Publications by authors named "Andras Bikov"

82 Publications

Circulating levels of clusterin and complement factor H in patients with obstructive sleep apnea.

Biomark Med 2021 Mar 5. Epub 2021 Mar 5.

Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UK.

Obstructive sleep apnea (OSA) activates the complement system; however, the levels of membrane attack complex (MAC) are unaltered suggesting regulatory mechanisms. Our aim was to investigate complement factor H (CFH) and clusterin, two important complement regulators in OSA. We analyzed clusterin and CFH levels in plasma of 86 patients with OSA and 33 control subjects. There was no difference in CFH levels between patients (1099.4/784.6-1570.5/μg/ml) and controls (1051.4/652.0-1615.1/μg/ml, p = 0.72). Clusterin levels were higher in patients with OSA (309.7/217.2-763.2/μg/ml vs 276.1/131.0-424.3/μg/ml, p = 0.048) with a trend for a positive correlation with disease severity (p = 0.073). Increase in clusterin levels may be protective in OSA by blocking the MAC formation.
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http://dx.doi.org/10.2217/bmm-2020-0533DOI Listing
March 2021

Blood eosinophils on hospital admission for COPD exacerbation do not predict the recurrence of moderate and severe relapses.

ERJ Open Res 2021 Jan 8;7(1). Epub 2021 Feb 8.

Department of Pulmonology, Semmelweis University, Budapest, Hungary.

Background And Objective: The relationship between hospitalisation with an eosinophilic acute exacerbation of COPD (AE-COPD) and future relapses is unclear. We aimed to explore this association by following 152 patients for 12 months after hospital discharge or until their first moderate or severe flare-up.

Methods: Patients hospitalised with AE-COPD were divided into eosinophilic and non-eosinophilic groups based on full blood count results on admission. All patients were treated with a course of systemic corticosteroid. The Cox proportional hazards model was used to study the association with the time to first re-exacerbation; a generalised linear regression model was applied to identify clinical variables related to the recurrence of relapses.

Results: We did not find a difference in the time to the next moderate or severe exacerbation between the eosinophilic (≥2% of total leukocytes and/or ≥200 eosinophils·µL, n=51, median (interquartile range): 21 (10-36) weeks) and non-eosinophilic groups (n=101, 17 (9-36) weeks, log-rank test: p=0.63). No association was found when other cut-off values (≥3% of total leukocytes and/or ≥300 eosinophils·µL) were used for the eosinophilic phenotype. However, the higher number of past severe exacerbations, a lower forced expiratory volume in 1 s (FEV) at discharge and higher pack-years were related to shorter exacerbation-free time. According to a subgroup analysis (n=73), 48.1% of patients with initial eosinophilic exacerbations had non-eosinophilic relapses on readmission.

Conclusions: Our data do not support an increased risk of earlier recurring moderate or severe relapses in patients hospitalised with eosinophilic exacerbations of COPD. Eosinophilic severe exacerbations present a variable phenotype.
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http://dx.doi.org/10.1183/23120541.00543-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869597PMC
January 2021

Using Blood Eosinophil Count as a Biomarker to Guide Corticosteroid Treatment for Chronic Obstructive Pulmonary Disease.

Diagnostics (Basel) 2021 Feb 3;11(2). Epub 2021 Feb 3.

Department of Internal Medicine, Respiratory Medicine Section, Herlev-Gentofte Hospital, 2900 Hellerup, Denmark.

Treating patients hospitalised with acute exacerbations of chronic obstructive pulmonary disease (COPD) usually involves administering systemic corticosteroids. The many unwanted side effects associated with this treatment have led to increased interest in minimising the accumulated corticosteroid dose necessary to treat exacerbations. Studies have shown that short-term treatment with corticosteroids is preferred, and recent trials have shown that biomarkers can be used to further reduce exposure to corticosteroids. Interestingly, high eosinophil counts in patients with acute exacerbations of COPD are indicative of an eosinophilic phenotype with a distinct response to treatment with corticosteroids. In addition, post-hoc analysis of randomised control trials have shown that higher blood eosinophil counts at the start of the study predict a greater response to inhaled corticosteroids in stable COPD. In this review, we examine the studies on this topic, describe how blood eosinophil cell count may be used as a biomarker to guide treatment with corticosteroids, and identify some relevant challenges.
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http://dx.doi.org/10.3390/diagnostics11020236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913607PMC
February 2021

Atherogenic Index of Plasma in Obstructive Sleep Apnoea.

J Clin Med 2021 Jan 22;10(3). Epub 2021 Jan 22.

Department of Pulmonology, University of Medicine and Pharmacy Timisoara, 300041 Timisoara, Romania.

Background: Dyslipidaemia is well recognised in obstructive sleep apnoea (OSA) and could contribute to the development of cardiovascular disease (CVD). Atherogenic index of plasma (AIP) predicts cardiovascular morbidity and mortality better than the individual lipid levels. The aim of this study was to investigate the AIP in patients with OSA in relation with disease severity.

Methods: Four hundred sixty-one patients with OSA and 99 controls participated in this study. AIP was assessed in the morning following a diagnostic sleep study. The association between lipid values and OSA were adjusted for age, gender, and body mass index.

Results: Patients with OSA had higher AIP and triglyceride, and lower high-density lipoprotein cholesterol (HDL-C) levels (all < 0.05). AIP significantly correlated with the Epworth Sleepiness Scale score ( = 0.19), the apnoea-hypopnoea index ( = 0.40) and oxygen desaturation index ( = 0.43, all < 0.05). However, there was no relationship between the AIP and markers of sleep quality such as total sleep time, sleep period time, sleep efficiency, arousal index or percentage of REM sleep (all > 0.05). AIP was not a better predictor for self-reported cardiovascular disease or diabetes than HDL-C.

Conclusions: AIP is elevated in OSA and is related to disease severity. However, it does not seem to have an additional clinical value compared to HDL-C.
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http://dx.doi.org/10.3390/jcm10030417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865393PMC
January 2021

Manifesto on united airways diseases (UAD): an Interasma (global asthma association - GAA) document.

J Asthma 2021 Mar 5:1-16. Epub 2021 Mar 5.

Department of Internal Medicine, University of Genoa, Genova, Italy.

Objective: The large amount of evidence and the renewed interest in upper and lower airways involvement in infectious and inflammatory diseases has led Interasma (Global Asthma Association) to take a position on United Airways Diseases (UAD).

Methods: Starting from an extensive literature review, Interasma executive committee discussed and approved this Manifesto developed by Interasma scientific network (INES) members.

