urinary eicosanoid release and are accompanied with decreased urine creatinine.

BACKGROUND: Treatment with acetylsalicylic acid (ASA) after desensitization may be a therapeutic option in patients with nonsteroidal anti-inflammatory drug exacerbated respiratory disease (NERD). The mechanisms that lead to improvement in rhinosinusitis and asthma symptoms remain unknown. AIM: To attribute the documented clinical effects of ASA treatment of chronic rhinosinusitis and/or asthma to the release of eicosanoid metabolites in urine. METHODS: Fourteen patients with NERD were successfully desensitized, and, eventually, eight patients were treated with 650 mg of ASA daily for 3 months. In addition to clinical assessments, nuclear magnetic resonance imaging and smell test were performed before and after treatment with ASA. Venous blood and urine were collected before desensitization and after 1 and 3 months of treatment. The levels of urinary leukotrienes (LT) (cysteinyl LT and LTE4) and tetranor PGDM (metabolite of prostaglandin D2) were measured by enzyme-linked immunosorbent assay. RESULTS: Treatment with ASA after desensitization alleviated symptoms of rhinosinusitis, improved nasal patency (mean, 50% decrease in peak nasal inspiratory flow) and sense of smell (fourfold increase in smell test score) in as early as 4 weeks. Clinical improvements were not accompanied by any change in sinonasal mucosa thickness as assessed with nuclear magnetic resonance. Urinary cysteinyl LTs, LTE4, and prostaglandin D2 metabolite remained relatively stable during ASA treatment and did not correlate with clinical improvements. Desensitization was associated with a progressive decrease of urinary creatinine. CONCLUSION: Clinical improvement in rhinosinusitis and/or asthma after ASA desensitization was not related to concentrations of urinary eicosanoid metabolites. A decrease of urinary creatinine requires further study to determine the renal safety of long-term treatment with ASA after desensitization.