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Background The burden of asthma and COPD among patients is high and people affected are frequently hospitalized due to exacerbations. There are numerous reasons for the lack of disease control in asthma and COPD patients. It is associated with non-adherence to guidelines on the part of the health care provider and with poor inhalation technique and/or non-adherence to the prescribed treatment plan by the patient. This study aims to present data on inhaler technique and its impact on quality of life (QoL) and symptom control in a typical population of patients with chronic lung disease from a randomized controlled trial on medication adherence. Methods For this cross-sectional analysis, 165 asthma and COPD patients were analyzed. Correct application of inhaler devices was tested using pre-defined checklists for each inhaler type. QoL and symptom control were investigated using COPD Assessment Test (CAT) and Asthma Control Test (ACT). Spirometry was used to measure forced vital capacity (FVC) and forced expiratory volume in one second (FEV 1 ). Results Overall, incorrect inhalation technique ranged from 0 to 53% depending on the type of inhaler. COPD patients with incorrect device application had a higher CAT sum score compared to those with a correct device application ( P  = .02). Moreover, COPD patients with incorrect device application were more likely to suffer from cough ( P  = .03) and were more breathless while walking uphill or a flight of stairs ( P  = .02). While there was no significance found in asthma patients, COPD patients who used their devices correctly had a significantly better mean FEV 1 % predicted at baseline compared to those who applied their devices incorrectly ( P  = .04). Conclusions Correct inhalation of prescribed medication is associated with improved health status and lung function. These findings should encourage health professionals to provide instructions on correct inhalation technique and to regularly re-evaluate the patients’ inhalation technique. Trial registration ClinicalTrials.gov: NCT0238672 , Registered 14 February 2014.

Background The PHARMACOP-intervention significantly improved medication adherence and inhalation technique for patients with COPD compared with usual care. This study aimed to evaluate its cost-effectiveness. Methods An economic analysis was performed from the Belgian healthcare payer’s perspective. A Markov model was constructed in which a representative group of patients with COPD (mean age of 70 years, 66% male, 43% current smokers and mean Forced Expiratory Volume in 1 second of % predicted of 50), was followed for either receiving the 3-month PHARMACOP-intervention or usual care. Three types of costs were calculated: intervention costs, medication costs and exacerbation costs. Outcome measures included the number of hospital-treated exacerbations, cost per prevented hospital-treated exacerbation and cost per Quality Adjusted Life-Year. Follow-up was 1 year in the basecase analysis. Sensitivity and scenario analyses (including long-term follow-up) were performed to assess uncertainty. Results In the basecase analysis, the average overall costs per patient for the PHARMACOP-intervention and usual care were €2,221 and €2,448, respectively within the 1-year time horizon. This reflects cost savings of €227 for the PHARMACOP-intervention. The PHARMACOP-intervention resulted in the prevention of 0.07 hospital-treated exacerbations per patient (0.177 for PHARMACOP versus 0.244 for usual care). Results showed robust cost-savings in various sensitivity analyses. Conclusions Optimization of current pharmacotherapy (e.g. close monitoring of inhalation technique and medication adherence) has been shown to be cost-saving and should be considered before adding new therapies.

