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High flow nasal cannula oxygen therapy (HFT) is increasingly used in intensive and emergency care departments. Patients suffering from respiratory failure, who are likely to benefit from HFT, may require aerosolized bronchodilators; therefore, combining nebulization with HFT may be relevant. This study aimed to identify the optimal settings for the implementation of nebulization within an adult HFT circuit.We assessed the mass and the particle size distribution of the aerosol emitted from the nasal cannula (inhalable mass) using mesh- and jet-nebulizers placed at various positions in the HFT circuit. Thereafter, the most relevant combination was used to evaluate the mass of salbutamol delivered downstream of an anatomical model reproducing aerosol deposition and leakage at the nasal and pharyngeal levels (respirable mass). The influence of HFT flow rate (30, 45, and 60 L/min), of breathing pattern (quiet and respiratory distress pattern) as well as of opened and closed mouth breathing was assessed.The most efficient position was that of a nebulizer placed upstream from the humidification chamber (inhalable mass ranging from 26% to 32% of the nebulizer charge). Using a mesh nebulizer, we observed a respirable mass ranging from 2% to 10% of the nebulizer charge. Higher HFT flow rates and open mouth breathing were associated with a lower efficiency. Simulating respiratory distress (i.e., increasing the simulated patient inspiratory flow) did not hamper drug delivery as compared to a quiet breathing pattern.Placing nebulizers within a HFT circuit upstream from the humidification chamber may enable to deliver clinically relevant masses of aerosol at the cannula outlet, but more importantly downstream of the nose and pharynx, even in case of high patients' inspiratory flow. This method of aerosol therapy is expected to produce a bronchodilatatory effect to be evaluated in the clinical settings.

Open-vent jet nebulizers are frequently used to promote drug deposition in the lung, but their clinical efficacy and indications are not clear. Our study compared lung deposition of amikacin using two different configurations of a jet nebulizer (Sidestream(®)): one vented (N1) and one unvented with a corrugated piece of tubing (N2).In vitro nebulizer performance was assessed by laser diffraction and filtering. Lung delivery was evaluated by scintigraphy in baboons as a child model, and by amikacin urinary drug concentration in seven healthy spontaneously breathing volunteers. Subjects were randomly assigned to the two nebulizer systems (N1 and N2).In vitro results showed a higher efficiency of N2 than N1 in terms of lung deposition prediction (95±3 mg vs. 70±0 mg; p0.0001). Radioactivity deposition in the baboons' lungs was lower with N1 than with N2 (1.8% vs. 4.7% of nebulizer charge; p0.05). The total daily amount of amikacin urinary excretion was lower with N1 than with N2 (29.5 mg vs. 40.1 mg; p0.01). Conversely, in vivo drug output rate was higher with N1 than with N2 (3.1 mg/min vs. 2.2 mg/min; p0.05). Using a corrugated piece of tubing with standard jet nebulizers delivers higher doses to the lungs than open-vent jet nebulizers. The open-vent jet nebulizer might be recommended for rapid administration of a lower dose to the lungs and the standard jet nebulizer with corrugated piece of tubing for a higher dose in the lungs.

We investigated the biodistribution, pharmacokinetics, safety profile, and feasibility of aerosolized gemcitabine (GCB) in patients with lung carcinoma.Eleven patients with carcinoma localized in the lungs were studied in a dose escalation study of aerosolized GCB administered 1 day/week for 9 consecutive weeks. Safety data, scintigraphic assessment of the delivered dose and pharmacokinetic monitoring were analyzed. Patients were treated with doses of between 1 mg/kg and 4 mg/kg (dose in the nebulizer), using a new inhaler device (Aeroneb Pro with an Idehaler Chamber).The total dose of GCB delivered to the patient's lung was 42±16% of the initial amount of dose in the nebulizer. Safety data showed no hematologic toxicity, nephrotoxicity or neurotoxicity. At 4 mg/kg, one patient experienced grade 4 pulmonary toxicity (bronchospasm), which was the dose-limiting toxicity. Grade 2 and 3 toxic effects included fatigue, vomiting, dyspnea, and cough. Overall response: minor response in one patient, stable disease in four patients, progressive disease in four patients. Pharmacokinetic data showed very low plasma GCB levels. Maximal plasma concentration was observed at the end of nebulization. Aerosolized gemcitabin was safe, with minimal toxicity, for patients with lung carcinoma.

