INTRODUCTION: Ventilatory efficiency (V'E/V'CO2 ) has been shown to predict postoperative pulmonary complications (PPCs) in lung resection candidates. V'E/V'CO2 is determined by arterial partial pressure of carbon dioxide (PaCO2 ) and by dead space to tidal volume ratio (VD/VT). We hypothesised PaCO2 and VD/VT contribute equally to the increase in V'E/V'CO2 in lung resection patients. METHODS: Consecutive lung resection candidates from two prior prospective studies were included in this post hoc analysis. All subjects underwent preoperative spirometry, cardiopulmonary exercise testing and arterial blood gas analysis at rest and peak exercise. PPCs were prospectively assessed during the first 30 postoperative days, or hospital stay. A t-test, Mann-Whitney U-test and two-tailed Fisher's exact test were used to compare patients with and without PPCs. p-values <0.05 were considered statistically significant. RESULTS: Of 398 patients, PPC developed in 64 (16%). Patients with PPCs more frequently underwent lobectomy by open thoracotomy, had longer hospital and ICU length of stay and higher 30- and 90-day mortality. Moreover, patients with PPCs exhibited a higher V'E/V'CO2 ratio both at rest and peak exercise. Both ratios were independently associated with PPCs. At rest, the contribution of PaCO2 and VD/VT to the increase in V'E/V'CO2 ratio in patients with PPCs was 45% and 55%, respectively. At peak exercise, the contribution of PaCO2 and VD/VT to the increase in V'E/V'CO2 ratio was 16% and 84%, respectively. CONCLUSIONS: VD/VT (V'/Q' mismatch and/or rapid shallow breathing pattern) is the dominant contributor to the increase in V'E/V'CO2 in lung resection candidates who develop PPCs.

• Publikační typ
• časopisecké články MeSH

The combination of aminophylline and salbutamol is frequently used in clinical practice in the treatment of obstructive lung diseases. While the side effects (including arrhythmias) of the individual bronchodilator drugs were well described previously, the side effects of combined treatment are almost unknown. We aimed to study the arrhythmogenic potential of combined aminophylline and salbutamol treatment in vitro. For this purpose, we used the established atomic force microscopy (AFM) model coupled with cardiac organoids derived from human pluripotent stem cells (hPSC-CMs). We focused on the chronotropic, inotropic, and arrhythmogenic effects of salbutamol alone and aminophylline and salbutamol combined treatment. We used a method based on heart rate/beat rate variability (HRV/BRV) analysis to detect arrhythmic events in the hPSC-CM based AFM recordings. Salbutamol and aminophylline had a synergistic chronotropic and inotropic effect compared to the effects of monotherapy. Our main finding was that salbutamol reduced the arrhythmogenic effect of aminophylline, most likely mediated by endothelial nitric oxide synthase activated by beta-2 adrenergic receptors. These findings were replicated and confirmed using hPSC-CM derived from two cell lines (CCTL4 and CCTL12). Data suggest that salbutamol as an add-on therapy may not only deliver a bronchodilator effect but also increase the cardiovascular safety of aminophylline, as salbutamol reduces its arrhythmogenic potential.

• MeSH
• albuterol * farmakologie   MeSH
• aminofylin * farmakologie   MeSH
• bronchodilatancia farmakologie   MeSH
• buněčné linie MeSH
• kardiomyocyty účinky léků   metabolismus   MeSH
• lidé MeSH
• mikroskopie atomárních sil MeSH
• pluripotentní kmenové buňky účinky léků   cytologie   MeSH
• srdeční arytmie * farmakoterapie   MeSH
• srdeční frekvence účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• hodnocení rizik MeSH
• lidé MeSH
• oxid uhličitý * MeSH
• předoperační péče * metody   MeSH
• spotřeba kyslíku MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• dopisy MeSH
• komentáře MeSH
• úvodníky MeSH

A number of respiratory patients receive combined bronchodilator (BD) treatment including beta2-sympathomimetics (ß2-SM), parasympatholytics and/or methylxanthines. Fenoterol and salbutamol are also used as doping substances. A long-term use of ß2-SM, parasympatholytics and methylxanthines may result in the development of cardiomyopathy (CMP), chronic heart failure (CHF), arrhytmias (CA) or sudden cardiac death. The effects of single BD molecules were studied previously using animal models. However, little is known about the combined effect of more classes of BD drugs on human cardiomyocytes and cardiac functions. We propose an in vitro study of single molecules as well as combined regimens of BD drugs ́ effects on human cardiomyocytes differentiated from pluripotent stem cells of embryonal origin. Parallel series of experiments will be performed on cardiac cells differentiated from skin biopsy-derived stem cells of patients diagnosed with a CMP, CHF or CA receiving long-term BD treatment. We will focus on arrhytmogenic and inotropic side effects of single BD molecules and combined BD

