EPOS2020/EUFOREA expert opinion on defining disease states and therapeutic goals in CRSwNP.

Severe chronic rhinosinusitis with nasal polyps (CRSwNP), a form of diffuse bilateral (usually type 2) CRS, is a debilitating disease with a significant impact on quality of life (QoL). With novel knowledge and treatment options becoming available, there is a growing need to update or revise key definitions to enable communication across different specialties dealing with CRS, and to agree on novel goals of care in CRSwNP. The European Forum for Research and Education in Allergy and Airway diseases (EUFOREA) and EPOS expert members discussed how to measure treatment responses and set new treatment goals for CRSwNP. In this paper a consensus on a list of definitions related to CRSwNP is provided: control, remission, cure, recurrence/exacerbation, treatable traits, remodeling, progression, and disease modification. By providing these definitions, the involved experts hope to improve communication between all stakeholders involved in CRSwNP treatment for use in routine care, basic and clinical research and international guidelines aimed to harmonize and optimize standard of care of patients with CRSwNP in the future.

EUFOREA summit in Brussels 2023: inspiring the future of allergy & respiratory care.

In March 2023, the European Forum for Research and Education in Allergy and Airways diseases (EUFOREA) organized its bi-annual Summit in Brussels with expert panel members of EUFOREA, representatives of the EUFOREA patient advisory board, and the EUFOREA board and management teams. Its aim was to define the research, educational and advocacy initiatives to be developed by EUFOREA over the next 2 years until the 10th anniversary in 2025. EUFOREA is an international non-for-profit organization forming an alliance of all stakeholders dedicated to reducing the prevalence and burden of chronic allergic and respiratory diseases via research, education, and advocacy. Based on its medical scientific core competency, EUFOREA offers an evidence-supported platform to introduce innovation and education in healthcare leading to optimal patient care, bridging the gap between latest scientific evidence and daily practice. Aligned with the mission of improving health care, the expert panels of asthma, allergic rhinitis (AR), chronic rhinosinusitis (CRS) & European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS), allergen immunotherapy (AIT) and paediatrics have proposed and elaborated a variety of activities that correspond to major unmet needs in the allergy and respiratory field. The current report provides a concise overview of the achievements, ambitions, and action plan of EUFOREA for the future, allowing all stakeholders in the allergy and respiratory field to be up-dated and inspired to join forces in Europe and beyond.

EPOS/EUFOREA update on indication and evaluation of Biologics in Chronic Rhinosinusitis with Nasal Polyps 2023.

Severe chronic rhinosinusitis with nasal polyps (CRSwNP) is a debilitating disease with a significant impact on the quality of life (QoL). It is typically characterized by a type 2 inflammatory reaction and by comorbidities such as asthma, allergies and NSAID-Exacerbated Respiratory Disease (N-ERD). Here, the European Forum for Research and Education in Allergy and Airway diseases discusses practical guidelines for patients on biologic treatment. Criteria for the selection of patients who would benefit from biologics were updated. Guidelines are proposed concerning the monitoring of the drug effects that provide recognition of responders to the therapy and, subsequently, the decision about continuation, switching or discontinuation of a biologic. Furthermore, gaps in the current knowledge and unmet needs were discussed.

Pre-asthma: a useful concept for prevention and disease-modification? A EUFOREA paper. Part 1-allergic asthma.

Asthma, which affects some 300 million people worldwide and caused 455,000 deaths in 2019, is a significant burden to suffers and to society. It is the most common chronic disease in children and represents one of the major causes for years lived with disability. Significant efforts are made by organizations such as WHO in improving the diagnosis, treatment and monitoring of asthma. However asthma prevention has been less studied. Currently there is a concept of pre- diabetes which allows a reduction in full blown diabetes if diet and exercise are undertaken. Similar predictive states are found in Alzheimer's and Parkinson's diseases. In this paper we explore the possibilities for asthma prevention, both at population level and also investigate the possibility of defining a state of pre-asthma, in which intensive treatment could reduce progression to asthma. Since asthma is a heterogeneous condition, this paper is concerned with allergic asthma. A subsequent one will deal with late onset eosinophilic asthma.

