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Yu Nakanishi,1 Hiroshi Iwamoto,1 Shintaro Miyamoto,1 Satoshi Nakao,1 Naoko Higaki,1 Kakuhiro Yamaguchi,1 Shinjiro Sakamoto,1 Yasushi Horimasu,1 Takeshi Masuda,1 Naoko Matsumoto,2 Taku Nakashima,1 Yojiro Onari,3 Kazunori Fujitaka,1 Yoshinori Haruta,4 Hironobu Hamada,5 Soichiro Hozawa,6 Noboru Hattori1 1Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan; 2Department of Respiratory Medicine, Hiroshima Red Cross Hospital & Atomic-Bomb Survivors Hospital, Hiroshima, Japan; 3Department of Respiratory Medicine, Hiroshima Mazda Hospital, Hiroshima, Japan; 4Haruta Respiratory Clinic, Hiroshima, Japan; 5Department of Physical Analysis and Therapeutic Sciences, Graduate School of Biomedical and Health Sciences Hiroshima University, Hiroshima, Japan; 6Hiroshima Allergy and Respiratory Clinic, Hiroshima, JapanCorrespondence: Hiroshi Iwamoto, Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan, Tel +81-82-257-5196, Email iwamotohiroshig@gmail.comPurpose: Asthma guidelines recommend considering the patient preference to optimize medication choices. Patient preference for inhaler medication may affect asthma outcomes, but evidence regarding this is lacking. This study investigated the associations between patient preference for inhaler medications and asthma outcomes.Patients and Methods: A multicenter questionnaire survey was conducted among 351 adult patients with asthma treated with regular inhaled corticosteroids. Agreement between patients’ preferences and current medication was evaluated using two questions: matched preference was defined as patients answering that the current inhaler medication was the most preferred treatment and they were satisfied with it. Mismatched preference was defined as when patients reported that the current inhaler medication was not the most preferred treatment and/or they were not satisfied with it. We investigated the factors associated with patient preference for asthma inhaler medications.Results: In total, 269 (76.6%) patients were classified into the matched preference group and 82 (23.4%) patients into the mismatched preference group. Multivariate analyses showed that matched preference was independently associated with higher asthma control test scores (P< 0.001), fewer exacerbations (P=0.009), less regular oral corticosteroid use (P=0.009), and better inhaler adherence (P=0.006) than the mismatched preference group. In subgroup analysis, younger age was associated with matched preference in patients using dry powder inhalers but not in those using pressurized metered dose inhalers.Conclusion: The use of preference-matched inhaler medication was associated with better asthma outcomes. Evaluation of patients’ preference for inhaler medication might provide useful information for individualized treatment with asthma inhaler medications.Keywords: patient preference, asthma control, inhaled corticosteroids, inhaler adherence, shared decision-making

