Validation of Clinical COPD Phenotypes for Prognosis of Long-Term Mortality in Swedish and Dutch Cohorts.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease with variable mortality risk. The aim of our investigation was to validate a simple clinical algorithm for long-term mortality previously proposed by Burgel et al. in 2017. Subjects with COPD from two cohorts, the Swedish PRAXIS study (n = 784, mean age (standard deviation (SD)) 64.0 years (7.5), 42% males) and the Rotterdam Study (n = 735, mean age (SD) 72 years (9.2), 57% males), were included. Five clinical clusters were derived from baseline data on age, body mass index, dyspnoea grade, pulmonary function and comorbidity (cardiovascular disease/diabetes). Cox models were used to study associations with 9-year mortality. The distribution of clinical clusters (1-5) was 29%/45%/8%/6%/12% in the PRAXIS study and 23%/26%/36%/0%/15% in the Rotterdam Study. The cumulative proportion of deaths at the 9-year follow-up was highest in clusters 1 (65%) and 4 (72%), and lowest in cluster 5 (10%) in the PRAXIS study. In the Rotterdam Study, cluster 1 (44%) had the highest cumulative mortality and cluster 5 (5%) the lowest. Compared with cluster 5, the meta-analysed age- and sex-adjusted hazard ratio (95% confidence interval) for cluster 1 was 6.37 (3.94-10.32) and those for clusters 2 and 3 were 2.61 (1.58-4.32) and 3.06 (1.82-5.13), respectively. Burgel's clinical clusters can be used to predict long-term mortality risk. Clusters 1 and 4 are associated with the poorest prognosis, cluster 5 with the best prognosis and clusters 2 and 3 with intermediate prognosis in two independent cohorts from Sweden and the Netherlands.

Different Relationships between FENO and COPD Characteristics in Smokers and Ex-Smokers.

Exhaled nitric oxide (FENO) is a marker of type-2 inflammation in asthma and is used in its management. However, smokers and ex-smokers have lower FENO values, and the clinical use of FENO values in COPD patients is unclear. Therefore, we investigated if FENO had a relationship to different COPD characteristics in smoking and ex-smoking subjects. Patients with COPD (n = 533, 58% females) were investigated while in stable condition. Measurements of FENO50, blood cell counts, IgE sensitisation and lung function were performed. Medication reconciliation was used to establish medication usage. Smokers (n = 150) had lower FENO50 9 (8, 10) ppb (geometric mean, 95% confidence interval) than ex-smokers did (n = 383) 15 (14, 16) ppb, p < 0.001. FENO50 was not associated with blood eosinophil or neutrophil levels in smokers, but in ex-smokers significant associations were found (r = 0.23, p < 0.001) and (r = -0.18, p = 0.001), respectively. Lower FENO values were associated with lower FEV1% predicted in both smokers (r = 0.17, p = 0.040) and ex-smokers (r = 0.20, p < 0.001). Neither the smokers nor ex-smokers with reported asthma or IgE sensitisation were linked to an increase in FENO50. Ex-smokers treated with inhaled corticosteroids (ICS) had lower FENO50 14 (13, 15) ppb than non-treated ex-smokers 17 (15, 19) ppb, p = 0.024. This was not found in smokers (p = 0.325). FENO is associated with eosinophil inflammation and the use of ICS in ex-smoking COPD subjects, but not in smoking subjects suggesting that the value of FENO as an inflammatory marker is more limited in smoking subjects. The association found between low FENO values and low lung function requires further investigation.

Hospital-based pulmonary rehabilitation in patients with COPD in Sweden--a national survey.

