The burden of chronic rhinosinusitis with nasal polyps and its relation to asthma in Finland

Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is commonly associated with asthma. Treatment of CRSwNP includes intranasal and systemic corticosteroids, with non-responsive patients commonly considered for endoscopic sinus surgery (ESS). This nationwide register-based study evaluated the incidence, prevalence, and treatment burden of CRSwNP in Finland, and their association with the presence and severity of comorbid asthma. Methods Electronic health records of patients diagnosed with CRSwNP between 1.1.2012 and 31.12.2018 in Finnish specialty and primary care were included in the study. The patients were divided into subgroups based on presence, severity, and control of asthma: no asthma, mild to moderate asthma, severe controlled asthma, and severe uncontrolled asthma. A mean cumulative count of ESS was calculated over time per subgroup. Results The prevalence of CRSwNP increased from 602.2 to 856.7 patients per 100,000 population between years 2012 and 2019 (p < 0.001). A total of 18,563 patients (59.9% male) had incident CRSwNP between 2012 and 2019, with 27% having asthma, 6% having severe asthma, and 1.5% having severe uncontrolled asthma. In the no asthma, severe controlled asthma, and severe uncontrolled asthma subgroups, systemic corticosteroids were used by 54.1%, 94.9% and 99.3% (p < 0.001), respectively, while the ESS count 3 years post diagnosis was 0.49, 0.68 and 0.80, respectively. Conclusions The prevalence of CRSwNP showed a significant increase in the recent decade in Finland. Comorbid asthma, and in particular severe asthma, increased the probability of receiving systemic corticosteroids and undergoing ESS. Thus, improved management of CRSwNP in patients with comorbid asthma is urgently needed.Peer reviewe

Type 2 Low Biomarker Stability and Exacerbations in Severe Uncontrolled Asthma

We investigated the stability of T2 low status, based on low levels of T2 biomarkers, and exacerbation rates in T2 low and non-T2 low asthma from clinical retrospective data of severe uncontrolled asthma patients. Knowledge of the T2 low biomarker profile is sparse and biomarker stability is uncharted. Secondary care patients with severe uncontrolled asthma and at least two blood eosinophil counts (BEC) and fractional exhaled nitric oxide (FeNO) measured for determination of type 2 inflammation status were evaluated from a follow-up period of 4 years. Patients were stratified into four groups: T2 low150 (n = 31; BEC 150 cells/µL and/or FeNO > 25 ppb), T2 low300 (n = 66; BEC 300 cells/µL and/or FeNO > 25 ppb). Exacerbation rates requiring hospital care, stability of biomarker status, and cumulative OCS and ICS doses were assessed during follow-up. Among patients with severe uncontrolled asthma, 18% (n = 31) were identified as T2 low150, and 39% (n = 66) as T2 low300. In these groups, the low biomarker profile was stable in 55% (n = 11) and 72% (n = 33) of patients with follow-up measures. Exacerbation rates were different between the T2 low and non-T2 low groups: 19.7 [95% CI: 4.3–45.6] in T2 low150 vs. 8.4 [4.7–13.0] in non-T2 low150 per 100 patient-years. BEC and FeNO are useful biomarkers in identifying T2 low severe uncontrolled asthma, showing a stable follow-up biomarker profile in up to 72% of patients. Repeated monitoring of these biomarkers is essential in identifying and treating patients with T2 low asthma.Peer reviewe

Need of education for dry powder inhaler storage and retention – a patient-reported survey

Background Dry powder inhalers (DPIs) are the most commonly used devices in asthma treatment in the Nordic countries. As new DPIs become available, patients are likely to be exposed to more than one type of device, with variable optimal handling. The aim was to examine real life storage and retention of multidose DPIs in patients with asthma. Methods This patient-reported survey on real life storage and retention of DPIs included asthma patients using multidose DPIs. Basic patient characteristics, information on inhaler use and storage, check of expiry date, and concurrent inhaler use was examined using an on line questionnaire. Results A total of 738 patients were included with a median age of 41 years, out of which 83 % were women. Sixty-three per cent reported storage conditions pre-defined as risk locations for their maintenance inhaler and 38 % of the responding patients had more than one maintenance inhaler in use at the same time. Two thirds of the study population checked inhaler expiry date less than monthly or not at all. Use after expiry date was frequently reported. Two thirds of the patients had not received information on DPI storage, either from their doctor and/or nurse or at the pharmacy. Conclusions This patient reported survey indicates that two thirds of the patients store their inhaler devices in suboptimal conditions, and only a minority had received instruction regarding inhaler handling. Non awareness of inhalers’ expiry dates and use of more than one maintenance inhaler simultaneously was common. As inhaler mishandling may impact device functionality, improved communication and patient education is needed

