[Task Force Dyspnoe unit (DU)]. / Task Force Dyspnoe Unit (DU).

Acute dyspnoea is one of the most common internal medicine symptoms in the emergency department. It arises from an acute illness or from the exacerbation of a chronic illness. Symptom-related emergency structures and corresponding structural guidelines already exist in the stroke and chest pain units for dealing with the leading symptoms of acute stroke and acute chest pain. These are lacking in Germany for the key symptom of dyspnoea, although the benefits of these structures have already been proven in other countries. The German Society for Pneumology and Respiratory Medicine (DGP) has now set up a task force together with the Association of Pneumology Clinics (VPK), in order to deal with the topic and develop appropriate structural guidelines for such "dyspnoea units" in Germany. At the end of the process, the certification of such units at German hospitals is optional.

Lung Deposition Using the Respimat® Soft Mist™ Inhaler Mono and Fixed-Dose Combination Therapies: An In Vitro/In Silico Analysis.

Tiotropium and olodaterol are mainstay treatments for chronic obstructive pulmonary disease (COPD) and yield important clinical improvements, especially when used in fixed-dose combination. Whilst previous studies have shown consistent delivery of tiotropium to the lungs with the Respimat® inhaler, no such study has been carried out for olodaterol or the components of their fixed-dose combination (TIO/OLO). Combining in vitro and in silico models, we measured the amount of drug retained in the mouth-throat area, entering the trachea and reaching the lung periphery. We applied a hybrid deposition model that considered the experimentally determined output of an Alberta throat model (in vitro - dose to lung) combined with a computational fluid dynamic model of the lungs (in silico). Regardless of the COPD breathing pattern, ≥50% of the nominal dose of either tiotropium, olodaterol, or TIO and OLO in the fixed-dose combination reached the lung. Of the dose reaching the lungs, greater than 50% is deposited in the lung periphery (from generation 8 onwards). Our study demonstrated that aerosol delivery via the Respimat inhaler achieved high deposition deep into the lung periphery with all formulations evaluated.

Position Paper for the State-of-the-Art Application of Respiratory Support in Patients with COVID-19.

Against the background of the pandemic caused by infection with the SARS-CoV-2 virus, the German Respiratory Society has appointed experts to develop therapy strategies for COVID-19 patients with acute respiratory failure (ARF). Here we present key position statements including observations about the pathophysiology of (ARF). In terms of the pathophysiology of pulmonary infection with SARS-CoV-2, COVID-19 can be divided into 3 phases. Pulmonary damage in advanced COVID-19 often differs from the known changes in acute respiratory distress syndrome (ARDS). Two types (type L and type H) are differentiated, corresponding to early- and late-stage lung damage. This differentiation should be taken into consideration in the respiratory support of ARF. The assessment of the extent of ARF should be based on arterial or capillary blood gas analysis under room air conditions, and it needs to include the calculation of oxygen supply (measured from the variables of oxygen saturation, hemoglobin level, the corrected values of Hüfner's factor, and cardiac output). Aerosols can cause transmission of infectious, virus-laden particles. Open systems or vented systems can increase the release of respirable particles. Procedures in which the invasive ventilation system must be opened and endotracheal intubation carried out are associated with an increased risk of infection. Personal protective equipment (PPE) should have top priority because fear of contagion should not be a primary reason for intubation. Based on the current knowledge, inhalation therapy, nasal high-flow therapy (NHF), continuous positive airway pressure (CPAP), or noninvasive ventilation (NIV) can be performed without an increased risk of infection to staff if PPE is provided. A significant proportion of patients with ARF present with relevant hypoxemia, which often cannot be fully corrected, even with a high inspired oxygen fraction (FiO2) under NHF. In this situation, the oxygen therapy can be escalated to CPAP or NIV when the criteria for endotracheal intubation are not met. In ARF, NIV should be carried out in an intensive care unit or a comparable setting by experienced staff. Under CPAP/NIV, a patient can deteriorate rapidly. For this reason, continuous monitoring and readiness for intubation are to be ensured at all times. If the ARF progresses under CPAP/NIV, intubation should be implemented without delay in patients who do not have a "do not intubate" order.