Pulmonary rehabilitation (PR) is an evidence-based, multidisciplinary and cost-effective intervention that leads to improved health in patients with chronic obstructive pulmonary disease, COPD. However, the availability of PR programs varies between and within different countries. The aim of this study was to investigate the availability and content of hospital-based PR programs in patients with COPD in Sweden. A cross-sectional descriptive design was applied using a web-based questionnaire which was sent out to all hospitals in Sweden. The questionnaire consisted of 32 questions that concerned availability and content of PR in patients with COPD during 2011. Seventy out of 71 hospitals responded the electronic survey. Forty-six (66%) hospitals offered PR for patients with COPD. Around 75% of the hospitals in southern and middle parts of Sweden and 33% of the hospitals in the northern part offered PR. Thirty-four percent of the patients declined participation. A total number of 1355 patients participated in PR which represents 0.2% of the COPD population in Sweden. All hospitals had exercise training as major component and 76% offered an educational program. Not even half a percent of the patients with COPD in Sweden took part in a hospital-based PR program during 2011. There was a considerable geographic discrepancy in availability over the country. To enable a greater part of the increasing number of patients with COPD to take part in this evidence-based treatment, there is a need of evaluating other settings of PR programs; in primary care, at home and/or over the internet.

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

OBJECTIVES: Combinations of inhaled corticosteroids (ICSs) and long-acting ß2 -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. METHODS: Patients with physician-diagnosed COPD and a record of postdiagnosis treatment with a fixed combination of budesonide/formoterol or fluticasone/salmeterol were included. Data from primary care medical records were linked to those from Swedish national hospital, drug and cause of death registers. Pairwise (1 : 1) propensity score matching was carried out at the index date (first prescription) by prescribed fixed ICS/LABA combination. Exacerbations were defined as hospitalizations, emergency visits and collection of oral steroids or antibiotics for COPD. Yearly event rates were compared using Poisson regression. RESULTS: Matching of 9893 patients (7155 budesonide/formoterol and 2738 fluticasone/salmeterol) yielded two cohorts of 2734 patients, comprising 19 170 patient-years. The exacerbation rates were 0.80 and 1.09 per patient-year in the budesonide/formoterol and fluticasone/salmeterol groups, respectively (difference of 26.6%; P < 0.0001); yearly rates for COPD-related hospitalizations were 0.15 and 0.21, respectively (difference of 29.1%; P < 0.0001). All other healthcare outcomes were also significantly reduced with budesonide/formoterol versus fluticasone/salmeterol. CONCLUSIONS: Long-term treatment with fixed combination budesonide/formoterol was associated with fewer healthcare utilization-defined exacerbations than fluticasone/salmeterol in patients with moderate and severe COPD.

A real-life cost-effectiveness evaluation of budesonide/formoterol maintenance and reliever therapy in asthma.

OBJECTIVE: To evaluate direct asthma-related costs in Swedish primary care in a real-life setting. DESIGN: 12-month open-label study. SETTING: Swedish primary care in a real-life setting. PARTICIPANTS: 1776 patients with persistent asthma. INTERVENTIONS: Patients with persistent asthma were randomised to one of three treatments: a free adjustable combination of budesonide (100-400 microg/inhalation) and formoterol (4.5 or 9 microg/inhalation) via separate inhalers plus terbutaline as needed; budesonide/formoterol (160/4.5 microg or 80/4.5 microg, two inhalations twice daily) plus terbutaline as needed; budesonide/formoterol (160/4.5 microg or 80/4.5 microg, one inhalation twice daily or two inhalations once daily), for maintenance plus additional inhalations as needed. Doses depended on previous inhaled corticosteroid dose. Patients attended the clinic at 0, 1.5, and 12 months. Telephone interviews were conducted at 4, 6, 8, and 10 months. MAIN OUTCOME MEASURES: The primary endpoint was direct asthma-related healthcare costs. RESULTS: Statistically significant reductions in annual direct costs per patient were observed with budesonide/formoterol maintenance and reliever therapy compared with the free adjustable combination of budesonide and formoterol (-13%, P<0.001) and fixed-dose budesonide/formoterol plus terbutaline (-20%, P<0.001). Time to first severe exacerbation did not differ significantly across treatment groups, with a mean reduction of 28% versus the free adjustable combination of budesonide and formoterol (P=0.076). Patients receiving budesonide/formoterol maintenance and reliever therapy used a significantly lower daily dose of budesonide compared with the conventional (P<0.001). CONCLUSIONS: This study reports direct cost savings with budesonide/formoterol maintenance and reliever therapy compared with conventional treatment regimens with at least equivalent efficacy.

