Treatment with the SQ tree sublingual immunotherapy tablet is safe and well tolerated in real-life.

BACKGROUND: The SQ tree sublingual immunotherapy (SLIT)-tablet is authorised for treatment of allergic rhinoconjunctivitis with or without asthma in trees of the birch homologous group in 21 European countries. The primary objective of this study was to explore the safety in real-life. METHODS: In a prospective, non-interventional post-authorisation safety study (EUPAS31470), adverse events (AEs) and adverse drug reactions (ADRs) at first administration and follow-up visits, symptoms, medication use, and pollen food syndrome were recorded by physicians in 6 European countries during the first 4-6 months of treatment. RESULTS: ADRs with the SQ tree SLIT-tablet were reported in 57.7% of 1069 total patients (median age 36.0 years, 53.7% female) during the entire observation period (severity, mild-to-moderate: 70.1%, severe: 4.7%, serious: 0.7%) and in 45.9% after first administration. ADRs were not increased with pollen exposure at first administration. With coadministration of the SQ tree and grass SLIT-tablet AEs were reported in 73.8% of patients and in 52.8% with the SQ tree SLIT-tablet alone. Nasal and eye symptoms improved in 86.9% and 80.9% of patients and use of symptomatic medication in 76.0%. PFS with symptoms was reported in 43.0% of patients at baseline and in 4.3% at the individual last visit. CONCLUSIONS: The results of this non-interventional safety study with the SQ tree SLIT-tablet confirm the safety profile from placebo-controlled clinical trials and support effectiveness in real-life according to the published efficacy data. Safety was not impaired by pollen exposure at first administration or co-administration with other SLIT-tablets.

Breathing Exercises for Patients with Asthma in Specialist Care: A Multicenter Randomized Clinical Trial.

Rationale: Moderate to severe asthma is associated with impaired asthma control and quality of life (QoL) despite access to specialist care and modern pharmacotherapy. Breathing exercises (BrEX) improve QoL in incompletely controlled mild asthma, but impact in moderate to severe asthma is unknown. Objectives: To investigate the effectiveness of BrEX as adjuvant treatment on QoL in patients with uncontrolled moderate to severe asthma. Methods: Adult patients with incompletely controlled asthma attending respiratory specialist clinics were randomized to usual specialist care (UC) or UC and BrEX (UC + BrEX) with three individual physiotherapist-delivered sessions and home exercises. Primary outcome was asthma-related QoL (Mini-Asthma Quality of Life Questionnaire [Mini-AQLQ]) at 6 months on the basis of intention-to-treat analysis. Secondary outcomes: Mini-AQLQ at 12 months, lung function, 6-minute-walk test, physical activity level, Nijmegen Questionnaire, Hospital Anxiety and Depression Scale, and adverse events. Repeated-measures mixed-effects models were used to analyze data. Poisson regression models were used to analyze adverse event incidence rate ratio. Results: A total of 193 participants were allocated to UC + BrEX (n = 94) or UC (n = 99). UC + BrEX was superior in the primary outcome (adjusted mean change difference, 0.35; 95% confidence interval [CI], 0.07 to 0.62). Superiority in Mini-AQLQ was sustained at 12 months (0.38; 95% CI, 0.12 to 0.65). A minor improvement in Hospital Anxiety and Depression Scale depression score at 6 months favoring UC + BrEX (-0.90; 95% CI, -1.67 to -0.14) was observed. Asthma-related adverse events occurred similarly in UC + BrEX and UC participants: 14.9% versus 18.1% (P = 0.38). Conclusions: BrEX as add-on to usual care improve asthma-related QoL in incompletely controlled asthma regardless of severity and with no evidence of harm. Clinical trial registered with www.clinicaltrials.gov (NCT03127059).

A Real-Life One-Year Non-Interventional Study Assessing Safety, Tolerability, and Treatment Outcome of the SQ HDM SLIT-Tablet (Acarizax®) in House Dust Mite Allergic Rhinitis With or Without Asthma.