Řada pneumologických pacientů užívá kombinace bronchodilatačních (BD) léků (skupiny beta2-sympatomimetik (ß2-SM), parasympatolytik, metylxantinů). Fenoterol a salbutamol jsou zneužívány i jako dopingové látky pro předpokládané anabolické účinky. Při dlouhodobém užívání ß2-SM, parasympatolytik a metylxantinů u některých osob může vzniknout kardiomyopatie, chronické srdeční selhání, arytmie či náhlá srdeční smrt. Efekty některých BD léků jsou popsány ze zvířecích modelů; málo je známo o kombinovaném účinku více tříd současně užívaných BD molekul na funkci kardiomyocytů a srdce. Účelem studie je laboratorními in vitro testy objasnit funkci BD léků jednotlivě i v kombinaci na celulární úrovni na humánní kardiomyocyty z embryonálních buněčných kultur i z buněk indukovaných z kožní biopsie pacientů se známou srdeční patologií. Zkoumán bude hlavně arytmogenní a (pozitivně či negativně) inotropní efekt BD molekul. Při průkazu nežádoucích efektů stávající BD léčby bude testován efekt alternativních BD molekul s cílem nalezení léčby s lepším bezpečnostním profilem (personalizovaná léčba).

• Klíčová slova
• arytmie, chronické srdeční selhání, kmenové buňky, stem cells, personalizovaná medicína, kardiomyopatie, cardiomyopathy, chronic heart failure, personalized treatment, kardiomyocyty, bronchodilatační léčba, bronchodilator treatment, human cardiomyocytes, arrhytmias,

• NLK Publikační typ
• závěrečné zprávy o řešení grantu AZV MZ ČR

INTRODUCTION: In recent years, ventilatory efficiency (minute ventilation (V'E)/carbon dioxide production (V'CO2 ) slope) and partial pressure of end-tidal carbon dioxide (PETCO2 ) have emerged as independent predictors of postoperative pulmonary complications (PPC). Single parameters may give only partial information regarding periprocedural hazards. Accordingly, our aim was to create prediction models with improved ability to stratify PPC risk in patients scheduled for elective lung resection surgery. METHODS: This post hoc analysis was comprised of consecutive lung resection candidates from two prior prospective trials. All individuals completed pulmonary function tests and cardiopulmonary exercise testing (CPET). Logistic regression analyses were used for identification of risk factors for PPC that were entered into the final risk prediction models. Two risk models were developed; the first used rest PETCO2 (for patients with no available CPET data), the second used V'E/ V'CO2 slope (for patients with available CPET data). Receiver operating characteristic analysis with the De-Long test and area under the curve (AUC) were used for comparison of models. RESULTS: The dataset from 423 patients was randomly split into the derivation (n=310) and validation (n=113) cohorts. Two final models were developed, both including sex, thoracotomy, "atypical" resection and forced expiratory volume in 1 s/forced vital capacity ratio as risk factors. In addition, the first model also included rest PETCO2 , while the second model used V'E/V'CO2 slope from CPET. AUCs of risk scores were 0.795 (95% CI: 0.739-0.851) and 0.793 (95% CI: 0.737-0.849); both p<0.001. No differences in AUCs were found between the derivation and validation cohorts. CONCLUSIONS: We created two multicomponental models for PPC risk prediction, both having excellent predictive properties.

• Publikační typ
• časopisecké články MeSH

Příručka a směrnice, které se zaměřují na diagnostiku a terapii chronické obstrukční plicní nemoci. Určeno praktickým lékařům.

