[Diagnosis and treatment of asthma: a guideline for respiratory specialists 2023 - published by the German Respiratory Society (DGP) e. V.] / S2k-Leitlinie zur fachärztlichen Diagnostik und Therapie von Asthma 2023.

The management of asthma has fundamentally changed during the past decades. The present guideline for the diagnosis and treatment of asthma was developed for respiratory specialists who need detailed and evidence-based information on the new diagnostic and therapeutic options in asthma. The guideline shows the new role of biomarkers, especially blood eosinophils and fractional exhaled NO (FeNO), in diagnostic algorithms of asthma. Of note, this guideline is the first worldwide to announce symptom prevention and asthma remission as the ultimate goals of asthma treatment, which can be achieved by using individually tailored, disease-modifying anti-asthmatic drugs such as inhaled steroids, allergen immunotherapy or biologics. In addition, the central role of the treatment of comorbidities is emphasized. Finally, the document addresses several challenges in asthma management, including asthma treatment during pregnancy, treatment of severe asthma or the diagnosis and treatment of work-related asthma.

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.

Home oxygen for moderate hypoxaemia in chronic obstructive pulmonary disease: a systematic review and meta-analysis.

BACKGROUND: Long-term oxygen therapy (LTOT) improves survival in patients with chronic obstructive pulmonary disease (COPD) and severe hypoxaemia. However, the best method of management of moderate hypoxaemia not qualifying for LTOT (including isolated nocturnal desaturation) is uncertain. We examined the effect of home oxygen (either LTOT or nocturnal oxygen therapy) on overall survival in patients with COPD and moderate hypoxaemia. METHODS: In this systematic review and meta-analysis, we searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, CINHAL, and Web of Science from database inception to Jan 13, 2022, for parallel-group randomised trials of long-term or nocturnal oxygen in patients with COPD and moderate daytime hypoxaemia or isolated nocturnal desaturation, or both. Control groups received usual care or ambient air through sham concentrators (placebo) throughout the study period. The primary outcome of interest was 3-year mortality. Crossover trials and trials of oxygen in severe hypoxaemia were excluded. Two reviewers applied inclusion and exclusion criteria to titles and abstracts and screened the full-text articles and reference lists of relevant studies. Aggregate data were extracted manually in duplicate using structured data collection forms. Methodological quality was assessed using the Cochrane Risk of Bias tool. Random-effects meta-analysis was used to pool individual studies. We considered the minimal clinically important difference for home oxygen to be a relative risk reduction in mortality at 3-year follow-up of 30-40%. The meta-analysis is registered on PROSPERO, CRD42021225372. FINDINGS: We identified 2192 studies and screened 1447 after removal of duplicates, of which 161 were subjected to full-text screening, and six were identified as being eligible for inclusion. These six randomised trials were published between 1992 and 2020 and the quality of evidence was high. In the primary meta-analysis (five trials; 1002 patients), we found the effect of home oxygen in reducing 3-year mortality to be small or absent (relative risk 0·91 [95% CI 0·72-1·16]; τ2 = 0·00), hence the lower limit of the 95% CI did not meet the prespecified minimal clinically important difference. INTERPRETATION: The results of our meta-analysis suggest that home oxygen probably makes little or no difference to 3-year mortality in patients with COPD and moderate hypoxaemia. The data do not support the widespread use of home oxygen in this patient population. FUNDING: None.

[Aerosol Therapy in Intensive Care Unit]. / Aerosoltherapie auf Intensivstation.

Inhalation therapy is a cornerstone especially in pulmonary diseases or comorbidities, either in invasive or noninvasive mechanical ventilation. In pediatric patients, mainly in respiratory failure of the premature born child inhalation of surfactant is crucial in the therapy. Additional drugs given by inhalation are antibiotics, mucoactive substances and drugs that treat pulmonary hypertension. This article describes main deposition mechanisms of inhalation therapies and presents recommendations for correct performance of inhalation therapy in invasively as well as noninvasively ventilated patients in ICU. Also safety aspects for patients and medical staff during aerosol therapy in the Corona pandemic era are discussed.