Results: The manifesto describes the evidence gathered to date and defines, states, advocates, and proposes issues on UAD (rhinitis, rhinosinusitis and nasal polyposis), and concomitant/comorbid lower airways disorders (asthma, chronic obstructive pulmonary disease, bronchiectasis, cystic fibrosis, obstructive sleep apnoea) with the aim of challenging assumptions, fostering commitment, and bringing about change. UAD refers to clinical pictures characterized by the coexistence of upper and lower airways involvement, driven by a common pathophysiological mechanism, leading to a greater burden on patient's health status and requiring an integrated diagnostic and therapeutic plan. The high prevalence of UAD must be taken into account. Upper and lower airways diseases influence disease control and patient's quality of life.

Conclusions: Patients with UAD need to have a timely and adequate diagnosis, treatment, and, when recommended, referral for management in a specialized center. Diagnostic testing including skin prick or serum specific IgE, lung function, fractional exhaled nitric oxide (FeNO), polysomnography, allergen-specific immunotherapies, biological therapies and home based continuous positive airway pressure (CPAP) whenever these are recommended, should be part of the management plan for UAD. Education of medical students, physicians, health professionals, patients and caregivers on the UAD is needed.
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http://dx.doi.org/10.1080/02770903.2021.1879130DOI Listing
March 2021

Characteristics of Hungarian patients with obstructive sleep apnoea

Orv Hetil 2020 12 13;161(50):2117-2123. Epub 2020 Dec 13.

1 Általános Orvostudományi Kar, Pulmonológiai Klinika, Semmelweis Egyetem, Budapest, Tömő u. 25-29., 1083.

Összefoglaló. Bevezetés és célkitűzés: Az obstruktív alvási apnoe (OSA) a felnőtt lakosság jelentős részét érintő betegség, mely ismert rizikófaktora a cardiovascularis és metabolicus betegségeknek és a korai halálozásnak. Mindazonáltal kevés magyarországi adat áll rendelkezésre az OSA-ban szenvedő betegek demográfiai és klinikai jellemzőiről, így vizsgálatunk célja ennek bemutatása volt. Módszer: Retrospektív vizsgálatunkban a Semmelweis Egyetem Pulmonológiai Klinikájának Alváslaboratóriumában kivizsgált 394 személy (58 [46-66] év, 73% férfi, testtömegindex [BMI] = 32,5 [29,2-37,5]) adatait elemeztük, akik kitöltötték az Epworth Álmosság Skálát, poliszomnográfiás vizsgálaton estek át; felvettük az anamnézist, és 255 esetben reggeli éhomi vérvétel történt. Eredmények: 282 esetben igazolódott OSA. Ebben a csoportban magasabb volt a férfiak aránya (66 vs. 35%), magasabb volt az életkor (59 [48-66] vs. 47 [39-60] év) és a BMI (32,11 [27,78-37,18] vs. 25,29 [22,04-29,03] kg/m2), magasabbak voltak a C-reaktív protein értékek (3,0 [1,71-5,34] mg/l vs. 1,71 [0,91-3,31] mg/l), illetve a betegek gyakrabban szenvedtek társbetegségekben a kontrollcsoporthoz képest (magas vérnyomás 74% vs. 39%, cukorbetegség 24% vs. 11%, dyslipidaemia 46% vs. 30%, szív- és érrendszeri betegség 22% vs. 5%, szívritmuszavar 27% vs. 16%; minden p<0,05). Bár az OSA valószínűsége progresszívan nőtt az életkorral és az Epworth Álmosság Skála emelkedésével, a trendekben szignifikáns különbségeket észleltünk a férfiak és a nők között (mindkettő p<0,05). Ezzel szemben az OSA valószínűségének BMI-függése nemektől független volt (p = 0,94). Következtetés: Az OSA valószínűsége progresszívan emelkedik a kor, a BMI és a nappali aluszékonyság függvényében, ugyanakkor ezt befolyásolja a nem is. Közleményünk rámutat a társbetegségek szűrésének fontosságára is az OSA különböző súlyossági fokaiban. Orv Hetil. 2020; 161(50): 2117-2123.

Summary:

Introduction And Objective: Obstructive sleep apnoea (OSA) is a common disease which is a known risk factor for cardiovascular and metabolic disease and mortality as well. However, the demographic and clinical characteristics of Hungarian patients with OSA are less known. The aim of this study was to describe them.

Method: We analysed the data of 394 subjects (58 [46-66] years, 73% male, body mass index [BMI] = 32.5 [29.2-37.5]) who attended the Sleep Laboratory of the Department of Pulmonology at Semmelweis University. The volunteers filled out the Epworth Sleepiness Scale, we performed a polysomnography and took medical history. In 255 subjects, fasting blood samples were collected.

Results: OSA was diagnosed in 282 cases. This group had higher proportion of males (66 vs. 35%) and comorbidities (hypertension 74% vs. 39%, diabetes 24% vs. 11%, dyslipidaemia 46% vs. 30%, cardiovascular diseases 22% vs. 5%, arrhythmia 27% vs. 16%), the patients were older (59 [48-66] vs. 47 [39-60] years) and had higher BMI (32.11 [27.78-37.18] vs. 25.29 [22.04-29.03] kg/m2) and C-reactive protein levels (3.0 [1.71-5.34] mg/l vs. 1.71 [0.91-3.31] mg/l, all p<0.05). There was a significant relationship between the propensity of OSA along increasing age, BMI and Epworth Sleepiness Scale; however, the relationship depended on gender for age and Epworth Sleepiness Scale (both p<0.05).

Conclusion: The propensity of OSA increases with age, BMI and symptoms burden and it is affected by the gender. Our study highlights the importance of screening comorbidities in different severity grades of OSA. Orv Hetil. 2020; 161(50): 2117-2123.
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http://dx.doi.org/10.1556/650.2020.31880DOI Listing
December 2020

The Role of Electronic Noses in Phenotyping Patients with Chronic Obstructive Pulmonary Disease.

Biosensors (Basel) 2020 Nov 11;10(11). Epub 2020 Nov 11.

Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester M23 9LT, UK.

Chronic obstructive pulmonary disease (COPD) is a common progressive disorder of the respiratory system which is currently the third leading cause of death worldwide. Exhaled breath analysis is a non-invasive method to study lung diseases, and electronic noses have been extensively used in breath research. Studies with electronic noses have proved that the pattern of exhaled volatile organic compounds is different in COPD. More recent investigations have reported that electronic noses could potentially distinguish different endotypes (i.e., neutrophilic vs. eosinophilic) and are able to detect microorganisms in the airways responsible for exacerbations. This article will review the published literature on electronic noses and COPD and help in identifying methodological, physiological, and disease-related factors which could affect the results.
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http://dx.doi.org/10.3390/bios10110171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7697924PMC
November 2020

The role of hyaluronic acid and hyaluronidase-1 in obstructive sleep apnoea.

