Static and dynamic hyperinflation during severe acute exacerbations of chronic obstructive pulmonary disease

Background: Static hyperinflation is known to be increased during moderate acute exacerbations of chronic obstructive pulmonary disease (COPD) (AECOPD), but few data exist in patients with severe exacerbations of COPD. The role of dynamic hyperinflation during exacerbations is unclear. Methods: In a prospective, observational cohort study, we recruited patients admitted to hospital for AECOPD. The following measurements were performed upon admission and again after resolution (stable state) at least 42 days later: inspiratory capacity (IC), body plethysmography, dynamic hyperinflation by metronome-paced IC measurement, health-related quality of life and dyspnea. Results: Forty COPD patients were included of whom 28 attended follow-up. The IC was low at admission (2.05 +/- 0.11 L) and increased again during resolution by 15.6%+/- 23.1% or 0.28 +/- 0.08 L (mean +/- standard error of the mean, p Conclusion: Static hyperinflation is increased during severe AECOPD requiring hospitalization compared with stable state. We could measure metronome-paced dynamic hyperinflation during severe AECOPD but found no increase

Hyperinflation and COPD exacerbations

Patients with COPD (chronic obstructive pulmonary disease) often suffer from periods with increased dyspnoea, especially during the influenza season. These periods are called exacerbations or lung attacks. Severe exacerbations require hospital admission. Wouter van Geffen is a consultant respiratory medicine who investigated these exacerbations. He concluded that dyspnoeic COPD patients admitted with an exacerbation of COPD often suffer from excess air in their lungs. Van Geffen and his team observed that during these attacks breathing was more difficult, because exhaling rather than inhaling is compromised. Their research showed that during exacerbations entrapment of air in the lungs during expiration occurs, causing the lungs to hyperinflate. This might be caused by increased obstruction of the airways and alveoli. During exacerbations, especially the patients with this entrapped air are dyspnoeic. In his thesis Van Geffen and his colleagues also discovered that the cause of the exacerbations can be detected faster with an electronic nose (E-Nose). Next steps were taken to find the most efficient way to remove the excess air during a lung attack. The most potential options to treat the hyperinflated lungs are stronger bronchodilators via inhalers and closure of the worst parts of the lungs e.g. via valves or airway bypasses

Emerging bronchoscopic treatments for chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by pathophysiological factors including airflow limitation, hyperinflation and reduced gas exchange. Treatment consists of lifestyle changes, lung rehabilitation and pharmacological therapies such as long acting beta-2-agonists (LABA) and long acting muscarinic antagonists (LAMA). More recently bronchoscopic treatments are emerging for COPD. Among them endobronchial valves (EBV) and endobronchial coils (EBC), next to endobronchial stents, sclerosing agents, targeted lung denervation and liquid nitrogen metered cryospray. In this review we aim to summarize the new emerging bronchoscopic treatments and their effect sizes compared with lung rehabilitation and pharmacological therapies

High-flow nasal cannula oxygen therapy for admitted COPD-patients:A retrospective cohort study

BACKGROUND: The use of High-flow nasal cannula (HFNC) is increasing in admitted COPD-patients and could provide a step in between non-invasive ventilation (NIV) and standard oxygen supply. Recent studies demonstrated that HFNC is capable of facilitating secretion removal and reduce the work of breathing. Therefore, it might be of advantage in the treatment of acute exacerbations of COPD (AECOPD). No randomized trials have assessed this for admitted COPD-patients on a regular ward and only limited data from non-randomized studies is available. OBJECTIVES: The aim of our study was to identify the reasons to initiate treatment with HFNC in a group of COPD-patients during an exacerbation, further identify those most likely to benefit from HFNC treatment and to find factors associated with treatment success on the pulmonary ward. MATERIAL AND METHODS: This retrospective study included COPD-patients admitted to the pulmonary ward and treated with HFNC from April 2016 until April 2019. Only patients admitted with severe acute exacerbations were included. Patients who had an indication for NIV-treatment where treated with NIV and were included only if they subsequently needed HFNC, e.g. when they did not tolerate NIV. Known asthma patients were excluded. RESULTS: A total of 173 patients were included. Stasis of sputum was the indication most reported to initiate HFNC-treatment. Treatment was well tolerated in 83% of the patients. Cardiac and vascular co-morbidities were significantly associated with a smaller chance of successful treatment (Respectively OR = 0.435; p = 0.013 and OR = 0.493;p = 0.035). Clinical assessment judged HFNC-treatment to be successful in 61% of the patients. Furthermore, in-hospital treatment with NIV was associated with a higher chance of HFNC failure afterwards (OR = 0.439; p = 0.045). CONCLUSION: This large retrospective study showed that HFNC-treatment in patients with an AECOPD was initiated most often for sputum stasis as primary reason. Factors associated with improved outcomes of HFNC-treatment was the absence of vascular and/or cardiac co-morbidities and no need for in-hospital NIV-treatment