INTRODUCTION: The aim of this study was to investigate the safety profile, tolerability, and outcome of the SQ® house dust mite (HDM) sublingual immunotherapy (SLIT)-tablet after 1 year of treatment in clinical practice among adults with HDM-related allergic rhinitis (AR) ± allergic asthma (AA). METHODS: In a non-interventional multicenter, observational study, patients were followed at 3 visits for 1 year. Adverse events (AE) were recorded at all visits. Patients graded their allergic symptoms as none, mild, moderate, or severe, and recorded AR and AA medication use. Asthma symptom control was assessed according to the Global Initiative for Asthma (GINA). RESULTS: One hundred and ninety-eight patients were included; 115 (58%) had AR without asthma and 83 (42%) had both AR and AA. One hundred and sixty-six (84%) patients completed the study. Eighty percent of patients experienced an AE: 151 (75%) AEs were mild, 42 (21%) moderate, and 4 (2%) severe. Three patients (1.5%) reported four events that were considered serious (SAEs). One SAE was considered possibly treatment-related. No anaphylactic reactions occurred. The proportion of patients experiencing allergy symptom reductions by at least one step were 75% (nasal), 62% (eye), 16% (skin), and 13% (other symptoms); 75% of patients with AA experienced a decrease of at least one step in bronchial symptoms. AR medication and inhaled corticosteroids were statistically significant reduced. CONCLUSION: The SQ HDM SLIT-tablet was safe and well tolerated; the type, frequency, and severity of AEs resembled what RCTs have previously demonstrated. As explorative endpoints, statistically significant reductions in AR and AA symptoms and medication use were seen along with improved asthma control after 1 year of treatment, implying that clinically meaningful changes were seen after 1 year of treatment with the SQ HDM SLIT-tablet.

Efficacy of omalizumab in children, adolescents, and adults with severe allergic asthma: a systematic review, meta-analysis, and call for new trials using current guidelines for assessment of severe asthma.

BACKGROUND: Omalizumab is approved for treating severe allergic asthma from age 6, but the definition of severe asthma including a systematic assessment to rule out difficult-to-treat asthma has changed since the drug was approved in 2003. METHODS: We conducted a systematic review and meta-analysis of two critical (exacerbation rate, oral corticosteroid (OCS) treatment) and eight important clinical outcomes in children, adolescents and adults, and specifically searched papers for systematic assessment of severe asthma. RESULTS: Adults: seven studies (n = 2159) ascertaining exacerbation rate showing a 37% (95% CI 21-50) reduction in favor of omalizumab, larger than the pre-specified minimal clinically important difference (MCID) of 25%. Only one open-label study (n = 82) was identified assessing the percentage of patients experiencing reduction of OCS-maintenance treatment showing a significantly greater decrease in the omalizumab group (- 45% vs. + 18.3%, p = 0.002). Children and adolescents: four studies (n = 1551) reported data on exacerbations (no meta-analysis conducted), showed overall improvements in exacerbation rate and some passed MCID. No OCS studies were identified. No included studies provided systematic assessment of severe asthma according to current guidelines. CONCLUSIONS: Omalizumab provides clinically relevant improvements in exacerbation rate among children, adolescents, and adults and in OCS-reduction among adults. New studies incorporating a guideline-approached definition of severe asthma are warranted.

Protocol for a multicentre randomised controlled trial to investigate the effect on asthma-related quality of life from breathing retraining in patients with incomplete asthma control attending specialist care in Denmark.

