Are the Reference Values for the Provocative Concentration of Methacholine Appropriate for Children?

Background: Preliminary data in a randomly selected pediatric cohort study in 8-year-olds suggested a rate of positivity to a methacholine challenge test that was unexpectedly high, roughly 30%. The current recommendation for a negative methacholine test is a 20% decrease in the forced expiratory volume in one second at a dose greater than 400 µg. This was derived from studies in adults using the obsolete English Wright nebulizer. One explanation for the high incidence of positivity in the study in 8-year-olds could be that children deposit more methacholine on a µg/kg basis than adults, due to differences in their breathing patterns. The purpose of this study was to determine if pediatric breathing patterns could result in a higher dose of methacholine depositing in the lungs of children based on µg/kg body weight compared with adults. Methods: An AeroEclipse Breath Actuated nebulizer delivered methacholine aerosol, generated from a 16 mg/mL solution, for one minute, using age-appropriate breathing patterns for a 70 kg adult and a 30 and 50 kg child produced by a breathing simulator. Predicted lung deposition was calculated from the collected dose of methacholine on a filter placed at the nebulizer outport, multiplied by the fraction of the aerosol mass contained in particles ≤5 µm. The dose of methacholine on the inspiratory filter was assayed by high performance liquid chromatography (HPLC). Particle size was measured using laser diffraction technology. Results: The mean (95% confidence intervals) predicted pulmonary dose of methacholine was 46.1 (45.4, 46.8), 48.6 (45.3, 51.9), and 36.1 (34.2, 37.9) µg/kg body weight for the 30 kg child, 50 kg child, and 70 kg adult, respectively. Conclusions: On a µg/kg body weight, the predicted pulmonary dose of methacholine was greater with the pediatric breathing patterns than with the adult pattern.

Evaluation of the quality and content of YouTube videos as an educational resource in developing patients' inhaler use skills.

BACKGROUND: YouTube has educational videos on inhalers. However, their content and quality are not adequately known. OBJECTIVES: This study investigated the quality and content of educational YouTube videos on inhalers. METHODS: This descriptive study analyzed 178 YouTube videos on inhalers between May and July 2022. Two researchers independently evaluated the videos. The Global Quality Score (GQS), Journal of American Medical Association (JAMA) Benchmark Criteria, and Inhaler Application Checklist (IAC) were used to assess the quality and content of the videos. Spearman's correlation, Kruskal-Wallis, Mann-Whitney U, ANOVA, and Post hoc analysis Bonferroni test were used for data analysis. RESULTS: The videos had a mean GQS score of 3.70 ± 1.24, and JAMA score of 2.22 ± 0.60. A negative correlation was between the quality score of the videos and views, likes, comments, duration, and likes/views (respectively; r = -0.237 p < 0.005, r = -0.217 p < 0.003, r = -0.220 p < 0.005, r = -0.147, p < 0.005). The videos narrated by nurses and doctors had significantly higher mean JAMA and GQS scores than others (p = 0.001). The videos missed some procedural steps [gargling (29.1%), adding no more than five ml of medication and device cleaning (41.9%), and exhaling through the nose (37.5%)]. Videos uploaded by individual missed significantly more procedural steps than professional organizations (p < 0.05). CONCLUSIONS: YouTube videos about inhaler techniques have a moderate level of quality. Videos uploaded by doctors and nurses as content narrators were of higher quality. The videos missed some procedural steps. Individual video uploaders had higher missed procedural steps. Counseling should be provided to patients regarding the reliability of online information.

[Chinese expert consensus on standardized inhaler device application in stable chronic airway diseases (2023)].

