Publications by authors named "Davor Plavec"

69 Publications

Third-Day Oxygenation Index is an Excellent Predictor of Survival in Children Mechanically Ventilated for Acute Respiratory Distress Syndrome.

Risk Manag Healthc Policy 2020 24;13:1739-1746. Epub 2020 Sep 24.

Institute of Medical Physiology "Richard Burian", Faculty of Medicine, University of Belgrade, Belgrade, Serbia.

Purpose: The aim of this study was to assess the association between oxygenation index (OI) and outcome in children with acute respiratory distress syndrome (ARDS).

Patients And Methods: Patients (age, >30 days) in the pediatric intensive care unit from April 2011 to March 2016 with ARDS and who were mechanically ventilated were included. Patients were divided into two age groups: infants (<12month) and older children. Lowest PaO/FiO and SpO/FiO ratios and highest mean airway pressure (MAP) were recorded on the first day of ARDS and after 72 h. OI was calculated on the first and third days of mechanical ventilation (MV) and its association with OI (first and third days) and short-term mortality evaluated at 28 days.

Results: MV was initiated a mean of 2.3 days after admission (median, 1.0 day; maximum 14 days). The average MV duration for all patients was 11.8 (median, 7.0) days. Mean (95% confidence interval (CI)) OI values on the first day of MV were 14.17 (11.94-16.41), 12.72 (10.68-14.75), and 13.24 (11.73-14.74) for infants, older children, and all participants, respectively. In survivors (n=39) mean OI was 11.66 (9.64-13.68) compared with 15.22 (13.03-17.40) in non-survivors (n=31). Logistic regression analysis revealed that OI on day 3 had highly significant prognostic value for mortality (odds ratio, 256.5, 95% CI 27.1-2424, p<0.001), with an AUC of 0.919 (cut-off value, 17; positive predictive value, 0.905; negative predictive value, 0.964; p=0.0001). In contrast, OI on day 1 did not have significant prognostic value (AUC, 0.634; p=0.056) for short-term mortality. Different modes of MV were not significantly associated with outcome (p>0.05).

Conclusion: OI is a simple, highly accurate, and sensitive predictor of the survival (short-term mortality) of children mechanically ventilated for ARDS.
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http://dx.doi.org/10.2147/RMHP.S253545DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7522416PMC
September 2020

Medical devices in allergy practice.

World Allergy Organ J 2020 Oct 30;13(10):100466. Epub 2020 Sep 30.

Hospital Quirónsalud Bizkaia, Erandio, Bilbao, Spain.

Medical devices provide people with some health benefits in terms of diagnosis, prevention, treatment, and monitoring of disease processes. Different medical specialties use varieties of medical devices more or less specific for them. Allergology is an interdisciplinary field of medical science and teaches that allergic reactions are of systemic nature but can express themselves at the level of different organs across the life cycle of an individual. Subsequently, medical devices used in allergology could be regarded as: 1) general, servicing the integral diagnostic and management principles and features of allergology, and 2) organ specific, which are shared by organ specific disciplines like pulmonology, otorhinolaryngology, dermatology, and others. The present position paper of the World Allergy Organization (WAO) is meant to be the first integral document providing structured information on medical devices in allergology used in daily routine but also needed for sophisticated diagnostic purposes and modern disease management. It is supposed to contribute to the transformation of the health care system into integrated care pathways for interrelated comorbidities.
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http://dx.doi.org/10.1016/j.waojou.2020.100466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529824PMC
October 2020

ARIA digital anamorphosis: Digital transformation of health and care in airway diseases from research to practice.

Authors:
Jean Bousquet Josep M Anto Claus Bachert Tari Haahtela Torsten Zuberbier Wienczyslawa Czarlewski Anna Bedbrook Sinthia Bosnic-Anticevich G Walter Canonica Victoria Cardona Elisio Costa Alvaro A Cruz Marina Erhola Wytske J Fokkens Joao A Fonseca Maddalena Illario Juan-Carlos Ivancevich Marek Jutel Ludger Klimek Piotr Kuna Violeta Kvedariene Ltt Le Désirée E Larenas-Linnemann Daniel Laune Olga M Lourenço Erik Melén Joaquim Mullol Marek Niedoszytko Mikaëla Odemyr Yoshitaka Okamoto Nikos G Papadopoulos Vincenzo Patella Oliver Pfaar Nhân Pham-Thi Christine Rolland Boleslaw Samolinski Aziz Sheikh Mikhail Sofiev Charlotte Suppli Ulrik Ana Todo-Bom Peter-Valentin Tomazic Sanna Toppila-Salmi Ioanna Tsiligianni Arunas Valiulis Erkka Valovirta Maria-Teresa Ventura Samantha Walker Sian Williams Arzu Yorgancioglu Ioana Agache Cezmi A Akdis Rute Almeida Ignacio J Ansotegui Isabella Annesi-Maesano Sylvie Arnavielhe Xavier Basagaña Eric D Bateman Annabelle Bédard Martin Bedolla-Barajas Sven Becker Kazi S Bennoor Samuel Benveniste Karl C Bergmann Michael Bewick Slawomir Bialek Nils E Billo Carsten Bindslev-Jensen Leif Bjermer Hubert Blain Matteo Bonini Philippe Bonniaud Isabelle Bosse Jacques Bouchard Louis-Philippe Boulet Rodolphe Bourret Koen Boussery Fluvio Braido Vitalis Briedis Andrew Briggs Christopher E Brightling Jan Brozek Guy Brusselle Luisa Brussino Roland Buhl Roland Buonaiuto Moises A Calderon Paulo Camargos Thierry Camuzat Luis Caraballo Ana-Maria Carriazo Warner Carr Christine Cartier Thomas Casale Lorenzo Cecchi Alfonso M Cepeda Sarabia Niels H Chavannes Ekaterine Chkhartishvili Derek K Chu Cemal Cingi Jaime Correia de Sousa David J Costa Anne-Lise Courbis Adnan Custovic Biljana Cvetkosvki Gennaro D'Amato Jane da Silva Carina Dantas Dejan Dokic Yves Dauvilliers Giulia De Feo Govert De Vries Philippe Devillier Stefania Di Capua Gerard Dray Ruta Dubakiene Stephen R Durham Mark Dykewicz Motohiro Ebisawa Mina Gaga Yehia El-Gamal Enrico Heffler Regina Emuzyte John Farrell Jean-Luc Fauquert Alessandro Fiocchi Antje Fink-Wagner Jean-François Fontaine José M Fuentes Perez Bilun Gemicioğlu Amiran Gamkrelidze Judith Garcia-Aymerich Philippe Gevaert René Maximiliano Gomez Sandra González Diaz Maia Gotua Nick A Guldemond Maria-Antonieta Guzmán Jawad Hajjam Yunuen R Huerta Villalobos Marc Humbert Guido Iaccarino Despo Ierodiakonou Tomohisa Iinuma Ewa Jassem Guy Joos Ki-Suck Jung Igor Kaidashev Omer Kalayci Przemyslaw Kardas Thomas Keil Musa Khaitov Nikolai Khaltaev Jorg Kleine-Tebbe Rostislav Kouznetsov Marek L Kowalski Vicky Kritikos Inger Kull Stefania La Grutta Lisa Leonardini Henrik Ljungberg Philip Lieberman Brian Lipworth Karin C Lodrup Carlsen Catarina Lopes-Pereira Claudia C Loureiro Renaud Louis Alpana Mair Bassam Mahboub Michaël Makris Joao Malva Patrick Manning Gailen D Marshall Mohamed R Masjedi Jorge F Maspero Pedro Carreiro-Martins Mika Makela Eve Mathieu-Dupas Marcus Maurer Esteban De Manuel Keenoy Elisabete Melo-Gomes Eli O Meltzer Enrica Menditto Jacques Mercier Yann Micheli Neven Miculinic Florin Mihaltan Branislava Milenkovic Dimitirios I Mitsias Giuliana Moda Maria-Dolores Mogica-Martinez Yousser Mohammad Steve Montefort Ricardo Monti Mario Morais-Almeida Ralph Mösges Lars Münter Antonella Muraro Ruth Murray Robert Naclerio Luigi Napoli Leyla Namazova-Baranova Hugo Neffen Kristoff Nekam Angelo Neou Björn Nordlund Ettore Novellino Dieudonné Nyembue Robyn O'Hehir Ken Ohta Kimi Okubo Gabrielle L Onorato Valentina Orlando Solange Ouedraogo Julia Palamarchuk Isabella Pali-Schöll Peter Panzner Hae-Sim Park Gianni Passalacqua Jean-Louis Pépin Ema Paulino Ruby Pawankar Jim Phillips Robert Picard Hilary Pinnock Davor Plavec Todor A Popov Fabienne Portejoie David Price Emmanuel P Prokopakis Fotis Psarros Benoit Pugin Francesca Puggioni Pablo Quinones-Delgado Filip Raciborski Rojin Rajabian-Söderlund Frederico S Regateiro Sietze Reitsma Daniela Rivero-Yeverino Graham Roberts Nicolas Roche Erendira Rodriguez-Zagal Christine Rolland Regina E Roller-Wirnsberger Nelson Rosario Antonino Romano Menachem Rottem Dermot Ryan Johanna Salimäki Mario M Sanchez-Borges Joaquin Sastre Glenis K Scadding Sophie Scheire Peter Schmid-Grendelmeier Holger J Schünemann Faradiba Sarquis Serpa Mohamed Shamji Juan-Carlos Sisul Mikhail Sofiev Dirceu Solé David Somekh Talant Sooronbaev Milan Sova François Spertini Otto Spranger Cristiana Stellato Rafael Stelmach Michel Thibaudon Teresa To Mondher Toumi Omar Usmani Antonio A Valero Rudolph Valenta Marylin Valentin-Rostan Marilyn Urrutia Pereira Rianne van der Kleij Michiel Van Eerd Olivier Vandenplas Tuula Vasankari Antonio Vaz Carneiro Giorgio Vezzani Frédéric Viart Giovanni Viegi Dana Wallace Martin Wagenmann De Yun Wang Susan Waserman Magnus Wickman Dennis M Williams Gary Wong Piotr Wroczynski Panayiotis K Yiallouros Osman M Yusuf Heather J Zar Stéphane Zeng Mario E Zernotti Luo Zhang Nan Shan Zhong Mihaela Zidarn

