Individualized aerosol medicine: Integrating device into the patient.

Pulmonary drug delivery is complex due to several challenges including disease-, patient-, and clinicians-related factors. Although many inhaled medications are available in aerosol medicine, delivering aerosolized medications to patients requires effective disease management. There is a large gap in the knowledge of clinicians who select and provide instructions for the correct use of aerosol devices. Since improper device selection, incorrect inhaler technique, and poor patient adherence to prescribed medications may result in inadequate disease control, individualized aerosol medicine is essential for effective disease management and control. The components of individualized aerosol medicine include: (1) Selecting the right device, (2) Selecting the right interface, (3) Educating the patient effectively, and (4) Increasing patient adherence to therapy. This paper reviews each of these components and provides recommendations to integrate the device and interface into the patient for better clinical outcomes.

Estimating Tiotropium Wasted Doses After Adding Revefenacin to an Inpatient Formulary: A Single-Center Cross-Sectional Study.

Introduction: Revefenacin is a once-daily nebulized long-acting muscarinic antagonist (LAMA). Revefenacin is supplied as single-use nebulized vials, which may be preferable and less costly for hospital and health-system pharmacies to dispense versus multidose tiotropium inhalers. Estimates of LAMA multidose inhaler wasted doses remains unknown. Methods: This was a single-center descriptive cross-sectional study conducted between January 1 2021 and December 31 2021. Adult patients 18 years and older admitted to a 500-bed academic medical center in the southern United States and were ordered multidose tiotropium packages or single-use revefenacin vials during the study period were included. Results: Among 602 inpatients, there were 705 LAMA orders: 541 tiotropium (76.7%) and 164 revefenacin (23.3%). Four hundred ninety-five tiotropium orders (91.5%) wasted between 20% and 90% of multidose packages. Approximately $24,000 tiotropium doses were wasted versus single-use revefenacin vials. Conclusion: Multidose inhalers of tiotropium dispensed to hospitalized patients contributed to wasted doses compared to nebulized single-use revefenacin vials. Opportunities exist to minimize wasted doses of multidose long-acting inhalers dispensed to hospitalized patients.

Formulation, Device, and Clinical Factors Influencing the Targeted Delivery of COVID-19 Vaccines to the Lungs.

The COVID-19 pandemic has proven to be an unprecedented health crisis in the human history with more than 5 million deaths worldwide caused to the SARS-CoV-2 and its variants ( https://www.who.int/emergencies/diseases/novel-coronavirus-2019 ). The currently authorized lipid nanoparticle (LNP)-encapsulated mRNA vaccines have been shown to have more than 90% vaccine efficacy at preventing COVID-19 illness (Baden et al. New England J Med 384(5):403-416, 2021; Thomas et al., 2021). In addition to vaccines, other small molecules belonging to the class of anti-viral and anti-inflammatory compounds have also been prescribed to reduce the viral proliferation and the associated cytokine storm. These anti-viral and anti-inflammatory compounds have also been shown to be effective in reducing COVID-19 exacerbations especially in reducing the host inflammatory response to SARS-CoV-2. However, all of the currently FDA-authorized vaccines for COVID-19 are meant for intramuscular injection directly into the systemic circulation. Also, most of the small molecules investigated for their anti-COVID-19 efficacy have also been explored using the intravenous route with a few of them explored for the inhalation route (Ramakrishnan et al. Lancet Respir Med 9:763-772, 2021; Horby et al. N Engl J Med 384(8):693-704, 2021). The fact that the SARS-CoV-2 enters the human body mainly via the nasal and airway route resulting in the lungs being the primary organs of infection as characterized by acute respiratory distress syndrome (ARDS)-mediated cytokine storm in the alveolar region has made the inhalation route gain significant attention for the purposes of targeting both vaccines and small molecules to the lungs (Mitchell et al., J Aerosol Med Pulm Drug Deliv 33(4):235-8, 2020). While there have been many studies reporting the safety and efficacy of targeting various therapeutics to the lungs to treat COVID-19, there is still a need to match the choice of inhalation formulation and the delivery device platform itself with the patient-related factors like breathing pattern and respiratory rate as seen in a clinical setting. In that perspective, this review aims to describe the various formulation and patient-related clinical factors that can play an important role in the judicious choice of the inhalation delivery platforms or devices for the development of inhaled COVID-19 vaccines.

Chronic obstructive pulmonary disease patients' experience using Trelegy as compared with other inhalers.

Introduction: Trelegy is a combination inhaler that is often reported to offer benefits over multiple inhalers. We compared Trelegy use with multiple inhalers for adherence, symptoms, medication beliefs, and medication attitudes. Methods: This cross-sectional survey of 58 patients compared the patient's experience with Trelegy (n = 18) versus any other inhaler (n = 40). Outcome variables consisted of Test of the Adherence to Inhalers scale, the Chronic obstructive pulmonary disease Assessment Test (CAT) scale, attitude items from the St. George's Respiratory Questionnaire, the Beliefs about Medicines Questionnaire (BMQ)-necessity subscale, and the BMQ-concerns subscale. Results: We found that patients using Trelegy had greater CAT symptoms (M = 19.8, SD = 7.75) in comparison with the any other inhaler group (M = 15.7, SD = 11.10; P = 0.04). We did not find any difference between the groups for adherence or any of the medication attitudes or beliefs. CAT score was positively correlated with the number of months patients were on their current inhaler (r s = 0.29, P < 0.05) and their use of a rescue inhaler (r s = 0.42, P < 0.01). Patients with more concern about their medications were negatively correlated with the use of a rescue inhaler (r s = -0.31, P < 0.05). Discussion: We found that patients using Trelegy had greater symptoms in comparison with the any other inhaler group, but did not differ for adherence, medication attitudes, or medication beliefs. Conclusion: We recommend that clinicians should regularly re-evaluate their Trelegy recommendations, as Trelegy use may not be the best therapy for certain patients. Also, a study with a larger sample size can be beneficial to confirm these findings.

Effect of functional principle, delivery technique, and connection used on aerosol delivery from different nebulizers: An in-vitro study.

OBJECTIVE: Nebulizers can be divided according to their functional principle into jet, ultrasonic and vibrating mesh nebulizers with intermittent or continuous aerosol delivery and may be used with many different adapters and connections and all can influence their efficiency. The aim of the present work was to evaluate the effect functional principle, delivery technique, and connection used on aerosol delivered from four different nebulizers. METHODS: Four nebulizers were used in the study; three of them were jet nebulizers (JNs; AeroEclipse, NebuTech, En ful Kit) and one of them was Aerogen Solo vibrating mesh nebulizers (VMN). AeroEclipse and NebuTech are intermittent output nebulizers, while the rest are continuous output nebulizers. Aerogen Solo was used with either a standard T-piece or Aerogen Ultra holding chamber, and En ful Kit was used with a standard T-piece or Circulaire II holding chamber. 2 ml of salbutamol was nebulized to determine the total emitted dose (TED) and aerodynamic droplet characteristics of the emitted aerosol from the 6 different sets (4 nebulizers with T-piece and 2 holding chambers). RESULTS: The mean ± SD TED from VMN was significantly higher than all the JNs (p < 0.05). Aerogen Ultra with VMN did not show a significant effect on TED compare to T-piece, but it significantly increased (p < 0.05) fine particle dose (FPD; 3091.5 ± 189.4 µg) and fine particle fraction (FPF; 72.7 ± 3.6%). However, the Circulaire II with En ful Kit had significantly higher TED, FPD, and FPF compared to T-piece (p < 0.05). Intermittent JNs (AeroEclipse and NebuTech) had significantly higher TED (p < 0.05) compared to the continuous JNs (En ful Kit) with no significant effect on the other parameters studied. AeroEclipse had the highest MMAD and Aerogen Solo Ultra has the lowest in MMAD. CONCLUSIONS: The functional principle, delivery technique, and connection used had a significant effect on aerosol delivered from nebulizers. VMNs are significantly better than JNs. Intermittent delivery has significantly better TED than continuous delivery. Holding chamber with both VMNs and JNs improved aerosol delivery compared to standard T-piece.

Aerosol drug delivery to tracheotomized patients with COVID-19: Pragmatic suggestions for clinicians.

Because of the wide and rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the number of hospitalized patients with coronavirus disease 2019 (COVID-19) has rapidly increased medically complex and resource-intensive treatment requirements in health care settings. Although tracheostomy is frequently needed for critically ill patients requiring extended mechanical ventilation, it has been described as an aerosol-generating procedure that puts health care professionals at an increased risk of viral transmission. In addition, the delivery of aerosolized medications to this patient population has become controversial because of concerns on the transmission of SARS-CoV-2 via droplets. Although aerosol therapy in spontaneously breathing patients with COVID-19 was described in recent publications, innovations in aerosol drug delivery to COVID-19 patients with tracheostomy have not been presented. Therefore, empirically based guidance on how to deliver aerosols safely and effectively to tracheotomized patients with COVID-19 is still lacking. This paper provides recommendations and rationales for device selection, interface selection, delivery techniques, and infection control based on the evolving body of literature.