The incidence of chronic airway diseases in China has been increasing every year, resulting in a high burden of disease. Inhalation therapy is widely used as a basic first-line treatment for such diseases. However, inappropriate selection of inhalation devices and usage methods is common, leading to poor disease control and prognosis, as well as a waste of medical resources. In order to facilitate the reasonable selection and appropriate use of inhaler devices, improve the efficacy of inhalation therapy, and increase patient compliance, the Inhalation Therapy and Respiratory Rehabilitation Group, Respiratory Equipment Committee of China Association of Medical Equipment, and Chinese Chronic Obstructive Pulmonary Disease Coalition organized experts to revise the Chinese expert consensus on standardized inhaler device application in stable chronic respiratory disease patients (2019 Edition) based on the latest evidence-based medical evidence and clinical diagnosis and treatment experience.Chronic airway diseases can affect the anatomical and physiological structure of the respiratory tract, which can affect the inhalation and delivery of drugs. In order to achieve the maximum effect of inhaled drugs, it is necessary for the drugs to be completely released from the device and to be deposited in the peripheral airways. Therefore, inhaler devices, patients, and medical staff can have a significant impact on the effectiveness of inhalation administration. The effectiveness of inhalation administration is influenced by several factors related to the inhaler device itself, including active or passive release, aerosol characteristics, and internal device resistance. For patients, the inhalation ability, the correct use of inhaler devices (inhalation technique), and regular and quantitative inhalation (treatment compliance) are essential to achieve the desired therapeutic effect. Medical staff can influence the efficacy and compliance of patients through proper assessment of their inhalation capacity and preferences, knowledge of different inhaler device characteristics, rational selection of inhaler devices, training in inhalation techniques, and guidance on inhaler device replacement. Standardized education can help minimize operational errors and improve patients' ability to use inhaler devices effectively. In addition, deep inspiratory volume, prolonged breath-hold time, airway clearance, and reduction of upper airway curvature and resistance can further improve the efficacy of inhaled drugs. The choice of inhalation device should be based on the patient's inspiratory flow rate, hand-lung coordination ability, device operation ability, and preference.The revised consensus version provides a clear understanding of the characteristics and operating principles of different types of inhaler devices, including pressurized metered-dose inhaler (pMDI), dry powder inhaler (DPI), soft mist inhaler (SMI), and small-volume nebulizers (SVN). The consensus categorizes pMDI as traditional pMDI (solution type, suspension type, and co-suspension type), extra-fine pMDI, and breath-actuated pMDI; and DPI into capsule, reservoir, and blister types. The inhalation device is evaluated based on three dimensions: drug delivery, device operation, and other characteristics. The indicators to assess drug delivery characteristics include lung deposition, oropharyngeal deposition, aerosol duration, aerosol plume velocities, MMAD, fine particle fractions, and dose repeatability. The indicators used to assess the operational device characteristics include inspiratory flow rate requirements, hand-breath coordination requirements, inspiratory synchronous drive, pre-use shaking, and operational steps. Other characteristic indicators include avoidance of humidity exposure, storage environment requirements, propellant, carrying convenience, counter, cleaning, and medication type. The consensus provides a detailed introduction to the personalized selection, switching, education, and follow-up of inhaler devices.1. Establishing a Chinese consensus on the individualized selection of inhaler devices for patients based on the characteristics of different devices includes the following steps:(1) Testing the patient's hand-breath coordination using an active release inhaler device (recommended: a short-acting bronchodilator inhaler). If the device is being used for the first time or is not being used correctly, it should be re-tested after instruction.(2) Testing the patient's peak inspiratory flow rates and whether they can consistently inhale at an inspiratory flow rate of 30 L/min for 3 seconds (an alternative assessment method is to continue eating yoghurt through a straw).(3) Assessing the need for non-invasive ventilation in patients with poor hand-breath coordination.(4) Based on the evaluation results, the recommendations for different inhaler devices are as follows:① Patients with good hand-breath coordination and the ability to inhale consistently at an inspiratory flow rate of 30 L/min (or more) for more than 3 seconds can use any inhaler device; ② Patients with poor hand-breath coordination who can achieve a peak inspiratory flow rate of 30L/min can use DPI or an active release device with a Spacer; ③ Patients with good hand-breath coordination, a peak inspiratory flow rate less than 30 L/min, and a constant inspiratory flow for more than 3 seconds can use SMI or an active release device with a Spacer; ④ Patients with poor hand-breath coordination, a peak inspiratory flow rate less than 30 L/min, and a constant inspiratory flow for more than 3 seconds can use SMI and an active release device with a Spacer; ⑤ Patients with a peak inspiratory flow rate less than 30 L/min and a constant inspiratory flow for less than 3 seconds can use an active release device with a Spacer; ⑥ Patients who require non-invasive ventilation can use an active release device and nebulizers(Active release devices include pMDI and SMI).2. Switching inhaler devices:The need to switch inhaler devices should be clear, and there are indications for switching:(1) inhaled drugs has been changed or added because of the patient's condition, requiring delivery by another inhaler device.(2) the patient was unable to use the inhaler device correctly after several training attempts.(3) patients were dissatisfied with the inhaler device and had poor adherence.(4) the patient used the device correctly, but the therapeutic effect was unsatisfactory.Once the decision to switch the inhaler device has been made, the following steps should be taken:(1) explain the necessity of switching the inhaler device.(2) retrain the patient in the use of the new inhaler device.(3) intensify follow-up to obtain patient feedback on the use of the new device and to check inhalation technique, drug consumption and efficacy.3. Education on inhalation technique:It is crucial to educate patients on proper inhalation technique. Teaching patients how to use inhaler devices in a standardized way is an important measure to ensure that they use the devices correctly. This helps to improve the accuracy of inhaler device operation, patient adherence, disease control, and reduce disease burden. Relying solely on the instructions provided with the inhaler device is not sufficient to adequately educate patients, and patients' inhalation technique may unintentionally change over time, resulting in decreased efficacy. Inhalation technique should be regularly reviewed and corrected at each visit.4. Follow-up of inhalation therapy:Follow-up management is a crucial part of maximizing patient efficacy, including assessing efficacy, correcting operation techniques, and promoting adherence.5. Other:When patients with chronic airway diseases are at risk of respiratory epidemic infectious diseases, the use of inhaler devices should strictly comply with the requirements for the prevention and control of such diseases.