Global airways â€" a novel Standard Tests for Asthma, allergic Rhinitis, and chronic Rhinosinusitis (STARR-15).

BACKGROUND: Global airway disease, with symptoms from both upper and lower airways, is a challenging problem for clinicians. Our goal is to design one single standard test for the awareness of global airway diseases to be used in clinical setting. MATERIAL AND METHODS: During 2019, rhinologists and pulmonologists generated a pool of items based on literature, patient-reported outcome measures and clinical experience. The items were administered to 206 patients with known asthma, CRS, allergic rhinitis, or a combination thereof. The patients also completed the Asthma Control Questionnaire (ACQ-5) and the Sino-Nasal Outcome Test (SNOT-22). Using a mix of clinical knowledge and data-driven methods a global airways questionnaire was developed. RESULTS: Mean ACQ score was highest in patients with all three, whereas the highest SNOT-22 score was observed in patients with CRS and asthma. After the development process, analysis of responses from 206 patients to 44 items on a new global airway’s questionnaire led to identification of 15 items that form the STARR-15 questionnaire with three underlying domains (an allergic rhinitis sub-factor, a CRS sub-factor and an asthma sub-factor). CONCLUSION: STARR-15 represents the first global airways questionnaire, to be used when examining patients with upper and lower airways symptoms. Future analyses are warranted to evaluate the clinical and psychometric properties of STARR-15.

The potential role of biological treatment of chronic rhinosinusitis with nasal polyps: a nationwide cohort study.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) can be a challenge to treat despite appropriate pharmacological therapy and endoscopic sinus surgery. With the introduction of biological treatment, costs will increase. In this study, we determine the number of patients with CRSwNP treated with endoscopic sinus surgery and revision surgery and thereby fulfil the main criterion for treatment with biologics in the newest European guidelines. Furthermore, we estimate a potential number of recipients of biologics nationwide. METHODS: All adult patients registered in the Danish National Patient Registry as having undergone first endoscopic sinus surgery for CRSwNP from 2012â€"2018 were included. The number of operations, surgery dates, and comorbidities were extracted. The Kaplan-Meier method was used to calculate the revision rate over time. Revision surgery was used as a surrogate to determine the pool of potential recipients of biologics, as these would fulfil the eligibility criteria and ensure the necessary cost-effectiveness. RESULTS: A total of 4667 operated patients with CRSwNP were included out of a population of 4.7 million adults (incidence 14/100,000 person-years). Approximately 18% (120 per year) was estimated to have revision surgery within seven years. The median time to revision surgery was 22 months. Of all analysed patients, 21% had registered asthma and/or allergic rhinitis, while these diseases were registered in 34% of patients treated with revision surgery. CONCLUSION: In Denmark, an average of 120 operated patients annually will have revision surgery within seven years and may benefit from treatment with biologics as an alternative option to revision surgery.

Mapping Cell Membrane Organization and Dynamics Using Soft Nanoimprint Lithography.

Membrane shape is a key feature of many cellular processes, including cell differentiation, division, migration, and trafficking. The development of nanostructured surfaces allowing for the in situ manipulation of membranes in living cells is crucial to understand these processes, but this requires complicated and limited-access technologies. Here, we investigate the self-organization of cellular membranes by using a customizable and benchtop method allowing one to engineer 1D SiO2 nanopillar arrays of defined sizes and shapes on high-performance glass compatible with advanced microscopies. As a result of this original combination, we provide a mapping of the morphology-induced modulation of the cell membrane mechanics, dynamics and steady-state organization of key protein complexes implicated in cellular trafficking and signal transduction.

Hypertrophic effect of inhaled beta2 -agonist with and without concurrent exercise training: A randomized controlled trial.