Bench testing of noninvasive ventilation masks with viral filters for the protection from inhalation of infectious respirable particles.

During the beginning of the SARS-CoV-2 pandemic, there was a shortage of masks and respirators for the protection of health care professionals. Masks for noninvasive ventilation (NIV) in combination with viral-proof filters, worn by healthcare workers, could serve as an alternative protection measure. We determined the simulated protection factor (SPF) of such devices in comparison to conventional surgical masks, N95, and FFP3 respirators. Masks and respirators were mounted on a ventilated mannequin head in a test-chamber. Isotonic saline containing 150 MBq 99mTC-DTPA (99mTc-diethylenetriamine pentaacetate (DTPA) was nebulized inside the box. The aerosol had a mass median aerodynamic diameter of 0.6 ± 0.4 µm. SPFs were measured using radioactive DTPA particles in the mannequin test system by calculating the ratio of unfiltered particles (Pu) and filtered particles (Pf) for each tested device (SPF = Pu/Pf). Simulated protection factors were 15.6 ± 3.6 for a ResMed AcuCare mask plus filter, 3.5 ± 0.2 for a ResMed Mirage Quattro FX mask plus filter, 9.5 ± 0.8 for a Loewenstein JOYCEclinc FF mask plus filter, 1.9 ± 0.2 for a surgical mask with a rubber band, 2.7 ± 0.7 for a surgical mask with ribbons, 2.3 ± 0.3 for an FFP3 respirator, and 3.6 ± 1.3 for an N95 respirator. The ResMed AcuCare and the Loewenstein JOYCEclinic FF mask were more effective than any other of the tested devices (p < 0.001). In conclusion, masks normally used for NIV with viral-proof filters can effectively filter respirable particles.

[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.

Impact of hypobaric flight simulation on walking distance and oxygenation in COPD patients.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a disease that compromises fitness to fly. OBJECTIVE: To investigate, whether hypobaric mid-distance flight simulation limits exercise endurance in COPD patients. METHODS: Patients with COPD GOLD stages 2-4 were challenged by hypobaric flight simulation. Patients completed 6-minute walking distances before and after the simulation test. Pulse oximetry and Borg dyspnea scale were measured every 30 min during the test. RESULTS: Thirty-five patients were included in the study. The distance of the 6-min walking exercise decreased from 343 ± 93 m to 308 ± 101 m (p < 0.0001). The oxygen saturation nadir for the whole group was 72.2% ± 9.1%. The Borg-dypnea-score did not correlate with oxygen desaturation (R-square 0.009, p > 0.05). CONCLUSIONS: A 3-h hypobaric flight simulation compromises exercise endurance by 35 m or 10%. Hypoxia was well tolerated and more liberal recommendations might by justifiable since hypoxemia appears to be unrelated to dyspnea perception.

Assessment of the Power Required for Optimal Use of Current Inhalation Devices.

Background: Inhalation of medications is the cornerstone in the treatment of patients with lung diseases. A variety of inhalation devices exists and each device has specific requirements to achieve optimum inhalation of the drug. The goal of this study was to establish a clear overview on performance requirements of standard inhalation devices that should be met by the patient's breathing power and to develop a new method to measure the individual performance data. Materials and Methods: An optimum and still acceptable required breathing power (P in watts) was calculated for each device with the aid of individual device flow rates (determined by a literature search) and the flow resistances (by measuring the pressure drop over the different inhalation devices). For the in vivo part of the study, peak inspiratory flow and peak inspiratory pressure drop were measured in 21 adult patients with asthma or chronic obstructive pulmonary disease and healthy volunteers and the peak inspiratory power (PIPO in watts) was calculated. Results: Nearly no power is needed to achieve optimum results when using pressurized metered dose inhalers. For dry powder inhalers, the required power depends on the specific inhalation device. Conclusions: Inhalation devices impose differing demands on the inspiratory breathing power of patients. To ensure adequate use of the different devices, a cheap and simple assessment of patients' PIPO may be one option.