Aerosol delivery systems for treating obstructive airway diseases during the SARS-CoV-2 pandemic.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes CoronaVirus Disease 2019 (COVID-19), has resulted in a worldwide pandemic and currently represents a major public health crisis. It has caused outbreaks of illness through person-to-person transmission of the virus mainly via close contacts, and droplets produced by an infected person's cough or sneeze. Aerosolised inhaled therapy is the mainstay for treating obstructive airway diseases at home and in healthcare settings, but there is heightened particular concern about the potential risk for transmission of SARS-CoV-2 in the form of aerosolised respiratory droplets during the nebulised treatment of patients with COVID-19. As a consequence of this concern, the use of hand-held inhalers, especially pressurised metered dose inhalers, has risen considerably as an alternative to nebulisers, and this switch has led to inadequate supplies of inhalers in some countries. However, there is no evidence supporting an increased risk of viral transmission during nebulisation in COVID-19 patients. Furthermore, some patients may be unable to adequately use their new device and may not benefit fully from the switch to treatment via hand-held inhalers. Thus, there is no compelling reason to alter aerosol delivery devices for patients with established nebuliser-based regimens. The purpose of this paper is to discuss the current evidence and understanding of the use of aerosolised inhaled therapies during the SARS-CoV-2 pandemic and to provide some guidance on the measures to be taken to minimise the risk of transmitting infection, if any, during aerosol therapies.

Containment of procedure-associated aerosols by an extractor tent: effect on nebulized drug particle dispersal.