Due to a high prevalence of asthma and exercise-induced bronchoconstriction in elite athletes, there is a high use of beta2 -adrenoceptor agonists (beta2 -agonists) in the athletic population. While anabolic in rodents, no study has been able to detect hypertrophy in humans after chronic beta2 -agonist inhalation. We investigated whether inhaled beta2 -agonist, terbutaline, alters body composition and metabolic rate with and without concurrent exercise training in healthy young men. Sixty-seven participants completed a 4-week intervention of daily terbutaline (8 × 0.5 mg) or placebo treatment without concurrent training (habitual; n = 23), with resistance (n = 23) or endurance (n = 21) training 3 times weekly. Before and after the interventions, participant's body composition was determined by dual-energy X-ray absorptiometry and resting metabolic rate and substrate oxidation by indirect calorimetry. Terbutaline increased lean body mass by 1.03 kg (95% CI 0.29-1.76; P < .05) and 1.04 kg (95% CI 0.16-1.93; P < .05) compared to placebo in the habitual and resistance training group, respectively, but had no effect compared to placebo in the endurance training group [-0.56 kg (95% CI -1.74-0.62; P > .05)]. Fat mass, bone mineral content, and resting metabolic rate did not change differently between treatments with the intervention. Daily inhalation of terbutaline in near-therapeutic doses induces skeletal muscle growth. This observation should be a concern for antidoping authorities.

Feasibility of high-intensity training in asthma.

Background: High-intensity interval training is an effective and popular training regime but its feasibility in untrained adults with asthma is insufficiently described. Objective: The randomized controlled trial 'EFFORT Asthma' explored the effects of behavioural interventions including high-intensity interval training on clinical outcomes in nonobese sedentary adults with asthma. In this article we present a sub analysis of data aiming to evaluate if patients' pre-intervention levels of asthma control, FEV1, airway inflammation and airway hyperresponsiveness (AHR) predicted their training response to the high-intensity interval training program, measured as increase in maximal oxygen consumption (VO2max). Design: We used data from the EFFORT Asthma Study. Of the 36 patients randomized to the 8-week exercise intervention consisting of high-intensity training three times per week, 29 patients (45% females) completed the study and were included in this data analysis. Pre-intervention assessment included the asthma control questionnaire (ACQ), spirometry, fractional exhaled nitric oxide (FeNO) and AHR to mannitol. VO2 max was measured during an incremental cycle test. Results: The majority of included patients had partly or uncontrolled asthma reflected by a mean (SD) ACQ at 1.7 (0.6). Median (IQR) FeNO was 28.5 (23.8) ppb and 75% had a positive mannitol test indicating AHR. The association between patients' training response measured as increase in VO2max and pre-intervention ACQ scores was not statistically significant (p = 0.49). Likewise, the association between patients' increase in VO2max and FeNO as well as AHR was not statistically significant (p = 0.80 and p = 0.58). Conclusions: Included asthma patients could adhere to the high-intensity interval protocol and improve their VO2max regardless of pre-intervention levels of asthma control, airway inflammation and AHR.

Oral prednisolone for 4 days does not increase exercise tolerance in men with COPD.

One of the primary objectives in management of chronic obstructive pulmonary disease (COPD) is preventing decrease in lung function and reducing the annual number of acute exacerbations of COPD (AECOPD). An oral course of systemic corticosteroids is a commonly used treatment in AECOPD. We hypothesize that this treatment also increases exercise performance and decreases muscle fatigue. In a randomized double-blinded, parallel, placebo-controlled trial, we investigated 14 men (8 on prednisolone 37.5 mg vs. 6 on placebo) with severe and very severe COPD. For 5 consecutive days, the patients performed a submaximal endurance test measuring time to exhaustion (TTE, primary endpoint), spirometry, maximal inspiratory and expiratory pressure and maximal isometric contraction of the quadriceps femoris muscle (maximum voluntary contraction (MVC)). At visits 2, 3 and 4, a fatigue protocol was carried out after 40 minutes of cycling at 40% of maximal effort. No differences between groups were found for TTE, lung function or maximal inspiratory or expiratory pressure, however, patients on prednisolone showed significant increased MVC: median 5.15 [3.35; 9.15] against placebo: -2 [-5.57; 3.95] ( p = 0.03). This finding indicates an impact of corticosteroids on muscle groups being exposed to submaximal endurance.

Objective confirmation of asthma diagnosis improves medication adherence.

