Gunilla Telg

Maintenance plus reliever budesonide/formoterol compared with a higher maintenance dose of budesonide/formoterol plus formoterol as reliever in asthma: an efficacy and cost-effectiveness study.

ABSTRACT Objective: To evaluate efficacy and costeffectiveness of budesonide/formoterol (Symbicort*) maintenance (one dose once or twice daily) plus additional doses as needed (Symbicort Maintenance And Reliever Therapy, SMART) compared with a higher fixed dose of budesonide/ formoterol with formoterol as needed in patients with persistent asthma. * Symbicort is a registered trade name of the AstraZeneca group of companies Study design and methods: 6‐month, open, randomised study of 465 patients either not well controlled on an inhaled corticosteroid (ICS), or well controlled on a combination of ICS and a long-acting β2‐agonist (LABA). Treatments: budesonide/formoterol 160/4.5 µg, one inhalation, once or twice daily maintenance plus additional doses as-needed (1 × SMART or 2 × SMART), or budesonide/formoterol 160/4.5 µg two inhalations twice daily plus formoterol 4.5 µg as needed (2 × 2 FIX + F). Children 6–11 years old used an 80/4.5 µg dose strength. Primary variables of efficacy were the changes in the Asthma Control Questionnaire (ACQ5) and morning peak expiratory flow (PEF). Results: Mean age of patients 40 years (range 6–82 years); 53% female. No differences between the groups were found in ACQ5 scores or asthma exacerbation rates. Morning PEF was higher in the 2 × 2 FIX + F group vs. the 1 × SMART and 2 × SMART groups (differences 13 L/min and 9 L/min, respectively; p < 0.002). The 1 × SMART group showed a significant decrease in asthma controlled days compared with the two other groups. No difference was seen between the 2 × SMART group and the 2 × 2 FIX + F group. Treatment costs were significantly lower in the SMART groups compared with the 2 × 2 FIX + F group. Conclusion: Compared with the 2 × 2 FIX + F treatment the use of budesonide/formoterol was 30–40% lower in the SMART groups while maintaining equal ACQ5 scores. Daily asthma control improved equally with 2 × SMART compared to 2 × 2 FIX + F with a reduction in asthma medication cost. The one dose once daily maintenance treatment (1 × SMART) resulted in a low level of treatment failure (exacerbations) but led to more days with symptoms. Therefore, a daily dose of two inhalations seems to be the lowest appropriate dose in patients with moderate persistent asthma.

Management, morbidity and mortality of COPD during an 11-year period: an observational retrospective epidemiological register study in Sweden (PATHOS)

Background: Chronic obstructive pulmonary disease (COPD) is one of the most common causes of mortality and a major contributor to morbidity. Longitudinal clinical practice data yielding information on the characteristics of the disease, its natural course, and management are limited. Aims: To investigate and describe the COPD population from a nationwide perspective during an 11-year period (1999–2009) with a focus on management, co-morbidity, and mortality. Methods: This observational retrospective epidemiological study linked electronic medical records data from patients with COPD in primary care to mandatory Swedish hospital, drug and Cause of Death registry data from 1999 to 2009 (PATHOS). Results: A total of 21,361 patients with a COPD diagnosis were included (mean age 68.0 years, 53% females). The proportion of patients diagnosed in primary care increased from 59% in 1999 to 81% in 2009 and the mean age at diagnosis decreased from 73 to 66 years. The number of exacerbations decreased from 3.0 to 1.3 and COPD-related hospitalisations decreased from 1.02 to 0.20 per patient per year. Prescriptions of long-acting muscarinic antagonists and fixed combinations of inhaled corticosteroid/long-acting β2-agonist inhalers increased from 0% to 36% and 37%, respectively. The most common co-morbidities were hypertension, heart failure, ischaemic heart disease, and diabetes. Overall life expectancy was 8.3±6.8 years shorter in patients with COPD than in the general population, and all-cause mortality was 3.5 times higher. Conclusions: Management of COPD in Sweden has improved during the 11-year study period. Despite this, patients with COPD have a substantially reduced life expectancy than the general population.

Combination of budesonide/formoterol more effective than fluticasone/salmeterol in preventing exacerbations in chronic obstructive pulmonary disease: the PATHOS study.

Combinations of inhaled corticosteroids (ICSs) and long‐acting β2‐agonists (LABAs) are recommended for patients with moderate and severe chronic obstructive pulmonary disease (COPD). However, it is not known whether different fixed combinations are equally effective. The aim of this study was to investigate exacerbation rates in primary care patients with COPD treated with budesonide/formoterol compared with fluticasone/salmeterol.

