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Summary: Background: Studies with inhaled corticosteroids (ICS) in smoking asthmatics have mostly shown poorer treatment responses than in non-smoking asthmatics. Methods: EuroSMART, an open, randomised, 6-month study, compared budesonide/formoterol (Symbicort ® Turbuhaler®) h [h] Neither the Symbicort SMART posology nor the dry powder formulation, Turbuhaler, is currently approved in the US. maintenance and reliever therapy (Symbicort SMART®) at two maintenance doses of budesonide/formoterol (160/4.5 μg), 1 × 2 and 2 × 2, in patients with asthma who were symptomatic despite treatment with ICS ± long-acting β2-agonists. The 8424 randomised patients included 886 smokers (11%; aged <40 years or with a smoking history <10 pack-years if older), who were compared with a propensity-matched group of non-smokers. At baseline, smokers had lower post-bronchodilator peak expiratory flow, lower peak flow reversibility and used more reliever medication per day. Severe asthma exacerbations were counted and changes in five-item Asthma Control Questionnaire (ACQ-5) scores from baseline calculated. Results: There were 48 and 47 exacerbations in smokers and non-smokers, respectively. Mean time to first severe exacerbation was not statistically different between the two groups. The mean change in ACQ-5 score was significantly greater in non-smokers. Considering the two treatment options there was a statistically significant prolonged time to first severe exacerbation with 2 × 2 versus 1 × 2 in the smokers, but not in the non-smokers. In smokers, the reductions in ACQ-5 scores, asthma symptoms, use of as-needed medication and awakenings were also all significant in favour of 2 × 2 with similar or greater changes than in smokers treated with 1 × 2. Conclusion: Asthmatic patients with a limited smoking history benefit from treatment with budesonide/formoterol maintenance and reliever therapy with dosing 2 × 2 being superior to 1 × 2. [ABSTRACT FROM AUTHOR]

Summary: Background: Inhaled corticosteroids (ICS) represent first-line treatment in persistent asthma with clinical studies showing benefits of initiating therapy early. Whether treatment should be started with a high or low dose remains controversial. We investigated the importance of disease duration on the response to the starting dose of the ICS, budesonide, in asthma patients not previously treated with ICS. Methods: Forty patients with newly detected asthma (symptoms for <12 months) and 41 patients with established asthma (mean duration 5.2 years, range 2–11) were randomized (double-blind, parallel-group) to treatment with budesonide Turbuhaler® 100 or 400μg twice daily or placebo for 12 weeks. Results: For morning peak expiratory flow (mPEF), all four budesonide treatments resulted in statistically significant improvements from baseline and, after 12 weeks, the changes in all four groups were statistically significantly greater than placebo. In patients receiving early treatment, no significant differences were seen between budesonide doses. In patients with established symptoms, 800μg/day improved mPEF significantly more than 200μg/day. The 800μg/day dose in the early treatment group improved mPEF significantly more than in the delayed treatment group. Changes in forced expiratory volume in 1s (FEV1), the concentration of inhaled histamine causing a 20% drop in FEV1, and use of as-needed medication behaved in very similar ways to mPEF. Asthma symptoms were reduced in all budesonide groups without a difference between doses. Conclusion: In patients with newly detected asthma treated early the initial ICS dose is not important. In contrast, in patients with symptoms for a longer duration a high starting dose improves airway function and hyperresponsiveness significantly better than a low dose. [Copyright &y& Elsevier]

The Finnish National Asthma Program 1994-2004 markedly improved asthma care in the 1990s. We evaluated the changes in costs during 26 years from 1987 to 2013. Direct and indirect costs were calculated by using data from national registries. Costs from both the societal and patient perspectives were included. The costs were based on patients with persistent, physician-diagnosed asthma verified by lung function measurements. We constructed minimum and maximum scenarios to assess the effect of improved asthma care on total costs. The number of patients with persistent asthma in the national drug reimbursement register increased from 83,000 to 247,583. Improved asthma control reduced health care use and disability, resulting in major cost savings. Despite a 3-fold increase in patients, the total costs decreased by 14%, from €222 million to €191 million. Costs for medication and primary care visits increased, but overall annual costs per patient decreased by 72%, from €2656 to €749. The theoretical total cost savings for 2013, comparing actual with predicted costs, were between €120 and €475 million, depending on the scenario used. The Finnish Asthma Program resulted in significant cost savings at both the societal and patient levels during a 26-year period. [ABSTRACT FROM AUTHOR]

Abstract: Sarcoidosis is a multiorgan immune-mediated disease of unknown etiology with varying clinical pictures. We studied 3 genes in the major histocompatibility complex region (HLA-DRB1 and complement C4A and C4B) in patients with resolved disease after a 2-year follow-up (n = 90) and in patients whose disease was still active at that time point (n = 98) and compared them with controls (n = 150). Our primary aim was to detect genetic differences between the patient groups. We observed that the susceptibility allele for sarcoidosis was HLA-DRB1*15:01 (p = 0.011; odds ratio [OR] = 1.67) and the protective allele was HLA-DRB1*01:01 (p = 0.001; OR = 0.43). HLA-DRB1*03:01 was associated with resolving disease when compared with the persistent group (p = 0.011; OR = 2.22). The probability of having resolving disease was even greater if the patient had HLA-DRB1*03:01 and did not have extrapulmonary lesions (p = 0.001; OR = 3.39). By evaluating amino acid variants of the HLA-DRB1 gene, we determined that specific amino acids in pockets 4, 7, and 9 were associated with the prognosis of sarcoidosis. Our results support the importance of HLA-DRB1 as a predisposing gene for sarcoidosis. Particularly, HLA-DRB1*03:01 and polymorphisms of DRB1 pocket residues were associated with a favorable prognosis. Thus, accurate categorization of disease phenotype and HLA-DRB1 sequencing offer a basis for disease course estimation of sarcoidosis. [Copyright &y& Elsevier]