OBJECTIVE: The impact of diagnostic work-up in asthma management on medication redemption and probably also drug adherence is largely unknown, but we hypothesized that a confirmed diagnosis of asthma in a hospital-based out-patient clinic increases the willingness to subsequent medication redemption in a real life setting. METHODS: In a retrospective register-based study, 300 medical records of patients referred with possible asthma during one year were examined, of whom 171 had asthma (57%). One-year data on dispensed medicine was collected using the Danish Registry of Medicinal Product Statistics. Patients who had a positive asthma (e.g. bronchial challenge) were classified as verified asthma, whereas unverified asthma refers to doctor's diagnosis of asthma with negative or no diagnostic tests performed. RESULTS: 111 (65%) had a verified diagnosis and patients with verified asthma were more frequently prescribed new therapy compared to those with unverified asthma (88.9% vs. 65.0%, respectively, p < 0.001). No difference was found in first time redemption of prescriptions (72% vs. 64%, respectively, p = 0.3), whereas the second (52% vs. 27%, p = 0.001) and third or more asthma redeemed prescriptions (37% vs. 17%, p = 0.006) showed increased redemption of prescription and probably adherence in the verified compared with the unverified patients with asthma. Furthermore, the use of inhaled corticosteroid (ICS) was calculated as Percent Days Covered (PDC), which was higher in the verified group compared with the non-verified asthma group (88% vs. 30%, p = 0.004). CONCLUSION: Objective verification of a diagnosis of asthma using asthma tests was associated with an improved redemption of prescription.

Exhaled and nasal nitric oxide in chronic rhinosinusitis patients with nasal polyps in primary care.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common inflammatory disorder associated with lower airway disease. However, only few studies of CRSwNP from outside secondary/tertiary care centres have been published. We recently reported an asthma frequency of 44% and 65% in primary and secondary care patients respectively. Therefore, we hypothesise that inflammation of the lower airways could be present in all CRSwNP patients, even without asthma. Here, we assessed the degree of lower and upper airway inflammation using exhaled and nasal nitric oxide (NO) in primary care CRSwNP patients with and without asthma. METHODS: Fifty-seven patients who met the EPOS criteria for CRSwNP were prospectively recruited from primary care ear, nose and throat clinics. Nasal endoscopy was performed by an ear, nose and throat specialist upon enrolment. Additionally, 30 healthy controls were enrolled. Expiratory and nasal NO measurements and thorough pulmonary evaluation were performed. Pulmonary disease was diagnosed by a respiratory physician. RESULTS: Fifty-nine percent of CRSwNP patients with asthma showed elevated expiratory NO; the same was seen in 29% of non-asthmatic CRSwNP patients. Compared with controls, a high level of exhaled NO was significantly more prevalent in CRSwNP irrespective of asthma-status. Nasal NO was significantly lower in patients with CRSwNP compared with controls. CONCLUSION: Subclinical eosinophilic lower airway inflammation is common in CRSwNP in the primary sector, even in the absence of asthma.

Overweight in childhood and adolescence: Does it lead to airway hyperresponsiveness in adulthood?

BACKGROUND: Obesity is increasing worldwide among children and adolescents, and has been associated with an increased incidence of asthma. However, the mechanisms underlying this association are incompletely understood. OBJECTIVE: In this cohort study we aimed to investigate whether being overweight in childhood and adolescence is associated with an increased risk of airway hyperresponsiveness (AHR), a hallmark of asthma, in early adulthood. METHODS: Of 527 subjects from a random population sample of children and adolescents (7-17 years) examined at baseline, a total of 184 subjects completed the follow-up visit 20 years later and were included in the present analysis. Both visits included assessment of height and weight, case history and spirometry. At both visits, bronchial provocation tests were performed using either histamine (baseline) or methacholine (follow-up). In addition, fractional exhaled nitric oxide (FeNO) was measured at follow-up. RESULTS: No significant difference in the prevalence of AHR at follow-up was found between subjects who were overweight or obese at baseline visit (n = 26) (pediatric definition, body mass index ≥ 85%percentile) and normal weight subjects (n = 158) (positive bronchial provocation tests: 15.4% vs. 22.2%, respectively, p = 0.35). Likewise, follow-up FeNO levels did not differ significantly between subjects who were lean and those who were overweight or obese at baseline (geometric mean (95% confidence interval [CI]) 15.1 (13.7, 16.6) parts per billion (ppb) versus 13.0 (10.6, 15.9) ppb, p = 0.23). CONCLUSION: In children and adolescents, being obese or overweight seems not to be associated with an increased risk of AHR or increased FeNO levels in early adulthood.