[Spacer, Aerosol Therapy through Space and Time]. / Spacer, Aerosoltherapie durch Raum und Zeit.

AIM OF THE LITERATURE REVIEW: Within this review, results of a literature analysis on the application of spacers with pressurized metered dose inhalers (pMDI) are described and evaluated. METHODS: Next to an extensive revision on effects of spacers, the impacts of current guidelines and the conditions for product authorisations on the use of spacers are described which result from the interplay of characteristics from dose inhalers with a spacer. RESULTS: Spacers are generally useful to avoid coordination problems concerning the actuation of a pMDI at the beginning of an inhalation. Furthermore, in comparison to the pMDI application without a spacer a reduced mouth-throat deposition is applicable to all pMDI spacer combinations. However, some new pMDI release the aerosol in a quality that may not necessarily require a spacer to avoid a high drug deposition in the mouth-throat area as the aerosol quality will not be greatly improved with a spacer. The delivered mass of the active ingredient as well as the aerosol quality released from a spacer vary substantially with the use of different spacers. A change of spacer while using the same dose inhaler can maximally result in a doubling or halving of the quantity of the active ingredient applied. These facts are nowadays considered by the European regulatory agency. CONCLUSION: If a spacer application is intended for pMDIs that were developed and approved after 2009, the correspondent SMP (Summary of Product Characteristics) should at least make one specific recommendation for a spacer that should be based upon relevant in vitro data or additional in vivo data. If a different spacer than the recommended one is used, the effectively applied dose cannot be correctly anticipated. This should be considered when choosing a spacer.

[Spacer, Aerosol Therapy through Space and Time]. / Spacer, Aerosoltherapie durch Raum und Zeit.

Aim of the literature review Within this review, results of a literature analysis on the application of spacers with pressurized metered dose inhalers (pMDI) are described and evaluated. Methods Next to an extensive revision on effects of spacers, the impacts of current guidelines and the conditions for product authorisations on the use of spacers are described which result from the interplay of characteristics from dose inhalers with a spacer. Results Spacers are generally useful to avoid coordination problems concerning the actuation of a pMDI at the beginning of an inhalation. Furthermore, in comparison to the pMDI application without a spacer a reduced mouth-throat deposition is applicable to all pMDI spacer combinations. However, some new pMDI release the aerosol in a quality that may not necessarily require a spacer to avoid a high drug deposition in the mouth-throat area as the aerosol quality will not be greatly improved with a spacer. The delivered mass of the active ingredient as well as the aerosol quality released from a spacer vary substantially with the use of different spacers. A change of spacer while using the same dose inhaler can maximally result in a doubling or halving of the quantity of the active ingredient applied. These facts are nowadays considered by the European regulatory agency. Conclusion If a spacer application is intended for pMDIs that were developed and approved after 2009, the correspondent SMP (Summary of Product Characteristics) should at least make one specific recommendation for a spacer that should be based upon relevant in vitro data or additional in vivo data. If a different spacer than the recommended one is used, the effectively applied dose cannot be correctly anticipated. This should be considered when choosing a spacer.

Hypoxic, anemic and cardiac hypoxemia: When does tissue hypoxia begin? / Hypoxische, anämische und kardial bedingte Hypoxämie: Wann beginnt die Hypoxie im Gewebe?

