Long-Term Weight Changes After Starting Anti-IL-5/5Ra Biologics in Severe Asthma: The Role of Oral Corticosteroids.

Background: Many patients with severe asthma are overweight or obese, often attributed to unintentional weight gain as a side effect of oral corticosteroids (OCSs). Anti-IL-5/5Ra biologics significantly reduce OCS use, but their long-term effects on weight are unknown.

Objectives: To examine (1) weight change up to 2 years after anti-IL-5/5Ra initiation in subgroups on the basis of maintenance OCS use at start of treatment and (2) whether cumulative OCS exposure before or changes in OCS exposure during treatment are related to weight change.

Anti-IL-5/5Ra biologics improve work productivity and activity in severe asthma: a RAPSODI registry-based cohort study.

Introduction: Severe asthma is associated with a serious disease burden, partially caused by limitations in activity and work impairment.

Aims And Objectives: This study aims to relate treatment with biologics targeting IL-5/5Ra to work productivity and activity in the long term in a real-world context.

Material And Methods: This is a registry-based multi-center cohort study evaluating data from adults with severe eosinophilic asthma included in the Dutch Register of Adult Patients with Severe Asthma for Optimal DIsease management (RAPSODI).

The demographics, clinical characteristics and quality of life of patients with chronic cough from the Isala Cough Clinic in the Netherlands.

Introduction: Chronic cough affects ∼10% of the population and adversely impacts quality of life. This retrospective observational cohort study aimed to identify the demographics, clinical characteristics and quality of life of the chronic cough population in a Dutch chronic cough clinic, at baseline and following treatment at 6 months. Patients were categorised based on the underlying phenotype and response to treatment.

Real-World Effectiveness of Reslizumab in Patients With Severe Eosinophilic Asthma - First Initiators and Switchers.

Background: Reslizumab, a biologic targeting IL-5, has been shown to reduce asthma exacerbations and maintenance oral corticosteroid use in randomized controlled trials and pre-post studies in patients with severe eosinophilic asthma. However, real-world effectiveness data of reslizumab are scarce, and it is unknown whether reslizumab has added value after switching from another type 2 biologic.

Objective: To evaluate (1) the real-world effectiveness of reslizumab on severe asthma exacerbations, maintenance oral corticosteroid use, and overall treatment response, both in biologic-naive patients who initiated reslizumab and in those who switched from another type 2 biologic; and (2) physicians' experience with reslizumab treatment.

[Chronic cough in adults].

Cough is a physiological defense mechanism. However, excessive cough is known to have a great impact on quality of life. Cough is considered to be chronic when it lasts longer than 8 weeks.

Quality of spirometry and related diagnosis in primary care with a focus on clinical use.

American and European societies' (ATS/ERS) criteria for spirometry are often not met in primary care. Yet, it is unknown if quality is sufficient for daily clinical use. We evaluated quality of spirometry in primary care based on clinical usefulness, meeting ATS/ERS criteria and agreement on diagnosis between general practitioners (GPs) and pulmonologists.

Mycoplasma amphoriforme vs M. pneumoniae: similarities and differences between patient characteristics in a regional hospital in the Netherlands.

Mycoplasma amphoriforme is a species closely related to Mycoplasma pneumoniae, thus far with unknown clinical impact. The application of optimized diagnostics, better capable of differentiating between these two micro-organisms, identified a significant patient population positive for M. amphoriforme.

Dapagliflozin for prednisone-induced hyperglycaemia in acute exacerbation of chronic obstructive pulmonary disease.

The aim of the present study was to compare the effectiveness and safety of add-on treatment with dapagliflozin to placebo in patients with prednisone-induced hyperglycaemia during treatment for acute exacerbation of chronic obstructive pulmonary disease (AECOPD). We enrolled 46 patients hospitalized for an AECOPD in a multicentre double-blind randomized controlled study in which add-on treatment with dapagliflozin 10 mg was compared with placebo. Glycaemic control and incidence of hypoglycaemia were measured through a blinded subcutaneous continuous glucose monitoring device.

Robot-assisted thoracoscopic lobectomy as treatment of a giant bulla.

Background: A bulla is a marked enlarged space within the parenchyma of the lung. Bullae may cause dyspnea by compressing healthy lung parenchyma and can cause a pneumothorax. Also, bullae are associated with malignancy, therefore surgical bullectomy is indicated on preventive basis.

Alterations in lipid and carbohydrate metabolism in patients with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

Background: Classic 21-hydroxylase deficiency (21HD) presents some traits of the metabolic syndrome.

Aim: To characterize discrete alterations of lipid and carbohydrate metabolism in children and young adults with classic 21HD, which could predict early atherogenesis.

Patients And Methods: Twenty-seven Caucasian patients with classic 21HD (4-31 years); 27 sex-, age- and BMI-matched controls.