Sci Rep 2020 11 10;10(1):19484. Epub 2020 Nov 10.

Manchester University NHS Foundation Trust, Manchester, M13 9WL, UK.

Biological functions of hyaluronic acid (HA) depend on its molecular size. High-molecular weight HA (HMW-HA) is an important component of the endothelial wall and has anti-inflammatory and antioxidant properties. Under inflammation or hypoxia, HMW-HA is degraded by hyaluronidases, such as HYAL-1 resulting in pro-inflammatory low-molecular weight fragments. Obstructive sleep apnoea (OSA) is characterised by intermittent hypoxia and systemic inflammation. Our aim was to evaluate circulating HMW-HA and HYAL-1 in OSA. We recruited 68 patients with OSA and 40 control volunteers. After full-night sleep study blood samples were taken for HMW-HA and HYAL-1 measurements. HYAL-1 levels were significantly higher in patients with OSA compared to controls (0.59/0.31-0.88/ng/mL vs. 0.31/0.31-0.58/ng/mL; p = 0.005) after adjustment for gender, age, BMI and smoking. There was a trend for reduced HMW-HA concentrations in OSA (31.63/18.11-59.25/ng/mL vs. 46.83/25.41-89.95/ng/mL; p = 0.068). Significant correlation was detected between circulating HMW-HA and apnoea-hypopnoea-index (r = - 0.195, p = 0.043), HYAL-1 and apnoea-hypopnoea-index (r = 0.30, p < 0.01) as well as oxygen desaturation index (r = 0.26, p < 0.01). Our results suggest that chronic hypoxia is associated with increased plasma HYAL-1 concentration and accelerated HMW-HA degradation. Altered hyaluronan metabolism may be involved in the inflammatory cascade potentially leading to endothelial dysfunction in OSA.
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http://dx.doi.org/10.1038/s41598-020-74769-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7655850PMC
November 2020

The Burden of Associated Comorbidities in Patients with Obstructive Sleep Apnea-Regional Differences in Two Central-Eastern European Sleep Centers.

J Clin Med 2020 Nov 6;9(11). Epub 2020 Nov 6.

Department of Pulmonology, University of Medicine and Pharmacy, Timisoara 300041, Romania.

Background: Obstructive sleep apnea (OSA) is usually associated with cardiovascular and cerebrovascular disease, metabolic syndrome and depression. Data on relevant OSA-associated comorbidities in Central-European populations are scarce. The aim of this study was to compare the prevalence of comorbidities in two OSA cohorts from Hungary and Romania.

Methods: Data from 588 (282 from Hungary, 306 from Romania) untreated patients with OSA were retrospectively analyzed. The prevalence rates of hypertension, diabetes, dyslipidemia, allergic rhinitis, asthma, chronic obstructive pulmonary disease (COPD), osteoporosis, cerebrovascular and cardiovascular disease, arrhythmia and depression were compared between the two populations following adjustment for demographics, body mass index, smoking history, comorbidities and sleep parameters.

Results: The prevalence rates of hypertension, arrhythmia, cerebrovascular and cardiovascular disease, diabetes and COPD in the whole study population were directly related to the severity of OSA. We found an inverse correlation between the prevalence of osteoporosis and OSA severity (all < 0.05). Following adjustment, the prevalence of dyslipidemia was higher in the Hungarian cohort, whilst the prevalence of asthma, cardiovascular and cerebrovascular diseases was higher in the Romanian cohort (all < 0.05).

Conclusions: There was no difference in the prevalence rate of most comorbidities in patients with OSA from the two cohorts, except for dyslipidemia, asthma, cardiovascular and cerebrovascular disease.
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http://dx.doi.org/10.3390/jcm9113583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694741PMC
November 2020

Core outcome set for the management of acute exacerbations of chronic obstructive pulmonary disease: the COS-AECOPD ERS Task Force study protocol.

ERJ Open Res 2020 Jul 14;6(3). Epub 2020 Sep 14.

Section of Respiratory Medicine, Dept of Internal Medicine, Herlev-Gentofte Hospital, Hellerup, Denmark.

Randomised controlled trials (RCTs) on the management of COPD exacerbations evaluate heterogeneous outcomes, often omitting those that are clinically important and patient relevant. This limits their usability and comparability. A core outcome set (COS) is a consensus-based minimum set of clinically important outcomes that should be evaluated in all RCTs in specific areas of health care. We present the study protocol of the COS-AECOPD ERS Task Force, aiming to develop a COS for COPD exacerbation management, that could remedy these limitations. For the development of this COS we follow standard methodology recommended by the COMET initiative. A comprehensive list of outcomes is assembled through a methodological systematic review of the outcomes reported in relevant RCTs. Qualitative research with patients with COPD will also be conducted, aiming to identify additional outcomes that may be important to patients, but are not currently addressed in clinical research studies. Prioritisation of the core outcomes will be facilitated through an extensive, multi-stakeholder Delphi survey with a global reach. Selection will be finalised in an international, multi-stakeholder meeting. For every core outcome, we will recommend a specific measurement instrument and standardised time points for evaluation. Selection of instruments will be based on evidence-informed consensus. Our work will improve the quality, usability and comparability of future RCTs on the management of COPD exacerbations and, ultimately, the care of patients with COPD. Multi-stakeholder engagement and societal support by the European Respiratory Society will raise awareness and promote implementation of the COS.
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http://dx.doi.org/10.1183/23120541.00193-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7487360PMC
July 2020

Beliefs and preferences regarding biological treatments for severe asthma.

World Allergy Organ J 2020 Jul 31;13(7):100441. Epub 2020 Jul 31.

Università di Genova, Dipartimento di Medicina Interna (DiMI), Italy.

Background: Severe asthma is a serious condition with a significant burden on patients' morbidity, mortality, and quality of life. Some biological therapies targeting the IgE and interleukin-5 (IL5) mediated pathways are now available. Due to the lack of direct comparison studies, the choice of which medication to use varies. We aimed to explore the beliefs and practices in the use of biological therapies in severe asthma, hypothesizing that differences will occur depending on the prescribers' specialty and experience.

Methods: We conducted an online survey composed of 35 questions in English. The survey was circulated via the INterasma Scientific Network (INESNET) platform as well as through social media. Responses from allergists and pulmonologists, both those with experience of prescribing omalizumab with (OMA/IL5) and without (OMA) experience with anti-IL5 drugs, were compared.

Results: Two hundred eighty-five (285) valid questionnaires from 37 countries were analyzed. Seventy-on percent (71%) of respondents prescribed biologics instead of oral glucocorticoids and believed that their side effects are inferior to those of Prednisone 5 mg daily. Agreement with ATS/ERS guidelines for identifying severe asthma patients was less than 50%. Specifically, significant differences were found comparing responses between allergists and pulmonologists (Chi-square test, p < 0.05) and between OMA/IL5 and OMA groups (p < 0.05).

