Glucocorticoid treatment in SLE is associated with infections, comorbidities and mortality-a national cohort study.

OBJECTIVES: Patients with SLE have an increased risk of comorbidities and impaired survival. We aimed to assess whether various thresholds of oral CS (OCS) can predict development of infections, comorbidities, malignancies and survival in SLE using data from national health registries in Sweden. METHODS: All incident SLE cases, age >18 years, in Sweden (n = 5309) between 2005 and 2020 and matched population controls (n = 26 545) were included and followed until 2020, a total of 257 942 patient years. Data from national registers were retrieved including information from the National Prescribed Drug Register. Risk factors were analysed using time-dependent Cox regression models. RESULTS: Compared with no OCS, >0 to <5.0 mg/day, 5.0-7.5 mg/day as well as >7.5 mg/day OCS predicted development of infections (pneumonia, influenza, herpes zoster and urinary tract infection), osteoporosis, osteonecrosis, gastroduodenal ulcers, cataracts, hypertension and mortality (all P < 0.05). OCS >0 to <5.0 mg/day was associated with lower hazard ratios for these comorbidities than higher doses of OCS. Fifteen years after diagnosis, 48% of patients were taking OCS at a median dose of 5.7 mg/day. A small reduction of OCS treatment 5 years after diagnosis in patients diagnosed with SLE 2006-10 compared with 2011-15 was observed, 49% vs 46% respectively (P = 0.039). CONCLUSION: Results highlight the potential harm associated with even low OCS dose treatment in SLE and the need to judiciously use OCS at the lowest possible dose to maximize efficacy and minimize harm.

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 FeNO < 25 ppb), non-T2 low150 (n = 138; BEC > 150 cells/µL and/or FeNO > 25 ppb), T2 low300 (n = 66; BEC < 300 cells/µL and FeNO < 25 ppb), and non-T2 low300 (n = 103; 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.

High use of short-acting ß2-agonists in COPD is associated with an increased risk of exacerbations and mortality.

Background: Short-acting ß2-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.

Exacerbations Predict Severe Cardiovascular Events in Patients with COPD and Stable Cardiovascular Disease-A Nationwide, Population-Based Cohort Study.

Objective: Patients with chronic obstructive pulmonary disease (COPD) commonly present with cardiovascular disease (CVD). We investigated the association between COPD exacerbations and major cardiovascular (CV) events in a COPD population with a history of CVD. Methods: This population-based and register-based cohort study identified all Danish COPD patients aged ≥40 years who visited a hospital-based, pulmonary outpatient clinic for COPD between 1st January, 2010, and 31st December, 2016, from a nationwide COPD registry. Patients with a history of a major CV event 36‒6 months prior to their COPD measurement date and no CV event 6 months before this date were included. During a 6-month assessment period, the risks of a new CV event (hospitalization with fatal/non-fatal stroke, myocardial infarction, or heart failure) and moderate and severe COPD exacerbations were evaluated. Odds ratios with 95% confidence intervals for CV events and death were estimated using adjusted logistic regression models. Results: Of the 1501 COPD patients included, 55% experienced a COPD exacerbation and 13% experienced both an exacerbation and a CV event during follow-up (6 months). The odds of a CV event were 1.5 times higher in patients with a moderate exacerbation and more than 6-times higher in those with a severe exacerbation vs patients with no exacerbation(s). The majority of CV events occurred within 30 days post exacerbation in patients who experienced both an exacerbation and a CV event. In total, 113 patients died during the study period: 28% of deaths were caused by CVD and 72% by reasons other than CVD, mostly COPD. Conclusion: In patients with known CVD, severe COPD exacerbations are associated with increased odds of major CV events that occur within 30 days post exacerbation, highlighting the need to prevent exacerbations in COPD patients with concomitant CVD to potentially improve both respiratory and CV health.

Distribution of type 2 biomarkers and association with severity, clinical characteristics and comorbidities in the BREATHE real-life asthma population.