How to deliver aerosolized medications through high flow nasal cannula safely and effectively in the era of COVID-19 and beyond: A narrative review.

BACKGROUND: The treatments of COVID-19 involve some degree of uncertainty. Current evidence also shows mixed findings with regards to bioaerosol dispersion and airborne transmission of COVID-19 during high flow nasal cannula (HFNC) therapy. While coping with this global pandemic created hot debates on the use of HFNC, it is important to bring detached opinions and current evidence to the attention of health care professionals (HCPs) who may need to use HFNC in patients with COVID-19. AIM: The purpose of this paper is to provide a framework on the selection, placement, and use of nebulizers as well as HFNC prongs, gas flow, and delivery technique via HFNC to help clinicians deliver aerosolized medications through HFNC safely and effectively in the era of COVID-19 and beyond. METHODS: We searched PubMed, Medline, CINAHL, and Science Direct to identify studies on aerosol drug delivery through HFNC using the following keywords: ("aerosols," OR "nebulizers") AND ("high flow nasal cannula" OR "high flow oxygen therapy" OR "HFNC") AND ("COVID-19," OR "SARS-CoV-2"). Twenty-eight articles including in vitro studies, randomized clinical trials, scintigraphy studies, review articles, prospective and retrospective research were included in this review. DISCUSSION AND RESULTS: It is not clear if the findings of the previous studies on bacterial contamination could be applied to viral transmission because they do not provide data that could be extrapolated to the risk of SARS-CoV-2 transmission. In the face of the unknown risk with the transmission of COVID-19 during HFNC therapy, the benefits of HFNC must be weighed against the risk of infection to HCPs and other patients. Due to the limited number of ventilators available in hospitals and the confirmed effectiveness of HFNC in treating hypoxemic respiratory failure, HFNC may prevent early intubation, and prolonged intensive care unit stays in patients with COVID-19. CONCLUSION: Clinicians should review the magnitude of this risk based on current evidence and use the suggested strategies of this paper for safe and effective delivery of aerosolized medications through HFNC in the era of COVID-19 and beyond.

Procedures in COVID-19 Patients: Part-I.

The number of cases with novel coronavirus disease-2019 (COVID-19) infection is increasing every day in the world, and India contributes a substantial proportion of this burden. Critical care specialists have accepted the challenges associated with the COVID-19 pandemic and are frontline warriors in this war. They have worked hard in streamlining workflow isolation of positive patients, clinical management of critically ill patients, and infection prevention practices. With no end in sight for this pandemic, intensive care unit (ICU) practitioners, hospital administrators, and policy makers have to join hands to prepare for the surge in critical care bed capacity. In this position article, we offer several suggestions on important interventions to the ICU practitioners for better management of critically ill patients. This position article highlights key interventions for COVID-19 treatment and covers several important issues such as endotracheal intubation and tracheostomy (surgical vs PCT), nebulization, bronchoscopy, and invasive procedures such as central venous catheters, arterial lines, and HD catheters. How to cite this article: Pande RK, Bhalla A, SN Myatra, Yaddanpuddi LN, Gupta S, Sahoo TK, et al. Procedures in COVID-19 Patients: Part-I. Indian J Crit Care Med 2020;24(Suppl 5):S263-S271.

Inhaled Cisplatin for NSCLC: Facts and Results.

Although we have new diagnostic tools for non-small cell lung cancer, diagnosis is still made in advanced stages of the disease. However, novel treatments are being introduced in the market and new ones are being developed. Targeted therapies and immunotherapy have brought about a bloom in the treatment of non-small cell lung cancer. Still we have to find ways to administer drugs in a more efficient and safe method. In the current review, we will focus on the administration of inhaled cisplatin based on published data.

Nebulization versus standard application for topical anaesthesia during flexible bronchoscopy under moderate sedation - a randomized controlled trial.

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 ; 13th October 2014).

Aerosol delivery during spontaneous breathing with different types of nebulizers- in vitro/ex vivo models evaluation.