Conclusions: Uncertainties and inconsistencies regarding the use of biological medications have been shown. The accuracy of prescribers to correctly identify asthma severity, according to guidelines criteria, is quite poor. Although a substantial majority of prescribers believe that biological drugs are safer than low dose long-term treatment with oral steroids, and that they must be used instead of oral steroids, every effort should be made to further increase awareness. Efficacy as disease modifiers, biomarkers for selecting responsive patients, timing for outcomes evaluation, and checks need to be addressed by further research. Practices and beliefs regarding the use of asthma biologics differ between the prescriber's specialty and experience; however, the latter seems more significant in determining beliefs and behavior. Tailored educational measures are needed to ensure research results are better integrated in daily practice.
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http://dx.doi.org/10.1016/j.waojou.2020.100441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7396819PMC
July 2020

FEV is a stronger mortality predictor than FVC in patients with moderate COPD and with an increased risk for cardiovascular disease.

Int J Chron Obstruct Pulmon Dis 2020 20;15:1135-1142. Epub 2020 May 20.

Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.

Purpose: Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death worldwide. Impaired lung function is associated with heightened risk for death, cardiovascular events, and COPD exacerbations. However, it is unclear if forced expiratory volume in one second (FEV) and forced vital capacity (FVC) differ in predictive value.

Patients And Methods: Data from 16,485 participants in the Study to Understand Mortality and Morbidity (SUMMIT) in COPD were analyzed. Patients were grouped into quintiles for each lung function parameter (FEV %predicted, FVC %predicted, FEV/FVC). The four highest quintiles (Q2-Q5) were compared to the lowest (Q1) to assess their relationship with all-cause mortality, cardiovascular events, and moderate-to-severe and severe exacerbations. Cox-regression was used, adjusted for age, sex, ethnicity, body-mass index, smoking status, previous exacerbations, cardiovascular disease, treatment, and modified Medical Research Council dyspnea score.

Results: Compared to Q1 (<53.5% FEV predicted), increasing FEV quintiles (Q2 53.5-457.5% predicted, Q3 57.5-461.6% predicted, Q4 61.6-465.8% predicted, and Q5 ≥65.8%) were all associated with significantly decreased all-cause mortality (20% (4-34%), 28% (13-40%), 23% (7-36%), and 30% (15-42%) risk reduction, respectively). In contrast, a significant risk reduction (21% (4-35%)) was seen only between Q1 and Q5 quintiles of FVC. Neither FEV nor FVC was associated with cardiovascular risk. Increased FEV and FEV/FVC quintiles were also associated with the reduction of moderate-to-severe and severe exacerbations while, surprisingly, the highest FVC quintile was related to the heightened exacerbation risk (28% (8-52%) risk increase).

Conclusion: Our results suggest that FEV is a stronger predictor for all-cause mortality than FVC in moderate COPD patients with heightened cardiovascular risk and that subjects with moderate COPD have very different risks.
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http://dx.doi.org/10.2147/COPD.S242809DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7247606PMC
May 2020

Treating asthma in the COVID-19 pandemic.

Thorax 2020 10 10;75(10):822-823. Epub 2020 Jun 10.

Division of Infection, Immunity & Respiratory Medicine, Faculty of Biology, Medicine and Health, School of Biological Sciences, The University of Manchester, Manchester, UK

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http://dx.doi.org/10.1136/thoraxjnl-2020-215118DOI Listing
October 2020

The Nitric Oxide Pathway in Pulmonary Arterial Hypertension: Pathomechanism, Biomarkers and Drug Targets.

Curr Med Chem 2020 ;27(42):7168-7188

Department of Pulmonology, Semmelweis University, Budapest, Hungary

The altered Nitric Oxide (NO) pathway in the pulmonary endothelium leads to increased vascular smooth muscle tone and vascular remodelling, and thus contributes to the development and progression of pulmonary arterial hypertension (PAH). The pulmonary NO signalling is abrogated by the decreased expression and dysfunction of the endothelial NO synthase (eNOS) and the accumulation of factors blocking eNOS functionality. The NO deficiency of the pulmonary vasculature can be assessed by detecting nitric oxide in the exhaled breath or measuring the degradation products of NO (nitrite, nitrate, S-nitrosothiol) in blood or urine. These non-invasive biomarkers might show the potential to correlate with changes in pulmonary haemodynamics and predict response to therapies. Current pharmacological therapies aim to stimulate pulmonary NO signalling by suppressing the degradation of NO (phosphodiesterase- 5 inhibitors) or increasing the formation of the endothelial cyclic guanosine monophosphate, which mediates the downstream effects of the pathway (soluble guanylate cyclase sensitizers). Recent data support that nitrite compounds and dietary supplements rich in nitrate might increase pulmonary NO availability and lessen vascular resistance. This review summarizes current knowledge on the involvement of the NO pathway in the pathomechanism of PAH, explores novel and easy-to-detect biomarkers of the pulmonary NO.
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http://dx.doi.org/10.2174/0929867327666200522215047DOI Listing
February 2021

Obstructive Sleep Apnea: A View from the Back Door.

Medicina (Kaunas) 2020 Apr 25;56(5). Epub 2020 Apr 25.

North West Lung Centre, Manchester University NHS Foundation Trust, Manchester M239LT, UK.

Obstructive sleep apnea (OSA) is a common disease that may affect up to 50% of the adult population and whose incidence continues to rise, as well as its health and socio-economic burden. OSA is a well-known risk factor for motor vehicles accidents and decline in work performance and it is frequently accompanied by cardiovascular diseases. The aim of this Special Issue is to focus on the characteristics of OSA in special populations which are less frequently investigated. In this regard, seven groups of experts in the field of sleep medicine gave their contribution in the realization of noteworthy manuscripts which will support all physicians in improving their understanding of OSA with the latest knowledge about its epidemiology, pathophysiology and comorbidities in special populations, which will serve as a basis for future research.
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http://dx.doi.org/10.3390/medicina56050208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279442PMC
April 2020

Change in blood eosinophils following treatment with inhaled corticosteroids may predict long-term clinical response in COPD.

Eur Respir J 2020 05 27;55(5). Epub 2020 May 27.

Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, The University of Manchester, Manchester, UK.