Allergy 2021 01 23;76(1):168-190. Epub 2020 Oct 23.

University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia.

Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.
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http://dx.doi.org/10.1111/all.14422DOI Listing
January 2021

Expiratory variability index (EVI) is associated with the severity of acute bronchial obstruction in small children: A proof-of-concept study.

Pediatr Allergy Immunol 2020 08 13;31(6):636-642. Epub 2020 May 13.

Department of Pulmonology and Allergology for Infants and Young Children, Srebrnjak Children's Hospital, Zagreb, Croatia.

Background: Lung function testing in small children is cumbersome. However, reduced variability of tidal breathing recorded using impedance pneumography (IP) during sleep was recently found to be a potential objective marker of wheeze in children aged 1-5 years. We aimed to investigate how an acute bronchial obstruction (BO) and its severity, and recovery thereof reflect in expiratory variability index (EVI).

Methods: EVI was measured using a wearable IP system (Ventica®) during sleep in 40 healthy controls (aged 1.5-5.9 years) and 30 patients hospitalized due to acute BO (aged 1.3-5.3 years). In healthy controls, EVI was measured for 1-3 nights at their homes. Patients were measured for several nights during hospitalization, as practically feasible, and at home 2 and 4 weeks post-discharge.

Results: We received 79 EVI results from 39 controls and 139 from 30 patients. 90% had previous BO episodes, 30% used asthma controller medication before and 100% after hospitalization. Compared to controls, EVI was significantly lower during hospitalization (P < .0001) having significant correlation with number of days to discharge (r = -.38, P = .004). At 2 or 4 weeks post-discharge, EVI was not significantly different from the controls (P = .14, P = .49, respectively). EVI was significantly associated with chest auscultation findings (P = .0001) being 17.5 (4.9) (median, IQR) with normal auscultation, 15.6 (7.4) in those with prolonged expiration and 11.4 (6.8) in those with wheeze and/or rales and crackles.

Conclusions: EVI was found to be a sensitive, objective marker of acute BO, showing strong association with changes in clinical status in wheezy children aged 1-5 years.
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http://dx.doi.org/10.1111/pai.13257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7496816PMC
August 2020

Association of bacterial load in drinking water and allergic diseases in childhood.

Clin Exp Allergy 2020 06 20;50(6):733-740. Epub 2020 Apr 20.

National Heart and Lung Institute, Imperial College London, London, UK.

Background: Treatment of drinking water may decrease microbial exposure.

Objective: To investigate whether bacterial load in drinking water is associated with altered risk of allergic diseases.

Methods: We recruited 1,110 schoolchildren aged 6-16 years between 2011 and 2013 in Požega-Slavonia County in Croatia, where we capitalized on a natural experiment whereby individuals receive drinking water through public mains supply or individual wells. We obtained data on microbial content of drinking water for all participants; 585 children were randomly selected for more detailed assessments, including skin prick testing. Since water supply was highly correlated with rural residence, we compared clinical outcomes across four groups (Rural/Individual, Rural/Public, Urban/Individual and Urban/Public). For each child, we derived quantitative index of microbial exposure (bacterial load in the drinking water measured during the child's first year of life).

Results: Cumulative bacterial load in drinking water was higher (median [IQR]: 6390 [4190-9550] vs 0 [0-0]; P < .0001), and lifetime prevalence of allergic diseases was significantly lower among children with individual supply (5.5% vs 2.3%, P = .01; 14.4% vs 6.7%, P < .001; 25.2% vs 15.1%, P < .001; asthma, atopic dermatitis [AD] and rhinitis, respectively). Compared with the reference group (Urban/Public), there was a significant reduction in the risk of ever asthma, AD and rhinitis amongst rural children with individual supply: OR [95% CI]: 0.14 [0.03,0.67], P = .013; 0.20 [0.09,0.43], P < .001; 0.17 [0.10,0.32], P < .001. Protection was also observed in the Rural/Public group, but the effect was consistently highest among Rural/Individual children. In the quantitative analysis, the risk of allergic diseases decreased significantly with increasing bacterial load in drinking water in the first year of life (0.79 [0.70,0.88], P < .001; 0.90 [0.83,0.99], P = .025; 0.80 [0.74,0.86], P < .001; current wheeze, AD and rhinitis).

Conclusions And Clinical Relevance: High commensal bacterial content in drinking water may protect against allergic diseases.
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http://dx.doi.org/10.1111/cea.13605DOI Listing
June 2020

Sources of variability in expiratory flow profiles during sleep in healthy young children.

Respir Physiol Neurobiol 2020 03 30;274:103352. Epub 2019 Nov 30.

Revenio Research Ltd., Vantaa, Finland. Electronic address:

Standard lung function tests are not feasible in young children, but recent studies show that the variability of expiratory tidal breathing flow-volume (TBFV) curves during sleep is a potential indirect marker of lower airway obstruction. However, the neurophysiological sources of the TBFV variability in normal subjects has not been established. We investigated sleep stages and body position changes as potential sources for the TBFV curve variability. Simultaneous impedance pneumography (IP), polysomnography (PSG) and video recordings were done in 20 children aged 1.4-6.9 years without significant respiratory disorders during sleep. The early part of expiratory TBFV curves are less variable between cycles of REM than NREM sleep. However, within individual sleep cycles, TBFV curves during N3 are the least variable. The differences in TBFV curve shapes between sleep stages are the main source of overnight variability in TBFV curves and the changes in body position have a lesser impact.
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http://dx.doi.org/10.1016/j.resp.2019.103352DOI Listing
March 2020

Next-generation ARIA care pathways for rhinitis and asthma: a model for multimorbid chronic diseases.