BACKGROUND: Several medical procedures involving the respiratory tract are considered as 'aerosol-generating procedures'. Aerosols from these procedures may be inhaled by bystanders, and there are consequent concerns regarding the transmission of infection or, specific to nebulized therapy, secondary drug exposure. AIM: To assess the efficacy of a proprietary high-efficiency-particulate-air-filtering extractor tent on reducing the aerosol dispersal of nebulized bronchodilator drugs. METHODS: The study was conducted in an unoccupied outpatient room at St. James's Hospital, Dublin, Ireland. A novel real-time, fluorescent particle counter, the Wideband Integrated Bioaerosol Sensor (WIBS), monitored room air continuously for 3 h. Baseline airborne particle count and count during nebulization of bronchodilator drug solutions were recorded. FINDINGS: Nebulization within the tent prevented any increase over background level. Nebulization directly into room air resulted in mean fluorescent particle counts of 4.75 x 105/m3 and 4.21 x 105/m3 for Ventolin and Ipramol, respectively, representing more than 400-fold increases over mean background level. More than 99.3% of drug particles were <2 µm in diameter and therefore small enough to enter the lower respiratory tract. CONCLUSION: The extractor tent was completely effective for the prevention of airborne spread of drug particles of respirable size from nebulized therapy. This suggests that extractor tents of this type would be efficacious for the prevention of airborne infection from aerosol-generating procedures during the COVID-19 pandemic.

Comparison between microcatheter and nebulizer for generating Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC).

BACKGROUND: This study compares an endoscopic microcatheter and a nebulizer for delivering Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC). METHODS: This is an in vitro and ex vivo study in an established model (inverted bovine urinary bladder). Four parameters were compared to determine the performance of a micro-perforated endoscopic spray catheter vs. state-of-the art, nozzle technology: (1) surface coverage and pattern with methylene blue on blotting paper at three different distances; (2) median aerodynamic diameter (MAD) of aerosol droplets with three different solutions (H2O, Glc 5% and silicon oil); (3) depth of tissue penetration of doxorubicin (DOX) and (4) tissue concentration of cisplatin (CIS) and DOX using standard clinical solutions. RESULTS: The spray area covered by the microcatheter was larger (p < 0.001) but its pattern was inhomogenous than with the nozzle technology. We found that aerosol droplets were larger in the test group than in the control group for all three solutions tested. Median tissue penetration of DOX was lower (980 µm) with the microcatheter than with the nebulizer (1235 µm) and distribution was more heterogeneous ( = 0.003) with the microcatheter. The median tissue concentration of DOX and CIS was lower and concentration of DOX was more heterogeneous with the microcatheter (p = 0.002). CONCLUSIONS: This investigation has revealed that microcatheter technology generates larger aerosol droplet size, less drug tissue penetration and lower drug tissue concentration than the current nozzle technology. In the absence of clinical studies, use of microcatheters for delivering PIPAC can not be recommended at this stage.

Heterogeneous approach to nebulization of antimicrobial agents in mechanically ventilated adults in a German tertiary care hospital: a cross-sectional survey.

There is lack of standardization of practices and limited evidence on efficacy and safety of nebulization of antimicrobials. We sought to determine inhalation practices in one tertiary care hospital by performing a cross-sectional survey. Eleven adult ICUs were included in the analysis. Three units followed established protocols. Ventilation circuit filters were exchanged at least daily in all but one units. Dosages of aminoglycosides and CMS depended on indication and unit. Nebulization of antimicrobials was generally regarded as safe and efficacious. Our data indicate that approach to nebulization of antimicrobials may be heterogeneous even in a single center.

Role of nebulized epinephrine in moderate bronchiolitis: a quasi-randomized trial.

BACKGROUND/AIMS: Bronchiolitis is the most common lower respiratory illness that characteristically affects the children below 2 years of age accounting about 2-3% of patients admitted to hospital each year [1-4]. We compared the effect of racemic epinephrine (RE) and 3% hypertonic saline (HS) nebulization on the length of stay (LOS) in the hospital. METHODS: We looked at the infants with moderate bronchiolitis, from October 2013 to March 2014. Out of eighty cases, 16 in HS and 18 in RE groups were enrolled. At the time of admission, 0.2 ml of RE added to 1.8 ml of distilled water was nebulized to RE group, as compared with 2 ml of 3% HS in nebulized form. RE was re-administered if needed on 6 h in comparison with 3% HS at the frequency of 1 to 4 h. RESULTS: One infant from RE group and three infants from HS group were excluded due to progression towards severe bronchiolitis. The LOS in RE group ranged between 18 and 160 h (mean 45 h), while in HS group, LOS was 18.50-206 h (mean 74.3 h). The LOS was significantly short in RE group (p value 0.015) which was statistically significant. CONCLUSION: Racemic epinephrine nebulization as first-line medication may significantly reduce the length of hospital stay in infants with moderate bronchiolitis in comparison with nebulized HS.