BACKGROUND: Nebulizers for spontaneous breathing have been evaluated through different study designs. There are limitations in simulated bench models related to patient and nebulizer factors. The aim of this study was to determine the correlation of inhaled drug mass between in vitro and ex vivo studies by testing aerosol deposition of various types of nebulizers. METHODS: Ten healthy subjects were recruited to receive aerosol therapy with five nebulizers in random order: 1) a jet nebulizer (JN); 2) a breath-enhanced nebulizer (BEN); 3) a manually triggered nebulizer (MTN), 4) a breath-actuated nebulizer (BAN), and 5) a vibrating mesh nebulizer (VMN) with valved-adapter. A unit dose of salbutamol containing 5 mg in 2.5 mL was placed into the nebulizer and administered for 10 min. For the ex vivo study, minute ventilation of healthy subjects was recorded for 1 min. For the in vitro study a breathing simulator was utilized with adult breathing patterns. Aerosolized drug from the nebulizers and the accessory tubes was captured using inspiratory and expiratory collecting filters. Captured drug was eluted, measured and expressed as inhaled and exhaled mass using spectrophotometry at a wavelength of 276 nm. RESULTS: 10 healthy subjects were recruited, aged 20.8 ±â€¯0.7 years old, with a mean height of 166.2 ±â€¯9.2 cm and weight of 64.7 ±â€¯12.4 kg. There was no significant difference in the inhaled drug dose between the JN and BEN (15.0 ±â€¯1.94% and 17.74 ±â€¯2.65%, respectively, p = .763), yet the inhaled doses were lower than the other three nebulizers (p < .001). The VMN delivered greater inhaled dose than the other four nebulizers (p < .01). The respiratory rate of the cohorts was significantly correlated with the inhaled drug dose. For the in vitro model, the JN delivered a lower inhaled dose (11.6 ±â€¯1.6, p < .001) than the other nebulizers, whereas the MTN and BAN deposited significantly lower exhaled doses (1.7 ±â€¯0.4 and 2.7 ±â€¯0.2, respectively, p < .001). The VMN demonstrated a greater drug dose with the in vitro study than the ex vivo model (44.0 ±â€¯0.9% and 35.5 ±â€¯6.3% respectively, p = .003), whereas the JN in the ex vivo model resulted in a greater inhaled drug dose (15.0 ±â€¯1.9% for ex vivo vs 11.6 ±â€¯1.6% for in vitro, p = .008). CONCLUSIONS: These in vitro/ex vivo model comparisons of nebulizers performance indicated that breath-related nebulizers can be estimated using an in vitro model; however, the JN and VMN delivered inhaled drug mass differed between models. There was a significant correlation between respiratory rate and inhaled mass, and the inhaled drug dose generated by VMN correlated with minute ventilation. This study demonstrated that the VMN produced greater inhaled drug dose and lowest residual dose, whereas the BEN, BAN, and MTN produced lower exhaled drug dose in both in vitro and ex vivo models.

Delivery of sevoflurane using a neonatal ventilator.

BACKGROUND: Most anesthetic ventilators are designed to cope with a wide range of patient sizes and may lack precision at the lowest end of the minute volume scale. Neonatal intensive care ventilators on the other hand are designed specifically for this patient group, but are not able to deliver volatile anesthesia. AIMS: We aimed to adapt the neonatal ventilator currently in use in our institution to deliver sevoflurane by incorporating a vaporizer and a scavenging system. METHODS: We used a Diamedica draw-over vaporizer incorporated into the ventilator circuit and a custom designed open interface scavenging system. A number of safety measures are described to ensure that this equipment is correctly inserted into the circuit. RESULTS: Bench testing revealed that the vaporizer output is linear and stable within the circuit flow range 4-8 L/min in all modes except high frequency oscillation where concentrations are not predictable. The scavenging system was found to be effective and did not affect volumes, pressures or waveforms when ventilating a test lung over a wide range of flows and pressures. This remained the case over the full range of scavenger flow adjustment. CONCLUSION: The addition of a Diamedica vaporizer to a Fabian neonatal ventilator was shown in bench testing to provide stable, linear vapor concentrations without compromise of ventilator function. The system should not be used in high frequency oscillation mode because concentrations will exceed those expected and will not maintain a linear relationship with the vaporizer setting.

Methoxyflurane for Procedural Analgesia at 4470 m Altitude.