Authors:
J Jean Bousquet Holger J Schünemann Alkis Togias Marina Erhola Peter W Hellings Torsten Zuberbier Ioana Agache Ignacio J Ansotegui Josep M Anto Claus Bachert Sven Becker Martin Bedolla-Barajas Michael Bewick Sinthia Bosnic-Anticevich Isabelle Bosse Louis P Boulet Jean Marc Bourrez Guy Brusselle Niels Chavannes Elisio Costa Alvaro A Cruz Wienczyslawa Czarlewski Wytske J Fokkens Joao A Fonseca Mina Gaga Tari Haahtela Maddalena Illario Ludger Klimek Piotr Kuna Violeta Kvedariene L T T Le Desiree Larenas-Linnemann Daniel Laune Olga M Lourenço Enrica Menditto Joaquin Mullol Yashitaka Okamoto Nikos Papadopoulos Nhân Pham-Thi Robert Picard Hilary Pinnock Nicolas Roche Regina E Roller-Wirnsberger Christine Rolland Boleslaw Samolinski Aziz Sheikh Sanna Toppila-Salmi Ioanna Tsiligianni Arunas Valiulis Erkka Valovirta Tuula Vasankari Maria-Teresa Ventura Samantha Walker Sian Williams Cezmi A Akdis Isabella Annesi-Maesano Sylvie Arnavielhe Xavier Basagana Eric Bateman Anna Bedbrook K S Bennoor Samuel Benveniste Karl C Bergmann Slawomir Bialek Nils Billo Carsten Bindslev-Jensen Leif Bjermer Hubert Blain Mateo Bonini Philippe Bonniaud Jacques Bouchard Vitalis Briedis Christofer E Brightling Jan Brozek Roland Buhl Roland Buonaiuto Giorgo W Canonica Victoria Cardona Ana M Carriazo Warner Carr Christine Cartier Thomas Casale Lorenzo Cecchi Alfonso M Cepeda Sarabia Eka Chkhartishvili Derek K Chu Cemal Cingi Elaine Colgan Jaime Correia de Sousa Anne Lise Courbis Adnan Custovic Biljana Cvetkosvki Gennaro D'Amato Jane da Silva Carina Dantas Dejand Dokic Yves Dauvilliers Antoni Dedeu Giulia De Feo Philippe Devillier Stefania Di Capua Marc Dykewickz Ruta Dubakiene Motohiro Ebisawa Yaya El-Gamal Esben Eller Regina Emuzyte John Farrell Antjie Fink-Wagner Alessandro Fiocchi Jean F Fontaine Bilun Gemicioğlu Peter Schmid-Grendelmeir Amiran Gamkrelidze Judith Garcia-Aymerich Maximiliano Gomez Sandra González Diaz Maia Gotua Nick A Guldemond Maria-Antonieta Guzmán Jawad Hajjam John O'B Hourihane Marc Humbert Guido Iaccarino Despo Ierodiakonou Maddalena Illario Juan C Ivancevich Guy Joos Ki-Suck Jung Marek Jutel Igor Kaidashev Omer Kalayci Przemyslaw Kardas Thomas Keil Mussa Khaitov Nikolai Khaltaev Jorg Kleine-Tebbe Marek L Kowalski Vicky Kritikos Inger Kull Lisa Leonardini Philip Lieberman Brian Lipworth Karin C Lodrup Carlsen Claudia C Loureiro Renaud Louis Alpana Mair Gert Marien Bassam Mahboub Joao Malva Patrick Manning Esteban De Manuel Keenoy Gailen D Marshall Mohamed R Masjedi Jorge F Maspero Eve Mathieu-Dupas Poalo M Matricardi Eric Melén Elisabete Melo-Gomes Eli O Meltzer Enrica Menditto Jacques Mercier Neven Miculinic Florin Mihaltan Branislava Milenkovic Giuliana Moda Maria-Dolores Mogica-Martinez Yousser Mohammad Steve Montefort Ricardo Monti Mario Morais-Almeida Ralf Mösges Lars Münter Antonella Muraro Ruth Murray Robert Naclerio Luigi Napoli Leila Namazova-Baranova Hugo Neffen Kristoff Nekam Angelo Neou Enrico Novellino Dieudonné Nyembue Robin O'Hehir Ken Ohta Kimi Okubo Gabrielle Onorato Solange Ouedraogo Isabella Pali-Schöll Susanna Palkonen Peter Panzner Hae-Sim Park Jean-Louis Pépin Ana-Maria Pereira Oliver Pfaar Ema Paulino Jim Phillips Robert Picard Davor Plavec Ted A Popov Fabienne Portejoie David Price Emmanuel P Prokopakis Benoit Pugin Filip Raciborski Rojin Rajabian-Söderlund Sietze Reitsma Xavier Rodo Antonino Romano Nelson Rosario Menahenm Rottem Dermot Ryan Johanna Salimäki Mario M Sanchez-Borges Juan-Carlos Sisul Dirceu Solé David Somekh Talant Sooronbaev Milan Sova Otto Spranger Cristina Stellato Rafael Stelmach Charlotte Suppli Ulrik Michel Thibaudon Teresa To Ana Todo-Bom Peter V Tomazic Antonio A Valero Rudolph Valenta Marylin Valentin-Rostan Rianne van der Kleij Olivier Vandenplas Giorgio Vezzani Frédéric Viart Giovanni Viegi Dana Wallace Martin Wagenmann De Y Wang Susan Waserman Magnus Wickman Dennis M Williams Gary Wong Piotr Wroczynski Panayiotis K Yiallouros Arzu Yorgancioglu Osman M Yusuf Heahter J Zar Stéphane Zeng Mario Zernotti Luo Zhang Nan S Zhong Mihaela Zidarn

Clin Transl Allergy 2019 9;9:44. Epub 2019 Sep 9.

260University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia.

Background: In all societies, the burden and cost of allergic and chronic respiratory diseases are increasing rapidly. Most economies are struggling to deliver modern health care effectively. There is a need to support the transformation of the health care system into integrated care with organizational health literacy.

Main Body: As an example for chronic disease care, MASK (Mobile Airways Sentinel NetworK), a new project of the ARIA (Allergic Rhinitis and its Impact on Asthma) initiative, and POLLAR (Impact of Air POLLution on Asthma and Rhinitis, EIT Health), in collaboration with professional and patient organizations in the field of allergy and airway diseases, are proposing real-life ICPs centred around the patient with rhinitis, and using mHealth to monitor environmental exposure. Three aspects of care pathways are being developed: (i) Patient participation, health literacy and self-care through technology-assisted "patient activation", (ii) Implementation of care pathways by pharmacists and (iii) Next-generation guidelines assessing the recommendations of GRADE guidelines in rhinitis and asthma using real-world evidence (RWE) obtained through mobile technology. The EU and global political agendas are of great importance in supporting the digital transformation of health and care, and MASK has been recognized by DG Santé as a Good Practice in the field of digitally-enabled, integrated, person-centred care.

Conclusion: In 20 years, ARIA has considerably evolved from the first multimorbidity guideline in respiratory diseases to the digital transformation of health and care with a strong political involvement.
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http://dx.doi.org/10.1186/s13601-019-0279-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6734297PMC
September 2019

Fraction of air coming from conductive airways has the negative balance in heat dissipation after maximal effort exercise-a physiological basis for exercise-induced bronchoconstriction.

J Breath Res 2019 08 20;13(4):046011. Epub 2019 Aug 20.

Medical Faculty Osijek, J.J. Strossmayer University, Osijek, Croatia

Exhaled breath temperature (EBT) has recently been used as a tool to assess the level of inflammation in airways. The newest technology can also assess EBT coming from different fractions of exhaled air (fEBT). We aimed to assess the changes in fEBT after a maximal cardio-pulmonary exercise test in healthy athletes. Forty-four healthy professional athletes (two females) were included. Their mean (±SD) age was 22.9 ± 4.8 years. An innovative device (FractAir) was used for fEBT measurement, dividing the exhaled air into three fractions (V1, V2 and V3) coming from different parts of the lungs; the large airways (anatomic dead space), conductive airways (functional dead space) and the peripheral part. For V3 an EBT point measured at 1200 ml of exhaled volume was used to obtain the information about the distant parts of the lungs while eliminating the difference in the volume of total exhaled air before and after the exercise. The difference (temperature gain) between the starting and peak EBT for each fraction was also calculated. The peak fEBT values before and after exercise did not differ significantly (p > 0.05 for all three fractions). Temperature gain analysis for each fEBT showed a significant fall after exercise for V2 (1.71 °C ± 0.43 versus 1.38 °C ± 0.50, p < 0.001), but not for the other two fractions (p > 0.05 for both). The lower heat emission from this part of the airway (conductive airway) after exercise could mean that during hyperventilation heat emission is increased in this specific fraction. We can conclude that the changes of fEBT after physical exercise are not linear. They affect different fractions of the lungs in different ways, and the relationship between flow and volume on one side and the temperature of exhaled air on the other can vary significantly.
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http://dx.doi.org/10.1088/1752-7163/ab3254DOI Listing
August 2019

Dynamics of exhaled breath temperature after smoking a cigarette and its association with lung function changes predictive of COPD risk in smokers: a cross-sectional study.

Arh Hig Rada Toksikol 2019 Jun;70(2):123-129

Department of Pulmonology, University Hospital Center Osijek, Osijek, Croatia.