Jing Gao,1,* Tanja Törölä,1,* Chuan-Xing Li,2 Steffen Ohlmeier,3 Tuula Toljamo,4 Pentti Nieminen,5 Noboru Hattori,6 Ville Pulkkinen,1 Hiroshi Iwamoto,6 Witold Mazur1 1Heart and Lung Centre, Department of Pulmonary Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; 2Pulmonomics Group, Respiratory Medicine Unit, Department of Medicine & Centre for Molecular Medicine, Karolinska Institute, Stockholm, Sweden; 3Proteomics Core Facility, Biocentre Oulu, Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland; 4Department of Pulmonary Medicine, Lapland Central Hospital, Rovaniemi, Finland; 5Medical Informatics and Statistics Group, University of Oulu, Oulu, Finland; 6Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan*These authors contributed equally to this workCorrespondence: Jing GaoHeart and Lung Centre, Department of Pulmonary Medicine, University of Helsinki and Helsinki University Hospital, FinlandTel +358417071559Email jing.gao@helsinki.fi, HelsinkiIntroduction: The vitamin D binding protein (VDBP, also known as GC-globulin) and vitamin D deficiency have been associated with chronic obstructive pulmonary disease (COPD). rs7041 and rs4588 are two single nucleotide polymorphisms of the VDBP gene, including three common allelic variants (GC1S, GC1F and GC2). Previous studies primarily assessed the serum levels of vitamin D and VDBP in COPD. However, less is known regarding the impact of the local release of VDBP on COPD lung function. Thus, we examined the association of sputum and plasma VDBP with lung function at baseline and at four years, and examined potential genetic polymorphism interactions.Methods: The baseline levels of sputum VDBP, plasma VDBP and plasma 25-OH vitamin D, as well as the GC rs4588 and rs7041 genotypes, were assessed in a 4-year Finnish follow-up cohort (n = 233) of non-smokers, and smokers with and without COPD. The associations between the VDBP levels and the longitudinal decline of lung function were further analysed.Results: High frequencies of the haplotypes in rs7041/rs4588 were homozygous GC1S/1S (42.5%). Higher sputum VDBP levels in stage I and stage II COPD were observed only in carriers with GC1S/1S genotype when compared with non-smokers (p = 0.034 and p = 0.002, respectively). Genotype multivariate regression analysis indicated that the baseline sputum VDBP and FEV1/FVC ratio at baseline independently predicted FEV1% at follow-up.Discussion and Conclusion: The baseline sputum VDBP expression was elevated in smokers with COPD among individuals with the GC1S/1S genotype, and predicted follow-up airway obstruction. Our results suggest that the GC polymorphism should be considered when exploring the potential of VDBP as a biomarker for COPD.Keywords: vitamin D binding protein, VDBP, genotype, COPD, prospective study, sputum

Jing Gao,1 Hiroshi Iwamoto,2 Jukka Koskela,3 Harri Alenius,4 Noboru Hattori,2 Nobuoki Kohno,5 Tarja Laitinen,6 Witold Mazur,1 Ville Pulkkinen1 1Heart and Lung Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; 2Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan; 3Clinical Research Unit of Pulmonary Diseases and Division of Pulmonology, Heart and Lung Center, University of Helsinki and Helsinki University Hospital, 4Unit of Systems Toxicology, Finnish Institute of Occupational Health, Helsinki, Finland; 5Hiroshima Cosmopolitan University, Hiroshima, Japan; 6Department of Pulmonary Diseases and Clinical Allergology, Turku University Hospital, University of Turku, Turku, Finland Abstract: Asthma–COPD overlap syndrome (ACOS) is a commonly encountered chronic airway disease. However, ACOS is still a consensus-based clinical phenotype and the underlying inflammatory mechanisms are inadequately characterized. To clarify the inflammatory mediatypical for ACOS, five biomarkers, namely interleukin (IL)-13, myeloperoxidase (MPO), neutrophil gelatinase-associated lipocalin (NGAL), chitinase-like protein (YKL-40), and IL-6, were selected. This study hypothesized that sputum biomarkers relevant for airway inflammation in asthma (IL-13), COPD (MPO, NGAL), or in both asthma and COPD (YKL-40, IL-6) could be used to differentiate ACOS from COPD and asthma. The aim of this study was to characterize the inflammatory profile and improve the recognition of ACOS. Induced sputum levels of IL-13, MPO, NGAL, YKL-40, and IL-6 were measured by enzyme-linked immunosorbent assay/Luminex assay in a Finnish discovery cohort (n=90) of nonsmokers, smokers, and patients with asthma, COPD, and ACOS and validated in a Japanese cohort (n=135). The classification accuracy of potential biomarkers was compared with area under the receiver operating characteristic curves. Only sputum NGAL levels could differentiate ACOS from asthma (P

Gao J, Iwamoto H, Koskela J, et al. International Journal of Chronic Obstructive Pulmonary Disease. 2016;11: 2457–2465. On page 2457, Abstract, line 3, the text “To clarify the inflammatory mediatypical for ACOS, five biomarkers, namely interleukin (IL)-13, myeloperoxidase (MPO), neutrophil gelatinase-associated lipocalin (NGAL), chitinase-like protein (YKL-40), and IL-6, were selected” should be “To clarify the inflammatory mediators typical for ACOS, five biomarkers, namely interleukin (IL)-13, myeloperoxidase (MPO), neutrophil gelatinase-associated lipocalin (NGAL), chitinase-like protein (YKL-40), and IL-6, were selected.” Read the original article