[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.

Inspiratory muscle training during rehabilitation in successfully weaned hypercapnic patients with COPD.

BACKGROUND: This study is aimed to evaluate the effect of inspiratory muscle training (IMT) added to rehabilitation in patients with chronic obstructive pulmonary disease (COPD) who remain hypercapnic and use non-invasive ventilation after successful weaning. METHODS: Patients received rehabilitation and were randomized to inspiratory muscle or sham training for 4 weeks. The primary outcome was distance walked within 6 min. Secondary outcomes were inspiratory muscle strength, endurance, lung function, and blood gas levels. RESULTS: Twenty-nine patients participated in this study. Walking distance of the sham group increased from 93 ± 52 m at baseline to 196 ± 85 m at week 4 (p = 0.019, 95% CI: 11-196 m). Patients in the IMT group significantly improved their walking distance from 94 ± 32 to 290 ± 75 m (p < 0.0001 [107-286 m]; p = 0.04 [3-186 m] for between-group comparison). Patients in the IMT group increased their maximal inspiratory pressure from -35 ± 8 to -55 ± 11 cmH2O (p = 0.001; -6 to -33 cmH2O), while the increase in the sham group failed to reach significance (-29 ± 10 to -37 ± 13 cmH2O [-22 to 6 cmH2O]). Inspiratory power increased from 9.6 ± 5.4 to 20.7 ± 9.7 joules/min (2.6-19.5 joules/min, p = 0.003) in the IMT group, while no significant change occurred in the sham group (7.6 ± 4.2 joules/min at study entry and 11.1 ± 6.9 joules/min [-5.2-12.3 joules/min] at study end). CONCLUSIONS: Rehabilitation of successfully weaned patients with COPD and persistent hypercapnia significantly improves functional exercise capacity. Additional IMT significantly enhances functional exercise capacity and increases respiratory muscle strength and power.

Inhalation device requirements for patients' inhalation maneuvers.

BACKGROUND: Inhaled drugs are the mainstay of treatment for lung diseases such as asthma and chronic obstructive pulmonary disease. However, failure to use inhalation devices correctly can lead to a poorly controlled status. A vast number of inhalation devices exist and each device has specific requirements to achieve optimum inhalation of the drug. Currently, there is no overview of inhalation requirements considering all devices. This article presents a review of the literature on different inhalation device requirements and incorporates the data into a new inhalation flow algorithm. METHODS: Data from literature on commercially available inhalation devices were evaluated and parameters, such as inhalation flow rate, flow acceleration, inhalation volume, and inspiration time assessed for the required inhalation maneuver specific to the device. All agreed upon data points were used to develop an inhalation flow algorithm. RESULTS: The literature analysis revealed availability of robust data for the required inhalation flow characteristics for most devices and thus for the development of an algorithm. For those devices for which these parameters are not published, the minimum required flow criteria were defined based on published data regarding individual aspects of aerosol quality. CONCLUSIONS: This review provides an overview of inhalation devices available on the market regarding requirements for an acceptable inhalation maneuver and shows which goals should be achieved in terms of inhalation flows. The presented algorithm can be used to develop a new computer based measurement system which could help to test and train patients' individual inhalation maneuvers with their inhalation devices.

An international randomized study of a home-based self-management program for severe COPD: the COMET.

