Tobacco Exposure and Efficacy of Biologic Therapy in Patients With Severe Asthma: A Nationwide Study From the Danish Severe Asthma Register.

BACKGROUND: Randomized trials of biologics in severe, uncontrolled asthma have excluded patients with a cumulative tobacco exposure of more than 10 pack-years. Therefore, our knowledge of the impact of smoking exposure on the clinical effects of biologics in severe asthma remains incomplete. However, because many patients with asthma are current or former smokers, investigating the potential impacts of tobacco exposure on the effects of biologic treatment is clinically important. OBJECTIVE: To investigate the impact of smoking history and tobacco exposure on the effectiveness of biologic therapy in real-life patients with severe asthma. METHODS: We used data from a complete nationwide cohort of patients with severe asthma who were receiving biologics, the Danish Severe Asthma Register. We divided patients according to smoking history and cumulative tobacco exposure and analyzed data at baseline and after 12 months of biologic treatment. RESULTS: A total of 724 bio-naive patients were identified in the Danish Severe Asthma Register, 398 of whom had never been smokers (55%), 316 were previous smokers (44%), and 10 were current smokers (1%). Within the group of current and former smokers, 37% had 1 to 9 pack-years of tobacco exposure, 26% had 10 to 19 pack-years, and 37% had 20 or more pack-years of tobacco exposure. Patients with tobacco exposure had similar reductions in the number of exacerbations, reductions in maintenance oral corticosteroid use, and improvements in asthma symptoms compared with patients with 0 pack-years. CONCLUSION: Former smoking history and lifetime tobacco exposure do not have an impact on the efficacy of biologics in patients with severe asthma.

Clinical Response and Remission in Patients With Severe Asthma Treated With Biologic Therapies.

BACKGROUND: The development of novel targeted biologic therapies for severe asthma has provided an opportunity to consider remission as a new treatment goal. RESEARCH QUESTION: How many patients with severe asthma treated with biologic therapy achieve clinical remission, and what predicts response to treatment? STUDY DESIGN AND METHODS: The Danish Severe Asthma Register is a nationwide cohort including all adult patients receiving biologic therapy for severe asthma in Denmark. This observational cohort study defined "clinical response" to treatment following 12 months as a ≥ 50% reduction in exacerbations and/or a ≥ 50% reduction in maintenance oral corticosteroid dose, if required. "Clinical remission" was defined by cessation of exacerbations and maintenance oral corticosteroids, as well as a normalization of lung function (FEV1 > 80%) and a six-question Asthma Control Questionnaire score ≤ 1.5 following 12 months of treatment. RESULTS: Following 12 months of treatment, 104 (21%) of 501 biologic-naive patients had no response to treatment, and 397 (79%) had a clinical response. Among the latter, 97 (24%) fulfilled the study criteria of clinical remission, corresponding to 19% of the entire population. Remission was predicted by shorter duration of disease and lower BMI in the entire population of patients treated with biologic therapy. INTERPRETATION: Clinical response was achieved in most adult patients initiating biologic therapy, and clinical remission was observed in 19% of the patients following 12 months of treatment. Further studies are required to assess the long-term outcome of achieving clinical remission with biologic therapy.

Compliance in subcutaneous and sublingual allergen immunotherapy: A nationwide study.

INTRODUCTION: Allergic rhino-conjunctivitis is a highly prevalent condition. In moderate to severe cases, allergen immunotherapy (AIT) is a cost-effective therapeutic option. Previous data have reported a large difference in treatment compliance of subcutaneously (SCIT) and sublingually (SLIT) administered AIT. METHODS: By use of the unique civil registration number assigned to all Danish citizens and the Danish National Health Service Prescription Database, compliance rates of all patients prescribed with grass pollen AIT from January 1998 until December 2016 were analysed annually during the three-year treatment period. RESULTS: The male/female ratio was close to 1:1 in SCIT, while SLIT was more frequently used by men. A large proportion of users was children or adolescents (32% and 45%, SCIT and SLIT, respectively). Compliance of both subcutaneous and sublingual treatment gradually fell each year; compliance in year 3 was 57% and 53% for subcutaneous and sublingual treatment, respectively. Compliance of grass pollen sublingual treatment was also analysed each year after registration on the Danish market. Compliance significantly increased following the introduction and stabilised on a relatively high level. CONCLUSION: Based on previous studies, we hypothesised that AIT compliance would be low, especially in SLIT. However, in Denmark, compliance in SCIT and SLIT was almost similar, and the majority of patients completed the three-year treatment period with a compliance in the last quintile.

The risk of osteoporosis in patients with asthma.