In case of hypoxemia, the oxygen content is often still in the lower normal range, so that there is no hypoxia in the tissue. If the hypoxia-threshold is reached in the tissue in hypoxic, anemic and also cardiac-related hypoxemia, identical counterregulations occur in the cell metabolism, regardless of the cause of hypoxemia. In clinical practice, this pathophysiologic fact is sometimes ignored, although depending on the cause of hypoxemia, assessment and therapy vary widely. While restrictive and generally accepted rules are specified in the transfusion guidelines for anemic hypoxemia, in the case of hypoxic hypoxia, the indication for invasive ventilation is made very early. The clinical assessment and indication are limited to the parameters oxygen saturation, oxygen partial pressure and oxygenation index. During the corona pandemic, misinterpretations of pathophysiology have become evident and may have led to unnecessary intubations. However, there is no evidence for the treatment of hypoxic hypoxia with ventilation. This review addresses the pathophysiology of the different types of hypoxia focusing on the problems associated with intubation and ventilation in the intensive care unit.

A retrospective database analysis on persistence with inhaled corticosteroid therapy: comparison of two dry powder inhalers during asthma treatment in Germany.

BACKGROUND: Asthma is one of the most common chronic diseases worldwide. Patient persistence with treatment is essential to achieve sufficient outcomes, in particular to avoid exacerbations. OBJECTIVE: To investigate inhaled corticosteroid (ICS) therapy with two different inhalers (Novolizer® and Turbuhaler®) by comparing persistence, concomitant use of additional asthma medication and occurrence of exacerbations in real life. STUDY DESIGN: A retrospective analysis of prescription data from outpatient treatment was performed using the IMS Disease Analyzer. It provides longitudinal anonymized patient data from ~ 3,000 office-based physicians in Germany. Treatment persistence of asthma patients (ICD 10 code: J45) using 200 µg budesonide either via Novopulmon®/Budecort® (Novolizer group = NOV) or Pulmicort® (Turbuhaler group = TUR) was compared. Eligible patients hadthe first prescription of ICS medication (index day) between June 2001 and September 2007 and a data history available for at least twelve months before and after the index day. RESULTS: Analysis of 1,780 NOV and 664 TUR patients revealed that 1 year after index day, 89% NOV patients remained on their ICS compared to 85% TUR patients. NOV patients changed significantly less often and later to another ICS (p = 0.0108; log-rank test). Significantly fewer NOV patients switched temporarily or permanently to another ICS during the observation time (NOV group: 14.7%; TUR group: 20.8%; p = 0.0002, log-rank test). On average, NOV and TUR patients received comparable prescriptions of short acting medication (NOV more SABA, TUR more formoterol). There was a trend towards fewer prescriptions of systemic corticosteroids in NOV patients. CONCLUSIONS: Our results suggest better therapy persistence with NOV compared to TUR during asthma treatment in Germany. This can be a marker of better compliance and may contribute to prevent exacerbations. However, the number of exacerbations per patient year in the NOV group (0.12) compared to the TUR group (0.18) was not statically significantly lower (p = 0.4096).

Conservative management of COVID-19 associated hypoxaemia.

This correspondence argues that happy hypoxaemic patients should not be intubated as long as they remain happy https://bit.ly/3csrpWO.

Conservative management of COVID-19 associated hypoxaemia.

Treat hypoxia, not hypoxaemia https://bit.ly/3hwPLCL.

Conservative management of COVID-19 associated hypoxaemia.

BACKGROUND: Invasive mechanical ventilation of hypoxaemic coronavirus disease 2019 (COVID-19) patients is associated with mortality rates of >50%. We evaluated clinical outcome data of two hospitals that agreed on a predefined protocol for restrictive use of invasive ventilation where the decision to intubate was based on the clinical presentation and oxygen content rather than on the degree of hypoxaemia. METHOD: Data analysis was carried out of patients with positive PCR-testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), typical history, and symptoms and pulmonary infiltrates who exhibited oxygen saturation values of <93%. RESULTS: We identified 78 patients who met the inclusion criteria. The oxygen saturation nadir was 84.4±6.5% for the whole group. 53 patients (68%) received nasal oxygen (group 1), 17 patients (22%) were treated with nasal high-flow continuous positive airway pressure (CPAP), noninvasive ventilation or a combination thereof (group 2), and eight patients (10%) were intubated (group 3). The Horovitz index was 216±8 for group 1, 157±13 for group 2 and 106±15 for group 3. Oxygen content was 14.5±2.5, 13.4±1.9 and 11.6±2.6 mL O2·dL-1 for the three respective groups. Overall mortality was 7.7%; the mortality of intubated patients was 50%. Overall, 93% of patients could be discharged on room air. CONCLUSION: Permissive hypoxaemia where decisions for the level of respiratory therapy were based on the clinical presentation and oxygen content resulted in low intubation rates, low overall mortality and a low number of patients who require oxygen after discharge.