Exhaled breath temperature (EBT) is a biomarker of inflammation and vascularity of the airways already shown to predict incident COPD. This cross-sectional study was aimed to assess the potential of EBT in identifying "healthy" smokers susceptible to cigarette smoke toxicity of the airways and to the risk of developing COPD by analysing the dynamics of EBT after smoking a cigarette and its associations with their demographics (age, smoking burden) and lung function. The study included 55 current smokers of both sexes, 29-62 years of age, with median smoking exposure of 15 (10-71.8) pack-years. EBT was measured at baseline and 5, 15, 30, 45, and 60 min after smoking a single cigarette. Lung function was measured with spirometry followed by a bronchodilator test. To compare changes in EBT between repeated measurements we used the analysis of variance and the area under the curve (EBTAUC) as a dependent variable. Multivariate regression analysis was used to look for associations with patient characteristics and lung function in particular. The average (±SD) baseline EBT was 33.42±1.50 °C. The highest significant increase to 33.84 (1.25) °C was recorded 5 min after the cigarette was smoked (p=0.003), and it took one hour for it to return to the baseline. EBTAUC showed significant repeatability (ICC=0.85, p<0.001) and was significantly associated with age, body mass index, number of cigarettes smoked a day, baseline EBT, and baseline FEF75 (R2=0.39, p<0.001 for the model). Our results suggest that EBT after smoking a single cigarette could be used as early risk predictor of changes associated with chronic cigarette smoke exposure.
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http://dx.doi.org/10.2478/aiht-2019-70-3211DOI Listing
June 2019

Ragweed pollen and allergic symptoms in children: Results from a three-year longitudinal study.

Sci Total Environ 2019 Sep 21;683:240-248. Epub 2019 May 21.

School of Environmental Sciences, University of East Anglia, Norwich NR4 7TJ, UK. Electronic address:

Common ragweed is a highly allergenic invasive species in Europe, expected to become widespread under climate change. Allergy to ragweed manifests as eye, nasal and lung symptoms, and children may retain these throughout life. The dose-response relationship between symptoms and pollen concentrations is unclear. We undertook a longitudinal study, assessing the association between ragweed pollen concentration and allergic eye, nasal and lung symptoms in children living under a range of ragweed pollen concentrations in Croatia. Over three years, 85 children completed daily diaries, detailing allergic symptoms alongside daily location, activities and medication, resulting in 10,130 individual daily entries. The daily ragweed pollen concentration for the children's locations was obtained, alongside daily weather and air pollution. Parents completed a home/lifestyle/medical questionnaire. Generalised Additive Mixed Models established the relationship between pollen concentrations and symptoms, alongside other covariates. Eye symptoms were associated with mean daily pollen concentration over four days (day of symptoms plus 3 previous days); 61 grains/m/day (95%CI: 45, 100) was the threshold at which 50% of children reported symptoms. Nasal symptoms were associated with mean daily pollen concentration over 12 days (day of symptoms plus 11 previous days); the threshold for 50% of children reporting symptoms was 40 grains/m/day (95%CI: 24, 87). Lung symptoms showed a relationship with mean daily pollen concentration over 19 days (day of symptoms plus 18 previous days), with a threshold of 71 grains/m/day (95%CI: 59, 88). Taking medication on the day of symptoms showed higher odds, suggesting responsive behaviour. Taking medication on the day prior to symptoms showed lower odds of reporting, indicating preventative behaviour. Different symptoms in children demonstrate varying dose-response relationships with ragweed pollen concentrations. Each symptom type responded to pollen exposure over different time periods. Using medication prior to symptoms can reduce symptom presence. These findings can be used to better manage paediatric ragweed allergy symptoms.
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http://dx.doi.org/10.1016/j.scitotenv.2019.05.284DOI Listing
September 2019

Inspiratory muscle strength affects anaerobic endurance in professional athletes.

Arh Hig Rada Toksikol 2019 Mar;70(1):42-48

Department of Pulmonology, University Hospital Centre Osijek, Osijek, Croatia.

To the best of our knowledge, little is known about the role of respiratory muscle strength and endurance on athlete performance in anaerobic conditions of maximal exertion. The aim of this cross-sectional study was therefore to examine the association between the strength/endurance of inspiratory muscles in a group of 70 healthy male professional athletes (team sports) and their ventilatory and metabolic parameters at the anaerobic threshold (second ventilatory threshold; VT2) and beyond it at maximum load during the cardiopulmonary exercise test (CPET) on a treadmill. Ventilatory parameters at VT2, at maximal effort, and their differences were tested for association with inspiratory muscle strength (PImax) and endurance (Tlim), measured as time to maintain inspiration at or above 80% of PImax. The difference in end-tidal oxygen tension (ΔPETO2) between VT2 and maximal effort was significantly associated with resting heart rate (HR) and systolic blood pressure (BP), PImax, and lean body mass (LBM) (r2=0.26, p=0.016; multivariate regression analysis). The difference in carbon dioxide output (ΔVCO2) was significantly associated with body mass index (BMI), resting HR, systolic BP, and PImax (r2=0.25, p=0.022; multivariate regression analysis). Our findings suggest that it is the inspiratory muscle strength and not endurance that affects the performance of professional athletes and that it should be tested and trained systematically.
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http://dx.doi.org/10.2478/aiht-2019-70-3182DOI Listing
March 2019

What is safe enough - asthma in pregnancy - a review of current literature and recommendations.

Asthma Res Pract 2018 27;4:11. Epub 2018 Dec 27.

1Faculty of Medicine, J.J. Strossmayer University of Osijek, Osijek, Croatia.

Background: Although asthma is one of the most serious diseases causing complications during pregnancy, half of the women discontinue therapy thus diminishing the control of the disease, mostly due to the inadequate education and fear of adverse events. Sadly, this is sometimes encouraged by insufficiently educated physicians. Since the incidence and the prevalence of asthma is increasing, it is important to arouse the importance of proper asthma therapy during pregnancy. Inadequate therapy, as well as interrupting or discontinuing therapy, may result in adverse perinatal outcomes for both mother and child.

Main Body: The main goal of asthma control during pregnancy is control of symptoms and prevention of exacerbations, same as in every asthmatic, but even more important. Maintaining optimal lung function, as well as regular daily activities, ensures maintenance of optimal fetal oxygenation. The therapy should be adapted depending on the frequency and severity of daily and nocturnal symptoms, demand for reliever therapy, by the limitations in everyday activities and the frequency of emergency asthma-related hospitalizations. Pre-conceptual education and therapy are very important and should be supported by an asthma action plan adjusted for the period of pregnancy. It is very important to note that most of the drugs used before pregnancy can be safely continued during pregnancy. Pharmacological and non-pharmacological therapy should be used in parallel. Pregnant women should be informed about the nature of the disease, therapy used during pregnancy, possible complications, avoidance of triggers, proper administration of therapy and, most important, why should the therapy be continued throughout the pregnancy on individual basis. Although drug treatment should be based on using drugs with less harm risk, if control of severe symptoms is needed to be achieved in order to protect both mother and child, any anti-asthmatic drug would have the beneficial benefit/harm ratio.

Conclusion: There is no solid evidence that asthma treatment during pregnancy causes adverse outcomes for the mother and child but for many, especially new drugs, there is not enough data gathered. On the other hand, harmfulness of uncontrolled asthma during pregnancy is well documented so every effort should be put on preserving good control of asthma during pregnancy.
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http://dx.doi.org/10.1186/s40733-018-0046-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6307305PMC
December 2018

ARIA pharmacy 2018 "Allergic rhinitis care pathways for community pharmacy": AIRWAYS ICPs initiative (European Innovation Partnership on Active and Healthy Ageing, DG CONNECT and DG Santé) POLLAR (Impact of Air POLLution on Asthma and Rhinitis) GARD Demonstration project.