Background: Type 2 (T2) high asthma is recognised as a heterogenous entity consisting of several endotypes; however, the prevalence and distribution of the T2 biomarkers in the general asthma population, across asthma severity, and across compartments is largely unknown. The objective of the present study was to describe expression and overlaps of airway and systemic T2 biomarkers in a clinically representative asthma population. Methods: Patients with asthma from the real-life BREATHE cohort referred to a specialist centre were included and grouped according to T2 biomarkers: blood and sputum eosinophilia (≥0.3×109 cells·L-1 and 3% respectively), total IgE (≥150 U·mL-1), and fractional exhaled nitric oxide (≥25 ppb). Results: Patients with mild-to-moderate asthma were younger (41 versus 49 years, p<0.001), had lower body mass index (25.9 versus 28.0 kg·m-2, p=0.002) and less atopy (47% versus 58%, p=0.05), higher forced expiratory volume in 1 s (3.2 versus 2.8 L, p<0.001) and forced vital capacity (4.3 versus 3.9 L, p<0.001) compared with patients with severe asthma, who had higher blood (0.22×109 versus 0.17×109 cells·L-1, p=0.01) and sputum (3.0% versus 1.5%, p=0.01) eosinophils. Co-expression of all T2 biomarkers was a particular characteristic of severe asthma (p<0.001). In patients with eosinophilia, sputum eosinophilia without blood eosinophilia was present in 45% of patients with mild-to-moderate asthma and 35% with severe asthma. Conclusion: Severe asthma is more commonly associated with activation of several T2 pathways, indicating that treatments targeting severe asthma may need to act more broadly on T2 inflammatory pathways. Implementation of airway inflammometry in clinical care is of paramount importance, as the best treatable trait is otherwise is overlooked in a large proportion of patients irrespective of disease severity.

Short-acting ß2 -agonist use and asthma exacerbations in Swedish children: A SABINA Junior study.

BACKGROUND: In adults and adolescents with asthma, use of ≥3 short-acting ß2 -agonist (SABA) canisters/year is associated with increased exacerbation risk. Whether this association is present in younger children remains unknown. In this SABA use IN Asthma (SABINA) Junior study, we assessed the association of SABA collection with exacerbation risk in the general Swedish pediatric asthma population. METHODS: This population-based cohort study utilized linked data from the Swedish national healthcare registries involving patients with asthma (<18 years) treated in secondary care between 2006-2015. Exacerbation risk, by baseline SABA collection (0-2 vs. ≥3 canisters, further examined as ordinal/continuous variable) and stratified on comorbid atopic disease (allergic rhinitis, dermatitis and eczema, and food/other allergies), was assessed for 1-year follow-up using negative binomial regression. RESULTS: Of 219,561 patients assessed, 45.4%, 31.7%, and 26.5% of patients aged 0-5, 6-11, and 12-17 years, respectively, collected ≥3 SABA canisters during the baseline year (high use). Collection of ≥3 SABA canisters (vs. 0-2) was associated with increased exacerbation risk during follow-up (incidence rate ratios [95% confidence interval]: 1.35 [1.29-1.42], 1.22 [1.15-1.29], and 1.26 [1.19-1.34] for 0-5-, 6-11-, and 12-17-year-olds, respectively); the association persisted with SABA as a continuous variable and was stronger among patients without atopic diseases (32%-44% increased risk versus. 14%-21% for those with atopic disease across groups). CONCLUSIONS: High SABA use was associated with increased asthma exacerbation risk in children, particularly in those without comorbid atopic diseases, emphasizing the need for asthma medication reviews and reformative initiatives by caregivers and healthcare providers on SABA use.

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.

Lack of COPD-Related Follow-Up Visits and Pharmacological Treatment in Swedish Primary and Secondary Care.