Difference in resistance to humidity between commonly used dry powder inhalers : an in vitro study

Multi-dose dry powder inhalers (DPIs) are commonly used in asthma and chronic obstructive lung disease (COPD) treatment. A disadvantage is their sensitivity to humidity. In real life, DPIs are periodically exposed to humid conditions, which may affect aerosol characteristics and lung deposition. This study compared DPI aerosol performance after exposure to humidity. Budesonide (BUD) inhalers (Turbuhaler; Novolizer; Easyhaler) and budesonide/formoterol (BUD/FORM) inhalers (Turbuhaler; Spiromax; Easyhaler) were stored in 75% relative humidity (RH) at both ambient temperature and at-0 degrees C. Delivered dose (DD) and fine-particle dose (FPD) were tested in vitro before and after storage. BUD inhalers: Turbuhaler and Novolizer showed only small decreases (&lt;15%) in FPD in 40 degrees C/75% RH, whereas FPD for Easyhaler decreased by &gt;60% (P = 0.01) after 1.5 months of storage. Easyhaler also decreased significantly after 6 months of storage in ambient/75% RH by 25% and 54% for DD and FPD, respectively, whereas only small decreases were seen for Turbuhaler and Novolizer (&lt;15%). BUD/FORM inhalers: Turbuhaler and Spiromax DD were unchanged in 40 degrees C/75% RH, whereas Easyhaler showed a small decrease. FPD (budesonide) decreased for Turbuhaler, Spiromax and Easyhaler by 18%, 10% and 68% (all significant), respectively, at 40 degrees C/75% RH. In ambient/75% RH, DD was unchanged for all inhalers, whereas FPD (budesonide) decreased for Spiromax (7%, P = 0.02) and Easyhaler (34%, (P&lt;0.01)). There are significant differences in device performance after exposure to humid conditions. A clinically relevant decrease of more than half FPD was seen for one of the inhalers, a decrease that may affect patients' clinical outcomes. Prescriber and patient knowledge on device attributes are essential to ensure optimal drug delivery to the lungs

High use of short-acting β2-agonists in COPD is associated with an increased risk of exacerbations and mortality

Background Short-acting β2-agonist (SABA) overuse has been associated with an increased risk of exacerbations in asthma; however, less is known about SABA use in COPD. Our aim was to describe SABA use and investigate potential associations between high SABA use and the risk of future exacerbations and mortality in COPD. Methods This observational study identified COPD patients in primary care medical records in Sweden. Data were linked to the National Patient Registry, the Prescribed Drug Registry and the Cause of Death Registry. The index date was 12 months after the date of COPD diagnosis. During a 12-month prior to index baseline period, information on SABA use was collected. Patients were followed with respect to exacerbations and mortality for 12 months post index. Results Of the 19 794 COPD patients included (mean age 69.1 years, 53.3% females), 15.5% and 7.0% had collected ≥3 or ≥6 SABA canisters during the baseline period, respectively. A higher level of SABA use (≥6 canisters) was independently associated with a higher risk of both moderate and severe exacerbations (hazard ratio (HR) 1.28 (95% CI 1.17‒1.40) and 1.76 (95% CI 1.50‒2.06), respectively) during follow-up. In total, 673 (3.4%) patients died during the 12-month follow-up period. An independent association was found between high SABA use and overall mortality (HR 1.60, 95% CI 1.07‒2.39). This association, however, was not found in patients using inhaled corticosteroids as maintenance treatment. Conclusion In COPD patients in Sweden, high SABA use is relatively common and associated with a higher risk of exacerbations and all-cause mortality