High fractional exhaled nitric oxide and sputum eosinophils are associated with an increased risk of future virus-induced exacerbations: A prospective cohort study.

BACKGROUND: The major trigger of asthma exacerbations is infection with a respiratory virus, most commonly rhinovirus. Type 2 inflammation is known to be associated with an increased risk of exacerbations in general. Whether type 2 inflammation at baseline increases the risk of future virus-induced exacerbations is unknown. OBJECTIVE: To assess whether type 2 inflammation is associated with an increased risk of virus-induced exacerbations of asthma. METHODS: Stable asthmatics had spirometry, skin prick test, measurement of FeNO and sputum induced for differential cell counts. Patients were followed up for 18 months, during which they were assessed at the research unit when they had symptoms of an exacerbation. Nasal swabs collected at these assessments underwent viral detection by PCR. RESULTS: A total of 81 asthma patients were recruited, of which 22 (27%) experienced an exacerbation during the follow-up period. Of these, 15 (68%) had a respiratory virus detected at exacerbation. Sputum eosinophils >1% at baseline increased the risk of having a subsequent virus-induced exacerbation (HR 7.6 95% CI: 1.6-35.2, P=.010) as did having FeNO >25 ppb (HR 3.4 95% CI: 1.1-10.4, P=.033). CONCLUSION AND CLINICAL RELEVANCE: Established type 2 inflammation during stable disease is a risk factor for virus-induced exacerbations in a real-life setting. Measures of type 2 inflammation, such as sputum eosinophils and FeNO, could be included in the risk assessment of patients with asthma in future studies.

Influence of exercise in normal and hot ambient conditions on the pharmacokinetics of inhaled terbutaline in trained men.

This study investigated the pharmacokinetics of inhaled terbutaline at rest and after exercise in normal and hot ambient conditions with respect to doping analysis. Thirteen trained young men participated in the study. Urine and blood samples were collected after inhalation of 4 mg terbutaline during three trials: exercise in hot ambient conditions (30-35 °C) (EXH), exercise in normal ambient conditions (20-25 °C) (EX), and rest (20-25 °C) (R). Exercise consisted of 130 min at various intensities. Adjustment of urine concentrations of terbutaline to a specific gravity (USG) of 1.02 g/mL was compared with no adjustment. Area under the serum concentration-time curve within the first 6 h was higher for EX (27 ± 3 ng/mL/h) (P ≤ 0.01) and EXH (25 ± 4 ng/mL/h) (P ≤ 0.05) than for R (20 ± 3 ng/mL/h). When unadjusted for USG, urine concentrations of terbutaline after 4 h were different in the order EXH > EX > R (P ≤ 0.01). When unadjusted for USG, urine concentrations of terbutaline were 299 ± 151 ng/mL higher (P ≤ 0.001) after 4 h compared with adjusted concentrations in EXH. Excretion rate of terbutaline was higher (P ≤ 0.001) for EX than for EXH and R within the first 0-1½ h. In conclusion, EXHs results in higher urine concentrations of terbutaline. This should be considered when evaluating doping cases of terbutaline.

Longitudinal stability of asthma characteristics and biomarkers from the Airways Disease Endotyping for Personalized Therapeutics (ADEPT) study.