Objective: The Swedish guidelines recommend that patients with chronic obstructive pulmonary disease (COPD) on maintenance treatment are monitored annually, and within six weeks after an exacerbation. We describe the patterns of COPD-related visits in Sweden, both regular follow-up and post-exacerbation visits. Methods: Patients (>40 years) with a first-time COPD diagnosis between 2006 and 2017 were identified in primary care medical records and linked to hospital contacts and administered drug data. The index date was defined as the first collection of inhaled COPD maintenance treatment after the diagnosis. Regular COPD visits within 15-months after the index, and post-exacerbation visits for COPD within six weeks and 15-months after an exacerbation were estimated using the cumulative incidence function adjusted for competing risk. Visits without a ICD code for COPD were not included in the analyses. Results: A total of 19,857 patients (mean age 69 years, 57% females) were included. The overall probability of having a regular follow-up visit for COPD within 15 months post-index was 39.1%. In total, 15,095 (76%) patients experienced at least one COPD exacerbation during the observation period. Among them, the probability of having a post-exacerbation visit was 7.0% within six weeks and 29.7% within 15-months. Patients without a regular COPD follow-up visit claimed significantly more oral corticosteroids (25.6% vs 15.6%), more respiratory antibiotics (39.1% vs 23.1%), and less maintenance treatment (10.9% vs 16.5%). Conclusion: Only 39% of COPD patients attended a regular follow-up visit within 15-months from the COPD diagnosis and one-third had a post-exacerbation visit. The adherence to guideline recommendations need to be improved.

Regional variation in intensity of inhaled asthma medication and oral corticosteroid use in Denmark, Finland, and Sweden.

Oral corticosteroids (OCS) are often prescribed to patients with asthma that remains uncontrolled with maintenance therapy. We performed a real-world analysis to describe the geographic distributions of patients with asthma and OCS dispensed in Nordic countries. This observational, retrospective study examined patient-level data from nationally prescribed drug registries from January to December 2018 for individuals aged ≥12 years in Denmark, Finland, and Sweden. Using an algorithm based on asthma treatment combinations defined by the Global Initiative for Asthma (GINA), we identified patients with asthma, those on GINA Step 4-5 treatments, and those being dispensed ≥2 courses of OCS and determined volumes of OCS dispensed to these patients over the 1-year analysis period. Data were plotted geographically within each country using colour-coded heat maps. The overall asthma prevalence rates were 7.4% in Denmark, 11.6% in Finland, and 8.1% in Sweden. In Denmark, Finland, and Sweden, respectively, the frequencies of patients on GINA Step 4-5 treatments were 19%, 15%, and 16%; among whom 10%, 23%, and 5% received ≥2 courses of OCS. The rates of patients on GINA Step 4-5 treatments who were dispensed OCS in each country were 23%, 30%, and 46%, of which 22%, 17%, and 10% were dispensed doses averaging ≥5 mg/day over the year. Heat maps revealed considerable heterogeneity in geographic densities of patients with asthma and OCS claims within each country. Taken together, these results demonstrate regional variations in estimated asthma severity, control, and OCS dispensed within and between countries. Patterns of medication use suggest that a high proportion of patients in Denmark, Finland, and Sweden are on GINA Step 4-5 treatments, many of whom are dispensed OCS; this poses a considerable corticosteroid burden to these patients. Geographic differences in medication use within and between Nordic countries may reflect variations in population characteristics and/or treatment approaches.

Annual and Post-Exacerbation Follow-Up of Asthma Patients in Clinical Practice - A Large Population-Based Study in Sweden.

Background: Symptom control has not improved in Swedish asthma patients during the last two decades. Guidelines recommend annual reviews for asthma patients treated with maintenance inhaled corticosteroids (ICS). We aimed to describe how visit patterns in an ICS-treated asthma population in Sweden were related to applicable asthma guidelines. Methods: Swedish electronic health data for incident asthma patients, ≥18 years, with at least one ICS collection (index date) between 2006 and 2017 were included. Exacerbations were defined as hospitalizations, emergency visits, or collection of oral corticosteroids (OCS). Probability of an asthma-related regular follow-up visit and probability of a follow-up visit after an exacerbation, both within 15 months, were estimated using the cumulative incidence function, time-to-event analysis, and incident rate ratios. Results: In 51,349 asthma patients (mean age 47.6 years, 63% females), 17,573 had a regular asthma visit in primary or secondary care within 15 months after the index, yielding an overall probability of a visit of 37.4%. Patients with a follow-up visit had higher ICS collection and lower OCS collection than patients without regular visits. Among 22,097 patients with acute exacerbations, the probability of a visit within 15 months after an exacerbation was 31.0%. The probability of having a visit increased during the study period. Conclusion: Only one-third of ICS-treated asthma patients, regardless of asthma severity, had a regular or post-exacerbation follow-up visit within a 15-month period. The consequences of this lack of adherence to guidelines need further evaluation to secure optimal asthma management.