• MeSH
• chronická obstrukční plicní nemoc diagnóza   terapie   MeSH
• praktické lékařství MeSH
• Publikační typ
• příručky MeSH
• směrnice pro lékařskou praxi MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• pneumologie a ftizeologie
• všeobecné lékařství
• NLK Publikační typ
• brožury

BACKGROUND AND OBJECTIVE: Theophylline has been used for decades in human medicine for its psychostimulant, anti-inflammatory, and bronchodilator effects. Historically, in pulmonary medicine, theophylline has been used in the treatment of obstructive pulmonary diseases such as bronchial asthma (BA) or chronic obstructive pulmonary disease (COPD). This review aims to determine whether theophylline still has its place in the therapy of obstructive pulmonary diseases or whether we can even extend its use to other diagnoses such as atropine-resistant cardiac arrests, apnea of prematurity, or others. Moreover, we also aim to determine if there is a rationale for using low-dose theophylline due to its immunomodulatory and anti-inflammatory effect, or if the future of methylxanthines lies in newly synthesized derivates of theophylline such as bamifylline, or doxofylline. METHODS: The narrative review is based on a literature search of the articles indexed in the PubMed database in 2023. We searched the database since the year 2009 using the MeSH terms "theophylline", "aminophylline", and "methylxanthines" and we included original articles in the English language. KEY CONTENT AND FINDINGS: Theophylline has a number of adverse drug reactions (ADRs), the most serious of which is its effect on the cardiovascular system. It can cause severe arrhythmias or even cardiac arrest when overdosed. On the other hand, there is still a substantial amount of its applications in current clinical practice. CONCLUSIONS: There is considerable controversy associated with its use in current medicine, which can be attributed both to its narrow therapeutic range and its mentioned cardiotoxic effect. Herein, we summarize the current state-of-art of theophylline and its use in human medicine.

• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND: Physical activity is a crucial demand on cystic fibrosis treatment management. The highest value of oxygen uptake (VO2peak) is an appropriate tool to evaluate the physical activity in these patients. However, there are several other valuable CPET parameters describing exercise tolerance (Wpeak, VO2VT1, VO2VT2, VO2/HRpeak, etc.), and helping to better understand the effect of specific treatment (VE, VT, VD/VT etc.). Limited data showed ambiguous results of this improvement after CFTR modulator treatment. Elexacaftor/tezacaftor/ivacaftor medication improves pulmonary function and quality of life, whereas its effect on CPET has yet to be sufficiently demonstrated. METHODS: We performed a single group prospective observational study of 10 adolescent patients with cystic fibrosis who completed two CPET measurements between January 2019 and February 2023. During this period, elexacaftor/tezacaftor/ivacaftor treatment was initiated in all of them. The first CPET at the baseline was followed by controlled CPET at least one year after medication commencement. We focused on interpreting the data on their influence by the novel therapy. We hypothesized improvements in cardiorespiratory fitness following treatment. We applied the Wilcoxon signed-rank test. The data were adjusted for age at the time of CPET to eliminate bias of aging in adolescent patients. RESULTS: We observed significant improvement in peak workload, VO2 peak, VO2VT1, VO2VT2, VE/VCO2 slope, VE, VT, RQ, VO2/HR peak and RR peak. The mean change in VO2 peak was 5.7 mL/kg/min, or 15.9% of the reference value (SD ± 16.6; p= 0.014). VO2VT1 improved by 15% of the reference value (SD ± 0.1; p= 0.014), VO2VT2 improved by 0.5 (SD ± 0.4; p= 0.01). There were no differences in other parameters. CONCLUSION: Exercise tolerance improved after elexacaftor/tezacaftor/ivacaftor treatment initiation. We suggest that the CFTR modulator alone is not enough for recovering physical decondition, but should be supplemented with physical activity and respiratory physiotherapy. Further studies are needed to examine the effect of CFTR modulators and physical therapy on cardiopulmonary exercise tolerance.

• MeSH
• aminofenoly * terapeutické užití   MeSH
• benzodioxoly * terapeutické užití   MeSH
• chinolony * terapeutické užití   MeSH
• cystická fibróza * farmakoterapie   patofyziologie   MeSH
• dítě MeSH
• fixní kombinace léků * MeSH
• indoly * terapeutické užití   MeSH
• kardiorespirační zdatnost MeSH
• lidé MeSH
• mladiství MeSH
• pilotní projekty MeSH
• prospektivní studie MeSH
• pyrazoly * terapeutické užití   MeSH
• pyridiny * terapeutické užití   MeSH
• pyrrolidiny MeSH
• pyrroly terapeutické užití   MeSH
• spotřeba kyslíku MeSH
• tolerance zátěže účinky léků   MeSH
• zátěžový test MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH