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3. Multivariate analysis and data mining help predict asthma exacerbations.

Author

Mihaicuta, Stefan, Udrescu, Lucretia, Militaru, Adrian, Nadasan, Valentin, Tiotiu, Angelica, Bikov, Andras, Ursoniu, Sorin, Birza, Romina, Popa, Alina Mirela, and Frent, Stefan

Subjects
DATA mining, MULTIVARIATE analysis, ASTHMA, OCCUPATIONAL exposure, DATA analysis
Abstract

Work-related asthma has become a highly prevalent occupational lung disorder. Our study aims to evaluate occupational exposure as a predictor for asthma exacerbation. We performed a retrospective evaluation of 584 consecutive patients diagnosed and treated for asthma between October 2017 and December 2019 in four clinics from Western Romania. We evaluated the enrolled patients for their asthma control level by employing the Asthma Control Test (ACT < 20 represents uncontrolled asthma), the medical record of asthma exacerbations, occupational exposure, and lung function (i.e. spirometry). Then, we used statistical and data mining methods to explore the most important predictors for asthma exacerbations. We identified essential predictors by calculating the odds ratios (OR) for the exacerbation in a logistic regression model. The average age was 45.42 ± 11.74 years (19–85 years), and 422 (72.26%) participants were females. 42.97% of participants had exacerbations in the past year, and 31.16% had a history of occupational exposure. In a multivariate model analysis adjusted for age and gender, the most important predictors for exacerbation were uncontrolled asthma (OR 4.79, p <.001), occupational exposure (OR 4.65, p <.001), and lung function impairment (FEV1 < 80%) (OR 1.15, p =.011). The ensemble machine learning experiments on combined patient features harnessed by our data mining approach reveal that the best predictor is professional exposure, followed by ACT. Machine learning ensemble methods and statistical analysis concordantly indicate that occupational exposure and ACT < 20 are strong predictors for asthma exacerbation. [ABSTRACT FROM AUTHOR]

Published
2024
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6. Severe Asthma or Chronic Obstructive Pulmonary Disease with Eosinophilic Inflammation? From Uncertainty to Remission under Anti IL-5R Therapy.

Author

Oprescu, Bianca, Raduna, Oana, Mihaicuta, Stefan, and Frent, Stefan

Subjects
CHRONIC obstructive pulmonary disease, PULMONARY eosinophilia, ASTHMA, BIOTHERAPY
Abstract

Background and Objectives: Severe adult-onset eosinophilic asthma and COPD with eosinophilic inflammation are two entities with a similar clinical course and are sometimes difficult to differentiate in clinical practice, especially in patients with a history of smoking. Anti-IL-5 or -IL-5R biological therapy has been shown to be highly effective in severe eosinophilic asthma but has not demonstrated significant benefit in patients with COPD with the eosinophilic phenotype. Our aim was to illustrate this issue in the form of a case report. Materials and Methods: We present the case of a 67-year-old patient who is a former smoker with late-onset severe uncontrolled asthma (ACT score < 15) who experienced frequent exacerbations requiring treatment with systemic corticosteroids. The patient's lung function gradually worsened to a nadir FEV1 = 18%, despite a high dose of ICS in combination with a LABA and intermittent courses of OCS, with negative allergic skin-tests, but with high blood eosinophils level. Biological treatment with an anti-IL5R monoclonal antibody (benralizumab) was initiated, despite the difficulty in the differential diagnosis between asthma and COPD with eosinophilic inflammation. Results: The patient's evolution was favorable; clinical remission was effectively achieved with significant improvement in lung function (FEV1 > 100%), but with persistence of residual mild fixed airway obstructive dysfunction (FEV1/FVC < 0.7). The therapeutic response has been maintained to date. Conclusions: Benralizumab was shown to be very effective in a patient with late-onset severe eosinophilic asthma presenting features of chronic obstructive disease—habitual exposure to tobacco and inhaled noxious substances, and persistent airflow limitation on spirometry. [ABSTRACT FROM AUTHOR]

Published
2024
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9. Subtle Pulse Electro-biological Recovery Apparatus (SPERA) as anti-inflammatory treatment for COVID-19 – A Proof of Concept Study

Author

Frent, Stefan-Marian, primary, Giles, Graham, additional, Paroczai, Dora, additional, Tudorache, Voicu, additional, Marincu, Iosif, additional, Raduna, Oana, additional, Herban, Sorin, additional, Marcu, Marius, additional, Pater, Flavius, additional, Law, Fergus, additional, Wise, Martin, additional, and Oancea, Cristian, additional

Published
2023
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15. Comparison of Composite Lipid Indices in Patients with Obstructive Sleep Apnoea

Author

Bikov,Andras, Frent,Stefan, Reisz,Daniela, Negru,Alina, Gaita,Laura, Breban Schwarzkopf,Daniel, Mihaicuta,Stefan, Bikov,Andras, Frent,Stefan, Reisz,Daniela, Negru,Alina, Gaita,Laura, Breban Schwarzkopf,Daniel, and Mihaicuta,Stefan