Management, asthma control and quality of life in Swedish adolescents with asthma.

AIM: In Sweden, paediatricians or general practitioners treat most adolescents with asthma. This study compares management, treatment goals and quality of life for adolescents aged 15-18 y in paediatric or primary care. MATERIAL AND METHODS: A random sample of patients answered a disease-specific and a quality-of-life (MiniAQLQ) questionnaire. RESULTS: The 146 adolescents in paediatric care had more years with asthma, better continuity of annual surveillance, higher use of inhaled steroids and a stated better knowledge of their asthma than the 174 patients in primary care. No difference could be detected in asthma control or quality of life. Of all 320 adolescents, approximately 20% had woken at night due to asthma symptoms during the last week. About 15% had made unscheduled, urgent care visits and a third had used short-acting beta-agonist relievers more than twice a week. Quality-of-life scores were high and similar in both settings. CONCLUSIONS: Swedish adolescents with asthma are managed and treated somewhat differently in paediatric and primary care but with equal and, for the most part, satisfying results. The difference between the two settings probably reflects both differences in severity of asthma and different treatment traditions. For all adolescents, better fulfilment of goals regarding symptoms and exacerbations would be desirable, whereas a good quality of life including normal physical activity seems to have been achieved.

Budesonide/formoterol adjustable maintenance dosing reduces asthma exacerbations versus fixed dosing.

A guided, adjustable-dosing regimen with budesonide/formoterol was investigated in asthma patients. In a randomised, open, multicentre study, 1034 patients received budesonide/ formoterol (Symbicort, Turbuhaler,) 80/4.5 microg or 160/4.5 microg (depending on pre-study inhaled corticosteroid dose) two inhalations twice daily for four weeks, followed by adjustable or fixed maintenance dosing for six months. Patients receiving adjustable dosing stepped down to one inhalation twice daily if symptoms were controlled and could, if symptoms worsened, step up to four inhalations twice daily for one or two weeks according to a self-guided management plan. The primary efficacy variable was occurrence of exacerbations. Compared with fixed dosing, adjustable dosing was associated with fewer patients experiencing exacerbations (6.2% vs 9.5%, NNT 30, p<0.05), fewer daily inhalations of budesonide/formoterol (2.35 vs 3.95, p<0.001), lower costs (six-month saving Euros 98, p<0.001) and was similarly well tolerated. Adjustable maintenance dosing with budesonide/formoterol provides more effective asthma control than fixed dosing, and reduces costs.

Living with asthma in Sweden--the ALMA study.

BACKGROUND: Recently performed studies have found a number of limitations in the daily lives of asthmatics, and a large disparity between the perception of the sufferers and what health care professionals believe matters to asthmatics. AIM: What matters to Swedish asthma patients, what medicines do they use, and are they compliant with given prescriptions? A further aim was to compare perceptions about asthma and asthma management in asthmatics and among Swedish general practitioners (GP). DESIGN: A structured telephone interview of a representative sample of Swedish asthmatics, and a mailed questionnaire survey among GPs from different parts of Sweden. METHODS: Screening by telephone of a random sample of 10,350 subjects aged 18-45. Of those, 240 were subsequently selected for a detailed structured telephone interview about their asthma. A mailed structured questionnaire containing similar questions to those asked of the asthmatics was sent to 600 GPs, and 139 returned completed answers. RESULTS: 16% of the asthmatics reported (asthma) symptoms occurring every day during the previous month. Nocturnal symptoms at least twice per week were reported by 19%. Both these were reported by considerably higher proportions of the asthmatics than the GPs had expected. A large majority classified their disease as mild or very mild, although great majority reported frequent symptoms. Activities or situations which caused symptoms of asthma often or "now and then" were physical exertion, 67%; bad weather, 59%; contact with animals/pets, 58%; and visits to cafes or restaurants, 36%; and several asthmatics avoided these activities due to their asthma. CONCLUSION: A great majority of asthmatics report a large number of symptoms and limitations in their daily living in proportions which were roughly expected by the GPs.