Physiological predictors Of peak inspiRatory flow using Observed lung function resultS (POROS): evaluation at discharge among patients hospitalized for a COPD exacerbation

David B Price,1,2 Sen Yang,1 Simon Wan Yau Ming,1 Antony Hardjojo,1 Claudia Cabrera,3,4 Andriana I Papaioannou,5 Stelios Loukides,5 Vicky Kritikos,6 Sinthia Z Bosnic-Anticevich,6 Victoria Carter,7 Paul M Dorinsky8 1Observational and Pragmatic Research Institute, Singapore, Singapore; 2Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK; 3Global Medical Affairs, AstraZeneca R and D, Mölndal, Sweden; 4Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden; 52nd Respiratory Medicine Department, Medical School, National and Kapodistrian University of Athens, Attikon General Hospital, Athens, Greece; 6Woolcock Institute of Medical Research, Quality Use of Respiratory Medicines Group, School of Medical Sciences, University of Sydney, Glebe, Australia; 7Optimum Patient Care, Cambridge, UK; 8Pearl – a member of the AstraZeneca Group, Durham, NC, USABackground: Peak inspiratory flow (PIF) as generated through the resistance of a dry powder inhaler (DPI) device is a critical patient-dependent maneuver impacting the success of DPI medication delivery. Despite its importance, it is not routinely measured in clinical practice. Little is currently known about the relationship, if any, between PIF through DPI devices, routine spirometry and disease outcomes.Aim: The aim of this study was to identify potential predictors of PIF for different DPIs from spirometric parameters and patient characteristics and explore the association between PIF and follow-up events.Patients and methods: A retrospective observational study at discharge among patients hospitalized for a COPD exacerbation at Attikon hospital, Athens, Greece. Spirometry was performed using an Easy on-PC™ spirometer. PIF was measured through four DPI resistances using the In-Check™ DIAL. Regression analyses were used to investigate the association between PIF through resistances and spirometric parameters obtained at discharge, comorbidities and demographic parameters.Results: Forty-seven COPD patients (mean [±SD], age 71 [±9] years, 72% males, 51% current smokers) were included in this study. Overall, 85% and 15% were classified as GOLD (2017) groups D and C, respectively. Most prevalent comorbidities were hypertension (70%) and cardiovascular disease (53%). In the final regression model, higher PIF was significantly associated with the following: higher FEV1 and % predicted peak expiratory flow (PEF) for Turbohaler® (R-squared value 0.374); higher FEV1 and diagnosis of gastroesophageal reflux disease (GERD) for Aerolizer® (R-squared value 0.209) and higher FEV1, younger age and diagnosis of ischemic heart disease (IHD) for Diskus® (R-squared value 0.350). However, R-squared values for all three devices were weak (<0.4).Conclusion: The study did not provide evidence to support the use of surrogate measurements for PIF through device resistance, which could assist in determining the appropriateness of inhaler device type. Although PIF measurement is feasible in patients at discharge and could be a valuable addition to the standard of care in COPD management, it needs to be measured directly. Keywords: hospital admission, COPD, dry powder inhaler devices, inhaler technique, resistance, spirometr

Increased Dose of Inhaled Corticosteroid versus Add-On Long-acting β-Agonist for Step-Up Therapy in Asthma.