Authors:
Sinthia Bosnic-Anticevich Elisio Costa Enrica Menditto Olga Lourenço Ettore Novellino Slawomir Bialek Vitalis Briedis Roland Buonaiuto Henry Chrystyn Biljana Cvetkovski Stefania Di Capua Vicky Kritikos Alpana Mair Valentina Orlando Ema Paulino Johanna Salimäki Rojin Söderlund Rachel Tan Dennis M Williams Piotr Wroczynski Ioana Agache Ignacio J Ansotegui Josep M Anto Anna Bedbrook Claus Bachert Mike Bewick Carsten Bindslev-Jensen Jan L Brozek Giorgio Walter Canonica Victoria Cardona Warner Carr Thomas B Casale Niels H Chavannes Jaime Correia de Sousa Alvaro A Cruz Wienczyslawa Czarlewski Giuseppe De Carlo Pascal Demoly Philippe Devillier Mark S Dykewicz Mina Gaga Yehia El-Gamal João Fonseca Wytske J Fokkens Maria Antonieta Guzmán Tari Haahtela Peter W Hellings Maddalena Illario Juan Carlos Ivancevich Jocelyne Just Igor Kaidashev Musa Khaitov Nikolai Khaltaev Thomas Keil Ludger Klimek Marek L Kowalski Piotr Kuna Violeta Kvedariene Désirée E Larenas-Linnemann Daniel Laune Lan T T Le Karin C Lodrup Carlsen Bassam Mahboub Dieter Maier Joao Malva Patrick J Manning Mário Morais-Almeida Ralph Mösges Joaquim Mullol Lars Münter Ruth Murray Robert Naclerio Leyla Namazova-Baranova Kristof Nekam Tshipukane Dieudonné Nyembue Kimi Okubo Robyn E O'Hehir Ken Ohta Yoshitaka Okamoto Gabrielle L Onorato Susanna Palkonen Petr Panzner Nikolaos G Papadopoulos Hae-Sim Park Ruby Pawankar Oliver Pfaar Jim Phillips Davor Plavec Todor A Popov Paul C Potter Emmanuel P Prokopakis Regina E Roller-Wirnsberger Menachem Rottem Dermot Ryan Bolesław Samolinski Mario Sanchez-Borges Holger J Schunemann Aziz Sheikh Juan Carlos Sisul David Somekh Cristiana Stellato Teresa To Ana Maria Todo-Bom Peter Valentin Tomazic Sanna Toppila-Salmi Antonio Valero Arunas Valiulis Errka Valovirta Maria Teresa Ventura Martin Wagenmann Dana Wallace Susan Waserman Magnus Wickman Panayiotis K Yiallouros Arzu Yorgancioglu Osman M Yusuf Heather J Zar Mario E Zernotti Luo Zhang Mihaela Zidarn Torsten Zuberbier Jean Bousquet

Allergy 2019 07 30;74(7):1219-1236. Epub 2019 Apr 30.

MACVIA-France, Fondation Partenariale FMC VIA-LR, Montpellier, France.

Pharmacists are trusted health care professionals. Many patients use over-the-counter (OTC) medications and are seen by pharmacists who are the initial point of contact for allergic rhinitis management in most countries. The role of pharmacists in integrated care pathways (ICPs) for allergic diseases is important. This paper builds on existing studies and provides tools intended to help pharmacists provide optimal advice/interventions/strategies to patients with rhinitis. The Allergic Rhinitis and its Impact on Asthma (ARIA)-pharmacy ICP includes a diagnostic questionnaire specifically focusing attention on key symptoms and markers of the disease, a systematic Diagnosis Guide (including differential diagnoses), and a simple flowchart with proposed treatment for rhinitis and asthma multimorbidity. Key prompts for referral within the ICP are included. The use of technology is critical to enhance the management of allergic rhinitis. However, the ARIA-pharmacy ICP should be adapted to local healthcare environments/situations as regional (national) differences exist in pharmacy care.
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http://dx.doi.org/10.1111/all.13701DOI Listing
July 2019

Current opinions for the management of asthma associated with ear, nose and throat comorbidities.

Eur Respir Rev 2018 Dec 21;27(150). Epub 2018 Nov 21.

NIHR Clinical Research Facility, Manchester University NHS Foundation Trust, Manchester, UK.

Ear, nose and throat (ENT) comorbidities are common in patients with asthma and are frequently associated with poorer asthma outcomes. All these comorbidities are "treatable traits" in asthma. Identification and management of these disorders may spare medication usage and contribute to improved asthma control and quality of life, and a decrease in exacerbation rates.This review summarises recent data about the prevalence, clinical impact and treatment effects of ENT comorbidities in asthma including allergic rhinitis, chronic rhinosinusitis with and without nasal polyposis, aspirin-exacerbated respiratory disease, obstructive sleep apnoea and vocal cord dysfunction.Many of these comorbidities are possible to be managed by the pulmonologist, but the collaboration with the ENT specialist is essential for patients with chronic rhinosinusitis or vocal cord dysfunction. Further rigorous research is needed to study the efficacy of comorbidity treatment to improve asthma outcomes, in particular with the development of biotherapies in severe asthma that can also be beneficial in some ENT diseases.
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http://dx.doi.org/10.1183/16000617.0056-2018DOI Listing
December 2018

Allergic Rhinitis and its Impact on Asthma (ARIA) Phase 4 (2018): Change management in allergic rhinitis and asthma multimorbidity using mobile technology.

Authors:
Jean Bousquet Peter W Hellings Ioana Agache Flore Amat Isabella Annesi-Maesano Ignacio J Ansotegui Josep M Anto Claus Bachert Eric D Bateman Anna Bedbrook Kazi Bennoor Mickael Bewick Carsten Bindslev-Jensen Sinthia Bosnic-Anticevich Isabelle Bosse Jan Brozek Luisa Brussino Giorgio W Canonica Victoria Cardona Thomas Casale Alfonso M Cepeda Sarabia Niels H Chavannes Lorenzo Cecchi Jaime Correia de Sousa Elisio Costa Alvaro A Cruz Wienczyslawa Czarlewski Giuseppe De Carlo Giulia De Feo Pascal Demoly Philippe Devillier Mark S Dykewicz Yehia El-Gamal Esben E Eller Joao A Fonseca Jean-François Fontaine Wytske J Fokkens Maria-Antonieta Guzmán Tari Haahtela Maddalena Illario Juan-Carlos Ivancevich Jocelyne Just Igor Kaidashev Musa Khaitov Omer Kalayci Thomas Keil Ludger Klimek Marek L Kowalski Piotr Kuna Violeta Kvedariene Desiree Larenas-Linnemann Daniel Laune Lan T T Le Karin Lodrup Carlsen Olga Lourenço Bassam Mahboub Alpana Mair Enrica Menditto Branislava Milenkovic Mario Morais-Almeida Ralph Mösges Joaquim Mullol Ruth Murray Robert Naclerio Leyla Namazova-Baranova Ettore Novellino Robyn E O'Hehir Ken Ohta Yoshitaka Okamoto Kimi Okubo Gabrielle L Onorato Susanna Palkonen Petr Panzner Nikos G Papadopoulos Hae-Sim Park Ema Paulino Ruby Pawankar Oliver Pfaar Davor Plavec Ted A Popov Paul Potter Emmanuel P Prokopakis Menachem Rottem Dermot Ryan Johanna Salimäki Boleslaw Samolinski Mario Sanchez-Borges Holger J Schunemann Aziz Sheikh Juan-Carlos Sisul Rojin Rajabian-Söderlund Talant Sooronbaev Cristiana Stellato Teresa To Ana-Maria Todo-Bom Peter-Valentin Tomazic Sanna Toppila-Salmi Antonio Valero Arunas Valiulis Erkka Valovirta Maria-Teresa Ventura Martin Wagenmann De Yun Wang Dana Wallace Susan Waserman Magnus Wickman Arzu Yorgancioglu Luo Zhang Nanshan Zhong Mihaela Zidarn Torsten Zuberbier

J Allergy Clin Immunol 2019 03 29;143(3):864-879. Epub 2018 Sep 29.

Comprehensive Allergy Center Charité, Department of Dermatology and Allergy, Charité-Universitätsmedizin Berlin, and Global Allergy and Asthma European Network (GA2LEN), Berlin, Germany.

Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline by using the best approach to integrated care pathways using mobile technology in patients with allergic rhinitis (AR) and asthma multimorbidity. The proposed next phase of ARIA is change management, with the aim of providing an active and healthy life to patients with rhinitis and to those with asthma multimorbidity across the lifecycle irrespective of their sex or socioeconomic status to reduce health and social inequities incurred by the disease. ARIA has followed the 8-step model of Kotter to assess and implement the effect of rhinitis on asthma multimorbidity and to propose multimorbid guidelines. A second change management strategy is proposed by ARIA Phase 4 to increase self-medication and shared decision making in rhinitis and asthma multimorbidity. An innovation of ARIA has been the development and validation of information technology evidence-based tools (Mobile Airways Sentinel Network [MASK]) that can inform patient decisions on the basis of a self-care plan proposed by the health care professional.
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http://dx.doi.org/10.1016/j.jaci.2018.08.049DOI Listing
March 2019

Modifiable Risk Factors for Common Ragweed () Allergy and Disease in Children: A Case-Control Study.

Int J Environ Res Public Health 2018 06 26;15(7). Epub 2018 Jun 26.

Department Children's Hospital Srebrnjak, Srebrnjak 100, 10000 Zagreb, Croatia.