BACKGROUND: Asthma is a biologically heterogeneous disease and development of novel therapeutics requires understanding of pathophysiologic phenotypes. There is uncertainty regarding the stability of clinical characteristics and biomarkers in asthma over time. This report presents the longitudinal stability over 12 months of clinical characteristics and clinically accessible biomarkers from ADEPT. METHODS: Mild, moderate, and severe asthma subjects were assessed at 5 visits over 12 months. Assessments included patient questionnaires, spirometry, bronchodilator reversibility, fractional exhaled nitric oxide (FENO), and biomarkers measured in induced sputum. RESULTS: Mild (n = 52), moderate (n = 55), and severe (n = 51) asthma cohorts were enrolled from North America and Western Europe. For all clinical characteristics and biomarkers, group mean data showed no significant change from visit to visit. However, individual data showed considerable variability. FEV1/FVC ratio showed excellent reproducibility while pre-bronchodilator FEV1 and FVC were only moderately reproducible. Of note bronchodilator FEV1 reversibility showed low reproducibility, with the nonreversible phenotype much more reproducible than the reversible phenotype. The 7-item asthma control questionnaire (ACQ7) demonstrated moderate reproducibility for the combined asthma cohorts, but the uncontrolled asthma phenotype (ACQ7 > 1.5) was inconstant in mild and moderate asthma but stable in severe asthma. FENO demonstrated good reproducibility, with the FENO-low phenotype (FENO < 35 ppb) more stable than the FENO-high phenotype (FENO ≥ 35 ppb). Induced sputum inflammatory phenotypes showed marked variability across the 3 sputum samples taken over 6 months. CONCLUSIONS: The ADEPT cohort showed group stability, individual stability in some parameters e.g. low FEV1/FVC ratio, and low FENO, but marked individual variability in other clinical characteristics and biomarkers e.g. type-2 biomarkers over 12 months. This variability is possibly related to seasonal variations in climate and allergen exposure, medication changes and acute exacerbations. The implications for patient selection strategies based on clinical biomarkers may be considerable.

IL-33 is related to innate immune activation and sensitization to HDM in mild steroid-free asthma.

BACKGROUND: IL-33 represents a potential link between the airway epithelium and induction of a Th2-type inflammatory response in asthma. However, the association with markers of eosinophilic airway inflammation has not previously been reported in patients with steroid-free asthma. AIM: To describe the relationship between airway IL-33 and markers of eosinophilic airway inflammation, as well potential triggers of IL-33, in mild, steroid-free asthma. METHODS: IL-33 mRNA expression and IL-33 immunoreactivity were measured in bronchial biopsies from patients with asthma untreated with inhaled steroids and healthy individuals. Furthermore, fractional exhaled nitric oxide (FeNO) and eosinophils in sputum and BAL were measured, as well as airway hyperresponsiveness to mannitol and methacholine. Epithelial integrity was assessed by computerized image analysis on haematoxylin-stained sections, and TLR mRNA expression by PCR. RESULTS: A total of 23 patients with asthma and 10 healthy individuals were examined (age: 24 years (20-40); females: 53%). The level of IL-33 mRNA expression was significantly higher in patients with asthma compared to healthy individuals (Median (IQR) 1.12 (0.78) vs. 0.86, P = 0.04). There was a positive correlation between IL-33 mRNA expression and the level of FeNO (r = 0.56, P = 0.01), whereas there was no association with airway or blood eosinophils. IL-33 expression was unrelated to loss of epithelial integrity, but correlated with an increased expression of TLR2 and TLR4 (TLR2: r = 0.47, P = 0.04; TLR4: 0.68, P < 0.001), as well allergy to house dust mites (HDMs). CONCLUSION: In mild untreated asthma, the expression of IL-33 mRNA in bronchial mucosa is related to innate immune activation and allergic sensitization to HDM, rather than epithelial damage, and correlates with FeNO. These findings suggest that in mild allergic asthma, IL-33 may represent a link between innate immune activation and FeNO production.

Distinct modulation of allergic T cell responses by subcutaneous vs. sublingual allergen-specific immunotherapy.

