21. Toward clinically applicable biomarkers for asthma: An EAACI position paper.
Diamant Z, Vijverberg S, Alving K, Bakirtas A, Bjermer L, Custovic A, Dahlen SE, Gaga M, Gerth van Wijk R, Giacco SD, Hamelmann E, Heaney LG, Heffler E, Kalayci Ö, Kostikas K, Lutter R, Olin AC, Sergejeva S, Simpson A, Sterk PJ, Tufvesson E, Agache I, Seys SF.
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Inflammation, structural, and functional abnormalities within the airways are key features of asthma. Although these processes are well documented, their expression varies across the heterogeneous spectrum of asthma. Type 2 inflammatory responses are characterized by increased levels of eosinophils, FeNO, and type 2 cytokines in blood and/or airways. Presently, type 2 asthma is the best-defined endotype, typically found in patients with allergic asthma, but surprisingly also in nonallergic patients with (severe) asthma. The etiology of asthma with non-type 2 inflammation is less clear. During the past decade, targeted therapies, including biologicals and small molecules, have been increasingly integrated into treatment strategies of severe asthma. These treatments block specific inflammatory pathways or single mediators. Single or composite biomarkers help to identify patients who will benefit from these treatments. So far, only a few inflammatory biomarkers have been validated for clinical application. The European Academy of Allergy & Clinical Immunology Task Force on Biomarkers in Asthma was initiated to review different biomarker sampling methods and to investigate clinical applicability of new and existing inflammatory biomarkers (point-of-care) to support diagnosis, targeted treatment, and monitoring of severe asthma. Subsequently, we discuss existing and novel targeted therapies for asthma as well as applicable biomarkers.
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22. Inflammatory profile in optimally treated patients with adult versus early-onset asthma.
Papaporfyriou A, Papaioannou AI, Hillas G, Konstantelou E, Tseliou E, Koulouris N, Papiris S, Bakakos P, Kostikas K, Loukides S.
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23. Treatment response in COPD: does FEV
Kostikas K, Greulich T, Mackay AJ, Lossi NS, Aalamian-Mattheis M, Nunez X, Pagano VA, Patalano F, Clemens A, Vogelmeier CF.
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The association between clinically relevant changes in patient-reported outcomes (PROs) and forced expiratory volume in 1 s (FEV
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24. Patients' perspectives on COPD: findings from a social media listening study.
Cook NS, Kostikas K, Gruenberger JB, Shah B, Pathak P, Kaur VP, Mudumby A, Sharma R, Gutzwiller FS.
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We utilised social media listening (SML) to obtain patients' perspectives on symptoms, diagnosis and comorbidities associated with chronic obstructive pulmonary disease (COPD) and its impact on patients' quality of life (QoL). A comprehensive search on social media platforms was performed for English language content posted between July 2016 and January 2018 using COPD-related terms. Social Studio, a social media data aggregator tool, was used to capture relevant records. The content was manually curated to analyse and map psychological aspects with descriptive statistics applied on aggregated findings. A total of 849 posts from patients or caregivers ("patient insights") were considered for the analysis, corresponding to postings of 695 unique individuals. Based on 734 mentions of symptoms from 849 posts by potential patients/caregivers, cough (27%), mucus (25%) and shortness of breath (21%) were the most frequent; analysis by perceived COPD severity indicated these to be common across all severities. Difficulty in mucus clearance (24% of 268 mentions) and sadness (40% of 129 mentions) were top among the aspects impacting physical and emotional QoL, respectively. SML from patients with COPD indicated that relief from cough, mucus production and shortness of breath would be the most desirable aspects of disease management from a patient's perspective.
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25. Serum levels of hyaluronic acid are associated with COPD severity and predict survival.
Papakonstantinou E, Bonovolias I, Roth M, Tamm M, Schumann D, Baty F, Louis R, Milenkovic B, Boersma W, Stieltjes B, Kostikas K, Blasi F, Aerts JG, Rohde GGU, Lacoma A, Torres A, Welte T, Stolz D.