Ragweed allergy is a major public health concern. Within Europe, ragweed is an introduced species and research has indicated that the amounts of ragweed pollen are likely to increase over Europe due to climate change, with corresponding increases in ragweed allergy. To address this threat, improving our understanding of predisposing factors for allergic sensitisation to ragweed and disease is necessary, specifically focusing upon factors that are potentially modifiable (i.e., environmental). In this study, a total of 4013 children aged 2⁻13 years were recruited across Croatia to undergo skin prick tests to determine sensitisation to ragweed and other aeroallergens. A parental questionnaire collected home environment, lifestyle, family and personal medical history, and socioeconomic information. Environmental variables were obtained using Geographical Information Systems and data from nearby pollen, weather, and air pollution stations. Logistic regression was performed (clustered on school) focusing on risk factors for allergic sensitisation and disease. Ragweed sensitisation was strongly associated with ragweed pollen at levels over 5000 grains m year and, above these levels, the risk of sensitisation was 12⁻16 times greater than in low pollen areas with about 400 grains m year. Genetic factors were strongly associated with sensitisation but nearly all potentially modifiable factors were insignificant. This included measures of local land use and proximity to potential sources of ragweed pollen. Rural residence was protective (odds ratio (OR) 0.73, 95% confidence interval (CI) 0.55⁻0.98), but the factors underlying this association were unclear. Being sensitised to ragweed doubled (OR 2.17, 95% CI 1.59⁻2.96) the risk of rhinoconjunctivitis. No other potentially modifiable risk factors were associated with rhinoconjunctivitis. Ragweed sensitisation was strongly associated with ragweed pollen, and sensitisation was significantly associated with rhinoconjunctivitis. Apart from ragweed pollen levels, few other potentially modifiable factors were significantly associated with ragweed sensitisation. Hence, strategies to lower the risk of sensitisation should focus upon ragweed control.
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http://dx.doi.org/10.3390/ijerph15071339DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6069153PMC
June 2018

Differences in Reporting the Ragweed Pollen Season Using Google Trends across 15 Countries.

Int Arch Allergy Immunol 2018 9;176(3-4):181-188. Epub 2018 May 9.

University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia.

Background: Google Trends (GT) searches trends of specific queries in Google, which potentially reflect the real-life epidemiology of allergic rhinitis. We compared GT terms related to ragweed pollen allergy in American and European Union countries with a known ragweed pollen season. Our aim was to assess seasonality and the terms needed to perform the GT searches and to compare these during the spring and summer pollen seasons.

Methods: We examined GT queries from January 1, 2011, to January 4, 2017. We included 15 countries with a known ragweed pollen season and used the standard 5-year GT graphs. We used the GT translation for all countries and the untranslated native terms for each country.

Results: The results of "pollen," "ragweed," and "allergy" searches differed between countries, but "ragweed" was clearly identified in 12 of the 15 countries. There was considerable heterogeneity of findings when the GT translation was used. For Croatia, Hungary, Romania, Serbia, and Slovenia, the GT translation was inappropriate. The country patterns of "pollen," "hay fever," and "allergy" differed in 8 of the 11 countries with identified "ragweed" queries during the spring and the summer, indicating that the perception of tree and grass pollen allergy differs from that of ragweed pollen.

Conclusions: To investigate ragweed pollen allergy using GT, the term "ragweed" as a plant is required and the translation of "ragweed" in the native language needed.
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http://dx.doi.org/10.1159/000488391DOI Listing
July 2018

The effects of physical activity on chronic subclinical systemic inflammation.

Arh Hig Rada Toksikol 2017 Dec;68(4):276-286

4Children's Hospital Srebrnjak, Srebrnjak 100, 10000, Zagreb, Croatia.

Chronic subclinical systemic inflammation (CSSI) is a pathogenic event and a common risk factor for many noncommunicable diseases like atherosclerosis, metabolic syndrome, cardiovascular disease, insulin resistance and type 2 diabetes, cancer, and obstructive lung disease. On the other hand, regular physical activity has been found to reduce this risk. Many studies of different design were conducted to assess the association between inflammatory mediators as markers of CSSI and regular physical activity. The aim of this review was to present the current level of evidence and understanding of potential mechanisms by which physical activity reduces inflammatory mediators involved in CSSI and the types of physical activity required for the expected effect. We have found that observational studies consistently report a positive association between regular physical activity and lower CSSI, but the design of these studies does not allow to infer a causal relationship. Interventional studies, in contrast, were not consistent about the causal relationship between regular physical activity and lower CSSI. The problem in interpreting these results lies in significant differences between these interventional studies in their design, sample size, study population, and intervention itself (intensity and extent, follow up, weight loss). We can conclude that the scientific community has to invest a significant effort into high-quality interventional trials focused on finding the type, intensity, and extent of physical activity that would produce the most favourable effect on CSSI.
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http://dx.doi.org/10.1515/aiht-2017-68-2965DOI Listing
December 2017

Predictors of short-term LAMA ineffectiveness in treatment naïve patients with moderate to severe COPD.

Wien Klin Wochenschr 2018 Apr 10;130(7-8):247-258. Epub 2018 Jan 10.

Faculty of Medicine, J.J. Strossmayer University of Osijek, Osijek, Croatia.

Background: No specific (only subgroup) recommendations for the use of long-acting muscarinic antagonists in chronic obstructive pulmonary disease (COPD) exist. The aim of this exploratory hypothesis generating study was to assess whether different phenotypic/endotypic characteristics could be determinants of the short-term ineffectiveness of the initial tiotropium bromide monotherapy in treatment naïve moderate to severe COPD patients.

Methods: A total of 51 consecutively recruited COPD patients were followed for 3 months after the initial evaluation and prescribed initial treatment (tiotropium). Short-term treatment ineffectiveness was assessed as a composite measure comprising COPD exacerbations, need for additional treatment, and no improvement in functional parameters, e.g. 6‑min walking test (6MWT), body-mass index, airflow obstruction, dyspnea, and exercise (BODE) index and forced expiratory volume in 1 s (FEV), and as single components.

Results: Treatment ineffectiveness was significantly associated with baseline hemoglobin level, COPD assessment test (CAT) score, modified Medical Research Council (mMRC) scale and BODE index (p = 0.002). Incident exacerbation during the follow-up was associated with baseline bronchoalveolar lavage fluid (BALF) alpha-amylase level and CAT score (p < 0.001), and change in treatment with leukocyte count, 6MWT desaturation and fatigue (p < 0.001). No improvement in 6MWT was associated with baseline CAT score, body mass index, mMRC, fatigue, 6MWT and BODE index (p = 0.002). No improvement in BODE index was associated with leukocyte count, serum interleukin 8 (IL-8) and BALF albumin levels (p < 0.001); and no improvement in FEV with CAT score, baseline vital capacity and BALF tumor necrosis factor alpha (TNF-alpha) level (p < 0.001).

Conclusion: Our results suggest that there is a possibility to identify predictors of short-term tiotropium ineffectiveness in patients with moderate to severe COPD.
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http://dx.doi.org/10.1007/s00508-017-1307-7DOI Listing
April 2018

The added value of exhaled breath temperature in respiratory medicine.

J Breath Res 2017 Aug 8;11(3):034001. Epub 2017 Aug 8.

Clinic of Allergy and Asthma, Medical University Sofia, Bulgaria.

Recognition of the huge economic burden chronic respiratory diseases pose for society motivated fundamental and clinical research leading to insight into the role of airway inflammation in various disease entities and their phenotypes. However, no easy, cheap and patient-friendly methods to assess it have found a place in routine clinical practice. Measurement of exhaled breath temperature (EBT) has been suggested as a non-invasive method to detect inflammatory processes in the airways as a result of increased blood flow within the airway walls. As EBT values are within a narrow range, the thermometers designed for the purpose of assessing it need to be precise and very sensitive. EBT increases linearly over the pediatric age range and seems to be influenced by gender, but not by height and body weight. In non-smoking individuals with no history of respiratory disease EBT has a natural circadian peak about noon and increases with food intake and physical exercise. When interpreting EBT in subjects with alleged airway pathology, the possibilities of tissue destruction (chronic obstructive pulmonary disease, cystic fibrosis) or excessive bronchial obstruction and air trapping (severe asthma) need to be considered, as these conditions drive (force) EBT down. A prominent advantage of the method is to assess EBT when patients are in a steady state of their disease and to use this 'personal best' to monitor them and guide their treatment. Individual devices outfitted with microprocessors and memory have been created, which can be used for personalized monitoring and disease management by telemedicine.
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http://dx.doi.org/10.1088/1752-7163/aa7801DOI Listing
August 2017

Mood disorders in adult asthma phenotypes.

J Asthma 2018 01 10;55(1):57-65. Epub 2017 May 10.

b Faculty of Medicine , J.J. Strossmayer University of Osijek , Osijek , Croatia.

