A narrative review of theophylline: is there still a place for an old friend?

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.

Allergic bronchopulmonary candidiasis: A review of the literature and a case report.

BACKGROUND: Allergic bronchopulmonary candidiasis (ABPC) is an uncommon clinical syndrome associated with immune hypersensitivity to Candida species. CASE PRESENTATION: The case presentation describes a 58-year-old man with acute respiratory failure and bilateral lung infiltrates. Due to high inflammatory markers and a chest X-ray indicating lung infiltration, he was initially treated for pneumonia with combined antibiotics. Despite comprehensive treatment at the ICU, the patient's clinical status deteriorated rapidly, and further investigations provided a rare diagnosis of ABPC. After several days of combined corticosteroid and antifungal therapy, we observed rapid clinical improvement and subsequent resolution of the pulmonary infiltrates. CONCLUSION: This case report presented a rare case of ABPC mimicking bilateral pneumonia and acute respiratory failure. Our case highlighted the importance of prompt corticosteroid and antifungal treatment initiation as it resulted in rapid clinical improvement and a near complete reversal of the bilateral lung infiltrates.

Aminophylline Induces Two Types of Arrhythmic Events in Human Pluripotent Stem Cell-Derived Cardiomyocytes.

Cardiac side effects of some pulmonary drugs are observed in clinical practice. Aminophylline, a methylxanthine bronchodilator with documented proarrhythmic action, may serve as an example. Data on the action of aminophylline on cardiac cell electrophysiology and contractility are not available. Hence, this study was focused on the analysis of changes in the beat rate and contraction force of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) and HL-1 cardiomyocytes in the presence of increasing concentrations of aminophylline (10 µM-10 mM in hPSC-CM and 8-512 µM in HL-1 cardiomyocytes). Basic biomedical parameters, namely, the beat rate (BR) and contraction force, were assessed in hPSC-CMs using an atomic force microscope (AFM). The beat rate changes under aminophylline were also examined on the HL-1 cardiac muscle cell line via a multielectrode array (MEA). Additionally, calcium imaging was used to evaluate the effect of aminophylline on intracellular Ca2+ dynamics in HL-1 cardiomyocytes. The BR was significantly increased after the application of aminophylline both in hPSC-CMs (with 10 mM aminophylline) and in HL-1 cardiomyocytes (with 256 and 512 µM aminophylline) in comparison with controls. A significant increase in the contraction force was also observed in hPSC-CMs with 10 µM aminophylline (a similar trend was visible at higher concentrations as well). We demonstrated that all aminophylline concentrations significantly increased the frequency of rhythm irregularities (extreme interbeat intervals) both in hPSC-CMs and HL-1 cells. The occurrence of the calcium sparks in HL-1 cardiomyocytes was significantly increased with the presence of 512 µM aminophylline. We conclude that the observed aberrant cardiomyocyte response to aminophylline suggests an arrhythmogenic potential of the drug. The acquired data represent a missing link between the arrhythmic events related to the aminophylline/theophylline treatment in clinical practice and describe cellular mechanisms of methylxanthine arrhythmogenesis. An AFM combined with hPSC-CMs may serve as a robust platform for direct drug effect screening.

Esophageal positions relative to the left atrium; data from 293 patients before catheter ablation of atrial fibrillation.

AIMS: Three-dimensional rotational angiography (3DRA) of the left atrium (LA) and the esophagus is a simple and safe method for analyzing the relationship between the esophagus and the LA during catheter ablation of atrial fibrillation. The purpose of this study is to describe the location of the esophagus relative to the LA and mobility of the esophagus during ablation procedure. METHODS: From 3/2011 to 9/2015, 3DRA of the LA and esophagus was performed in 326 patients before catheter ablation of atrial fibrillation. 3DRAwas performed with visualization of the esophagus via peroral administration of a contrast agent. The positions of the esophagus were determined at the beginning of the procedure, for part of patients also at the end of procedure with contrast esophagography. RESULTS: The most frequent position is behind the center of the LA (91 pts., 31.9%) The least frequent position is behind the right pulmonary veins (27 pts., 9.4%). The average shift of the esophagus position was 3.36±2.15mm, 3.59±2.37mm and 3.67±3.23mm for superior, middle and inferior segment resp. CONCLUSIONS: The position of the esophagus to the LA is highly variable. The most common position of the esophagus relative to the LA is behind the middle and left part of the posterior wall of the LA. The least frequently observed position is behind the right pulmonary veins. No significant position change of esophagus motion from before to after the ablation procedure in the majority (≥95%) of the patients was observed.

Three-dimensional rotational angiography of the left atrium and the oesophagus: the short-term mobility of the oesophagus and the stability of the fused three-dimensional model of the left atrium and the oesophagus during catheter ablation for atrial fibrillation.

AIMS: The objective of this study was to evaluate the mobility of the oesophagus and the stability of the three-dimensional (3D) model of the oesophagus using 3D rotational angiography (3DRA) of the left atrium (LA) and the oesophagus, fused with live fluoroscopy during catheter ablation for atrial fibrillation. METHODS AND RESULTS: From March 2015 to September 2015, 3DRA of the LA and the oesophagus was performed in 33 patients before catheter ablation for atrial fibrillation. Control contrast oesophagography was performed every 30 min. The positions of the oesophagograms and the 3D model of the LA and the oesophagus were repeatedly measured and compared with the spine. The average shift of the oesophagus ranged from 2.7 ± 2.2 to 5.0 ± 3.5 mm. The average real-time oesophageal shift ranged from 2.7 ± 2.2 to 3.8 ± 3.4 mm. No significant shift was detected until the 90th minute of the procedure. The average shift of the 3D model of the LA and the oesophagus ranged from 1.4 ± 1.8 to 3.3 ± 3.0 mm (right-left direction) and from 0.9 ± 1.2 to 2.2 ± 1.3 mm (craniocaudal direction). During the 2 h procedure, there were no significant shifts of the model. CONCLUSION: During catheter ablation for atrial fibrillation, there is no significant change in the position of the oesophagus until the 90th minute of the procedure and no significant shift in the 3D model of the LA and the oesophagus. The 3D model of the oesophagus reliably depicts the position of the oesophagus during the entire procedure.