There is an emerging role for blood eosinophil count (EOS) as a biomarker to guide inhaled corticosteroid (ICS) therapy in COPD. Since ICS administration could influence EOS, we hypothesised that change in EOS following treatment with ICS may predict outcomes of long-term therapy.In a analysis of ISOLDE, a 3-year, double-blind trial comparing 500 µg fluticasone propionate twice daily with placebo in 751 patients with moderate-to-severe COPD, we evaluated whether the initial changes in EOS during ICS treatment were predictive of ICS treatment response.EOS change within 1 year after the introduction of ICS was strongly predictive of treatment response. A suppressed EOS was associated with treatment effect. Characteristically, in patients with EOS suppression of ≥200 cells·μL, ICS use was associated with a decelerated rate of decline of forced expiratory volume in 1 s (FEV), by 32 mL·year, and a 30% reduction in the exacerbation rate. In contrast, in patients experiencing an increase in EOS of ≥200 cells·μL, ICS use was associated with an accelerated rate of decline of FEV, by 37 mL·year and an 80% increase in the exacerbation rate (p<0.0001). EOS change was not predictive of clinical response with regards to health status evaluated using the St George's Respiratory Questionnaire.These findings suggest that EOS change after ICS administration may predict clinical response to ICS therapy in patients with moderate-to-severe COPD at risk of exacerbations. ICS administration may be associated with more frequent exacerbations and an accelerated lung function decline in the 20% of patients in whom EOS increases after the administration of ICS. These hypothesis-generating observations will need validation in prospectively designed studies.The ISOLDE trial was conducted before the ICJME recommended a prospective registration of RCT protocols.
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http://dx.doi.org/10.1183/13993003.02119-2019DOI Listing
May 2020

Circulating Soluble Urokinase-Type Plasminogen Activator Receptor in Obstructive Sleep Apnoea.

Medicina (Kaunas) 2020 Feb 14;56(2). Epub 2020 Feb 14.

Department of Pulmonology, Semmelweis University, 1083 Budapest, Hungary.

: Obstructive sleep apnoea (OSA) is associated with heightened systemic inflammation and a hypercoagulation state. Soluble urokinase-type plasminogen activator receptor (suPAR) plays a role in fibrinolysis and systemic inflammation. However, suPAR has not been investigated in OSA. : A total of 53 patients with OSA and 15 control volunteers participated in the study. Medical history was taken and in-hospital sleep studies were performed. Plasma suPAR levels were determined by ELISA. : There was no difference in plasma suPAR values between patients with OSA (2.198 ± 0.675 ng/mL) and control subjects (2.088 ± 0.976 ng/mL, = 0.62). Neither was there any difference when patients with OSA were divided into mild (2.134 ± 0.799 ng/mL), moderate (2.274 ± 0.597 ng/mL) and severe groups (2.128 ± 0.744 ng/mL, = 0.84). There was no significant correlation between plasma suPAR and indices of OSA severity, blood results or comorbidities, such as hypertension, diabetes, dyslipidaemia or cardiovascular disease. Plasma suPAR levels were higher in women when all subjects were analysed together (2.487 ± 0.683 vs. 1.895 ± 0.692 ng/mL, < 0.01), and also separately in controls (2.539 ± 0.956 vs. 1.411 ± 0.534 ng/mL, = 0.02) and patients (2.467 ± 0.568 vs. 1.991 ± 0.686 ng/mL, < 0.01). : Our results suggest that suPAR does not play a significant role in the pathophysiology of OSA. The significant gender difference needs to be considered when conducting studies on circulating suPAR.
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http://dx.doi.org/10.3390/medicina56020077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7074407PMC
February 2020

Oscillometrically Measured Aortic Pulse Wave Velocity Reveals Asymptomatic Carotid Atherosclerosis in a Middle-Aged, Apparently Healthy Population.

Biomed Res Int 2020 16;2020:8571062. Epub 2020 Jan 16.

Heart Institute, Medical School, University of Pécs, Pécs, Hungary.

Background: Asymptomatic atherosclerosis is a common entity even at young age. Studies have suggested a strong relationship between increased arterial stiffness and asymptomatic carotid atherosclerosis (ACA) in general population, particularly in those with high cardiovascular risk, but no data exist from a younger population free from recognized cardiovascular disease. . We hypothesized there is an association between ACA and aortic pulse wave velocity (PWVao) in middle-aged, apparently healthy, normotensive population to reveal increased cardiovascular risk.

Methods: We examined the relationship between ACA and PWVao in 236 apparently healthy, asymptomatic, normotensive, middle-aged subjects (age 47 ± 8 years; 52% women). PWVao was measured with the oscillometric method (Arteriograph). ACA was assessed by carotid artery ultrasonography.

Results: ACA was present in 51 subjects. Subjects with ACA were older ( < 0.009), more likely to be smokers ( < 0.009), more likely to be smokers ( < 0.009), more likely to be smokers ( < 0.009), more likely to be smokers ( < 0.009), more likely to be smokers ( < 0.009), more likely to be smokers ( < 0.009), more likely to be smokers ( < 0.009), more likely to be smokers (.

Conclusions: PWVao measured by the Arteriograph proved to be an independent marker of ACA. Our study may reveal high CV risk, detected as increased PWVao, which according to our study is related in a very high probability to asymptomatic carotid atherosclerosis in apparently healthy, young, and middle-aged subjects.
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http://dx.doi.org/10.1155/2020/8571062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6991166PMC
November 2020

Obstructive sleep apnea and hypertriglyceridaemia share common genetic background: Results of a twin study.

J Sleep Res 2020 08 6;29(4):e12979. Epub 2020 Jan 6.

Department of Pulmonology, Semmelweis University, Budapest, Hungary.

Obstructive sleep apnea is associated with an increased risk of hypertension, diabetes and dyslipidaemia. Both obstructive sleep apnea and its comorbidities are at least partly heritable, suggesting a common genetic background. Our aim was to analyse the heritability of the relationship between obstructive sleep apnea and its comorbidities using a twin study. Forty-seven monozygotic and 22 dizygotic adult twin pairs recruited from the Hungarian Twin Registry (mean age 51 ± 15 years) attended an overnight diagnostic sleep study. A medical history was taken, blood pressure was measured, and blood samples were taken for fasting glucose, total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and lipoprotein (a). To evaluate the heritability of obstructive sleep apnea and its comorbidities bivariate analysis was performed with an adjustment for age, gender, body mass index (BMI) and smoking after false discovery rate correction and following exclusion of patients on lipid-lowering and antidiabetic medications. There was a significant correlation between indices of obstructive sleep apnea severity, such as the apnea-hypopnea index, oxygen desaturation index and percentage of sleep time spent with oxygen saturation below 90%, as well as blood pressure, serum triglyceride, lipoprotein (a) and glucose levels (all p < .05). The bivariate analysis revealed a common genetic background for the correlations between serum triglyceride and the oxygen desaturation index (r = .63, p = .03), as well as percentage of sleep time spent with oxygen saturation below 90% (r = .58, p = .03). None of the other correlations were significantly genetically or environmentally determined. This twin study demonstrates that the co-occurrence of obstructive sleep apnea with hypertriglyceridaemia has a genetic influence and heritable factors play an important role in the pathogenesis of dyslipidaemia in obstructive sleep apnea.
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http://dx.doi.org/10.1111/jsr.12979DOI Listing
August 2020

Dysregulation of the endothelial nitric oxide pathway is associated with airway inflammation in COPD.