Abstract

Andras Bikov,1,2 Stefan Frent,3 Daniela Reisz,4 Alina Negru,5,6 Laura Gaita,7 Daniel Breban Schwarzkopf,8 Stefan Mihaicuta3 1North West Lung Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UK; 2Division of Immunology, Immunity to Infection and Respiratory Medicine, University of Manchester, Manchester, UK; 3Center for Research and Innovation in Precision Medicine of Respiratory Diseases, Department of Pulmonology, “Victor Babes” University of Medicine and Pharmacy Timisoara, Timisoara, Romania; 4Department of Neurology, “Victor Babes” University of Medicine and Pharmacy Timisoara, Timisoara, Romania; 5Department of Cardiology (II), “Victor Babes” University of Medicine and Pharmacy Timisoara, Timisoara, Romania; 6Department of Clinical Research, Institute of Cardiovascular Diseases, Timisoara, Romania; 7Second Department of Internal Medicine, “Victor Babes” University of Medicine and Pharmacy Timisoara, Timisoara, Romania; 8Department of Anatomy, “Victor Babes” University of Medicine and Pharmacy Timisoara, Timisoara, RomaniaCorrespondence: Stefan Frent; Daniela Reisz, Email frentz.stefan@umft.ro; reisz.daniela@umft.roPurpose: Obstructive sleep apnoea (OSA) is a recognised risk factor for cardiovascular disease. However, it is difficult to evaluate the risk of cardiovascular disease in patients with OSA due to multiple shared risk factors. Composite lipid indices, such as atherogenic index of plasma (AIP), visceral adiposity index (VAI) and lipid accumulation product (LAP) have been shown to predict cardiovascular disease better than their individual lipid components. This study aimed to evaluate these indices in patients with OSA.Patients and Methods: Six hundred sixty-seven (667) patients with OSA and 139 non-OSA control volunteers participated in the study. Fasting serum triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C) levels were measured

Published
2022

16. Clinical Profile of 24 AIDS Patients with Cryptococcal Meningitis in the HAART Era: A Report from an Infectious Diseases Tertiary Hospital in Western Romania

Author

Marincu, Iosif, primary, Citu, Cosmin, additional, Vidican, Iulia, additional, Bratosin, Felix, additional, Mares, Mihai, additional, Suciu, Oana, additional, Frent, Stefan, additional, Bota, Adrian Vasile, additional, Timircan, Madalina, additional, Bratu, Melania Lavinia, additional, and Grigoras, Mirela Loredana, additional

Published
2021
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24. Early Clinically Important Improvement (ECII) and Exacerbation Outcomes in COPD Patients

Author

Kostikas,Konstantinos, Mackay,Alexander J, Vogelmeier,Claus F, Frent,Stefan-Marian, Gupta,Pritam, Banerji,Donald, Patalano,Francesco, Pfister,Pascal J, and Wedzicha,Jadwiga A

Subjects
International Journal of Chronic Obstructive Pulmonary Disease
Abstract

Konstantinos Kostikas,1 Alexander J Mackay,2 Claus F Vogelmeier,3 Stefan-Marian Frent,4 Pritam Gupta,5 Donald Banerji,6 Francesco Patalano,7 Pascal J Pfister,7 Jadwiga A Wedzicha8 1Respiratory Medicine Department, University of Ioannina Medical School, Ioannina, Greece; 2National Heart and Lung Institute, Imperial College London, London, UK; 3Department of Medicine, Pulmonary and Critical Care Medicine, Philipps-Universität Marburg, Member of the German Center for Lung Research (DZL), Marburg, Germany; 4Department of Pulmonology, University of Medicine and Pharmacy Timisoara, Timisoara, Romania; 5Novartis Healthcare Pvt. Ltd., Hyderabad, India; 6Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 7Novartis Pharma AG, Basel, Switzerland; 8Respiratory Clinical Science Section, National Heart and Lung Institute, Imperial College London, London, UKCorrespondence: Konstantinos KostikasRespiratory Medicine Department, University of Ioannina Medical School, Ioannina 45110, GreeceTel +30-6944780616Email ktkostikas@gmail.comBackground: Chronic obstructive pulmonary disease (COPD) exacerbations are difficult outcomes to measure in clinical trials. It would be valuable to be able to predict which patients are likely to benefit in terms of exacerbation prevention based on their early response in lung function and symptoms.Methods: This was a post-hoc analysis from the 52-week, randomized, double-blind, double-dummy, non-inferiority FLAME trial. Early clinically important improvement (ECII) was defined as achievement of minimal clinically important difference in trough forced expiratory volume in 1 second (FEV1; ≥ 100 mL increase) and one patient-reported outcome (PRO): either St. George’s Respiratory Questionnaire for COPD (≥ 4-unit reduction; D1), or COPD assessment test (≥ 2-point reduction; D2) at Week 4 or 12.Results: Approximately 18– 20% of patients achieved ECII at Week 4 or 12 post-randomization according to any of the two definitions. The rate of subsequent exacerbations was lower in patients who achieved ECII at Week 4 (D1: ratio of rates [95% CI], 0.85 [0.74 to 0.98]; D2, 0.88 [0.77 to 1.00]) or at Week 12 (D1, 0.85 [0.74 to 0.98]; D2, 0.86 [0.75 to 1.00]) versus patients not achieving ECII. Patients who achieved ECII experienced longer time-to-first exacerbation between Week 4 or 12 to end of study. More patients achieved ECII with indacaterol/glycopyrronium versus salmeterol/fluticasone according to both definitions at Week 4 (D1, odds ratio [95% CI], 1.69 [1.40 to 2.04]; D2, 1.61 [1.34 to 1.93]), and 12 (D1, 2.01 [1.66 to 2.44]; D2, 1.80 [1.48 to 2.18]).Conclusion: ECII is a novel composite endpoint, based on clinically relevant improvement in lung function and PROs in the early phase of treatment intervention that may predict subsequent exacerbation risk and may be used in clinical trials.Keywords: exacerbations, ECII, indacaterol/glycopyrronium, lung function, PROs