Objectives SARS-Cov-2 virus preferentially binds to the Angiotensin Converting Enzyme 2 (ACE2) on alveolar epithelial type II cells, initiating an inflammatory response and tissue damage which may impair surfactant synthesis contributing to alveolar collapse, worsening hypoxia and leading to respiratory failure. The objective of this study is to evaluate the feasibility, safety and efficacy of nebulised surfactant in COVID-19 adult patients requiring mechanical ventilation for respiratory failure. Trial design This study is a dose-escalating randomized open-label clinical trial of 20 COVID-19 patients. Participants This study is conducted in two centres: University Hospital Southampton and University College London Hospitals. Eligible participants are aged ≥18, hospitalised with COVID-19 (confirmed by PCR), who require endotracheal intubation and are enrolled within 24 hours of mechanical ventilation. For patients unable to consent, assent is obtained from a personal legal representative (PerLR) or professional legal representative (ProfLR) prior to enrolment. The following are exclusion criteria: imminent expected death within 24 hours; specific contraindications to surfactant administration (e.g. known allergy, pneumothorax, pulmonary hemorrhage); known or suspected pregnancy; stage 4 chronic kidney disease or requiring dialysis (i.e., eGFR < 30); liver failure (Child-Pugh Class C); anticipated transfer to another hospital, which is not a study site, within 72 hours; current or recent (within 1 month) participation in another study that, in the opinion of the investigator, would prevent enrollment for safety reasons; and declined consent or assent. Intervention and comparator Intervention: The study is based on an investigational drug/device combination product. The surfactant product is Bovactant (Alveofact®), a natural animal derived (bovine) lung surfactant formulated as a lyophilized powder in 108 mg vials and reconstituted to 45 mg/mL in buffer supplied in a prefilled syringe. It is isolated by lung lavage and, by weight, is a mixture of: phospholipid (75% phosphatidylcholine, 13% phosphatidylglycerol, 3% phosphatidylethanolamine, 1% phosphatidylinositol and 1% sphingomyelin), 5% cholesterol, 1% lipid-soluble surfactant-associated proteins (SP-B and SP-C), very low levels of free fatty acid, lyso-phosphatidylcholine, water and 0.3% calcium. The Drug Delivery Device is the AeroFact-COVID™ nebulizer, an investigational device based on the Aerogen® Solo vibrating mesh nebulizer. The timing and escalation dosing plans for the surfactant are as follows. Cohort 1: Three patients will receive 10 vials (1080 mg) each of surfactant at dosing times of 0 hours, 8 hours and 24 hours. 2 controls with no placebo intervention. Cohort 2: Three patients will receive 10 vials (1080 mg) of surfactant at dosing times of 0 hours and 8 hours, and 30 vials (3240 mg) at a dosing time of 24 hours. 2 controls with no placebo intervention. Cohort 3 : Three patients will receive 10 vials (1080 mg) of surfactant at a dosing time of 0 hours, and 30 vials (3240 mg) at dosing times of 8 hours and 24 hours. 2 controls with no placebo intervention. Cohort 4: Three patients will receive 30 (3240 mg) vials each of surfactant at dosing times of 0 hours, 8 hours and 24 hours. 2 controls. 2 controls with no placebo intervention. The trial steering committee, advised by the data monitoring committee, will review trial progression and dose escalation/maintenance/reduction after each cohort is completed (48-hour primary outcome timepoint reached) based on available feasibility, adverse event, safety and efficacy data. The trial will not be discontinued on the basis of lack of efficacy. The trial may be stopped early on the basis of safety or feasibility concerns. Comparator: No placebo intervention. All participants will receive usual standard of care in accordance with the local policies for mechanically ventilated patients and all other treatments will be left to the discretion of the attending physician. Main outcomes The co-primary outcome is the improvement in oxygenation (PaO 2 /FiO 2 ratio) and pulmonary ventilation (Ventilation Index (VI), where VI = [RR x (PIP − PEEP) × PaCO 2 ]/1000) at 48 hours after study initiation. The secondary outcomes include frequency and severity of adverse events (AEs), Adverse Device Effects (ADEs), Serious Adverse Events (SAEs) and Serious Adverse Device Events (SADEs), change in pulmonary compliance, change in positive end-expiratory pressure (PEEP) requirement of ventilatory support at 24 and 48 hours after study initiation, clinical improvement defined by time to one improvement point on the ordinal scale described in the WHO master protocol (2020) recorded while hospitalised, days of mechanical ventilation, mechanical ventilator free days (VFD) at day 21, length of intensive care unit stay, number of days hospitalised and mortality at day 28. Exploratory end points will include quantification of SARS-CoV-2 viral load from tracheal aspirates using PCR, surfactant dynamics (synthesis and turnover) and function (surface tension reduction) from deep tracheal aspirate samples (DTAS), surfactant phospholipid concentrations in plasma and DTAS, inflammatory markers (cellular and cytokine) in plasma and DTAS, and blood oxidative stress markers. Randomisation After informed assent, patients fulfilling inclusion criteria will be randomised to 3:2 for the treatment and control arms using an internet-based block randomization service (ALEA tool for clinical trials, FormsVision BV) in combination with electronic data collection. Randomisation will be done by the recruiting centre with a unique subject identifier specific to that centre. Blinding (masking) This is an open-labelled unblinded study. Numbers to be randomised (sample size) The total sample size is 20 COVID-19 mechanically ventilated patients (12 intervention; 8 control). Trial Status Current protocol version is V2 dated 5 th of June 2020. The recruitment is currently ongoing and started on the 14 th of October 2020. The anticipated study completion date is November 2021. Trial registration ClinicalTrials.gov: NCT04362059 (Registered 24 April 2020), EUDAMED number: CIV-GB-20-06-033328, EudraCT number: 2020-001886-35 (Registered 11 May 2020) Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1 ). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2 ).