Respir Res 2019 Jul 16;20(1):156. Epub 2019 Jul 16.

Department of Pulmonology, Semmelweis University, Diós árok 1/c, Budapest, 1125, Hungary.

Background: Chronic obstructive pulmonary disease (COPD) is related to endothelial dysfunction and the impaired generation of nitric oxide (NO) from L-arginine by the endothelial NO synthase (eNOS). The relationship between eNOS dysfunctionality and airway inflammation is unknown. We assessed serum asymmetric and symmetric dimethylarginine (ADMA and SDMA) and nitrite/nitrate concentrations, indicators of eNOS function, in patients with COPD and correlated them with markers of inflammation.

Methods: We recruited 15 control smokers, 29 patients with stable and 32 patients with exacerbated COPD requiring hospitalization (20 of them were measured both at admission and discharge). Serum L-arginine, ADMA, SDMA, nitrite and nitrate were measured and correlated with airway inflammatory markers (fractional exhaled nitric oxide concentration - FENO, sputum nitrite and nitrate, sputum cellularity), serum C-reactive protein - CRP, white blood cell count, lung function and blood gases. ANOVA, t-tests and Pearson correlation were used (mean ± SD or geometric mean ± geometric SD for nitrite/nitrate).

Results: Serum L-arginine/ADMA, a marker of substrate availability for eNOS, was lower in stable (214 ± 58, p < 0.01) and exacerbated COPD (231 ± 68, p < 0.05) than in controls (287 ± 64). The serum concentration of SDMA, a competitor of L-arginine transport, was elevated during an exacerbation (0.78 ± 0.39 μM) compared to stable patients (0.53 ± 0.14 μM, p < 0.01) and controls (0.45 ± 0.14 μM, p < 0.001). ADMA correlated with blood neutrophil percentage (r = 0.36, p < 0.01), FENO (r = 0.42, p < 0.01) and a tendency for positive association was observed to sputum neutrophil count (r = 0.33, p = 0.07). SDMA correlated with total sputum inflammatory cell count (r = 0.61, p < 0.01) and sputum neutrophil count (r = 0.62, p < 0.01). Markers were not related to lung function, blood gases or CRP. L-arginine/ADMA was unchanged, but serum SDMA level decreased (0.57 ± 0.42 μM, p < 0.05) after systemic steroid treatment of the exacerbation. Serum nitrite level increased in stable and exacerbated disease (4.11 ± 2.12 and 4.03 ± 1.77 vs. control: 1.61 ± 1.84 μM, both p < 0.001).

Conclusions: Our data suggest impaired eNOS function in stable COPD, which is transiently aggravated during an exacerbation and partly reversed by systemic steroid treatment. Serum ADMA and SDMA correlate with airway inflammatory markers implying a possible effect of anti-inflammatory therapy on endothelial dysfunction. Serum nitrite can serve as a compensatory pool for impaired endothelial NO generation.
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http://dx.doi.org/10.1186/s12931-019-1133-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6636120PMC
July 2019

Genetic influences on the onset of obstructive sleep apnoea and daytime sleepiness: a twin study.

Respir Res 2019 Jun 17;20(1):125. Epub 2019 Jun 17.

Department of Pulmonology, Semmelweis University, Budapest, Hungary.

Background: Obstructive sleep apnoea (OSA) is one of the major sources of the excessive daily sleepiness, cognitive dysfunction, and it increases cardiovascular morbidity and mortality. Previous studies suggested a possible genetic influence, based on questionnaires but no objective genetic study was conducted to understand the exact variance underpinned by genetic factors.

Methods: Seventy-one Hungarian twin pairs involved from the Hungarian Twin Registry (48 monozygotic, MZ and 23 dizygotic, DZ pairs, mean age 51 ± 15 years) underwent overnight polysomnography (Somnoscreen Plus Tele PSG, Somnomedics GMBH, Germany). Apnoea hypopnea index (AHI), respiratory disturbance index (RDI) and oxygen desaturation index (ODI) were registered. Daytime sleepiness was measured with the Epworth Sleepiness Scale (ESS). Bivariate heritability analysis was applied.

Results: The prevalence of OSA was 41% in our study population. The heritability of the AHI, ODI and RDI ranged between 69% and 83%, while the OSA, defined by an AHI ≥5/h, was itself 73% heritable. The unshared environmental component explained the rest of the variance between 17% and 31%. Daytime sleepiness was mostly determined by the environment, and the variance was influenced in 34% by the additive genetic factors. These associations were present after additional adjustment for body mass index.

Conclusion: OSA and the indices of OSA severity are heritable, while daytime sleepiness is mostly influenced by environmental factors. Further studies should elucidate whether close relatives of patients with OSA may benefit from early family risk based screening.
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http://dx.doi.org/10.1186/s12931-019-1095-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6580623PMC
June 2019

Exhaled carbon monoxide levels in obstructive sleep apnoea.

J Breath Res 2019 06 7;13(3):036012. Epub 2019 Jun 7.

Department of Pulmonology, Semmelweis University, 1/C Dios arok, 1125, Budapest, Hungary.

Background: Obstructive sleep apnoea (OSA) is characterised by chronic intermittent hypoxia, which enhances airway inflammation and oxidative stress. Exhaled carbon monoxide (eCO), a marker for oxidative stress, has been investigated in OSA. However, previous studies could be biased as they did not differentiate patients with OSA based on smoking history, a known factor influencing eCO levels. The aim of this study to investigate eCO levels in patients with OSA and non-OSA controls and compare evening to morning results.

Methods: Exhaled carbon monoxide concentration was measured in the evening and in the morning following an in-hospital cardiorespiratory polygraphy in 60 never-smoker OSA patients, 14 ex-smoker OSA patients, 39 current-smoker OSA patients, 10 never-smoker asthmatic patients with OSA, 16 COPD patients with OSA and 20 never-smoker non-OSA controls. OSA was diagnosed based on the apnoea-hypopnoea index (AHI > 5/h).

