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

Understanding the role of long-acting muscarinic antagonists in asthma treatment

Objective: Long-acting muscarinic antagonists (LAMAs) have been used in the treatment of obstructive pulmonary diseases for years. Long-acting muscarinic antagonists were previously mainly used as bronchodilators in chronic obstructive pulmonary disease, but the use of LAMAs in the treatment of asthma has gained great interest. There is now ample evidence of the efficacy and safety of LAMAs as add-on therapy to inhaled corticosteroid (ICS) plus long-acting β 2-agonist (LABA) combinations in patients with moderate to severe uncontrolled asthma. Long-acting muscarinic antagonists have subsequently been included in asthma guidelines. This review summarizes the scientific evidence on the use of LAMAs in asthma and aims to provide a better understanding of the role of LAMAs in the asthma treatment care algorithm and the current gaps in our knowledge. Data sources: PubMed review using the following words: long-acting muscarinic antagonists, asthma, muscarinic receptors, tiotropium, glycopyrronium, umeclidinium. Study selections: This review focused on the key trials that led to the inclusion of LAMAs in asthma guidelines. In addition, we highlighted a number of studies with other study designs and populations. Results: We identified 6 major studies that led to inclusion in asthma guidelines and 3 studies with other study designs and populations. Conclusion: Long-acting muscarinic antagonists add-on therapy to ICS-LABA improves lung function, reduces exacerbations, and modestly improves asthma control in patients with moderate to severe asthma who are uncontrolled despite the use of ICS-LABA. Long-acting muscarinic antagonists are effective in all asthma phenotypes and endotypes

Initiation of home mechanical ventilation at home:A randomised controlled trial of efficacy, feasibility and costs

SummaryIntroductionHome mechanical ventilation (HMV) in the Netherlands is normally initiated in hospital, but this is expensive and often a burden for the patient. In this randomised controlled study we investigated whether initiation of HMV at home in patients with chronic respiratory failure is non-inferior to an in hospital based setting.MethodsSeventy-seven patients were included, of which 38 patients started HMV at home. All patients were diagnosed with chronic respiratory failure due to a neuromuscular or thoracic cage disease. Primary outcome was the arterial carbon dioxide (PaCO2) while quality of life and costs were secondary outcomes. Telemonitoring was used in the home group to provide therapeutic information, for example; transcutaneous carbon dioxide, oxygen saturation and ventilator information, to the caregivers. Follow-up was six months.ResultsPaCO2, improved by 0.72 (SE ± 0.16) kPa in the hospital group and by 0.91 (±0.20) in the home group, both improvements being significant and the latter clearly not inferior.There were also significant improvements in quality of life in both groups, again not being inferior with home treatment.ConclusionThis study is the first to show that initiation of HMV at home in a selective group of patients with chronic respiratory failure is as effective for gas exchange and quality of life as hospital initiation. In addition we found that it is safe, technically feasible and that more than € 3000 per patient can be saved compared to our standard care

Predicted values for the forced expiratory flow adjusted for forced vital capacity, a descriptive study

Background: The forced expiratory flows (FEFs) towards the end of the expiration may be more sensitive in detecting peripheral airways obstruction compared to the forced expiratory volume in 1 s and forced vital capacity (FVC). However, they are highly variable. A partial solution is to adjust the FEFs for FVC (FEF/FVC). Here we provide reference equations for these adjusted FEFs at 25%, 50%, 75% and 25-75% of FVC, which are currently lacking. Methods: We included pulmonary healthy, never-smoker adults; 14 472 subjects from Lifelines, a biobank for health research, and 338 subjects from the department's control cohorts (NORM and Fiddle). Reference equations were obtained by linear regression on 80% of the Lifelines dataset and validated on the remaining data. The best model was defined as the one with the highest adjusted R2-value. The difference in variability between adjusted and unadjusted FEFs was evaluated using the coefficient of variation. Results: For all adjusted FEFs, the best model contained age, height and weight. The adjustment improved the coefficient of variation of the FEF75 from 39% to 36% and from 43% to 40%, respectively, in males and females. The highest percentage of explained variance by the reference equation was obtained for FEF75/FVC, 32%-38% for males, and 41%-46% for females, depending on the validation set. Conclusion: We developed reference equations for FVC-adjusted FEF values. We demonstrated minimally yet significantly improved variability. Future studies in obstructive airway diseases should demonstrate whether it is worthwhile to use these (predicted) adjusted FEF values

Responsivity and Reproducibility of Sputum Inflammatory Biomarkers During COPD Exacerbation and Stable Phases - A Pilot Study

Introduction: There is a great interest to identify airway biomarkers to evaluate the potential and efficacy of anti-inflammatory therapeutic interventions. In this pilot study, we compared cytokine mRNA and protein levels of IL-6, IL-8, CCL2, CCL4, and TNF-α, as well as LTB-4 expression regarding their reproducibility and responsivity in induced sputum in COPD patients. Methods: We recruited a cohort of 17 patients with a moderate COPD exacerbation, necessitating antibiotics and/or oral corticosteroids. Patients were followed for two consecutive stable phase visits. Cytokine mRNA and protein levels were measured in induced sputum samples. Results: IL-6 and CCL4 protein levels decreased from exacerbation to stable phase, whereas their mRNA expression showed the same trend (not statistically significant). Coefficients of variation were overall lower (ie, more favorable for responsiveness) at protein levels compared to mRNA levels. No significant differences were observed in the reproducibility between cytokine mRNA expression and protein measurements. IL-6, IL-8, CCL2, and TNF-α gene expression levels yielded moderate to high intraclass correlation coefficients and/or Spearman correlation coefficients between both stable phase samples in contrast to their protein levels. Conclusion: Our findings suggest that several protein levels yield better responsivity with lower noise-to-signal ratios compared to their respective mRNA levels. In contrast, cytokine mRNA expression was more reproducible as it varied less in a stable state than proteins. Future studies are needed with a larger sample size to further evaluate the differences of responsivity and reproducibility between cytokine mRNA and protein measurements, not only during exacerbations