Background Endobronchial administration of lidocaine is commonly used for cough suppression during diagnostic bronchoscopy. Recently, nebulization of lidocaine during bronchoscopies under deep sedation with fiberoptic intubation using a distinct spray catheter has been shown to have several advantages over conventional lidocaine administration via syringe. However, there are no data about this approach in bronchoscopies performed under moderate sedation. Therefore, this study compared the tolerability and safety of nebulized lidocaine with conventional lidocaine administration via syringe in patients undergoing bronchoscopy with moderate sedation. Methods Patients requiring diagnostic bronchoscopy were randomly assigned to receive topical lidocaine either via syringe or via nebulizer. Endpoints were consumption of lidocaine and sedative drugs, as well as patient tolerance and safety. Results Sixty patients were included in the study ( n  = 30 in each group). Patients required lower doses of endobronchial lidocaine when given via nebulizer versus syringe (164.7 ± 20.8 mg vs. 250.4 ± 42.38 mg; p  < 0.0001) whereas no differences in the dosage of sedative drugs were observed between the two groups (all p  > 0.05). Patients in the nebulizer group had higher mean oxygen saturation (96.19 ± 2.45% vs. 94.21 ± 3.02%; p  = 0.0072) and a lower complication rate (0.3 ± 0.79 vs. 1.17 ± 1.62 per procedure; p  = 0.0121) compared with those in the syringe group. Conclusions Endobronchial lidocaine administration via nebulizer was well-tolerated during bronchoscopies under moderate sedation and was associated with reduced lidocaine consumption, a lower complication rate and better oxygenation compared with lidocaine administration via syringe. Trial registration The study was registered with clinicaltrials.gov ( NCT02262442 ; 13 th October 2014).

Delivery of inhaled medications via an inhaler device underpins the effectiveness of treatment for patients with chronic obstructive pulmonary disease (COPD). Correct inhaler technique among patients is also a predictor of achieving treatment compliance and adherence. Reporting of patient satisfaction with inhalers is therefore gaining increasing attention and is now recognized as an important patient-reported outcome in clinical trials involving patients with COPD or asthma. In this cross-sectional study, we use the validated Patient Satisfaction and Preference Questionnaire (PASAPQ) to assess the handling and satisfaction for Respimat(®) Soft Mist™ Inhaler (SMI) compared with the Breezhaler(®) dry powder inhaler (DPI) among patients with COPD in Spain. Patients were already assigned to therapy with either SPIRIVA(®) (tiotropium) Respimat(®) or with Hirobriz(®)/Onbrez(®)/Oslif(®) (indacaterol) Breezhaler(®) for at least 3 but not more than 6 months before completing the PASAPQ at a single visit to the study site. The primary endpoint of the trial was the mean total PASAPQ score. Secondary endpoints were the performance score domain of the PASAPQ, the convenience score domain of the PASAPQ, and the overall satisfaction score of the PASAPQ. For the primary endpoint, the mean PASAPQ total score in the Respimat(®) and Breezhaler(®) groups was 80.7 and 79.9, respectively (difference of 0.8, 95% confidence interval [CI] -2.9 to 4.5; P=0.67). The mean total performance scores were 82.5 and 78.2 (difference of 4.3, 95% CI -0.3 to 8.9; P=0.06), and the mean total convenience scores were 78.6 and 81.9 (difference of -3.3, 95% CI -7.0 to 0.4; P=0.08) for the Respimat(®) and Breezhaler(®) groups, respectively. Patients gave the Respimat(®) SMI and the Breezhaler(®) DPI overall satisfaction PASAPQ scores of 6.0 and 5.9, respectively, which shows that patients were satisfied with these inhalers.