Results: There was no difference between the never-smoker controls and never-smoker patients with OSA either in the evening (1.98 ± 1.00 ppm versus 1.95 ± 1.28 ppm, p = 0.57, OSA versus controls, respectively) or morning (1.95 ± 0.96 ppm versus 1.80 ± 0.95 ppm, p = 0.42), however there was a weak correlation between eCO and AHI in the evening (r = 0.31, p = 0.01). Accordingly, patients with severe OSA had higher eCO levels in the evening (2.43 ± 1.12 ppm) compared to mild OSA patients (1.57 ± 0.87 ppm, p < 0.01). Ex-smoker (3.07 ± 2.23 ppm), current-smoker (13.13 ± 11.35 ppm), asthmatic (2.70 ± 1.16 ppm) and COPD (18.25 ± 18.60 ppm) patients with OSA had higher levels of eCO compared to the non-smoker OSA group.

Conclusion: Exhaled carbon monoxide is elevated only in severe never-smoker OSA suggesting accelerated oxidative stress. Previous smoking history is a major influencing factor which may explain differences between our findings and those of previous studies. Although our results show some impact of OSA on eCO measurements, the bias is small, and it does not significantly affect the clinical utility of eCO to monitor smoking cessation.
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http://dx.doi.org/10.1088/1752-7163/ab231dDOI Listing
June 2019

Decreased Levels of Anti-Aging Klotho in Obstructive Sleep Apnea.

Rejuvenation Res 2020 Jun 26;23(3):256-261. Epub 2019 Jun 26.

Department of Pulmonology, Semmelweis University, Budapest, Hungary.

The klotho protein is secreted primarily by the kidneys. It is responsible for phosphate homeostasis and has an anti-aging, anti-inflammatory, and anti-oxidative stress role. Obstructive sleep apnea (OSA) is associated with an enhanced systemic inflammation and oxidative stress, but mechanisms that regulate these processes are poorly understood. The aim of the study was to investigate the plasma levels of klotho in OSA. Twenty-one previously untreated patients with OSA (56 ± 13 years, 12 males) and 41 non-OSA control volunteers (48 ± 16 years, 8 males) participated in the study. Medical history has been taken; participants filled out the Epworth Sleepiness Scale. C-reactive protein and renal function, glucose and lipid profile measurements were performed in sera; klotho was determined in citrate-treated plasma samples. Levels of plasma klotho were decreased in OSA (519.1 ± 164.9 pg/mL) versus controls (700.8 ± 431.4 pg/mL,  = 0.02). Reduced klotho concentrations were associated with markers of overnight hypoxemia determined with O desaturation index ( = -0.31,  = 0.01), percentage of sleep time spent with saturation <90% ( = -0.41,  < 0.01), and minimal saturation during sleep ( = 0.33,  = 0.01). Interestingly, there was no relationship with apnea-hypopnea index, total sleep time, or arousal index (all  > 0.05). Significant association was also found between low plasma klotho levels and the presence of hypertension ( < 0.05). Our results suggest that chronic intermittent hypoxia reduces the levels of klotho in OSA, which may contribute to the development of hypertension. Decreased klotho levels may play a role in enhanced systemic inflammation in OSA and may be a future target for drug development.
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http://dx.doi.org/10.1089/rej.2019.2183DOI Listing
June 2020

Research highlights from the 2018 European Respiratory Society International Congress: airway disease.

ERJ Open Res 2019 Feb 18;5(1). Epub 2019 Mar 18.

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

The annual European Respiratory Society (ERS) International Congress (held in Paris in 2018) was once again a platform for discussion of the highest-quality scientific research, cutting-edge techniques and innovative new therapies within the respiratory field. This article discusses only some of the high-quality research studies presented at this year's Congress, with a particular focus on airway diseases including asthma, chronic obstructive pulmonary disease (COPD), bronchiectasis and cough, as presented through Assembly 5 of the ERS (Airway Diseases: Asthma and COPD). The authors establish the key take-home messages of these studies, compare their findings and place them in the context of current understanding.
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http://dx.doi.org/10.1183/23120541.00225-2018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6421359PMC
February 2019

Soluble Urokinase-Type Plasminogen Activator Receptor and Arterial Stiffness in Patients with COPD.

Lung 2019 04 28;197(2):189-197. Epub 2019 Feb 28.

Department of Pulmonology, Semmelweis University, Diós árok Street. 1/c, Budapest, 1125, Hungary.

Introduction: Soluble urokinase-type plasminogen activator receptor (suPAR) is upregulated by inflammation and plays a role in the pathogenesis of atherosclerosis. Chronic obstructive pulmonary disease (COPD) is associated with enhanced systemic inflammation and increased risk for atherosclerosis, however, studies analysing the circulating suPAR levels in COPD are contradictory. The aim of the study was to investigate plasma suPAR concentrations together with markers of arterial stiffness in COPD.

Materials And Methods: Twenty-four patients with COPD and 18 non-COPD, control subjects participated in the study. Plasma suPAR was measured, together with lung volumes, symptom burden, exacerbation history, markers of arterial stiffness and soluble inflammatory biomarkers, such as endothelin-1, high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6).

Results: Plasma suPAR levels were higher in COPD (2.84 ± 0.67 ng/ml vs. 2.41 ± 0.57 ng/ml, p = 0.03) and were related to lung function measured with FEV (r = - 0.65, p < 0.01) and symptom burden determined with the modified Medical Research Council questionnaire (r = 0.55, p < 0.05). Plasma suPAR concentrations correlated with various measures of arterial stiffness in all subjects, but only with ejection duration in COPD (r = - 0.44, p = 0.03).

Conclusions: Plasma suPAR levels are elevated in COPD and relate to arterial stiffness. Our results suggest that suPAR may be a potential link between COPD and atherosclerosis.
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http://dx.doi.org/10.1007/s00408-019-00211-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6486892PMC
April 2019

Comprehensive coronary plaque assessment in patients with obstructive sleep apnea.

J Sleep Res 2019 10 6;28(5):e12828. Epub 2019 Feb 6.

Cardiovascular Imaging Research Group, Heart and Vascular Center, Semmelweis University, Budapest, Hungary.

Obstructive sleep apnea (OSA) is associated with an increased risk of cardiovascular disease. Previous studies have assessed the relationship between OSA and coronary artery disease (CAD) using coronary artery calcium score (CAC) measurements. However, limited data are available regarding the association of OSA with non-calcified plaque burden. We therefore aimed to assess the relationship between CAD severity as assessed by coronary computed tomography angiography (CTA) and OSA. Forty-one adult subjects (59 ± 9 years, 15 men) underwent a 256-slice coronary CTA, which was followed by a diagnostic attended cardiorespiratory polygraphy (n = 13) or polysomnography (n = 28). Segment involvement score (SIS), segment stenosis score (SSS) and CAC were used to quantify total CAD burden. Correlation analysis was used to assess potential associations between CAD and OSA. Twenty-two patients were diagnosed with OSA. SIS and SSS were elevated in OSA (2.90 ± 2.78 versus 1.79 ± 2.39 and 4.91 ± 5.94 versus 1.79 ± 4.54, OSA versus controls, SIS and SSS respectively, both p < 0.01) and correlated with OSA severity as measured by the apnea-hypopnea index (AHI, r = 0.41 and 0.43, p < 0.01) and oxygen desaturation index (ODI, r = 0.45 and 0.46, p < 0.01). However, no significant correlation was observed between CAC and OSA. Compared to CAC, SIS and SSS provide additional information on coronary plaque burden in OSA, which shows a significant association with OSA.
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http://dx.doi.org/10.1111/jsr.12828DOI Listing
October 2019

Association Between Serum Lipid Profile and Obstructive Respiratory Events During REM and Non-REM Sleep.

