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). Patients that started with anti-IL-5/5Ra biologics and completed the work productivity and activity improvement questionnaire, were included. Study and patient characteristics were compared between the employed and unemployed patients. Work productivity and activity impairment are related to accompanying improvements in clinical outcomes. RESULTS: At baseline, 91 of 137 patients (66%) were employed which remained stable throughout the follow-up period. Patients in the working age category were younger and had significantly better asthma control (p = 0.02). Mean overall work impairment due to health decreased significantly from 25.5% (SD2.6) to 17.6% (SD 2.8) during 12 months anti-IL-5/5Ra biologics treatment (P = 0.010). There was a significant association between ACQ6 and overall work improvement after targeted therapy (ß = 8.7, CI 2.1-15.4, P = 0.01). The improvement of asthma control of 0.5 points on the asthma Control Questionnaire was associated with an overall work impairment of -9%. CONCLUSIONS: Work productivity and activity in severe eosinophilic asthma improved after starting anti-IL-5/5Ra biologics. Clinically relevant improvement in asthma control was associated with an overall work impairment score of -9% in this study.

COVID-19 in critically ill patients in North Brabant, the Netherlands: Patient characteristics and outcomes.

PURPOSE: Since the SARS-CoV-2 pandemic, countries are overwhelmed by critically ill Coronavirus disease 2019 (COVID-19) patients. As ICU capacity becomes limited we characterized critically ill COVID-19 patients in the Netherlands. METHODS: In this case series, COVID-19 patients admitted to the ICU of the Jeroen Bosch Hospital were included from March 9 to April 7, 2020. COVID-19 was confirmed by a positive result by a RT-PCR of a specimen collected by nasopharyngeal swab. Clinical data were extracted from medical records. RESULTS: The mean age of the 50 consecutively included critically ill COVID-19 patients was 65 ± 10 years, the mean BMI was 29 ± 4.7 and 66% were men. Seventy-eight percent of patients had ≥1 comorbidity, 34% had hypertension. Ninety-six percent of patients required mechanical ventilation and 80% were ventilated in prone position. Venous thromboembolism was recognized in 36% of patients. Seventy-four percent of patients survived and were successfully discharged from the ICU, the remaining 26% died (median follow up 86 days). The length of invasive ventilation in survivors was 15 days (IQR 12-31). CONCLUSIONS: The survival rate of COVID-19 critically ill patients in our population is considerably better than previously reported. Thrombotic complications are commonly found and merit clinical attention. TRIAL REGISTRATION NUMBER: NL2020.07.04.01.

[Practice guideline 'Medical treatment of COPD']. / Richtlijn 'Medicamenteuze behandeling van COPD'.

The practice guideline 'Medical treatment of COPD' completes the practice guideline for diagnostics and non-medicinal treatment. Patients with stable chronic obstructive pulmonary disease (COPD) and minor complaints can be treated with short-acting beta-2-adrenoceptor agonists or anticholinergics or a combination of these. In cases of insufficient clinical control of the condition or if patients use their medication for maintenance, a long-acting bronchodilator is the drug of choice. In patients with severe or very severe COPD (stage III-IV of the criteria of the Global Initiative for Obstructive Lung Disease (GOLD) or with cardiac comorbidity, there is a slight preference for the long-acting anticholinergic tiotropium. Inhaled corticosteroids (ICS) reduce the exacerbation frequency in patients with moderate to severe or very severe COPD (GOLD stage II-IV) and recurrent exacerbations. A combination of ICS with long-acting beta-2-adrenoceptor agonists (LABA) is prescribed in patients with GOLD stage III-IV with at least 2 exacerbations in the past year, a deterioration of the quality of life and with symptoms, if treatment with a LABA alone or an ICS alone results in insufficient improvement. Anticholinergics and beta-2-adrenoceptor agonists have a similar effect on bronchodilation in patients with an acute exacerbation of COPD. If improvement is inadequate, patients with an exacerbation should be treated with prednisolone 30 mg for a period of 7 to 14 days. In outpatients and clinical patients with an exacerbation ofCOPD, an antibiotic is added to prednisolone in very poor lung function (forced expiratory volume in 1 second (FEV1) < 30%) or another risk factor of a severe disease course, such as a respiratory rate > or = 30/min, a systolic blood pressure < 90 mmHg, and disorientation in time, place or person.