Abstract Background: The Easyhaler® (EH) device-metered dry powder inhaler containing budesonide and formoterol is being developed for asthma and chronic obstructive pulmonary disease (COPD). As a part of product optimization, a series of in vitro and in vivo studies on flow rate dependency were carried out. Methods: Inspiratory flow parameters via EH and Symbicort® Turbuhaler® (TH) inhalers were evaluated in 187 patients with asthma and COPD. The 10th, 50th, and 90th percentile flow rates achieved by patients were utilized to study in vitro flow rate dependency of budesonide/formoterol EH and Symbicort TH. In addition, an exploratory pharmacokinetic study on pulmonary deposition of active substances for budesonide/formoterol EH in healthy volunteers was performed. Results: Mean inspiratory flow rates through EH were 64 and 56 L/min in asthmatics and COPD patients, and through TH 79 and 72 L/min, respectively. Children with asthma had marginally lower PIF values than the adults. The inspiratory volumes were similar in all groups between the inhalers. Using weighted 10th, 50th, and 90th percentile flows the in vitro delivered doses (DDs) and fine particle doses (FPDs) for EH were rather independent of flow as 98% of the median flow DDs and 89%–93% of FPDs were delivered already at 10th percentile air flow. Using±15% limits, EH and TH had similar flow rate dependency profiles between 10th and 90th percentile flows. The pharmacokinetic study with budesonide/formoterol EH in healthy subjects (n=16) revealed a trend for a flow-dependent increase in lung deposition for both budesonide and formoterol. Conclusions: Comparable in vitro flow rate dependency between budesonide/formoterol EH and Symbicort TH was found using the range of clinically relevant flow rates. The results of the pharmacokinetic study were in accordance with the in vitro results showing only a trend of flow rate-dependant increase in lung deposition of active substances with EH.

The design of electronic cigarette (EC) atomizing units has evolved since their introduction over 10 years ago. The purpose of this study was to evaluate atomizer design in ECs sold between 2011–2017. Atomizers from 34 brands representing three generations of ECs were dissected and photographed using a stereoscopic microscope. Five distinct atomizer design categories were identified in first generation products (cig-a-like/cartomizer) and three categories were found in the third generation. Atomizers in most cig-a-like ECs contained a filament, thick wire, wire joints, air-tube, wick, sheath, and fibers, while some later models lacked some of these components. Over time design changes included an increase in atomizer size; removal of solder joints between wires; removal of Polyfil fibers; and removal of the microprocessor from Vuse. In second and third generation ECs, the reservoirs and batteries were larger, and the atomizing units generally lacked a thick wire, fibers, and sheath. These data contribute to an understanding of atomizer design and show that there is no single design for ECs, which are continually evolving. The design of the atomizer is particularly important as it affects the performance of ECs and what transfers into the aerosol.