Case characteristics, resource use, and outcomes of 10 021 patients with COVID-19 admitted to 920 German hospitals: an observational study.

Background Nationwide, unbiased, and unselected data of hospitalised patients with COVID-19 are scarce. Our aim was to provide a detailed account of case characteristics, resource use, and outcomes of hospitalised patients with COVID-19 in Germany, where the health-care system has not been overwhelmed by the pandemic. METHODS: In this observational study, adult patients with a confirmed COVID-19 diagnosis, who were admitted to hospital in Germany between Feb 26 and April 19, 2020, and for whom a complete hospital course was available (ie, the patient was discharged or died in hospital) were included in the study cohort. Claims data from the German Local Health Care Funds were analysed. The data set included detailed information on patient characteristics, duration of hospital stay, type and duration of ventilation, and survival status. Patients with adjacent completed hospital stays were grouped into one case. Patients were grouped according to whether or not they had received any form of mechanical ventilation. To account for comorbidities, we used the Charlson comorbidity index. FINDINGS: Of 10 021 hospitalised patients being treated in 920 different hospitals, 1727 (17%) received mechanical ventilation (of whom 422 [24%] were aged 18-59 years, 382 [22%] were aged 60-69 years, 535 [31%] were aged 70-79 years, and 388 [23%] were aged ≥80 years). The median age was 72 years (IQR 57-82). Men and women were equally represented in the non-ventilated group, whereas twice as many men than women were in the ventilated group. The likelihood of being ventilated was 12% for women (580 of 4822) and 22% for men (1147 of 5199). The most common comorbidities were hypertension (5575 [56%] of 10 021), diabetes (2791 [28%]), cardiac arrhythmia (2699 [27%]), renal failure (2287 [23%]), heart failure (1963 [20%]), and chronic pulmonary disease (1358 [14%]). Dialysis was required in 599 (6%) of all patients and in 469 (27%) of 1727 ventilated patients. The Charlson comorbidity index was 0 for 3237 (39%) of 8294 patients without ventilation, but only 374 (22%) of 1727 ventilated patients. The mean duration of ventilation was 13·5 days (SD 12·1). In-hospital mortality was 22% overall (2229 of 10 021), with wide variation between patients without ventilation (1323 [16%] of 8294) and with ventilation (906 [53%] of 1727; 65 [45%] of 145 for non-invasive ventilation only, 70 [50%] of 141 for non-invasive ventilation failure, and 696 [53%] of 1318 for invasive mechanical ventilation). In-hospital mortality in ventilated patients requiring dialysis was 73% (342 of 469). In-hospital mortality for patients with ventilation by age ranged from 28% (117 of 422) in patients aged 18-59 years to 72% (280 of 388) in patients aged 80 years or older. INTERPRETATION: In the German health-care system, in which hospital capacities have not been overwhelmed by the COVID-19 pandemic, mortality has been high for patients receiving mechanical ventilation, particularly for patients aged 80 years or older and those requiring dialysis, and has been considerably lower for patients younger than 60 years. FUNDING: None.

Effect of incorrect use of dry powder inhalers on management of patients with asthma and COPD.