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Hyaluronic acid (HA) and its degradation products play an important role in lung pathophysiology and airway remodelling in chronic obstructive pulmonary disease (COPD).We investigated if HA and its degrading enzyme hyaluronidase (HYAL)-1 are associated with COPD severity and outcome.Serum HA was assessed in a discovery cohort of 80 COPD patients at stable state and exacerbations. HA, HYAL-1 and HYAL-1 enzymatic activity were evaluated at stable state, exacerbations and 4 weeks after exacerbations in 638 COPD patients from the PROMISE validation cohort.In the discovery cohort, serum HA was higher at exacerbations compared with the stable state (p=0.015). In the validation cohort, HA was higher at moderate and severe exacerbations than at baseline (p<0.001), and remained higher after 4 weeks (p<0.001). HA was strongly predictive for overall survival since it was associated with time to death (p<0.001) independently of adjusted Charlson score, annual exacerbation rate and BODE (body mass, airflow obstruction, dyspnoea, exercise capacity) index. Serum HYAL-1 was increased at moderate (p=0.004) and severe (p=0.003) exacerbations, but decreased after 4 weeks (p<0.001). HYAL-1 enzymatic activity at stable state was inversely correlated with FEV
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26. Microbiota and asthma: Clinical implications.
Katsoulis K, Ismailos G, Kipourou M, Kostikas K.
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27. Treatment response to indacaterol/glycopyrronium versus salmeterol/fluticasone in exacerbating COPD patients by gender: a post-hoc analysis in the FLAME study.
Wedzicha JA, Singh D, Tsiligianni I, Jenkins C, Fucile S, Fogel R, Shen S, Goyal P, Mezzi K, Kostikas K.
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28. Reply to Lan and Shi: Different Background, Short Duration, and Inappropriate Participants May Harm Your Conclusion.
Chapman KR, Hurst JR, Fogel RB, Pfister P, Kostikas K, Wedzicha JA.
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29. Real-world retrospective cohort study ARCTIC shows burden of comorbidities in Swedish COPD versus non-COPD patients.
Ställberg B, Janson C, Larsson K, Johansson G, Kostikas K, Gruenberger JB, Gutzwiller FS, Jorgensen L, Uhde M, Lisspers K.
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This study aimed to generate real-world evidence to assess the burden of comorbidities in COPD patients, to effectively manage these patients and optimize the associated healthcare resource allocation. ARCTIC is a large, real-world, retrospective cohort study conducted in Swedish COPD patients using electronic medical record data collected between 2000 and 2014. These patients were studied for prevalence of various comorbidities and for association of these comorbidities with exacerbations, mortality, and healthcare costs compared with an age-, sex-, and comorbidities-matched non-COPD reference population. A total of 17,479 patients with COPD were compared with 84,514 non-COPD reference population. A significantly higher prevalence of various comorbidities was observed in COPD patients 2 years post-diagnosis vs. reference population, with the highest percentage increase observed for cardiovascular diseases (81.8% vs. 30.7%). Among the selected comorbidities, lung cancer was relatively more prevalent in COPD patients vs. reference population (relative risk, RR = 5.97, p < 0.0001). Ischemic heart disease, hypertension, depression, anxiety, sleep disorders, osteoporosis, osteoarthritis, and asthma caused increased mortality rates in COPD patients. Comorbidities that were observed to be significantly associated with increased number of severe exacerbations in COPD patients included heart failure, ischemic heart disease, depression/anxiety, sleep disorders, osteoporosis, lung cancer, and stroke. The cumulative healthcare costs associated with comorbidities over 2 years after the index date were observed to be significantly higher in COPD patients (€27,692) vs. reference population (€5141) (p < 0.0001). The data support the need for patient-centered treatment strategies and targeted healthcare resource allocation to reduce the humanistic and economic burden associated with COPD comorbidities.
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30. Dual bronchodilation vs triple therapy in the "real-life" COPD DACCORD study.
Buhl R, Criée CP, Kardos P, Vogelmeier CF, Kostikas K, Lossi NS, Worth H.
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31. Revisiting IL-13 blockade: can we reach the wonderland the inhaled way?
Papaioannou AI, Loukides S, Kostikas K.
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32. Single-Inhaler Triple versus Dual Therapy in Patients with COPD.
Wedzicha JA, Banerji D, Kostikas K.
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33. Efficacy and safety of the direct switch to indacaterol/glycopyrronium from salmeterol/fluticasone in non-frequently exacerbating COPD patients: The FLASH randomized controlled trial.