Methoxyflurane is a volatile, fluorinated anesthetic agent with analgesic properties. Although no longer used as an anesthetic due to concerns regarding renal toxicity in high doses, it has enjoyed a resurgence as an inhaled analgesic in prehospital care and in the emergency department. The agent is nonflammable and leads to rapid, titratable analgesia without intravenous access. The Penthrox inhaler device is light, robust, and straightforward to administer. Consequently, it has been proposed as an ideal analgesic for the remote high altitude setting. We report its use for procedural analgesia during suprapubic aspiration for acute urinary retention at a remote rescue post at night, in cold winter conditions, at 4470 m altitude in Machermo, Nepal. We found that methoxyflurane provided rapid, effective analgesia for our patient's visceral and procedural pain. The inhaler was easy to administer, and the patient remained responsive to voice, with satisfactory oxygen saturation and respiratory rate throughout. We also briefly review the administration, dosing, efficacy, and safety of methoxyflurane and its role in remote medical care.

Nebulization of Single-Chain Tissue-Type and Single-Chain Urokinase Plasminogen Activator for Treatment of Inhalational Smoke-Induced Acute Lung Injury.

Single-chain tissue-type plasminogen activator (sctPA) and single-chain urokinase plasminogen activator (scuPA) have attracted interest as enzymes for the treatment of inhalational smoke-induced acute lung injury (ISALI). In this study, the pulmonary delivery of commercial human sctPA and lyophilized scuPA and their reconstituted solution forms were demonstrated using vibrating mesh nebulizers (Aeroneb® Pro (active) and EZ Breathe® (passive)). Both the Aeroneb® Pro and EZ Breathe® vibrating mesh nebulizers produced atomized droplets of protein solution of similar size of less than about 5 µm, which is appropriate for pulmonary delivery. Enzymatic activities of scuPA and of sctPA were determined after nebulization and both remained stable (88.0% and 93.9%). Additionally, the enzymatic activities of sctPA and tcuPA were not significantly affected by excipients, lyophilization or reconstitution conditions. The results of these studies support further development of inhaled formulations of fibrinolysins for delivery to the lungs following smoke-induced acute pulmonary injury.

Effects of ventilator settings, nebulizer and exhalation port position on albuterol delivery during non-invasive ventilation: an in-vitro study.

BACKGROUND: Few studies have investigated the factors affecting aerosol delivery during non-invasive ventilation (NIV). Our aim was to investigate, using a bench-top model, the effect of different ventilator settings and positions of the exhalation port and nebulizer on the amount of albuterol delivered to a lung simulator. METHODS: A lung model simulating spontaneous breathing was connected to a single-limb NIV ventilator, set in bi-level positive airway pressure (BIPAP) with inspiratory/expiratory pressures of 10/5, 15/10, 15/5, and 20/10 cmH2O, or continuous positive airway pressure (CPAP) of 5 and 10 cmH2O. Three delivery circuits were tested: a vented mask with the nebulizer directly connected to the mask, and an unvented mask with a leak port placed before and after the nebulizer. Albuterol was collected on a filter placed after the mask and then the delivered amount was measured with infrared spectrophotometry. RESULTS: Albuterol delivery during NIV varied between 6.7 ± 0.4% to 37.0 ± 4.3% of the nominal dose. The amount delivered in CPAP and BIPAP modes was similar (22.1 ± 10.1 vs. 24.0 ± 10.0%, p = 0.070). CPAP level did not affect delivery (p = 0.056); in BIPAP with 15/5 cmH2O pressure the delivery was higher compared to 10/5 cmH2O (p = 0.033) and 20/10 cmH2O (p = 0.014). Leak port position had a major effect on delivery in both CPAP and BIPAP, the best performances were obtained with the unvented mask, and the nebulizer placed between the leak port and the mask (p < 0.001). CONCLUSIONS: In this model, albuterol delivery was marginally affected by ventilatory settings in NIV, while position of the leak port had a major effect. Nebulizers should be placed between an unvented mask and the leak port in order to maximize aerosol delivery.

A spray-based technique for the production of MnS thin films.

A spray-based technique, originally developed for the production of semiconductor nanocrystals, is utilized for the preparation of high-quality nanocrystalline thin films, as demonstrated with manganese sulfide. The films are formed by the use of pneumatic-assisted thermospray or pneumatic nebulizers. Our simple, low-cost, and low-temperature process results in a dense and phase-pure grain structure. The concepts and benefits of this technique are described and discussed. The film characteristics show dependence on the experimental parameters, in particular the rate of solvent vaporization. Three alternative film formation mechanisms are suggested for cases with varied experimental conditions.

Deposition of Particles in the Alveolar Airways: Inhalation and Breath-Hold with Pharmaceutical Aerosols.