Ventolin Diskus and Inspyril Turbuhaler: an in vitro comparison.

Dose delivery (total emitted dose, or TED) from dry powder inhalers (DPIs), pulmonary deposition, and the biological effects depend on drug formulation and device and patient characteristics. The aim of this study was to measure, in vitro, the relationship between parameters of inhalation profiles recorded from patients, the TED and fine particle mass (FPM) of Diskus and Turbuhaler inhalers. Inhalation profiles (IPs) of 25 patients, a representative sample of a wide range of 1500 IPs generated by 10 stable asthmatics, 3 x 16 (mild/moderate/severe) COPD patients and 15 hospitalized patients with an exacerbation asthma or COPD, were selected for each device. These 25 IPs were input IPs for the Electronic Lung (a computerdriven inhalation simulator) to determine particle size distribution from Ventolin Diskus and Inspyril Turbuhaler. The TED and FPM of Diskus and FPM of Turbuhaler were affected by the peak inspiratory flow (PIF) and not by slope of the pressure-time curve, inhaled volume and inhalation time. This flow-dependency was more marked at lower flows (PIF < 40 L/min). Both the TED and FPM of Diskus were significantly higher as compared to those of the Turbuhaler [mean (SD) TED(_diskus) (%label claim) 83.5 (13.9) vs. TED(_turbuhaler) (72.5 (11.1) (p = 0.004), FPM(_diskus) (%label claim) 36.8 (9.8) vs FPM(_turbuhaler) (28.7 (7.7) (p < 0.05)]. The TED and FPM of Diskus and FPM of Turbuhaler were affected by PIF, the flow-dependency being greater at PIF values below 40 L/min. Lower PIFs occurred more often when using Turbuhaler than Diskus, since Turbuhaler have a higher resistivity, requires substantially higher pressure in order to generate the same flow as Diskus. TED, dose consistency and the FPM were higher for Diskus as compared to Turbuhaler. The flow dependency of TED and FPM was substantially influenced by inhalation profiles when not only profiles of the usual outpatient population were included but also the real outliers from exacerbated patients.

Tremor side effects of salbutamol, quantified by a laser pointer technique.

OBJECTIVE: To study tremor side effects of salbutamol an easily applicable, quick and low-priced method is needed. A new method using a commercially available, pen-shaped laser pointer was developed. Aim of the study was to determine sensitivity, reproducibility, reference values and the agreement with a questionnaire. METHODS: Tremor was measured using a laser pointer technique. To determine sensitivity we assessed tremor in 44 patients with obstructive lung disease after administration of cumulative doses of salbutamol. Subjects were asked to aim at the centre of a target, subdivided in concentric circles, from 5 m distance. The circle in which the participant succeeded to aim was recorded in millimetres radius. In another series of measurements, reproducibility and reference values of the tremor was assessed in 65 healthy subjects in three sessions, at 9 a.m., 4 p.m. and 9 a.m., respectively, 1 week later. Postural tremor was measured with the arm horizontally outstretched rest tremor with the arm supported by an armrest and finally tremor was measured after holding a 2-kg weight until exhaustion. Inter-observer variability was measured in a series of 10 healthy subjects. Tremor was measured simultaneously by two independent observers. RESULTS: Salbutamol significantly increased tremor severity in patients in a dose-dependent way. Within healthy adults no age-dependency could be found (b = 0.262 mm/year; P = 0.72). There was no agreement between the questionnaire and tremor severity (r = 0.093; P = 0.53). Postural tremor showed no significant difference between the first and third session (P = 0.07). Support of the arm decreased tremor severity, exhaustion increased tremor severity significantly. A good agreement was found between two independent observers (interclass correlation coefficient 0.72). DISCUSSION: Quantifying tremor by using an inexpensive laser pointer is, with the exception of children (<12 years) a sensitive and reproducible method.