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 rehospitalization, mortality, and the management of patients with asthma who had been hospitalized because of an asthma exacerbation. METHODS: National Swedish health registries were linked for patients 6 years or older who were admitted to hospital because of asthma (index date) between January 1, 2006, and December 31, 2015. Exacerbations were defined as asthma-related hospitalization, emergency visits, or collection of oral steroids. Patients were followed for rehospitalizations 12 months after the index date, 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 rehospitalization and mortality. RESULTS: A total of 15,691 patients (mean age, 51.5 years; 63% females) were included, of whom 1,892 (12%) were rehospitalized for asthma within 12 months. Rehospitalized patients had a markedly increased risk of subsequent asthma-related mortality (adjusted hazard ratio, 2.80; 95% CI, 1.95-4.01) compared with those not rehospitalized. Two-third of the patients were not followed up by a hospital-based specialist, and 60% did not collect enough inhaled corticosteroid doses to cover daily treatment the year postindex. CONCLUSIONS: In this study, more than 1 in 10 patients were rehospitalized because of asthma within 12 months, and rehospitalizations were associated with asthma-related mortality. Few patients were seen by a hospital-based specialist, and few used inhaled corticosteroid continuously. Closer monitoring after hospitalization is needed.

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 ß2-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.

Severe asthma is related to high societal costs and decreased health related quality of life.

BACKGROUND: The aim of the present study was to estimate the societal costs and the key cost drivers for patients with severe asthma in Sweden. In addition, health-related quality of life (HRQOL) and morbidity of patients with severe asthma is described. METHODS: The study population comprised adults with severe asthma recruited from a large asthma cohort within the Obstructive Lung Disease in Northern Sweden (OLIN) studies. During 2017, patients were interviewed quarterly over telephone regarding their resource utilization and productivity losses. RESULTS: Estimated mean annual asthma-related costs per patient with severe asthma amounted to €6,500, of which approximately €2400 and €4100 were direct and indirect costs, respectively. The main cost drivers for direct costs were hospitalizations followed by drugs: approximately €1000 and €800, respectively. Patients on treatment with regular oral corticosteroids (OCS) had greater direct costs compared with those without regular OCS treatment. Co-morbid conditions were common and the costs were substantial also for co-morbid conditions, with a total cost of approximately €4200. The OCS group had significantly lower HRQOL compared to the non-OCS group. CONCLUSIONS: The societal costs due to severe asthma were substantial. Costs for co-morbid conditions contributed substantially to both direct and indirect costs. The direct costs were significantly higher in the maintenance OCS-group compared to the non-maintenance OCS-group. These results indicate a need for improved management and treatment regimens for patients with severe asthma.

Overuse of short-acting ß2-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 ß2-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 ≥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 ≥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 ≥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 ≥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.

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.

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.

Health care resource utilization and cost for asthma patients regularly treated with oral corticosteroids - a Swedish observational cohort study (PACEHR).