Previous studies have demonstrated that factors such as airway wall motion, inhalation waveform, and geometric complexity influence the deposition of aerosols in the alveolar airways. However, deposition fraction correlations are not available that account for these factors in determining alveolar deposition. The objective of this study was to generate a new space-filling model of the pulmonary acinus region and implement this model to develop correlations of aerosol deposition that can be used to predict the alveolar dose of inhaled pharmaceutical products. A series of acinar models was constructed containing different numbers of alveolar duct generations based on space-filling 14-hedron elements. Selected ventilation waveforms were quick-and-deep and slow-and-deep inhalation consistent with the use of most pharmaceutical aerosol inhalers. Computational fluid dynamics simulations were used to predict aerosol transport and deposition in the series of acinar models across various orientations with gravity where ventilation was driven by wall motion. Primary findings indicated that increasing the number of alveolar duct generations beyond 3 had a negligible impact on total acinar deposition, and total acinar deposition was not affected by gravity orientation angle. A characteristic model containing three alveolar duct generations (D3) was then used to develop correlations of aerosol deposition in the alveolar airways as a function of particle size and particle residence time in the geometry. An alveolar deposition parameter was determined in which deposition correlated with d2t over the first half of inhalation followed by correlation with dt2, where d is the aerodynamic diameter of the particles and t is the potential particle residence time in the alveolar model. Optimal breath-hold times to allow 95% deposition of inhaled 1, 2, and 3 µm particles once inside the alveolar region were approximately >10, 2.7, and 1.2 s, respectively. Coupling of the deposition correlations with previous stochastic individual path (SIP) model predictions of tracheobronchial deposition was demonstrated to predict alveolar dose of commercial pharmaceutical products. In conclusion, this study completes an initiative to determine the fate of inhaled pharmaceutical aerosols throughout the respiratory airways using CFD simulations.

Indicators for childhood asthma in Spain, using the Rand method.

OBJECTIVE: To develop quality indicators to measure asthma care in primary health care. METHOD: A modified RAND was used, which included the systematic review of the literature in Embase, Cochrane and Pubmed Quality Agencies and Database. The work group identified the indicators, translated them into Spanish and resolved any duplicates. Each indicator is composed of several dimensions (access to care, clinical effectiveness, patient-centred quality and patient safety). A multidisciplinary panel of 98 professionals from all over Spain were invited to score each indicator using a Likert scale. After calculating the average and median of each indicator, this information was sent to those who responded (n=38) for a second round and further scoring. The agreement percentage for the group was obtained for each indicator. RESULTS: Of the 105 asthma indicators reviewed, we selected 46 that were presented to the panel of experts. In both Delphi phases, 37.1% of the members of the initial panel of experts responded. Of these, 26 were primary care paediatricians, six were pulmonologists, three were nurses, two were pharmacists and one was an allergist. For 32 indicators, agreement exceeded 70% and seven of those scored highest for the various care aspects for asthmatic children. CONCLUSION: Quality indicators are presented for the follow-up of asthma and their implementation in primary care, which have undergone a strict selection and agreement process by a multidisciplinary work group.

Nebulisation of Paclitaxel, Sotatercept and Iloprost for pulmonary hypertension for lung cancer. From In vitro to In vivo.

Background: Pulmonary hypertension is common symptom among several diseases. The consequences are severe for several organs. Pulmonary hypertension is usually under-diagnosed and the main symptom observed is dyspnea with or without exercise. Currently we have several treatment modalities administered orally, via inhalation, intravenously and subcutaneously. In advanced disease then heart or lung transplantation is considered. The objective of the study was to investigate the optimum method of aerosol production for the drugs: iloprost, paclitaxel and the novel sotatercept. Materials and Methods: In our experiment we used the drugs iloprost, paclitaxel and the novel sotatercept, in an experimental concept of nebulization. We performed nebulization experiments with 3 jet nebulizers and 3 ultrasound nebulizers with different combinations of residual cup designs, and residual cup loadings in order to identify which combination produces droplets of less than 5µm in mass median aerodynamic diameter. Results: We concluded that paclitaxel cannot produce small droplets and is also still very greasy and possible dangerous for alveoli. However; iloprost vs sotatercept had smaller droplet size formation at both inhaled technologies (1.37<2.23 and 1.92<3.11, jet and ultrasound respectively). Moreover; residual cup designs C and G create the smallest droplet size in both iloprost and sotatercept. There was no difference for the droplet formation between the facemask and cone mouthpieces. Discussion: Iloprost and sotatercept can be administered as aerosol in any type of nebulisation system and they are both efficient with the residual cups loaded with small doses of the drug (2.08 and 2.12 accordingly).