INTRODUCTION AND AIM: Uncontrolled asthma is a global health challenge with substantial impact on quality of life (QoL) and overall healthcare costs. Unrecognised and/or unmanaged comorbidities often contribute to presence of uncontrolled asthma. Abnormalities in breathing pattern are termed dysfunctional breathing and are not only common in asthma but also lead to asthma-like symptoms and reduced QoL, and, in keeping with this, improvement with breathing normalisation. Evidence-based guidelines recommend breathing retraining interventions as an adjuvant treatment in uncontrolled asthma. Physiotherapy-based breathing pattern modification interventions incorporating relaxation have been shown to improve asthma-related QoL in primary care patients with impaired asthma control. Despite anecdotal reports, effectiveness of breathing retraining in patients referred to secondary care with incomplete asthma control has not been formally assessed in a randomised controlled trial (RCT). We aim to investigate the effect of breathing exercises on asthma-related QoL in patients with incomplete asthma control despite specialist care. METHODS AND ANALYSIS: This two-armed assessor-blinded multicentre RCT will investigate the effect of physiotherapist-delivered breathing retraining on asthma QoL questionnaire (MiniAQLQ) in addition to usual specialist care, recruiting from seven outpatient departments and one specialised clinic representing all regions of Denmark during 2017-2019. We will include 190 consenting adults with incomplete asthma control, defined as Asthma Control Questionnaire 6-item score ≥0.8. Participants will randomly be allocated to either breathing exercise programme in addition to usual care (BrEX +UC) or UC alone. BrEX compiles three physiotherapy sessions and encouragement to perform home exercise daily. Both groups continue usual secondary care management. Primary outcome is between-group difference in MiniAQLQ at 6 months. Secondary outcomes include patient-reported outcome measures, spirometry and accelerometer. ETHICS AND DISSEMINATION: Ethics Committee, Region Zealand (SJ-552) and Danish Data Protection Agency (REG-55-2016) approved the trial. Results will be reported in peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER: NCT03127059; Pre-results.

Efficacy, adverse events, and inter-drug comparison of mepolizumab and reslizumab anti-IL-5 treatments of severe asthma - a systematic review and meta-analysis.

Background: New, complex, and expensive therapies targeting Interleukin-5 (IL-5) to treat severe eosinophilic asthma are emerging. Objective: To assess efficacy, adverse events, and inter-drug comparison of mepolizumab and reslizumab for treating severe eosinophilic asthma. Design: A systematic review and meta-analysis on randomized, placebo-controlled, clinical trials elucidating two critical (exacerbation rate and oral corticosteroid (OCS) use) and six important clinical outcomes on the efficacy and safety of mepolizumab and reslizumab. Results: Five studies (N = 2197) contributed with data for exacerbation rate, showing a reduction of 53% (95% CI 46; 59) in favour of anti-IL-5, corresponding to -0.94 annual exacerbations (95% CI -1.08;-0.82), thus exceeding the predefined minimal clinical important difference (MCID) of 25% reduction of the estimated ≥2 annual exacerbations. Quality of evidence was considered moderate, with low heterogeneity in study findings (I2 = 0%). One study (N = 135) contributed with data on percentage of patients experiencing ≥50% reduction inoral corticosteroid treatment, showing an effect of 20% (95% CI 2.3;47) in favour of anti-IL-5 treatment (mepolizumab), thus exceeding the predefined MCID of 10%. Quality of evidence was considered low. Compared to placebo, anti-IL-5 showed significant improvements in lung function, asthma control, and asthma-related quality of life, but below the MCIDs. No differences were observed for serious adverse events and number of patients, who dropped out. No studies evaluating sickleave or head-to-head comparisons were identified. By indirect comparison, we found no significant difference between mepolizumab and reslizumab in any ofthe predefined clinical outcomes. OCS treatment reduction could not be compared due to lack of reslizumab studies investigating this outcome. Conclusions: Mepolizumab and reslizumab provide significant and clinically relevant improvements in exacerbation rate and OCS reduction. Indirect, inter-study comparisons revealed no differences between the anti-IL-5 drugs in efficacy or safety measures.

[Late diagnostics and inadequate follow-up of asthma exacerbation].

Late diagnostics and inadequate follow-up of an asthma patient could have been avoided by use of accessible initiatives. Several differential diagnoses to dyspnoea and oppression of the chest exist and in this case a spirometry would have established the asthma diagnosis. Increasing specialization causes necessity to focus on differential diagnosis from nearby specialities. After hospitalization with asthma, the patient should be followed closely until asthma control is achieved and the necessary education is given so that inhalation technique and adherence is optimized.