BACKGROUND: Allergen-specific immunotherapy is the only curative treatment for type I allergy. It can be administered subcutaneously (SCIT) or sublingually (SLIT). The clinical efficacy of these two treatment modalities appears to be similar, but potential differences in the immunological mechanisms involved have not been fully explored. OBJECTIVE: To compare changes in the allergen-specific T cell response induced by subcutaneous vs. sublingual administration of allergen-specific immunotherapy (AIT). METHODS: Grass pollen-allergic patients were randomized into groups receiving either SCIT injections or SLIT tablets or neither. PBMCs were tested for Timothy grass (TG)-specific cytokine production by ELISPOT after in vitro expansion with TG-peptide pools. Phenotypic characterization of cytokine-producing cells was performed by FACS. RESULTS: In the SCIT group, decreased IL-5 production was observed starting 10 months after treatment commenced. At 24 months, T cell responses showed IL-5 levels significantly below the before-treatment baseline. No significant reduction of IL-5 was observed in the SLIT or untreated group. However, a significant transient increase in IL-10 production after 10 months of treatment compared to baseline was detected in both treatment groups. FACS analysis revealed that IL-10 production was associated with CD4(+) T cells that also produced IFNγ and therefore may be associated with an IL-10-secreting type 1 cell phenotype. CONCLUSION AND CLINICAL RELEVANCE: The most dominant immunological changes on a cellular level were a decrease in IL-5 in the SCIT group and a significant, transient increase of IL-10 observed after 10 months of treatment in both treated groups. The distinct routes of AIT administration may induce different immunomodulatory mechanisms at the cellular level.

Airway responsiveness to mannitol in asthma is associated with chymase-positive mast cells and eosinophilic airway inflammation.

BACKGROUND: Airway hyperresponsiveness (AHR) to inhaled mannitol is associated with indirect markers of mast cell activation and eosinophilic airway inflammation. It is unknown how AHR to mannitol relates to mast cell phenotype, mast cell function and measures of eosinophilic inflammation in airway tissue. We compared the number and phenotype of mast cells, mRNA expression of mast cell-associated genes and number of eosinophils in airway tissue of subjects with asthma and healthy controls in relation to AHR to mannitol. METHODS: Airway hyperresponsiveness to inhaled mannitol was measured in 23 non-smoking, corticosteroid-free asthmatic individuals and 10 healthy controls. Mast cells and eosinophils were identified in mucosal biopsies from all participants. Mast cells were divided into phenotypes based on the presence of chymase. mRNA expression of mast cell-associated genes was measured by real-time PCR. RESULTS: The proportion of submucosal MCTC was higher in asthmatic individuals with AHR to mannitol compared with asthmatic individuals without AHR (median: 40.3% vs. 18.7%, P = 0.03). Increased submucosal MCTC numbers were associated with increased levels of mRNA for thymic stromal lymphopoietin (TSLP) and CPA3 in asthmatics. Reactivity to mannitol correlated significantly with eosinophils in submucosa (r(s): 0.56, P = 0.01). CONCLUSION: Airway hyperresponsiveness to inhaled mannitol is associated with an altered submucosal mast cell profile in asthmatic individuals. This mast cell profile is associated with increased levels of TSLP and CPA3. The degree of AHR to mannitol is correlated with the degree of eosinophilic inflammation in the airway submucosa.

Effects of acute and 2-week administration of oral salbutamol on exercise performance and muscle strength in athletes.

Our objective was to investigate effects of acute and 2-week administration of oral salbutamol on repeated sprint ability, exercise performance, and muscle strength in elite endurance athletes. Twenty male elite athletes [VO2max: 69.4 ± 1.8 (Mean ± SE) mL/min/kg], aged 25.9 ± 1.4 years, were included in a randomized, double-blinded and placebo-controlled parallel study. At baseline, after acute administration, and again after 2-week administration of the study drugs (8 mg salbutamol or placebo), subjects' maximal voluntary contraction (MVC) of m. quadriceps and isometric endurance of m. deltoideus were measured, followed by three repeated Wingate tests. Exercise performance at 110% of VO2max was determined on a bike ergometer. Acute administration of salbutamol increased peak power during first Wingate test by 4.1 ± 1.7% (P < 0.05). Two-week administration of salbutamol increased (P < 0.05) peak power during first and second Wingate test by 6.4 ± 2.0 and 4.2 ± 1.0%. Neither acute nor 2-week administration of salbutamol had any effect on MVC, exercise performance at 110% of VO2max or on isometric endurance. No differences were observed in the placebo group. In conclusion, salbutamol benefits athletes' sprint ability. Thus, the present study supports the restriction of oral salbutamol in competitive sports.