Nationwide Real-world Cohort Study of First-line Tyrosine Kinase Inhibitor Treatment in Epidermal Growth Factor Receptor-mutated Non-small-cell Lung Cancer

Most trials regarding tyrosine kinase inhibitors in patients with advanced epidermal growth factor receptor-mutated non-small-cell lung cancer comprised selected series from Asian populations. We found that Western European patients with epidermal growth factor receptor-mutated non-small-cell lung cancer who received first-line treatment with regular tyrosine kinase inhibitors have a median overall survival of 20.2 months in our large nationwide real-world cohort. In patients with brain metastasis, erlotinib showed superior results compared with gefitinib and was similar to afatinib. Background: Only a few randomized trials directly compared the relative efficacy of tyrosine kinase inhibitors (TKIs) in patients with advanced epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC), and most trials comprised selected series from Asian populations. Therefore, the aim of this study was to assess the overall survival (OS) of advanced EGFR-mutated NSCLC in a large white population and to evaluate variation between different TKIs and identify predictors of survival. Patients and Methods: Information about clinical characteristics, treatment, and survival for 873 patients with stage IV EGFR + NSCLC, diagnosed from 2015 through 2017, was derived from the Netherlands Cancer Registry. OS was evaluated by actuarial analysis and multivariable Cox regression. Prognostic factors are reported as hazard ratios and 95% confidence intervals. Results: A total of 596 (68%) patients received first-line treatment with regular TKIs, providing a median survival of 20.2 months. Forty-five percent of patients were 70 years and older, and 54% of patients had distant metastasis in multiple organs. In the multivariate analysis, survival was significantly worse for men, and patients with higher age, poorer performance, and >= 3 organs with metastasis. Compared with erlotinib, OS was worse for gefitinib users (adjusted hazard ratio, 1.30; 95% confidence interval, 1.02-1.64), predominantly in patients with brain metastasis. Conclusion: Dutch patients with EGFR-mutated NSCLC who received first-line treatment with regular TKIs have a median OS of 20.2 months in a nationwide real-world cohort. In patients with brain metastasis, erlotinib showed superior results compared with gefitinib and was similar to afatinib. (C) 2020 Elsevier Inc. All rights reserved

Long-acting dual bronchodilator therapy (indacaterol/glycopyrronium) versus nebulized short-acting dual bronchodilator (salbutamol/ipratropium) in chronic obstructive pulmonary disease:A double-blind, randomized, placebo-controlled trial