BACKGROUND: Incorrect usage of inhaler devices might have a major influence on the clinical effectiveness of the delivered drug. This issue is poorly addressed in management guidelines. METHODS: This article presents the results of a systematic literature review of studies evaluating incorrect use of established dry powder inhalers (DPIs) by patients with asthma or chronic obstructive pulmonary disease (COPD). RESULTS: Overall, we found that between 4% and 94% of patients, depending on the type of inhaler and method of assessment, do not use their inhalers correctly. The most common errors made included failure to exhale before actuation, failure to breath-hold after inhalation, incorrect positioning of the inhaler, incorrect rotation sequence, and failure to execute a forceful and deep inhalation. Inefficient DPI technique may lead to insufficient drug delivery and hence to insufficient lung deposition. As many as 25% of patients have never received verbal inhaler technique instruction, and for those that do, the quality and duration of instruction is not adequate and not reinforced by follow-up checks. CONCLUSIONS: This review demonstrates that incorrect DPI technique with established DPIs is common among patients with asthma and COPD, and suggests that poor inhalation technique has detrimental consequences for clinical efficacy. Regular assessment and reinforcement of correct inhalation technique are considered by health professionals and caregivers to be an essential component of successful asthma management. Improvement of asthma and COPD management could be achieved by new DPIs that are easy to use correctly and are forgiving of poor inhalation technique, thus ensuring more successful drug delivery.

The Pharmacological Treatment of Chronic Obstructive Pulmonary Disease.

BACKGROUND: Inhaled corticosteroids (ICS) are markedly less effective against chronic obstructive pulmonary disease (COPD) than against asthma, and also have worse side effects. Whether ICS should be used to treat COPD is currently a matter of debate. METHODS: This review is based on pertinent articles retrieved by a selective search in PubMed and the Excerpta Medica Database (EMBASE) carried out in May 2015. We analyzed clinical trials of ICS for the treatment of COPD with a duration of at least one year, along with meta-analyses and COPD guidelines. RESULTS: ICS lower the frequency and severity of COPD exacerbations in comparison to monotherapy with a long-acting ß2-agonist, but have no effect on mortality. Compared to placebo, ICS monotherapy lessens the decline of forced expiratory volume in one second (FEV1) over one year by merely 5.80 mL (statistically insignificant; 95% confidence interval: [-0.28; 11.88]) and only marginally improve quality of life. ICS use in patients with COPD increases the risk of pneumonia. A combination of ICS with a long-acting bronchodilator improves FEV1 by 133 mL [105; 161] and lowers the frequency of severe exacerbations by 39% . The frequency of exacerbations is lowered mainly in patients who have many exacerbations; thus, ICS treatment is suitable only for patients with grade III or IV COPD. CONCLUSION: ICS monotherapy has no clinically useful effect on pulmonary function in COPD. The main form of drug treatment for COPD is with broncho - dilators, either alone or in combination with ICS. ICS can be given to patients with grade III or IV COPD to make exacerbations less frequent. Patients with an asthma-COPD overlap syndrome (ACOS) can benefit from ICS treatment.

[Importance of air-trapping in patients with COPD. Pathophysiological principle]. / Bedeutung der Uberblähung bei COPD. Pathophysiologische Grundlagen.

Exertional dyspnea is the leading symptom in patients with COPD. The main causes are progressive weakness of skeletal muscles, reduction of diffusing capacity in emphysema and above all dynamic hyperinflation as a result of the collapsibility of bronchioli with expiratory flow limitation. The exercise-induced hyperinflation leads to a reduction of inspiratory capacity. Therefore, patients are unable to increase the minute volume under exercise. The inadequate ventilatory answer to an increased ventilatory drive is perceived as dyspnea. The inhalation of long-acting bronchodilators reduces hyperinflation and increases exercise capacity.

[Inhalation therapy: techniques and use of devices--main mistakes]. / Inhalative Atemwegstherapie: Technik und Handhabung der Devices--häufigste Fehler.