Patient perspectives on living with severe asthma in Denmark and Sweden

Background: Severe asthma has an acknowledged impact on health-related quality of life (HRQOL) and is associated with substantial health care costs. This study aimed to investigate the patients’ own experiences of the disease, perceptions of HRQOL, and awareness of disease management. Methods: This study included severe asthma patients in Sweden and Denmark. A quantitative Web-based survey and qualitative in-depth interviews (IDIs) were conducted. The survey included St. George’s Respiratory Questionnaire (SGRQ), Asthma Control Test (ACT), Work Productivity and Activity Impairment (WPAI), and a study-specific questionnaire on quality of care and disease awareness. Telephone-based IDIs were conducted by medical interviewers following a semi-structured interview guide. Results: A total of 93 patients participated in the Web survey, and 33 participated in the IDIs. In the survey, the vast majority (77%; 72/93) had uncontrolled asthma (ACT<20). Mean total SGRQ score was 47.4 (59.7 symptom, 53.7 activity, 39.9 impact scores). Nearly 60% were treated in primary care. The IDIs revealed a long path to diagnosis, substantial and constant need for adaptations because of disease limitations, high burden on family members, social restrictions, and sick leaves and income losses. Patient awareness about guidelines, treatment goals, and available therapies was poor, and a low level of satisfaction by primary health care was seen. Conclusions: The vast majority of this severe asthma population had uncontrolled asthma and poor access to lung expert physicians. Impaired HRQOL despite patients’ adaptations was indicated. These findings highlight the need for structured patient education and greater access to units with disease-specific knowledge

Management and Risk of Mortality in Patients Hospitalised Due to a First Severe COPD Exacerbation

Background: Reducing the need for hospitalisation in patients with chronic obstructive pulmonary disease (COPD) is an important goal in COPD management. The aim of this study was to evaluate re-hospitalisation, treatment, comorbidities and mortality in patients with COPD who were hospitalised for the first time due to a COPD exacerbation. Methods: This was a retrospective, population-based observational cohort study of Swedish patients using linked data from three mandatory national health registries to assess re-hospitalisation rates, medication use and mortality. Rate of hospitalisation was calculated using the number of events divided by the number of person-years at risk; risk of all-cause and COPD-related mortality were assessed using Cox proportional hazard models. Results: In total, 51,247 patients were identified over 10 years; 35% of patients were not using inhaled corticosteroid, long-acting muscarinic antagonist or long-acting beta(2)-agonist treatment prior to hospitalisation, 38% of whom continued without treatment after being discharged. Re-hospitalisation due to a second severe exacerbation occurred in 11.5%, 17.8% and 24% of the patients within 30, 90 and 365 days, respectively. Furthermore, 24% died during the first year following hospitalisation and risk of all-cause and COPD-related mortality increased with every subsequent re-hospitalisation. Comorbidities, including ischaemic heart disease, heart failure and pneumonia, were more common amongst patients who were re-hospitalised than those who were not. Conclusion: Following hospitalisation for first severe COPD exacerbation, many patients did not collect the treatment recommended by current guidelines. Risk of mortality increased with every subsequent re-hospitalisation. Patients with concurrent comorbidities had an increased risk of being re-hospitalised

Risk of rehospitalization and death in patients hospitalized due to asthma

BACKGROUND: Asthma is a heterogeneous inflammatory airway disease that continues to cause considerable morbidity across the world, with poor asthma control leading to hospitalizations. OBJECTIVE: The present study investigated the risk of re-hospitalization, mortality and the management of asthma patients that had been hospitalized due to an asthma exacerbation. METHODS: National Swedish health registries were linked for patients aged ≥6 years who were admitted to hospital due to asthma (index date) between 01/01/06 and 12/31/15. Exacerbations were defined as asthma-related hospitalization, emergency visits, or collection of oral steroids. Patients were followed for re-hospitalizations 12-months post index, health care resource utilization and treatment for 36-months, and mortality to study end. Regression models for time-to-event analyses were applied to assess risk factors for re-hospitalization and mortality. RESULT: A total of 15,691 patients (mean age 51.5 years, 63% females) were included, of whom 1892 (12%) were re-hospitalized for asthma within 12-months. Re-hospitalized patients had a markedly increased risk of subsequent asthma related mortality (adjusted HR 2.80, 95% CI: 1.95 - 4.01) compared to those not re-hospitalized. Two thirds of the patients were not followed up by a hospital-based specialist and 60% did not collect enough inhaled corticosteroids (ICS) doses to cover daily treatment the year post index. CONCLUSION: In this study, more than one in ten patients were re-hospitalized due to asthma within 12 months, re-hospitalizations were associated with asthma related mortality. Few patients were seen by a hospital-based specialist and few used ICS continuously. Closer monitoring after hospitalization is needed