BackgroundThe comparative safety of oxygen versus air-driven nebulised bronchodilators in patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) is uncertain. A randomised controlled trial was performed to assess the effect on the arterial partial pressure of carbon dioxide of nebulised bronchodilator driven with oxygen versus air in stable severe COPD.MethodsIn an open label randomised study, 18 subjects with stable severe COPD attended on 2 days to receive nebulised bronchodilator therapy driven by air or oxygen. Subjects received 5 mg salbutamol and 0.5 mg ipratropium bromide by nebulisation over 15 min, then, after 5 min, 5 mg salbutamol nebulised over 15 min, followed by 15 min of observation. Transcutaneous carbon dioxide tension (Ptco2) and oxygen saturations were recorded at 5 min intervals during the study. The primary outcome was the Ptco2 after the completion of the second bronchodilator treatment.ResultsPtco2 was higher with nebulised bronchodilator therapy delivered by oxygen, but decreased back to the level associated with air nebulisation 15 min after completion of the second nebulised dose. One subject experienced an increase in Ptco2 of 11 mm Hg after the first bronchodilator nebulisation driven by oxygen. The mean Ptco2 difference between the oxygen and air groups after the second nebulisation was 3.1 mm Hg (95% CI 1.6 to 4.5, p<0.001).ConclusionNebulisers driven with oxygen result in significantly higher levels of Ptco2 than those driven with air in patients with severe COPD.Clinical trial registration numberThe study was registered on the Australian New Zealand Clinical Trials Registry (ACTRN12610000080022).

At present, the newly available antibiotics for the treatment of MDRGNB pneumonia in China is limited. [...]Chinese Medical Association (CMA) still define MIC ≤ 2 ug/mL as susceptible according to the previous versions of CLSI before 2020 or the 10th version of European Committee on Antimicrobial Susceptibility Testing (EUCAST), to guide clinical treatment. The international approved and recognized method for susceptibility testing of polymyxins is broth microdilution (BMD), but its manual operation is complex and time-consuming, making it difficult for laboratories to routinely carry out. [...]most laboratories still use automated or semi-automated instruments nowadays to detect the susceptibility, and the accuracy of the results still needs further evaluation. Some guidelines recommended that for polymyxin B the AUCss,24h should be about 50 mg h/L and possibly 50–100 mg h/L, with the latter corresponding to an average steady-state concentration across 24 h (Css,avg) of 2–4 ug/mL for pathogens with MIC of ≤ 2 ug/mL [3]. [...]careful interpretation is needed for the susceptible judgment of polymyxins, the optimal PK/PD index, and the effectiveness of antibiotic therapy. [...]it is recommended an urgent need for high-quality education to bring practice into line with evidence-based guidelines.

ABSTRACT BACKGROUND Patients are asked to assume greater responsibility for care, including use of medications, during transitions from hospital to home. Unfortunately, medications dispensed via respiratory inhalers to patients with asthma or chronic obstructive pulmonary disease (COPD) can be difficult to use. OBJECTIVES To examine rates of inhaler misuse and to determine if patients with asthma or COPD differed in their ability to learn how to use inhalers correctly. DESIGN A cross-sectional and pre/post intervention study at two urban academic hospitals. PARTICIPANTS Hospitalized patients with asthma or COPD. INTERVENTION A subset of participants received instruction about the correct use of respiratory inhalers. MAIN MEASURES Use of metered dose inhaler (MDI) and Diskus® devices was assessed using checklists. Misuse and mastery of each device were defined as <75% and 100% of steps correct, respectively. Insufficient vision was defined as worse than 20/50 in both eyes. Less-than adequate health literacy was defined as a score of <23/36 on The Short Test of Functional Health Literacy in Adults (S-TOFHLA). KEY RESULTS One-hundred participants were enrolled (COPD n  = 40; asthma n  = 60). Overall, misuse was common (86% MDI, 71% Diskus®), and rates of inhaler misuse for participants with COPD versus asthma were similar. Participants with COPD versus asthma were twice as likely to have insufficient vision (43% vs. 20%, p  = 0.02) and three-times as likely to have less-than- adequate health literacy (61% vs. 19%, p  = 0.001). Participants with insufficient vision were more likely to misuse Diskus® devices (95% vs. 61%, p  = 0.004). All participants (100%) were able to achieve mastery for both MDI and Diskus® devices. CONCLUSIONS Inhaler misuse is common, but correctable in hospitalized patients with COPD or asthma. Hospitals should implement a program to assess and teach appropriate inhaler technique that can overcome barriers to patient self-management, including insufficient vision, during transitions from hospital to home.