Introduction: Most guidelines recommend long-acting bronchodilators over short-acting bronchodilators for patients with chronic obstructive pulmonary disease (COPD). The available evidence for the guidelines was based on dry powder or pressurized metered dose inhalers, but not nebulizations. Nevertheless, there is considerable, poorly evidenced based, use of short acting nebulized bronchodilators. Methods: This was an investigator initiated, randomized, active controlled, cross-over, double-blind and double-dummy single centre study in patients with stable COPD. The active comparators were indacaterol/glycopyrronium 110/50 μg as Ultibro® via Breezhaler® (IND/GLY) and salbutamol/ipratropium 2,5/0,5 mg via air driven nebulization (SAL/IPR), both given as a single dose on separate days. The primary end point was the area under the FEV1 curve from baseline till 6 h. Secondary end points included change in Borg dyspnoea score, adverse events and change in hyperinflation measured by the inspiratory capacity. Results: A total of 33 COPD patients completed the trial and were evaluable, most of them were ex-smokers. The difference between the tested regimens for the primary endpoint, FEV1 AUC 0–6 h, 2965 ± 1544 mL (mean ± SD) for IND/GLY versus 3513 ± 1762 mL for SAL/IPR, was not significant (P = 0.08). The peak in FEV1 was higher and was reached faster with SAL/IPR compared to IND/GLY. No other significant differences were detected for the secondary endpoints including the Borg score, or adverse events. Conclusion: Among patients with stable COPD, dry powder long-acting single inhalation of a LABA and a LAMA (IND/GLY) was not superior compared to nebulized short-acting salbutamol plus ipratropium (SAL/IPR) in its bronchodilating effects over 6 h.The effects of the nebulization kicked in faster and peaked higher. The observed differences may be caused by the difference in dosing between the two regimens. The improvement in Borg dyspnoea score did not favour the nebulization. Long-term outcomes were not assessed in this study

Bronchodilators delivered by nebuliser versus pMDI with spacer or DPI for exacerbations of COPD

Background Bronchodilators are a central component for treating exacerbations of chronic obstructive pulmonary disease (COPD) all over the world. Clinicians often use nebulisers as a mode of delivery, especially in the acute setting, and many patients seem to benefit from them. However, evidence supporting this choice from systematic analysis is sparse, and available data are frequently biased by the inclusion of asthma patients. Therefore, there is little or no formal guidance regarding the mode of delivery, which has led to a wide variation in practice between and within countries and even among doctors in the same hospital. We assessed the available randomised controlled trials (RCTs) to help guide practice in a more uniform way. Objectives To compare the effects of nebulisers versus pressurised metered dose inhalers (pMDI) plus spacer or dry powder inhalers (DPI) in bronchodilator therapy for exacerbations of COPD. Search methods We searched the Cochrane Airways Group Trial Register and reference lists of articles up to 1 July 2016. Selection criteria RCTs of both parallel and cross-over designs. We included RCTs during COPD exacerbations, whether measured during hospitalisation or in an outpatient setting. We excluded RCTs involving mechanically ventilated patients due to the different condition of both patients and airways in this setting. Data collection and analysis Two review authors independently assessed studies for inclusion, extracted data and assessed the risk of bias. We report results with 95% confidence intervals (CIs). Main results This review includes eight studies with a total of 250 participants comparing nebuliser versus pMDI plus spacer treatment. We identified no studies comparing DPI with nebulisers. We found two studies assessing the primary outcome of 'change in forced expiratory volume in one second (FEV1) one hour after dosing'. We could not pool these studies, but both showed a non-significant difference in favour of the nebuliser group, with similar frequencies of serious adverse events. For the secondary outcome, 'change in FEV1 closest to one hour after dosing': we found a significant difference of 83 ml (95% CI 10 to 156, P = 0.03) in favour of nebuliser treatment. For the secondary outcome of adverse events, we found a non-significant odds ratio of 1.65 (95% CI 0.42 to 6.48) in favour of the pMDI plus spacer group. Authors' conclusions There is a lack of evidence in favour of one mode of delivery over another for bronchodilators during exacerbations of COPD. We found no difference between nebulisers versus pMDI plus spacer regarding the primary outcomes of FEV1 at one hour and safety. For the secondary outcome 'change in FEV1 closest to one hour after dosing' during an exacerbation of COPD, we found a greater improvement in FEV1 when treating with nebulisers than with pMDI plus spacers. A limited amount of data are available (eight studies involving 250 participants). These studies were difficult to pool, of low quality and did not provide enough evidence to favour one mode of delivery over another. No data of sufficient quality have been published comparing nebulisers versus DPIs in this setting. More studies are required to assess the optimal mode of delivery during exacerbations of COPD