BACKGROUND: Patients with severe uncontrolled asthma may receive oral corticosteroid (OCS) treatment regularly. The present study investigated the health care resource utilization and cost in regularly OCS treated Swedish asthma patients. METHODS: Primary care medical records data were linked to data from Swedish national health registries. Patients ≥18 years with a drug claim for obstructive pulmonary diseases during 2007-2009 (index date) and a prior asthma diagnosis, were classified by their OCS claims during the 12-months' post index period: regular OCS equals ≥5 mg per day; periodic OCS less than 5 mg per day; or non-OCS users. Cost of asthma- and OCS-morbidity-related health care resource utilization were calculated. RESULTS: A total of 15,437 asthma patients (mean age 47.8, female 62.6%), whereof 223 (1.44%) were regular OCS users, 3054 (19.7%) were periodic, and 12,160 (78.7%) were non-OCS users. Regular OCS users were older and more often females, had lower lung function, greater eosinophil count and more co-morbidities at baseline compared with the other groups. Age-adjusted annual total health care cost was three-times greater in the regular OCS group (€5615) compared with the non-OCS users (€1980) and twice as high as in the periodic OCS group (€2948). The major cost driver in the non-OCS and periodic OCS groups were primary care consultations, whereas inpatient costs were the major cost driver in the regular OCS group. The asthma related costs represented 10-12% of the total cost in all three groups. CONCLUSION: In this real-life asthma study in Sweden, the total yearly cost of health care resource utilization for a regular OCS user was three times greater than for a patient with no OCS use, indicating substantial economic and health care burden for asthma patients on regular oral steroid treatment.

Prevalence, characteristics and management of frequently exacerbating asthma patients: an observational study in Sweden (PACEHR).

The aim of the study was to investigate the prevalence, management and characteristics of asthma patients with frequent exacerbations.Data from asthma patients (aged ≥18 years) identified in primary care medical records were linked to Swedish national health registries. Exacerbations were defined as hospitalisations, emergency visits and/or collection of oral steroids. Frequent exacerbations were defined as two or more exacerbations per year during the 3-year observation period.Of 18 724 asthma patients, 81.49% had no exacerbations and 6.3% had frequent exacerbations in the year prior to the index date. Frequent exacerbations were observed yearly for 1.8% of the patients. Frequent exacerbators were older, more often females, and had increased eosinophil and neutrophil counts, lower lung function, and more comorbidities than patients without exacerbations. There was a slight increase in asthma medication claims and a slight decrease in physician visits compared with baseline, both in the group with and the group without frequent exacerbations.Patients with frequent exacerbations were characterised by greater age, female predominance, high eosinophil and neutrophil counts, and high prevalence of comorbidities. This study indicates that the Swedish healthcare system lacks efficiency to adjust treatment and management for this patient group. With new treatment options targeting severe asthma available, identification of these patients should be in focus to ensure reduction of exacerbations.

Comorbidity, disease burden and mortality across age groups in a Swedish primary care asthma population: An epidemiological register study (PACEHR).

BACKGROUND: Asthma is often associated with other diseases. To identify and manage comorbidities is important, as these conditions may increase the disease burden. OBJECTIVE: To describe the prevalence of comorbidities, disease burden and mortality across age groups in a large Swedish primary care real-life asthma population. METHODS: Observational cohort study of asthma patients, all ages, identified from electronic medical records by ICD-10-CM code, data from 36 primary care centers. Data were linked to national mandatory Swedish health registers. Comorbidities were identified by ICD-10-CM codes and collected from electronic medical records and the National Patient Registers, mortality data from the Cause of Death Register. Exacerbations were defined as hospitalizations due to asthma, and/or emergency visits at hospital and/or prescription claims of oral steroids. RESULTS: In total 33,468 patients (58% women) were included. The most prevalent comorbidities were acute upper respiratory tract infection (53%), rhinitis (25%), acute lower respiratory tract infection (25%), hypertension (21%), anxiety and depression (20%). The comorbidities associated with highest risk for an exacerbation were COPD OR 1.98 (95%CI: 1.80-2.19), nasal polyps OR 1.75 (95%CI: 1.49-2.05) and rhinitis OR 1.52 (95%CI: 1.41-1.63). All-cause mortality was similar to the Swedish population, 1011 deaths per 100,000 person/year compared with 1058 deaths (standardized risk = 0.99 [95%CI:0.95-1.04]). The pulmonary related death rate was greater in the study population versus the Swedish population (122 versus 72 per 100,000person/year). CONCLUSION: Comorbid disease was frequent in this large real-life asthma population with an impact on exacerbations. To identify and treat comorbidities with impact on asthma outcomes are essential to improve asthma care.