Objective: Studies show high comorbidity of mood disorders in asthma. As asthma is a highly heterogeneous disease with different phenotypes it can be expected that there is a difference in this association with different asthma phenotypes. The aim of our cross-sectional study was to assess the association of specific asthma phenotypes with anxiety and/or depression and their impact on asthma control.

Methods: A cross-sectional study in 201 consecutive adult outpatients with asthma (≥18 years of age) was conducted. Each patient underwent physical examination, detailed medical history, Hospital Anxiety and Depression Scale, Asthma Control Questionnaire, Asthma Control Test, together with measurements of lung function and fraction of exhaled nitric oxide. Phenotypes were assessed using cluster analysis, and a multivariate analysis was used to identify associations of mood disorders with different phenotypes.

Results: Five asthma phenotypes were identified: allergic (AA, 43.8%), aspirin-exacerbated respiratory disease (AERD, 21.9%), late-onset (LOA, 18.9%), obesity-associated (OAA, 10.0%), and respiratory infections associated asthma (RIAA, 5.5%). A multivariate analysis showed a significant association of anxiety with LOA and comorbid hypertension (LOA, odds ratio (OR) = 2.12; hypertension, OR = 2.37, p = 0.012), and depression with AA, RIAA, hypertension, and ACQ score (AA, OR = 6.07; RIAA, OR = 4.73; hypertension, OR = 5.67; ACQ, OR = 1.87; p < 0.001). Comorbid anxiety/depression was associated with AA, LOA, RIAA, hypertension, and ACQ score (AA, OR = 10.15; LOA, OR = 2.98; RIAA, OR = 6.29; hypertension, OR = 5.15; ACQ, OR = 1.90; p < 0.001.

Conclusion: Mood disorders were significantly associated with AA, LOA, and infection-associated asthma, together with comorbid hypertension and the level of asthma control.
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http://dx.doi.org/10.1080/02770903.2017.1306546DOI Listing
January 2018

Long-term predictors of anxiety and depression in adult patients with asthma.

Wien Klin Wochenschr 2017 Oct 18;129(19-20):665-673. Epub 2017 Apr 18.

Faculty of Medicine, J.J. Strossmayer University of Osijek, Osijek, Croatia.

Background: It is well established that anxiety and depression are associated with asthma, but there is limited evidence about the persistence of anxiety/depression in asthma. The aim of our study was to assess the long-term predictors of anxiety and depression in adult asthmatic patients.

Methods: A total of 90 adult asthma patients (63 women, age 18-50 years) with different levels of disease control (28 uncontrolled and 34 partially controlled) were assessed at baseline and at follow-up after 7 years for anxiety, depression and asthma control. The same work-up on both occasions included: demographics, living conditions, medical history (e.g. comorbidities, adherence and exacerbations), Hospital Anxiety and Depression Scale (HADS), Asthma Quality of Life Questionnaire (AQLQ), disease control and lung function. Persistence was defined as the HADS scores for anxiety and depression present at baseline and follow-up.

Results: The HADS results at follow-up visit showed 36 (40%) asthma patients with anxiety and 13 (14%) with depression, with the persistence of anxiety in 17 (19%) and of depression in 7 (8%) patients. Significant predictors of anxiety at follow-up were HADS and AQLQ results at baseline and several parameters of asthma control at follow-up (area under the curve AUC 0.917, 95% confidence interval CI 0.829-0.969, p < 0.001) and for depression AQLQ mood disorder domain, asthma control and lung function (AUC 0.947, 95% CI 0.870-0.986, p < 0.001).

Conclusion: Anxiety and depression persist over years in some patients with asthma. The association between mood disorders and asthma suggests potential mutual treatability.
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http://dx.doi.org/10.1007/s00508-017-1203-1DOI Listing
October 2017

Micronucleus, cell-free DNA, and plasma glycan composition in the newborns of healthy and diabetic mothers.

Mutat Res 2017 03 7;815:6-15. Epub 2017 Feb 7.

Genos Glycoscience Research Laboratory, Zagreb, Croatia.

Diabetes is associated with certain environmental exposures, heritable factors, and metabolic conditions of intrauterine development due to diabetes in the mother. We evaluated genomic damage, cell-free DNA, N-glycosylation of umbilical cord plasma proteins (PG), and nuclear division index (NDI) as possible prognostic biomarkers of health risk in the newborns of mothers with treated pregestational diabetes (NBDM; 22 mothers), compared these parameters with those from newborns of healthy mothers (NBHM; 89 mothers), and associated the results with the mothers' lifestyle in both groups, based on a detailed questionnaire. Genomic damage was estimated by the in vitro micronucleus (MN) assay. NDI was detected on MN slides. Glycans were analyzed by ultra-performance liquid chromatography that separates the plasma N-glycome into 46 glycan peaks. Cell-free DNA was analyzed by real-time PCR. For the association between biomarkers and individual characteristics, generalized linear/nonlinear analysis was performed. No significant difference was found between NBHM and NBDM for cell-free DNA levels. There was no association between cell-free DNA levels and lifestyle. MN frequency was significantly higher in NBDM than in NBHM (median, 0.6 vs. 0.3%, p<0.001). MN frequency and NDI were significantly associated with residence (urban vs. rural). PG differed significantly between NBHM and NBDM (p<0.001). A significant association was found between PG and increase of MN frequency (p<0.001). As both MN frequency and altered N-glycosylation are associated with cancer risk, our study indicates need for further investigations.
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http://dx.doi.org/10.1016/j.mrgentox.2017.01.002DOI Listing
March 2017

Early detection of COPD patients in GOLD 0 population: an observational non-interventional cohort study - MARKO study.

BMC Pulm Med 2017 02 10;17(1):36. Epub 2017 Feb 10.

Faculty of Medicine, J.J. Strossmayer University of Osijek, Ulica cara Hadrijana 10E, Osijek, Croatia.

Background: Main risk factor for the development of chronic obstructive pulmonary disease (COPD) is smoking, although only less than 1/3 of smokers develop clinically manifest COPD. COPD's progressive nature with high disability and mortality makes it plausible to detect it as early as possible thus allowing for an early intervention. The only tool for an early diagnosis that could be used on the global scale is spirometry, even though symptoms and deprivation of health related quality of life (HRQoL) precede relevant spirometric changes. Existing HRQoL questionnaires are too complicated or not developed for an early detection of COPD. The aim of our study was to develop a new simple HRQoL tool that will allow (alone or in combination with other markers) early detection of patients with COPD.

Methods: A multicenter prospective cohort study recruiting 500 subjects at risk for COPD (smokers/ex-smokers ≥20 pack-years, 40-65 years, both sexes, with no prior diagnosis of COPD) will be carried out in two phases: (1) cross-sectional - development and validation of a new questionnaire; and (2) prospective - follow-up of a cohort of patients at risk for COPD. Subjects were recruited by 25 GPs and assessed for COPD by dedicated pulmonologists in 7 hospital centers using a predefined protocol: HRQoL, history, physical, blood sampling, exhaled breath temperature (EBT), lung function, 6-min walk test (6MWT). Patients without COPD and those in GOLD stage 1 at initial assessment will be reassessed for disease progression by the same pulmonologist after 2 and 5 years.

Discussion: This is one of the first cohort studies attempting to establish the incidence of COPD in the pre-symptomatic stage before significant end organ damage. We intend to assess the validity, predictability and discriminative power ('healthy' smokers vs. pre-symptomatic phase in newly developed COPD) of newly developed HRQoL tool alone or in combination with other markers; EBT, lung function, 6MWT, genomics, transcriptomics, proteomics). We expect that the results of this study can improve our understanding of the development of COPD, identify some new underlying pathophysiological pathways, and offer to sensitive smokers/ex-smokers new preventive and early intervention measures thus improving the management of COPD.

Trial Registration: Clinicaltrial.gov NCT01550679 retrospectively registered February 28, 2012.
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http://dx.doi.org/10.1186/s12890-017-0378-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5303263PMC
February 2017

Development and the initial validation of a new self-administered questionnaire for an early detection of health status changes in smokers at risk for chronic obstructive pulmonary disease (MARKO questionnaire).

Croat Med J 2016 Oct;57(5):425-433

Davor Plavec, Head of Research Department, Children's Hospital Srebrnjak, Srebrnjak 100, 10000 Zagreb, Croatia,

Aim: To develop and do an initial validation of a new simple tool (self-administered questionnaire) that would be sensitive and specific enough to detect early changes in smokers leading to future development of chronic obstructive pulmonary disease (COPD).