Frith PA, Ashmawi S, Krishnamurthy S, Gurgun A, Hristoskova S, Pilipovic V, Hamann AM, Backer A, Olsson P, Kostikas K, Diaz DV.
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34. Capturing Exacerbations of Chronic Obstructive Pulmonary Disease with EXACT. A Subanalysis of FLAME.
Frent SM, Chapman KR, Larbig M, Mackay A, Fogel R, Gutzwiller FS, Shen S, Patalano F, Banerji D, Kostikas K, Wedzicha JA.
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35. Collagen Degradation and Formation Are Elevated in Exacerbated COPD Compared With Stable Disease.
Schumann DM, Leeming D, Papakonstantinou E, Blasi F, Kostikas K, Boersma W, Louis R, Milenkovic B, Aerts J, Sand JMB, Wouters EFM, Rohde G, Prat C, Torres A, Welte T, Tamm M, Karsdal M, Stolz D.
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36. Indacaterol/glycopyrronium versus salmeterol/fluticasone in the prevention of clinically important deterioration in COPD: results from the FLAME study.
Anzueto AR, Kostikas K, Mezzi K, Shen S, Larbig M, Patalano F, Fogel R, Banerji D, Wedzicha JA.
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37. Long-Term Triple Therapy De-escalation to Indacaterol/Glycopyrronium in Patients with Chronic Obstructive Pulmonary Disease (SUNSET): A Randomized, Double-Blind, Triple-Dummy Clinical Trial.
Chapman KR, Hurst JR, Frent SM, Larbig M, Fogel R, Guerin T, Banerji D, Patalano F, Goyal P, Pfister P, Kostikas K, Wedzicha JA.
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38. Indacaterol/glycopyrronium reduces the risk of clinically important deterioration after direct switch from baseline therapies in patients with moderate COPD: a post hoc analysis of the CRYSTAL study.
Greulich T, Kostikas K, Gaga M, Aalamian-Mattheis M, Lossi NS, Patalano F, Nunez X, Pagano VA, Fogel R, Vogelmeier CF, Clemens A.
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39. Exacerbation heterogeneity in COPD: subgroup analyses from the FLAME study.
Vogelmeier CF, Chapman KR, Miravitlles M, Roche N, Vestbo J, Thach C, Banerji D, Fogel R, Patalano F, Olsson P, Kostikas K, Wedzicha JA.
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40. Patient-reported Outcomes for the Detection, Quantification, and Evaluation of Chronic Obstructive Pulmonary Disease Exacerbations.
Mackay AJ, Kostikas K, Murray L, Martinez FJ, Miravitlles M, Donaldson G, Banerji D, Patalano F, Wedzicha JA.
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An exacerbation of chronic obstructive pulmonary disease (COPD) is an acute worsening of respiratory symptoms accompanied by a variable degree of physiological deterioration. The traditional assessment of an exacerbation consists of the reporting of symptoms by the patient to a clinician and subsequent clinical assessment. It would be valuable to also gather symptom reports directly from patients, and thus patient-reported outcome (PRO) tools should be ideally suited to the evaluation of COPD exacerbations. However, most pharmaceutical industry- and large academy-sponsored studies have used a healthcare resource use definition alone, which is based on sustained worsening of a patient's condition from the stable state that requires a change in regular medication. This Review explores the use of PROs for the detection, quantification, and evaluation of COPD exacerbations. It examines symptom diary cards as exacerbation detection tools and their evolution into electronic diaries used in pharmaceutical trials. This paper also describes the development of specifically designed PROs that have been used in exacerbation settings, focusing on the Exacerbations and Symptoms in COPD e-Diary, Exacerbations of Chronic Obstructive Pulmonary Disease Tool, COPD Assessment Test, and Chronic Respiratory Disease Questionnaire, highlighting the strengths and weaknesses of these instruments. We describe the effectiveness of these tools to enhance exacerbation reporting; quantify exacerbation characteristics, including the frequency, duration, and severity of events; and evaluate the outcome. We also explore the potential use of PROs in future studies to discriminate the effect of therapies on different exacerbation phenotypes and thus enhance personalized therapeutic approaches.
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