A controlled intervention study concerning the effect of intended temperature rise on house dust mite load.

In epidemiological studies, increased indoor temperature--producing a lower relative humidity--is associated with low house dust mite (HDM) load. Twenty-eight dwellings were allocated for either intervention (12/15 completed) or control (11/13 completed). In the intervention group, participants were asked to increase the bedroom temperature by at least 3 degrees C compared to the self-assessed temperature of the previous winter. Dust samples were repeatedly collected from mattress and floor, and bedroom temperature and relative humidity were recorded hourly throughout one year. Dust was analysed for allergen (Der f 1 + Der p 1 + Der m 1 = Der 1) by ELISA and HDMs were counted. Changes in mite and in mite allergen concentration were the same in the control and intervention groups, and measured temperatures did not differ during intervention period in the groups (18 degrees C and 19 degrees C). Groups turned out not to be comparable with respect to initial (self-assessed) bedroom temperature (lowest in the intervention group). There was a significant seasonal variation, with doubled Der 1 concentrations in dust collected in July-November compared to January-May samples. No effect was obtained on mites or mite allergens, but this may be due either to a general lack of effect of increase in bedroom temperature, or to an insufficient increase in temperature in our intervention group. Seasonal variations in HDM and HDM allergens must be accounted for when data on exposure are interpreted.

Decay of house-dust mite allergen Der f 1 at indoor climatic conditions.

BACKGROUND: The decay of house-dust mite allergens is important for the outcome of avoidance measures for house-dust mite-allergic patients. OBJECTIVE: To quantify the stability of Der f 1 from mattress dust when exposed to domestic conditions. METHODS: Three samples of mattress dust were individually homogenized and divided into 64 subsamples. Mites were killed by freezing for 48 hours at -30 degrees C. The subsamples were exposed in eight homes, three storerooms, and one greenhouse, where temperature and relative humidity were recorded. Der f 1 was determined in extracts of subsamples (enzyme-linked immunoadsorbent assay) at 0, 3, 12, and 24 months. RESULTS: In the three samples of mattress dust, the initial concentrations of Der f 1 (mean +/- standard deviation; STD) were: 169 (12), 3.9 (0.4), and 31 (2.6) microg/g, respectively. Median half-life of Der f 1 in the mattress dust samples was 10 years in the exposure homes, 18 years in the store rooms, and 1.0 year in the greenhouse. No correlations among preserved Der f 1 and temperature, relative humidity, and absolute humidity in homes were found (Spearman rank correlation test). CONCLUSION: Natural decay of Der f 1, with an estimated half-life of 10 years at housing conditions, has no practical consequence in reducing allergen exposure. Therefore, avoidance measures should include an active removal of the allergens.

House dust mites and their allergens in Danish mattresses -- results from a population based study.

The purpose of this study was to identify the level of house dust mites (HDMs) and their allergens in mattresses, not selected on their owners atopic status, and to find associated factors. Dust was collected from 68 mattresses. The recruitment was population-based and conducted during the screening phase of a HDM intervention study. The visited persons declared to have had a "cold" bedroom the previous winter. HDMs were counted and dust was analysed by ELISA for Der 1 (= Der f 1+ Der p 1+ Der m 1). Multiple regression analysis was carried out to find housing conditions associated with high HDM levels. Type of housing, mattress age and self-assessed winter bedroom-temperature explained 47% of Der 1. Median concentrations were 3.77 microg Der 1/g and 1 HDM/0.1 g dust. Both immunochemically and microscopically Dermatophagoides farinae was dominant; D. pteronyssinus less frequent but important; and D. microceras insignificant. In 62% of these suburban homes the mattress dust exceeded 2 microg Der 1/g; and measurement of both Der f 1 and Der p 1 was necessary and sufficient to evaluate HDM allergen exposure. The association with a high HDM level was highest and most consistent for one-family houses.