Published
2020

33. COPD Pharmacological Management Update

Author

Frent, Stefan-Marian

Subjects
Medical
Abstract

Chronic obstructive pulmonary disease (COPD) is a significant cause of morbidity and mortality worldwide. Although it is considered both preventable and treatable, COPD still represents an important public health challenge. The classes of pharmacological agents widely used for the maintenance treatment are bronchodilators (SABA, SAMA, LABA, LAMA) and inhaled corticosteroids (ICS). While it is largely accepted that inhaled bronchodilators, which are effective and well tolerated in patients with stable disease, are the cornerstone of the pharmacological management of COPD, there is an ongoing debate regarding the role of inhaled corticosteroids. This is also reflected in the last versions of the GOLD recommendations, which suffered dramatic changes in the recent years. The trend for personalized medicine led to the search for biomarkers which could guide the therapeutic decisions. Recent studies demonstrated that blood eosinophils can reasonably predict the ICS relative efficacy in preventing COPD exacerbations and thus could inform the disease management.

Published
2018

39. Persistent blood eosinophilia and COPD exacerbation risk after ICS withdrawal from triple therapy in the SUNSET study

Author

Hurst, John R., primary, Kostikas, Konstantinos, additional, Chapman, Kenneth R., additional, Frent, Stefan-Marian, additional, Larbig, Michael, additional, Fogel, Robert, additional, Guerin, Tadhg, additional, Banerji, Donald, additional, Patalano, Francesco, additional, Goyal, Pankaj, additional, Pfister, Pascal, additional, and Wedzicha, Jadwiga A., additional

Published
2018
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40. 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

Author

Chapman, Kenneth R., primary, Hurst, John R., additional, Frent, Stefan-Marian, additional, Larbig, Michael, additional, Fogel, Robert, additional, Guerin, Tadhg, additional, Banerji, Donald, additional, Patalano, Francesco, additional, Goyal, Pankaj, additional, Pfister, Pascal, additional, Kostikas, Konstantinos, additional, and Wedzicha, Jadwiga A., additional

Published
2018
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46. Rates and predictors of uncontrolled bronchial asthma in elderly patients from western Romania

Author

Marincu,Iosif, Frent,Stefan, Tomescu,Mirela, Mihaicuta,Stefan, Marincu,Iosif, Frent,Stefan, Tomescu,Mirela, and Mihaicuta,Stefan

Abstract

Iosif Marincu,1 Stefan Frent,1 Mirela Cleopatra Tomescu,2 Stefan Mihaicuta1 1Department of Infectious Diseases, Pulmonology, Epidemiology and Parasitology, 2Department of Internal Medicine I, Victor Babes University of Medicine and Pharmacy, Timisoara, Romania Purpose: Bronchial asthma (BA) is a chronic inflammatory disorder of the airways, featuring variable and often reversible airflow limitations. An accurate assessment of BA control is difficult in practice, especially in the elderly, requiring the assessment of several clinical and paraclinical parameters that are influenced not only by asthma, but also by comorbidities. The purpose of this study was to evaluate the predictors of uncontrolled BA in a group of elderly patients from western Romania.Patients and methods: We retrospectively evaluated 126 elderly patients (aged ≥ 65 years), who were consecutively evaluated in the Pulmonology Department of Victor Babes Hospital, Timisoara, Romania, between March 2009 and July 2012. We collected demographic data, performed pulmonary function testing and an asthma control test (ACT), and evaluated the level of BA control based on the 2012 Global Initiative for Asthma guidelines. Statistical processing of the data was done using the Epi Info and STATA programs.Results: In our study group, 36 (29%) patients were men and 90 (71%) were women; their mean age was 74.42±8.32 years (range: 65–85 years). A total of 14.28% of patients were smokers. About 30.15% of patients had an ACT score <19, 54.76% had an ACT score 20–24, and 15.09% had an ACT of 25. Moreover, 59.52% had normal spirometry results. Infectious exacerbations were found in 58.73% of patients. A history of allergies was demonstrated in 48.41% of patients, 34.12% had occupational exposure, and 82.53% of patients were treated with inhaled corticosteroids. Our results showed that 30.15% of patients had uncontrolled BA. We found six predictive factors for uncontrol

Published
2015

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