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 °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 (<15%) in FPD in 40 °C/75% RH, whereas FPD for Easyhaler decreased by >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 (<15%). BUD/FORM inhalers: Turbuhaler and Spiromax DD were unchanged in 40 °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 °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<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.

Prevalence, clinical characteristics and morbidity of the Asthma-COPD overlap in a general population sample

ABSTRACT Objective: Although asthma and chronic obstructive pulmonary disease (COPD) have been regarded as distinct conditions, emerging literature suggests that overlapping phenotypes, called asthma-COPD overlap (ACO), exists. The aim of this study was to describe prevalence, patient characteristics and morbidity of ACO. Methods: From a cross-sectional population sample, the West Sweden Asthma Study, subjects with suspected asthma, chronic bronchitis or COPD, and a random sample, were invited to clinical examinations. ACO was defined as doctor-diagnosed asthma, or clear clinical signs of asthma at examination, with a FEV1/FVC < 0.7. Results: Subjects were categorized as ACO (N = 181), COPD only (N = 89), asthma only (N = 651) or healthy (n = 1036) based on clinical examinations. Prevalence of ACO was 3.4% in the random sample (N = 1172) and 18.1% among asthmatics (N = 138) in the random sample. Subjects with ACO (mean age 59 years, 54% women) had an age and gender distribution in between asthma only (45 years, 63% women) and COPD only (62 years, 41% women). Ever-smoking was reported by 71%, 48% and 74% in the ACO, asthma only and COPD only groups, respectively. Subjects with ACO had worse lung function (mean FEV1% of predicted normal 76%) than asthma only (100%) and COPD only (87%) and reported more respiratory symptoms. Also respiratory related emergency visits were more common in ACO compared to asthma only and COPD only, respectively. Conclusions: ACO is present in 3.4% of the population and common among subjects with both asthma and COPD. Subjects with ACO had worse lung function and more symptoms than subjects with asthma or COPD only.

Budesonide inhaler device switch patterns in an asthma population in Swedish clinical practice (ASSURE)

Dry powder inhaler (DPI) device switch in asthma treatment could potentially increase with the entrance of new devices. We examined the switch patterns of budesonide (BUD) DPI analogues available in Sweden.

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.

Impact of changes to reimbursement of fixed combinations of inhaled corticosteroids and long-acting β2-agonists in obstructive lung diseases: a population-based, observational study

In 2010, the Icelandic government introduced a new cost‐saving policy that limited reimbursement of fixed inhaled corticosteroid/long‐acting β2‐agonist (ICS/LABA) combinations.

Symptoms and quality of life in patients with chronic obstructive pulmonary disease treated with aclidinium in a real-life setting

Introduction Chronic obstructive pulmonary disease (COPD) is a progressive disease with symptoms that can have a major impact on patients’ physical health. The aim of this study was to evaluate quality of life (QoL), symptom severity and dyspnoea in COPD patients treated with aclidinium up to 24 weeks. Methods In this prospective non-interventional multicentre study (198 centres in Sweden, Denmark, and Norway), COPD patients (age ≥40 years) who started treatment with aclidinium (initial therapy, change of treatment, or add-on therapy) could be included. Health-related QoL was obtained by COPD assessment test (CAT). Symptoms were evaluated on a 6-point Likert scale. The modified Medical Research Council (mMRC) Dyspnoea Scale was used as a simple grading system to assess the level of dyspnoea/shortness of breath from0 to 4. Patients on treatment with aclidinium who completed baseline and at least one follow-up visit (week 12 or 24) were included in the study population. Results Overall, 1,093 patients were enrolled (mean 69 years, 54% females), one-third had ≥1 exacerbation the year prior to baseline. At enrolment, 48% were LAMA naïve. Mean (standard deviation, SD) CAT score decreased from 16.9 (7.7) at baseline to 14.3 (7.3) at week 24 (p<0.01) with a decrease in all individual CAT items (p<0.05). Mean difference in morning and night-time symptoms from baseline to week 24 was −0.60 (SD 2.51) and −0.44 (SD 2.48), respectively (both p<0.001). Mean (SD) mMRC Dyspnoea Scale changed from 1.6 (1.0) at baseline to 1.5 (1.0) at week 24 (p<0.001). Conclusion In this observational study of a Nordic real-life COPD population, treatment with aclidinium was associated with a clinically important improvement in QoL and morning and night-time symptoms, most pronounced in the LAMA naïve group. However, there is still room for improvement in the management of symptomatic COPD patients.

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. Room for improvement exists in identification and management of frequently exacerbating asthma patients in Sweden http://ow.ly/qqN030ktv8T