INTRODUCTION: Most hospitalizations and costs related to COPD are due to exacerbations and insufficient disease management. The COPD patient Management European Trial (COMET) is investigating a home-based multicomponent COPD self-management program designed to reduce exacerbations and hospital admissions. DESIGN: Multicenter parallel randomized controlled, open-label superiority trial. SETTING: Thirty-three hospitals in four European countries. PARTICIPANTS: A total of 345 patients with Global initiative for chronic Obstructive Lung Disease III/IV COPD. INTERVENTION: The program includes extensive patient coaching by health care professionals to improve self-management (eg, develop skills to better manage their disease), an e-health platform for reporting frequent health status updates, rapid intervention when necessary, and oxygen therapy monitoring. Comparator is the usual management as per the center's routine practice. MAIN OUTCOME MEASURES: Yearly number of hospital days for acute care, exacerbation number, quality of life, deaths, and costs.

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.

[Inhalation devices used in combination therapy in chronic airway disease]. / Inhalationsdevices in der modernen Kombinationstherapie chronischer Atemwegserkrankungen.

New fixed combinations of long acting ß2-agonists and anti-muscarinic agents have been launched in the therapy of chronic obstructive airway disease. The clinical benefit of the different drug combinations appears to be comparable. Differences however exist in the performance of the respective device. Proper training and repeated patient education is paramount for efficient therapy and appears to be more important than the choice of the drug itself.

Humidification of inspired oxygen is increased with pre-nasal cannula, compared to intranasal cannula.

BACKGROUND: Oxygen therapy is usually combined with a humidification device, to prevent mucosal dryness. Depending on the cannula design, oxygen can be administered pre- or intra-nasally (administration of oxygen in front of the nasal ostia vs cannula system inside the nasal vestibulum). The impact of cannula design on intra-nasal humidity, however, has not been investigated to date. OBJECTIVE: First, to develop a system, that samples air from the nasal cavity and analyzes the humidity of these samples. Second, to investigate nasal humidity during pre-nasal and intra-nasal oxygen application, with and without humidification. METHODS: We first developed and validated a sampling and analysis system to measure humidity from air samples. By means of this system we measured inspiratory air samples from 12 subjects who received nasal oxygen with an intra-nasal and pre-nasal cannula at different flows, with and without humidification. RESULTS: The sampling and analysis system showed good correlation to a standard hygrometer within the tested humidity range (r = 0.99, P < .001). In our subjects intranasal humidity dropped significantly, from 40.3 ± 8.7% to 35.3 ± 5.8%, 32 ± 5.6%, and 29.0 ± 6.8% at flows of 1, 2, and 3 L, respectively, when oxygen was given intra-nasally without humidification (P = .001, P < .001, and P < .001, respectively). We observed no significant change in airway humidity when oxygen was given pre-nasally without humidification. With the addition of humidification we observed no significant change in humidity at any flow, and independent of pre- or intranasal oxygen administration. CONCLUSIONS: Pre-nasal administration of dry oxygen achieves levels of intranasal humidity similar to those achieved by intranasal administration in combination with a bubble through humidifier. Pre-nasal oxygen simplifies application and may reduce therapy cost.

Handling of and preferences for available dry powder inhaler systems by patients with asthma and COPD.

The correct handling of dry powder inhalers (DPIs) is crucial for efficient therapy, and acceptance of the device can improve compliance. The handling of seven different dry powder inhalers was studied in 72 patients with asthma and chronic obstructive pulmonary disease (COPD). The aim of this study was to identify possible handling errors and investigate patient preferences. Patients inhaled twice with each inhaler; first after reading the device leaflet, and second after device handling was explained by the investigator. The investigator identified handling errors and critical handling errors, which might lead to insufficient or no dose delivery. Afterward, the patients selected their preferred device and judged different aspects of device handling. The lowest number of patients with critical handling errors was observed for the Diskus/Accuhaler, the highest numbers for the Jethaler and the Easyhaler (% of patients during first/second use): Diskus/Accuhaler 25%/13.9% (group A) and 38.9%/8.3% (group B); Clickhaler 50.0%/52.8%, Cyclohaler 58.3%/13.9%, Jethaler 66.7%/30.6% (group A) and Benosid N Inhaler 52.8%/22.2%, Novolizer 52.8%/25.0%, Easyhaler 72.2%/47.2% (group B). Device handling improved after instruction by the investigator. Device handling and preferences of patients closely correlated in this study. Both devices producing the lowest numbers of handling errors (Diskus/Accuhaler and Clickhaler) had the highest preference by the subjects (score from 1 = very good to 7 = very bad): Diskus/Accuhaler 2.21 (group A) and 2.02 (group B); Clickhaler 2.21, Cyclohaler 2.80, Jethaler 3.16 (group A); Novolizer 2.33, Easyhaler 2.37, Benosid N Inhaler 2.43 (group B). Critical handling errors may reduce therapy outcome due to a reduced dose delivery. In addition, reduced patients acceptance of a device, being dependent on device handling, may have a similar effect by reducing patients' compliance.