Lung 2019 08 2;197(4):443-450. Epub 2019 Feb 2.

Department of Pulmonology, Semmelweis University, 1/C Dios arok, Budapest, 1125, Hungary.

Purpose: Obstructive sleep apnoea (OSA) represents a risk for dyslipidaemia. Obstructive respiratory events during rapid eye movement (REM) sleep are more strongly related to the development of hypertension and diabetes than in non-REM. However, the relationship between sleep phases and serum lipid profile is unclear. We aimed to analyse the relationship between obstructive respiratory events in REM and non-REM sleep as well as serum lipid profile.

Methods: Polysomnography was performed in 94 adult subjects who did not take any lipid-modifying medications. Fasting venous blood sample was taken the following morning for total cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, lipoprotein(a), apoprotein A1 (ApoA1) and for apoprotein B (ApoB) measurements. Lipid profiles were correlated with apnoea-hypopnoea index (AHI) during REM (AHI) and non-REM (AHI) stages in all subjects. In addition, lipid profiles were compared between REM-dependent OSA patients (AHI ≥ 5/h, but AHI < 5/h) and control subjects (both AHI and AHI < 5/h).

Results: AHI correlated only with triglyceride concentrations (p = 0.04, Spearman's rho, ρ = 0.21). In contrast, there was a significant association between AHI and triglyceride (p = 0.02, ρ = 0.23), ApoB (p = 0.03, ρ = 0.21), HDL-C (p < 0.01, ρ = - 0.32) as well as ApoA1 levels (p = 0.04, ρ = - 0.21). However, these correlations were not present after adjustment for BMI (all p > 0.05). There was no difference in the lipid profile of REM-dependent OSA subjects and healthy controls (p > 0.05).

Conclusions: Altered serum lipid profile is equally associated with a disturbed REM and non-REM sleep in OSA. Obesity must be considered as a strong covariate when interpreting lipid data in sleep apnoea.
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http://dx.doi.org/10.1007/s00408-019-00195-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6647223PMC
August 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

LABA/LAMA Fixed Dose Combination in Chronic Obstructive Pulmonary Disease: The Impact on Health-Related Quality of Life.

Respiration 2018;96(4):370-381. Epub 2018 Sep 18.

Department of Biomedical Sciences, Humanitas University, Milano, Italy.

Background: While fixed dose combinations (FDCs) of long-acting beta 2-agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) are increasingly tested on their efficacy in improving lung function, their effectiveness on Patient Reported Outcomes (PROs) such as Health Related Quality of Life (HRQoL) and Health Status (HS) deserve more attention.

Objectives: To review current available evidence about the treatment effect of fixed LABA/LAMA FDCs on HRQoL.

Methods: A systematic literature search for randomized controlled trials (RCTs) about the impact of LABA/LAMA FDCs versus placebo, LABA or LAMA or LABA/ICS on HRQoL in Chronic obstructive pulmonary disease (COPD) patients has been performed.

Results: Twenty-eight RCTs (n = 32, 165 COPD patients) investigating the impact of fixed LABA/LAMA combinations on HRQoL were included. Using the St George' s Respiratory Questionnaire, 27 out of 28 trials assessed HRQoL. LABA/LAMA FDCs significantly improved HRQoL versus placebo in 9 out of 11 trials, while change when compared to other LABA or LAMA monocomponents was significantly better in 11 out 24. In 5 out of 6 RCTs having LABA/ICS as comparators, LABA/LAMA FDC had a similar effect and only 1 showed significant improvement in HRQL compared to LABA/ICS FDC.

Conclusion: LABA/LAMA FDCs may be helpful in improving HRQoL, but because of the heterogeneity of performed trials, strong conclusions cannot be drawn. Moreover, due to the different molecule properties, treatment schedule, and device characteristics of each FDC, a generalized judgment seems inappropriate. Pragmatic trials powered to detect real-life differences in HRQoL and head-to-head comparison are needed to guide clinical practice in terms of PROs.
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http://dx.doi.org/10.1159/000491673DOI Listing
October 2019

Changes in the Burden of Comorbidities in Patients with COPD and Asthma-COPD Overlap According to the GOLD 2017 Recommendations.

Lung 2018 10 14;196(5):591-599. Epub 2018 Jul 14.

Pereszteg-Pinnye General Practitioner Praxis, Petofi Sandor u. 29, Pereszteg, 9484, Hungary.

Purpose: Comorbidities associated with chronic obstructive pulmonary disease (COPD) affect quality of life and increase mortality. Asthma-COPD overlap (ACO) may express a different profile of comorbidities compared to COPD alone. It is unclear how recent changes in GOLD recommendations affect the profile of comorbidities in COPD and ACO.

Methods: Eight hundred and thirty-four patients with COPD were recruited from 67 Hungarian secondary care outpatient clinics, 469 of them had ACO. Comorbidities were defined by respiratory specialists based on medical history, patient report, and medications. COPD grades were defined according to the old 2016 and the new 2017 GOLD document. Comorbidities were compared along COPD ABCD groups determined by the old and new GOLD.

Results: 66 and 72% of the COPD patients in groups C and D (GOLD 2016) were recategorized to groups A and B (GOLD 2017), respectively. There was no difference in the prevalence of disorders along the 2016 GOLD categories except for osteoporosis in ACO (p = 0.01). When the patients were categorized according to the 2017 GOLD criteria, the prevalence of osteoporosis (p = 0.01) was different among the four groups in all COPD patients. Subgroup analysis of non-ACO COPD patients revealed inter-group differences for cardiac arrhythmia (p < 0.01). No alteration was seen in the prevalence of coronary artery disease, hypertension, diabetes, or the total number of comorbidities.

Conclusion: A significant number of patients are recategorized according to the GOLD 2017 criteria. This change only marginally affects the profile of comorbidities; still this needs to be considered when assessing the patients in daily practice.
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http://dx.doi.org/10.1007/s00408-018-0141-7DOI Listing
October 2018