Inhalation therapy is the main route of drug administration in patients with obstructive pulmonary diseases. The efficacy of inhalation therapy depends on several factors including the individual choice of the device, its correct use, and patients' compliance. Metered-dose inhalers and dry-powder inhalers require completely different inhalation maneuvers. Poor inhalation technique is associated with poorer disease control. Appropriate education when prescribing inhalation devices and evaluation of inhalation technique are of overwhelming importance.

Comparing usability of NEXThaler(®) with other inhaled corticosteroid/long-acting ß2-agonist fixed combination dry powder inhalers in asthma patients.

BACKGROUND: Inhaler mishandling is a common issue among patients suffering from asthma and is associated with poor clinical outcomes and greater consumption of health-care resources. Ease of use can improve inhaler technique and, possibly, patients' preference for their inhaler device, which in turn may lead to better adherence to therapy. METHODS: This study investigated usability characteristics of NEXThaler(®) versus two other dry powder inhalers (DPIs; Diskus(®) and Turbuhaler(®)). Sixty-six adult patients with asthma (mean age 42.9±17.7 years) and with no previous experience of using a DPI were included in a randomized crossover comparison of the three devices. The main measures of usability were the number of steps failed for each device and the number of people who were able to use the device successfully (effectiveness), the time it took patients to set up the device and the time to read the instructions for use (IFU; efficiency), and patient preferences (satisfaction). Inhaler technique was evaluated after the IFU leaflet was read. RESULTS: NEXThaler was found to be superior to the other two DPIs in terms of the number of device use failures (p<0.001), time to set up (p<0.001), and time to read IFU (p<0.001). Additionally, the proportion of participants who completed a successful inhalation without any errors at all was significantly higher for NEXThaler than for Diskus and Turbuhaler (p<0.001). Patients rated NEXThaler as the easiest to use and most preferred inhaler to own (p<0.001). CONCLUSIONS: NEXThaler displayed better usability compared with Diskus and Turbuhaler. The improved usability and higher satisfaction with the device may contribute to increased patient adherence to asthma treatment.

Delivery characteristics of a low-resistance dry-powder inhaler used to deliver the long-acting muscarinic antagonist glycopyrronium.

OBJECTIVES: The long-acting muscarinic antagonist (LAMA) glycopyrronium (NVA237) has recently been approved as a once-daily treatment for COPD. The objectives of this study were to determine the dose delivery characteristics of glycopyrronium and compare them with those of the LAMA tiotropium, both delivered by their respective capsule-based dry-powder inhalers (DPIs). RESEARCH DESIGN AND METHODS: Seven inhalation profiles derived from patients with moderate and severe COPD were reproduced to determine the aerodynamic particle size distribution of glycopyrronium delivered by the Breezhaler device, a low-resistance DPI†. Theoretical respiratory tract deposition was estimated using a semi-empirical model for healthy lungs. These results were compared with those of tiotropium delivered by the high-resistance HandiHaler‡ device obtained in a previous study using the same set of inhalation profiles. Study limitations are that fine particle fraction (FPF) and particle size are generated by the inhalers are not a direct measure of lung deposition, and the bronchodilator effect of inhaled drugs does not depend solely upon the percentage of the total dose that reaches the lung. RESULTS: The mean FPF (≤4.7 µm) was 42.6% of the nominal dose (which refers to the content of the capsule) for glycopyrronium and 9.8% for tiotropium while the mass median aerodynamic diameter (MMAD) was 2.8 µm and 3.9 µm for glycopyrronium and tiotropium, respectively. The mean estimated intrathoracic drug deposition as a percentage of the mean dose delivered to the Next Generation Impactor was 39% for glycopyrronium and 22% for tiotropium. CONCLUSIONS: The glycopyrronium capsule-based DPI delivered a higher FPF and greater and more consistent intrathoracic deposition irrespective of age and disease severity compared to the tiotropium capsule-based DPI, suggesting that it may be suitable for use by patients with a wide range of COPD severities.