GINA 2020: what's new and why?

The Global initiative against asthma (GINA) 2020 strategy has been released with some changes and updates. GINA recommends the continuation of medications, avoidance of nebulization and spirometry, and ensuring a written asthma action plan in COVID-19 times. GINA 2020 specifies which step of management is to be followed according to the patient's symptoms in an easy flowchart. Clinicians need to be aware of the changes and the evidence behind them.

Nebulised surfactant for the treatment of severe COVID-19 in adults (COV-Surf): A structured summary of a study protocol for a randomized controlled trial.

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 (PaO2/FiO2 ratio) and pulmonary ventilation (Ventilation Index (VI), where VI = [RR x (PIP - PEEP) × PaCO2]/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 5th of June 2020. The recruitment is currently ongoing and started on the 14th 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).

A narrative review of hydrogen-oxygen mixture for medical purpose and the inhaler thereof.

Recent development regarding mixture of H2 (concentration of ~66%) with O2 (concentration of ~34%) for medical purpose, such as treatment of coronavirus disease-19 (COVID-19) patients, is introduced. Furthermore, the design principles of a hydrogen inhaler which generates mixture of hydrogen (~66%) with oxygen (~34%) for medical purpose are proposed. With the installation of the liquid blocking module and flame arresters, the air pathway of the hydrogen inhaler is divided by multiple isolation zones to prevent any unexpected explosion propagating from one zone to the other. An integrated filtering/cycling module is utilized to purify the impurity, and cool down the temperature of the electrolytic module to reduce the risk of the explosion. Moreover, a nebulizer is provided to selectively atomize the water into vapor which is then mixed with the filtered hydrogen-oxygen mix gas, such that the static electricity of a substance hardly occurs to reduce the risk of the explosion. Furthermore, hydrogen concentration detector is installed to reduce the risk of hydrogen leakage. Result shows that the hydrogen inhaler implementing the aforesaid design rules could effectively inhibit the explosion, even ignition at the outset of the hydrogen inhaler which outputs hydrogen-oxygen gas (approximately 66% hydrogen: 34% oxygen).

Combination budesonide/formoterol inhaler as sole reliever therapy in Maori and Pacific people with mild and moderate asthma.

AIM: In the PRACTICAL study, as-needed budesonide/formoterol reduced the rate of severe exacerbations compared with maintenance budesonide plus as-needed terbutaline. In a pre-specified analysis we analysed the efficacy in Maori and Pacific peoples, populations with worse asthma outcomes. METHOD: The PRACTICAL study was a 52-week, open-label, parallel group, randomised controlled trial of 890 adults with mild to moderate asthma, who were randomised to budesonide/formoterol Turbuhaler 200/6mcg one actuation as required or budesonide Turbuhaler 200mcg one actuation twice daily and terbutaline Turbuhaler 250mcg two actuations as required. The primary outcome was rate of severe exacerbations. The analysis strategy was to test an ethnicity-treatment interaction term for each outcome variable. RESULTS: Seventy-two participants (8%) identified as Maori, 36 participants (4%) as Pacific ethnicity. There was no evidence that ethnicity was an effect modifier for severe exacerbations (P interaction 0.70). CONCLUSION: The reduction in severe exacerbation risk with budesonide-formoterol reliever compared with maintenance budesonide was similar in Maori and Pacific adults compared with New Zealand European/Other.

Colistin dry powder inhalation with the Twincer™: An effective and more patient friendly alternative to nebulization.