Impact of breathing pattern on work of breathing in healthy subjects and patients with COPD.

The impact of the respiratory pattern on respiratory muscle workload represents an unresolved controversy and is important for the treatment of patients with respiratory disorders and respiratory muscle failure. We designed this study to investigate the relationship of respiratory pattern and inspiratory workload. We measured esophageal pressure and inspiratory flow and calculated work of breathing, tidal volume and respiratory rate. Ten healthy subjects and 10 COPD patients participated and performed five different breathing patterns starting from respiratory rate 12 and tidal volume 1l or quiet breathing, respectively. They were instructed to increase respiratory rate by 50 and 100% as well as tidal volume by 50 and 100% while maintaining constant minute-ventilation. In healthy subjects Delta VT was the single best parameter to predict Delta WOB (R=0.958, R(2)=0.918, p<0.0001). The relationships of changes in tidal volume, respiratory rate and rapid shallow breathing index to changes in WOB were linear. In the COPD Delta VT was also the single best parameter to predict changes in work of breathing (R=0.777, R(2)=0.604, p<0.0001), however the relation of respiratory rate and rapid shallow breathing index to work of breathing was exponential (e-function) with lower indices generating higher workload. We conclude that rapid shallow breathing might be a strategy to compensate for burdensome respiratory mechanics. In COPD patients however we observed a critical threshold where any further increases in rapid shallow breathing index will be of no further benefit.

Short-term effect of controlled instead of assisted noninvasive ventilation in chronic respiratory failure due to chronic obstructive pulmonary disease.

BACKGROUND: Noninvasive positive-pressure ventilation (NPPV) unloads respiratory muscles. Spontaneous-breathing ventilation modes require patient effort to trigger the ventilator, whereas controlled modes potentially economize on patient triggering effort and thus achieve more complete respiratory muscle rest. Data on controlled NPPV have not been published to date. We hypothesize that controlled ventilation is feasible in patients with hypercapnic chronic obstructive pulmonary disease. METHODS: We measured blood gas values, respiratory muscle strength, spontaneous breathing pattern, and lung function before and after a 3-month period of NPPV in 305 patients (213 male, mean +/- SD age 61.3 +/- 8.6 y). The subjects used a controlled NPPV mode when they could tolerate it. RESULTS: Ninety-one percent of the patients were able to adapt to a controlled NPPV mode. In those patients, daytime P(CO(2)) decreased from 56.7 +/- 7.5 mm Hg to 47.5 +/- 6.6 mm Hg (p < 0.001) and P(O(2)) increased from 49.2 +/- 8.8 mm Hg to 56.2 +/- 8.5 mm Hg (p < 0.001). Their mean maximum inspiratory pressure increased from 42.3 +/- 16.9 cm H(2)O to 48.4 +/- 18.0 cm H(2)O (p < 0.001). Their mean vital capacity increased from 1.89 +/- 0.62 L to 1.99 +/- 0.67 L (p = 0.004). And their spontaneous breathing pattern became less rapid and shallow. CONCLUSIONS: Controlled NPPV is feasible in patients with hypercapnic chronic obstructive pulmonary disease. We observed improved blood gas values, lung function, and inspiratory muscle strength.