I(Kr) contributes to the altered ventricular repolarization that determines long-term cardiac memory.

Objective: Cardiac memory (CM) is characterized by an altered T-wave morphology, which reflects altered repolarization gradients. We hypothesized that the delayed rectifier currents, I(Kr) and I(Ks), might contribute to these repolarization changes.

Methods: We studied conscious, chronically instrumented dogs paced from the postero-lateral left ventricular (LV) wall at rates 5-10% faster than sinus rate for 3 weeks.

Cardiac memory: mechanisms and clinical implications.

Cardiac memory (CM) is identified as an altered T wave on electrocardiogram and vectorcardiogram that is seen when sinus rhythm resumes after a period of abnormal myocardial activation. Specifically, the sinus rhythm T wave tracks the QRS vector of the abnormal impulse. CM frequently is induced by ventricular pacing or arrhythmias and historically has been considered of minor relevance to medical practice.

The cAMP response element binding protein modulates expression of the transient outward current: implications for cardiac memory.

Objective: Long-term cardiac memory (LTCM), expressed as a specific pattern of T-wave change on ECG, is associated with 1) reduced transient outward potassium current (I(to)), 2) reduced mRNA for the pore-forming protein of I(to), Kv4.3, 3) reduced cAMP response element binding protein (CREB), and 4) diminished binding to its docking site on the DNA, the cAMP response element (CRE). We hypothesized a causal link between the decrease of the transcription factor CREB and down-regulation of I(to) and one of its channel subunits, KChIP2, in LTCM.

Developmental evolution of the delayed rectifier current IKs in canine heart appears dependent on the beta subunit minK.

Objectives: We tested the hypothesis that the developmental changes occurring in I(Kr) and I(Ks) can be explained by changes in the expression of ERG encoding I(Kr), and KCNQ1, the beta subunit minK, and the recently reported subunit FHL2 encoding I(Ks).

Background: The delayed rectifier current contributes importantly to the developmental evolution of the canine myocardial action potential. Specifically, in left ventricular epicardial myocytes, I(Ks) is absent and I(Kr) is the major repolarizing current until age 4 weeks.

Cardiac memory evolves with age in association with development of the transient outward current.

Background: Calcium-insensitive transient outward current (I(to)) is important to the development of cardiac memory (CM), which itself reflects the capacity of the heart to remodel electrophysiologically. We used cardiac pacing to test the hypothesis that CM evolution can be explained by developmental maturation of I(to).

Methods And Results: Acutely anesthetized dogs from 1 day old to adult were paced from the left ventricle (VP, n=29) or left atrial appendage (AP, n=12) to induce CM.

Molecular determinants of cardiac memory and their regulation.

Cardiac memory is characterized by an altered T-wave on electrocardiogram or vectorcardiogram recorded during sinus rhythm, having been induced by a preceding period of abnormal ventricular activation. This phenomenon reflects the dynamic ability of the heart to adapt to new circumstances, in this instance, an altered electrical activation pattern. The result of this adaptation is a changed electrical substrate expressed in cardiac repolarization.

Cardiac memory is associated with decreased levels of the transcriptional factor CREB modulated by angiotensin II and calcium.

Cardiac memory (CM) has short- (STCM) and long-term (LTCM) components modulated by calcium and angiotensin II. LTCM is associated with reduced Ito and Kv4.3 mRNA levels.

Role of L-type calcium channels in pacing-induced short-term and long-term cardiac memory in canine heart.

Background: We tested the hypothesis that ICa,L is important to the development of cardiac memory.

Methods And Results: The effects of L-type Ca2+ channel blockade and beta-blockade were tested on acutely anesthetized and on chronically instrumented, conscious dogs. Short-term memory (STM) was induced by 2 hours of ventricular pacing and long-term memory (LTM) by ventricular pacing for 21 days.

Tachycardia induced electrical remodeling of the atria and the autonomic nervous system in goats.

Atrial fibrillation (AF) shortens the atrial effective refractory period (AERP). To investigate the role of the autonomic nervous system during this so-called electrical remodeling of the atria (ERA) and during recovery from ERA we analyzed heart rate variability (HRV). In 12 goats atrioventricular (300:150 beats/min) pacing was performed for 24 hours, interrupted at 4, 8, 16, and 24 hours for recording of 500 atrial (AA) intervals during sinus rhythm and measurement of the AERP(430ms) at 7.

Digoxin delays recovery from tachycardia-induced electrical remodeling of the atria.

Background: Atrial fibrillation (AF) induces electrical remodeling, which is thought to be responsible for the low success rate of antiarrhythmic treatment in AF of longer duration. Electrical remodeling seems to be related to tachycardia-induced intracellular calcium overload. Due to its vagomimetic action, digoxin is widely used to control the ventricular rate during AF, but it also increases intracellular calcium.