RATIONALE: Guidelines advocate adding long-acting β-agonist (LABA) to inhaled corticosteroid as the preferred step-up therapy to increasing inhaled corticosteroid dose for patients with uncontrolled asthma on inhaled corticosteroid monotherapy. However, less than 5% of patients with asthma qualify for the randomized controlled trials on which guidelines are based. Thus, real-world data are needed to complement the results of randomized trials with narrow entry criteria. OBJECTIVES: To compare the effectiveness of stepping up asthma therapy with an increased dose of various types of inhaled corticosteroid as compared with add-on LABA. METHODS: We performed a historical matched cohort study using large primary care databases to compare asthma step-up therapy with small- and standard size-particle inhaled corticosteroid versus added LABA for patients 12-80 years old. As outcomes, we examined a composite of asthma control and rates of severe exacerbations. MEASUREMENTS AND MAIN RESULTS: The odds of asthma control and rates of severe exacerbations over one outcome year were comparable with increased inhaled corticosteroid dose versus added LABA. The adjusted odds ratios (95% confidence interval) for achieving asthma control with increased inhaled corticosteroid dose versus inhaled corticosteroid/LABA were 0.99 (0.88-1.12) for small-particle inhaled corticosteroid (n = 3,036 per cohort) and 0.85 (0.67-1.07) for standard size-particle inhaled corticosteroid (n = 809 per cohort). The adjusted rate ratios (95% confidence interval) for severe exacerbations, compared with inhaled corticosteroid/LABA combination inhaler, were 1.04 (0.91-1.20) and 1.18 (0.92-1.54), respectively. The results were not affected by smoking status. CONCLUSIONS: When applied to a broad primary care population, antiinflammatory therapy using increased doses of small- or standard size-particle inhaled corticosteroid is as effective as adding LABA, as measured by outcomes important to both patients and providers. Real-world populations and outcomes need to be taken into consideration when formulating treatment recommendations

Acute bronchodilator responses decline progressively over 4 years in patients with moderate to very severe COPD.

We previously reported a progressive decline in absolute responses of FEV1 and FVC to a near-maximal dose of 2 different short-acting bronchodilators over 4 years. Since varying host factors and the method of expressing the response may impact the time trend of acute bronchodilator responses, we now examined the potential influence of salient host characteristics on changes in bronchodilator responses over time expressed in different ways.This article is freely available via Open Access. Click on the Additional Link above to access the full-text via the publisher's website

The effects of positive end-expiratory pressure on respiratory system mechanics and hemodynamics in postoperative cardiac surgery patients

We prospectively evaluated the effects of positive end-expiratory pressure (PEEP) on the respiratory mechanical properties and hemodynamics of 10 postoperative adult cardiac patients undergoing mechanical ventilation while still anesthetized and paralyzed. The respiratory mechanics was evaluated by the inflation inspiratory occlusion method and hemodynamics by conventional methods. Each patient was randomized to a different level of PEEP (5, 10 and 15 cmH2O), while zero end-expiratory pressure (ZEEP) was established as control. PEEP of 15-min duration was applied at 20-min intervals. The frequency dependence of resistance and the viscoelastic properties and elastance of the respiratory system were evaluated together with hemodynamic and respiratory indexes. We observed a significant decrease in total airway resistance (13.12 ± 0.79 cmH2O l-1 s-1 at ZEEP, 11.94 ± 0.55 cmH2O l-1 s-1 (P<0.0197) at 5 cmH2O of PEEP, 11.42 ± 0.71 cmH2O l-1 s-1 (P<0.0255) at 10 cmH2O of PEEP, and 10.32 ± 0.57 cmH2O l-1 s-1 (P<0.0002) at 15 cmH2O of PEEP). The elastance (Ers; cmH2O/l) was not significantly modified by PEEP from zero (23.49 ± 1.21) to 5 cmH2O (21.89 ± 0.70). However, a significant decrease (P<0.0003) at 10 cmH2O PEEP (18.86 ± 1.13), as well as (P<0.0001) at 15 cmH2O (18.41 ± 0.82) was observed after PEEP application. Volume dependence of viscoelastic properties showed a slight but not significant tendency to increase with PEEP. The significant decreases in cardiac index (l min-1 m-2) due to PEEP increments (3.90 ± 0.22 at ZEEP, 3.43 ± 0.17 (P<0.0260) at 5 cmH2O of PEEP, 3.31 ± 0.22 (P<0.0260) at 10 cmH2O of PEEP, and 3.10 ± 0.22 (P<0.0113) at 15 cmH2O of PEEP) were compensated for by an increase in arterial oxygen content owing to shunt fraction reduction (%) from 22.26 ± 2.28 at ZEEP to 11.66 ± 1.24 at PEEP of 15 cmH2O (P<0.0007). We conclude that increments in PEEP resulted in a reduction of both airway resistance and respiratory elastance. These results could reflect improvement in respiratory mechanics. However, due to possible hemodynamic instability, PEEP should be carefully applied to postoperative cardiac patients