It is well-known that use of continuous systemic corticosteroids (SG) affects bone metabolism, bone mineral density (BMD), and ultimately increases the risk of osteoporosis. In patients with asthma, on the other hand, the effects of long-term high-dose inhaled corticosteroids (ICS) on BMD and risk of osteoporotic fractures is controversial. The reasons for this inconsistency could be explained by the fact that only few long-term studies investigating the effect of ICS in patients with asthma exist. The studies are characterized by different study designs and duration of ICS exposure, small study populations, and differences between the used ICS. The aim of this article is to unravel which factors, if any, that contribute to an increased risk of osteoporosis in patients with asthma and to summarize the evidence regarding adverse effects of ICS on bone metabolism, BMD and osteoporotic fractures in patients with asthma.

Clinical Application of Nasal Filters: An Observational Study on the Usability of Nasal Filters in Managing Seasonal Allergic Rhinitis.

BACKGROUND: A recent park study found a substantial preventive effect of a new nasal filter for seasonal allergic rhinitis. However, the nasal filter still needs to prove that it is sufficiently convenient and comfortable for everyday use during a regular pollen season. OBJECTIVE: The objective of this study was to evaluate the usability of the nasal filter (Rhinix, Rhinix ApS, Aarhus, Denmark) in a large population. METHODS: An observational, open-label study (NCT02108379) conducted during the main grass pollen season in 2014 in Denmark included 1073 participants with seasonal allergic rhinitis, with or without asthma. Participants received the filters for a 2-week use period. Identical online questionnaires were answered after each week of use. End points included ratings on satisfaction, usage, and interest in continued use, stratified by allergy and asthma severity. RESULTS: There were 834 filter users in week 1; 634 of these continued use in week 2. After week 1, 630 (76%) expressed interest in continued use of the filters. Participants who continued use in week 2 had higher screening scores for nasal symptoms (P = .01), had more severe asthma for those with asthma (P = .04), and were more dissatisfied with their usual treatment compared with the participants who discontinued use (P = .03). CONCLUSIONS: Of 834 new users, 630 stated interest in continued use of the filters. On the basis of the findings of this large observational usability study, the nasal filters appear sufficiently convenient and comfortable to use and thus clinically relevant for symptom management for many allergy sufferers.

[Methotrexate may be a useful corticosteroid reducing treatment of severe asthma]. / Methotrexat kan anvendes som steroidbesparendebehandling af svær astma.

Asthma is a chronic airway disease affecting many people worldwide. Less than 1% suffers from difficult-to-treat asthma and requires systemic corticosteroid treatment to achieve symptom control. The therapeutic options for these patients are limited and often we have to accept a lesser degree of symptom control. Methotrexate has been evaluated in 13 studies, where the mean corticosteroid dose reduction was 35%. Despite the adverse effects, we find that methotrexate may be a useful treatment of severe asthma in certain patients under close observation.

Preventive effect of nasal filters on allergic rhinitis: A randomized, double-blind, placebo-controlled crossover park study.

BACKGROUND: A recently reported small, out-of-season environmental exposure unit study found nasal filters to be efficacious in preventing seasonal allergic rhinitis (AR). However, nasal filters still need to show efficacy in a natural setting in a regular pollen season. OBJECTIVE: We sought to evaluate the efficacy of nasal filters (Rhinix; Rhinix ApS, Aarhus, Denmark) for the prevention of symptoms related to seasonal AR. METHODS: The trial was a single-center, randomized (1:1), double-blind, placebo-controlled crossover clinical trial (NCT02108574) conducted over 2 days in the main grass pollen season in June 2014 in Aarhus, Denmark, on 65 adults with proven grass allergy. A total nasal symptom score (TNSS) consisting of blocked nose, runny nose, nasal itching, and sneezing was used to evaluate symptoms. The difference in daily∑ TNSS (the sum of 13 ratings) was the primary outcome measure. The difference in maximum TNSS (highest score, 13 ratings) was also evaluated. RESULTS: The nasal filters significantly reduced daily∑ TNSSs (P = .03) and maximum TNSSs (P = .03) compared with placebo. Median relative reductions were 40% for daily∑ TNSSs (P = .02), 43% for maximum TNSSs (P = .004), 83% for daily∑ sneezing (P = .001), 75% for daily∑ watery eyes (P = .02), and 53% for daily∑ runny nose (P = .005) when compared with placebo. The nasal filters were well tolerated, and no serious adverse events were recorded. CONCLUSION: Statistically significant and clinically relevant reductions were achieved for the primary outcome measure of daily∑ TNSS, for maximum TNSS and for a subset of individual symptoms. The results support the preventive role of nasal filters for managing seasonal AR.

[Methotrexate may be a useful corticosteroid reducing treatment of severe asthma].

Asthma is a chronic airway disease affecting many people worldwide. Less than 1% suffers from difficult-to-treat asthma and requires systemic corticosteroid treatment to achieve symptom control. The therapeutic options for these patients are limited and often we have to accept a lesser degree of symptom control. Methotrexate has been evaluated in 13 studies, where the mean corticosteroid dose reduction was 35%. Despite the adverse effects, we find that methotrexate may be a useful treatment of severe asthma in certain patients under close observation.