Methods: 224 consecutive participants (50.9% women), with mean±standard deviation age of 52.3±6.7 years, 37.5±16.7 pack-years smoking history (85.8% active smokers), and no prior diagnosis of COPD were recruited. The MARKO questionnaire was self-administered twice; at the general practitioner's office and after 2-4 weeks at the tertiary care hospital. Participants were assessed for COPD by a pulmonologist after filling in a quality of life (QoL) questionnaires, history-taking, physical examination, lung function test, 6-minute walk test, and laboratory tests. They were divided into four subgroups: "healthy" smokers, symptomatic smokers, and smokers with mild and moderately severe COPD.

Results: Psychometric analyses indicated that the 18-item questionnaire had a very good internal consistency (Cronbach's alpha=0.91) and test-retest reliability for a four week period (c=0.89, 95% confidence interval [CI] 0.85-0.92, Lin's concordance). A significant correlations of MARKO scores were found with two QoL questionnaires; r=0.69 (P<0.001) and r=0.81 (P<0.001). Receiver operating characteristic curve analysis showed an area under the curve of 0.753 (95% CI 0.691-0.808, <0.001), with a sensitivity of 71.83% and specificity of 64.24% to discriminate "healthy" smokers from other subgroups.

Conclusion: Based on psychometric analyses and high convergent validity correlation with already validated QoL questionnaires, the newly developed MARKO questionnaire was shown to be a reliable self-administered short health status assessment tool.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5141460PMC
http://dx.doi.org/10.3325/cmj.2016.57.425DOI Listing
October 2016

Effects of allergic diseases and age on the composition of serum IgG glycome in children.

Sci Rep 2016 09 12;6:33198. Epub 2016 Sep 12.

Genos Glycoscience Research Laboratory, Zagreb, Croatia.

It is speculated that immunoglobulin G (IgG) plays a regulatory role in allergic reactions. The glycans on the Fc region are known to affect IgG effector functions, thereby possibly having a role in IgG modulation of allergic response. This is the first study investigating patients' IgG glycosylation profile in allergic diseases. Subclass specific IgG glycosylation profile was analyzed in two cohorts of allergen sensitized and non-sensitized 3- to 11-year-old children (conducted at University of Aberdeen, UK and Children's Hospital Srebrnjak, Zagreb, Croatia) with 893 subjects in total. IgG was isolated from serum/plasma by affinity chromatography on Protein G. IgG tryptic glycopeptides were analyzed by liquid chromatography electrospray ionization mass spectrometry. In the Zagreb cohort IgG glycome composition changed with age across all IgG subclasses. In both cohorts, IgG glycome composition did not differ in allergen sensitized subjects, nor children sensitized to individual allergens, single allergen mean wheal diameter or positive wheal sum values. In the Zagreb study the results were also replicated for high total serum IgE and in children with self-reported manifest allergic disease. In conclusion, our findings demonstrate no association between serum IgG glycome composition and allergic diseases in children.
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http://dx.doi.org/10.1038/srep33198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5018987PMC
September 2016

Allergen-Specific IgE Measurement: Intermethod Comparison of Two Assay Systems in Diagnosing Clinical Allergy.

J Clin Lab Anal 2017 May 8;31(3). Epub 2016 Sep 8.

Children's Hospital Srebrnjak, Zagreb, Croatia.

Background: Our aim was to examine the performance of IMMULITE 2000 assay for specific IgE (sIgE) by comparing it with ImmunoCAP technology in light of a clinical background.

Methods: Measurements of sIgE were done in a selected patient group (N = 569; varied sample size for each allergen) and in a random sample group (N = 100; 8 allergens). sIgE results were correlated with skin-prick test results (selected patients) and medical history (nonselected patients).

Results: We have detected fair to excellent correlation and agreement between the results of both assays, despite their methodological differences, both in selected and nonselected patient group (ρc = 0.431-0.976; ρc = 0.390-0.972, respectively). Associations of sIgE levels with skin-prick test (SPT) levels and medical history have shown significant correlation for both assays for majority of tested allergens, where applicable (D. pteronyssinus, cat dander, egg white, milk, peanut, orchard grass, Alternaria tenuis, and common ragweed in selected patients; birch, cat dander, common ragweed, D. pteronyssinus, and orchard grass in nonselected; P < 0.05 for all).

Conclusions: Laboratory testing for sIgE can be successfully accomplished by IMMULITE 2000 immunoanalyzer at a diagnostic accuracy relative to SPT, comparable to the results acquired by CAP technology but not fully comparable on the level of an individual patient.
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http://dx.doi.org/10.1002/jcla.22047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6816900PMC
May 2017

Diagnostic accuracy of a pocket screening spirometer in diagnosing chronic obstructive pulmonary disease in general practice: a cross sectional validation study using tertiary care as a reference.

BMC Fam Pract 2016 08 19;17(1):112. Epub 2016 Aug 19.

Faculty of Medicine, J.J. Strossmayer University of Osijek, Ulica cara Hadrijana 10E, Osijek, Croatia.

Background: COPD-6™ is a lung function testing device for a rapid pre-spirometry testing to screen-out at-risk individuals not having COPD and indicating those at risk. The aim of this study was to validate COPD-6™ lung function testing (index test) in general practice in discriminating patients with COPD out of the population at risk - smokers/ex-smokers with no previous diagnosis of COPD, using measurements at tertiary care as reference standard.

Methods: Consecutive 227 subjects (115 women, 185 smokers/42 ex-smokers, ≥20 pack-years) with no previous diagnosis of COPD, aged 52.5 (SD 6.8) years from 26 general practitioners (GPs) were recruited, lung function tested with COPD-6™, referred to the tertiary institution for repeated COPD-6™ testing followed by spirometry with a bronchodilator (salbutamol), examination, and pulmonologist consultation for the diagnosis and severity of COPD.

Results: COPD was diagnosed in 43 subjects (18.9 %), with an AUC of 0.827 (95 % CI 0.769-0.875, P < 0.001) for the diagnosis of COPD when lung function was measured using COPD-6™ in GP's office with a specificity of 100 % (95 % CI, 97.95-100 %) but a very low sensitivity of 32.56 % (95 % CI, 20.49-47.48 %). Significant agreement for forced expiratory volume in 1 s measured at GP's office and at lung function lab was found (mean difference 0.01 L, p = 0.667) but not for other measured parameters (p < 0.001 for all).

Conclusions: Our study results point out that active case finding in a population at risk for COPD should be instituted (almost 20 % of undiagnosed COPD). Based on our results lung function testing with COPD-6™ can substitute spirometry testing in cases where it is not readily available to the patient/physician taken into account that the traditional FEV1/FEV6 cutoff value of <0.7 is not the only criterion for diagnosis and/or further referral.

Trial Registration: ClinicalTrials.gov Identifier NCT01550679 Registered 28 September 2014, retrospectively registered.
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http://dx.doi.org/10.1186/s12875-016-0518-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4992327PMC
August 2016

The effect of mouth breathing on exercise induced fall in lung function in children with allergic asthma and rhinitis.

Int J Pediatr Otorhinolaryngol 2016 Jul 19;86:53-6. Epub 2016 Apr 19.

Reference Center for Clinical Pediatric Allergology of the Ministry of Health, Children's Hospital Srebrnjak, 10 000 Zagreb, Croatia; Faculty of Medicine, Josip Juraj Strossmayer University Osijek, Trg Svetog Trojstva 3, 31000 Osijek, Croatia.

Objectives: Exercise induced bronchospasm (EIB) represents a common feature of childhood asthma which is most commonly revealed during free running. On the other hand aerobic exercise shows significant beneficial effects in asthmatics especially on the reduction of the level of systemic inflammation and is recommended as part of its treatment. The aim of this study was to test how mandatory mouth breathing influences the exercise induced level of decrease in lung function according to the level of severity of allergic rhinitis (AR).

Methods: Free 6-minute running test preceded and followed by spirometry done with and without a nose clip a day apart was conducted in 55 children with moderate persistent asthma and AR. Children were divided into two groups according to the severity of nasal symptoms.

Results: There was a greater fall in forced expiratory volume in one second after exercise with a nose clip in children with less nasal symptoms than in children with more nasal symptoms (mean ± SD; -5.28 (7.91) vs. -0.08 (4.58), p = 0.0228) compared to testing without the nose clip (mean ± SD; LNS, -1.31 ± 3.89%, p = 0.2408; MNS, -1.47 ± 3.68%, p = 0.2883).

Conclusion: Our results show that regular mouth breathing due to nasal congestion may lessen the degree of EIB in patients with persistent AR and allergic asthma.
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http://dx.doi.org/10.1016/j.ijporl.2016.04.020DOI Listing
July 2016