Oral corticosteroid use, morbidity and mortality in asthma : A nationwide prospective cohort study in Sweden

Background: Patterns and determinants of long-term oral corticosteroid (OCS) use in asthma and related morbidity and mortality are not well-described. In a nationwide asthma cohort in Sweden, we evaluated the patterns and determinants of OCS use and risks of OCS-related morbidities and mortality. Methods: Data for 217 993 asthma patients (aged ≥ 6 years) in secondary care were identified between 2007 and 2014 using Swedish national health registries. OCS use at baseline was categorized: regular users (≥5 mg/d/y; n = 3299; 1.5%); periodic users (>0 but <5 mg/d/y; n = 49 930; 22.9%); and nonusers (0 mg/d/y; n = 164 765; 75.6%). Relative risks of becoming a regular OCS user and for morbidity and mortality were analysed using multivariable Cox regression. Results: At baseline, 24% of asthma patients had used OCS during the last year and 1.5% were regular users. Of those not using OCS at baseline, 26% collected at least one OCS prescription and 1.3% became regular OCS users for at least 1 year during the median follow-up of 5.3 years. Age at asthma diagnosis, increasing GINA severity and Charlson Comorbidity Index were associated with regular OCS use. Compared to periodic and non-OCS use, regular use was associated with increased incidence of OCS-related morbidities and greater all-cause mortality, adjusted HR 1.34 (95% CI 1.24-1.45). Conclusions: Oral corticosteroids use is frequent for asthma patients, and many are regular users. Regular OCS use is associated with increased risk of morbidity and mortality. These findings indicate that there is a need of other treatment options for patients with severe asthma who are using regular OCS

Overuse of short-acting beta(2)-agonists in asthma is associated with increased risk of exacerbation and mortality : a nationwide cohort study of the global SABINA programme

Background: Overuse of short-acting beta(2)-agonists (SABA) may indicate poor asthma control and adverse health outcomes. Contemporary population-based data on use, risk factors and impact of SABA (over)use on asthma exacerbations and mortality are scarce, prompting initiation of the global SABINA (SABA use IN Asthma) programme. Methods: By linking data from Swedish national registries, asthma patients aged 12-45 years with two or more collections of drugs for obstructive lung disease during 2006-2014 were included. SABA overuse was defined as collection of more than two SABA canisters in a 1-year baseline period following inclusion. SABA use was grouped into 3-5, 6-10 and &gt;= 11 canisters per baseline-year. Cox regression was used to examine associations between SABA use and exacerbation (hospitalisations and/or oral corticosteroid claims) and mortality. Results: The analysis included 365 324 asthma patients (mean age 27.6 years; 55% female); average follow-up was 85.4 months. 30% overused SABA, with 21% collecting 3-5 canisters per year, 7% collecting 6-10 canisters per year and 2% collecting &gt;= 11 canisters per year. Increasing number of collected SABA canisters was associated with increased risk of exacerbation, as follows. 3-5 canisters: hazard ratio (HR) 1.26 (95% CI 1.24-1.28); 6-10 canisters: 1.44 (1.41-1.46); and &gt;= 11 canisters: 1.77 (1.72-1.83), compared to two or fewer canisters per year. Higher SABA use was associated with incrementally increased mortality risk (2564 deaths observed), as follows. 3-5 canisters: HR 1.26 (95% CI 1.14-1.39); 6-10 canisters 1.67 (1.49-1.87); and &gt;= 11 canisters: 2.35 (2.02-2.72) compared to two or fewer canisters per year. Conclusion: One-third of asthma patients in Sweden collected three or more SABA canisters annually. SABA overuse was associated with increased risks of exacerbation and mortality. These findings emphasise that monitoring of SABA usage should be key in improving asthma management