BACKGROUND: Nebulization of antimicrobial drugs such as tobramycin and colistin is a cornerstone in the treatment of patients with cystic fibrosis (CF) infected with Pseudomonas aeruginosa. However, nebulization has a high treatment burden. The Twincer™ is a dry powder inhaler specifically developed for the inhalation of antibiotics such as colistin. The aim of this study was to compare patient outcomes and experience with colistin dry powder by the Twincer with nebulization of colistin or tobramycin in adult CF patients in a real-life setting. METHODS: This was a retrospective study from 01-01-2015 until 01-07-2018. Effectiveness was evaluated by comparing FEV1 decline and exacerbation rate during a mean of 4.1 years of nebulization therapy prior to the initiation of the Twincer against the same values during a mean of 1.7 years of treatment with the Twincer. RESULTS: Twenty-one patients were evaluated, of whom twelve could be included in the effectiveness analysis, with a total of twenty patient years. Of all patients 71.4% preferred therapy with the Twincer over nebulization. Twincer use resulted in high treatment adherence with an average adherence rate of 92.5%. There was no significant difference in annual decline in FEV1%pred prior to and after start changing from nebulization to the use of the Twincer powder inhaler (median decline -1.56 [-5.57-5.31] and 1.35 [-8.45-6.36]) respectively, p = 0.45 (linear mixed effect model)). No significant difference was found in the number of intravenous or combined total intravenous and oral antibiotic courses during Twincer therapy compared to when using nebulization (1.68 and 2.49 courses during Twincer therapy versus 1.51 and 2.94 courses during nebulization, p = 0.88 and p = 0.63). CONCLUSION: Colistin dry powder inhalation with the Twincer is a more patient friendly alternative to nebulization, and we did not observe significant differences in the clinical outcome, regarding lung function and exacerbation rates.

Fabrication and Characterization of Thickness Mode Piezoelectric Devices for Atomization and Acoustofluidics.

We present a technique to fabricate simple thickness mode piezoelectric devices using lithium niobate (LN). Such devices have been shown to atomize liquid more efficiently, in terms of flow rate per power input, than those that rely on Rayleigh waves and other modes of vibration in LN or lead zirconate titanate (PZT). The complete device is composed of a transducer, a transducer holder, and a fluid supply system. The fundamentals of acoustic liquid atomization are not well known, so techniques to characterize the devices and to study the phenomena are also described. Laser Doppler vibrometry (LDV) provides vibration information essential in comparing acoustic transducers and, in this case, indicates whether a device will perform well in thickness vibration. It can also be used to find the resonance frequency of the device, though this information is obtained more quickly via impedance analysis. Continuous fluid atomization, as an example application, requires careful fluid flow control, and we present such a method with high-speed imaging and droplet size distribution measurements via laser scattering.

Respiratory support in patients with COVID-19 (outside intensive care unit). A position paper of the Respiratory Support and Chronic Care Group of the French Society of Respiratory Diseases.

With first cases noted towards the end of 2019 in China, COVID-19 infection was rapidly become a devastating pandemic. Even if most patients present with a mild to moderate form of the disease, the estimated prevalence of COVID-19-related severe acute respiratory failure (ARF) is 15-20% and 2-12% needed intubation and mechanical ventilation. In addition to mechanical ventilation some other techniques of respiratory support could be used in some forms of COVID-19 related ARF. This position paper of the Respiratory Support and Chronic Care Group of the French Society of Respiratory Diseases is intended to help respiratory clinicians involved in care of COVID-19 pandemic in the rational use of non-invasive techniques such as oxygen therapy, CPAP, non-invasive ventilation and high flow oxygen therapy in managing patients outside intensive care unit (ICU). The aims are: (1) to focus both on the place of each technique and in describing practical tips (types of devices and circuit assemblies) aimed to limit the risk of caregivers when using those techniques at high risk spreading of viral particles; (2) to propose a step-by-step strategy to manage ARF outside ICU.