The fraction of inspired oxygen (FiO(2)) during oxygen-driven jet nebulization is unknown. In the case of air-driven jet nebulization, oxygen is often added through a nasal device, and again, the FiO(2) is unknown. The aim of this experimental study was to measure FiO(2) during oxygen- and air-driven jet nebulization, oxygen being added through a nasal device, and to compare the values observed with those measured during standard oxygen therapy.An endotracheal tube was inserted into the distal tracheal extremity of a cadaveric head and neck specimen and connected to a pump, simulating different respiratory patterns. FiO(2) was measured using an electrochemical oxygen analyzer under different nebulization and oxygen delivery conditions. Variables were compared using canonical analysis and analysis of simple and multiple variance.FiO(2) was significantly influenced by the mode of oxygen delivery (p = 0.001). The highest FiO(2) was observed when oxygen was delivered via a nasopharyngeal catheter associated with air-driven jet nebulization. For oxygen flow rates of 12 and 15 L/min, a nasal cannula combined with air-driven jet nebulization resulted in a similar FiO(2). The FiO(2) was significantly lower in the case of oxygen-driven jet nebulization. The FiO(2) decreased with increasing respiratory rate (p0.001) and tidal volume (p0.001).Oxygen delivery through a nasal device during air-driven jet nebulization significantly increases the FiO(2), whereas oxygen-driven jet nebulization dramatically decreases FiO(2) compared with standard oxygen therapy.

Ventilator-associated pneumonia (VAP) caused by methicillin-resistant Staphylococcus aureus is a major cause of mortality in mechanically ventilated patients. Nebulization of teicoplanin is an alternative way of administration that may provide higher lung tissue concentrations than intravenous (IV) delivery. The aim of this study was to compare the administration of teicoplanin via aerosol with the IV route by measuring the lung and the serum teicoplanin concentrations in a rat model.Eighty healthy male Sprague-Dawley rats were anesthetized and received a single dose of teicoplanin by the IV or aerosol route. After sacrifice, lung and blood samples were collected and teicoplanin concentrations were measured with fluorescence polarization. A noncompartmental approach was used. The area under the concentration curve/minimal inhibition concentration ratio (AUC/MIC), AUC, absorbed fraction, mean residence time (MRT), and mean absorption time (MAT) of teicoplanin were calculated.Mean±SD lung tissue concentrations of teicoplanin in the aerosol group were significantly higher than those in the IV group (p0.0001). The mean lung tissue concentration achieved at 15 min was 1.94±1.33 mg/g in the aerosol group and 0.04±0.01 mg/g in the IV group. The mean AUClung was 67.4 mg hr(-1)g(-1) after aerosol and 0.8 mg hr(-1)g(-1) after the IV route. In the aerosol group, AUCserum/MIC ratio was 605/2, and in the IV route, AUCserum/MIC ratio was 682/2. MAT was longer after aerosol than after the IV route (0.91 hr versus 0.06 hr), and MRT was longer after aerosol than after IV bolus administration (6.52 hr versus 5.61 hr).Teicoplanin concentrations in the lung tissue of the rat model were significantly higher by the aerosol route than by the IV route. The AUClung after nebulization was 84 times higher than delivery by the IV route, and the AUClung/MIC ratio after nebulization met the recommended target to eradicate Staphylococcus aureus. Administration of teicoplanin by the aerosol route could represent one of the new therapeutic weapons of the treatment of the VAP.

The Mastersizer X (Malvern Instruments) used to be the reference device for assessing droplet size distribution of aerosols by laser diffraction, but it has not been updated and has gradually been replaced by the Spraytec (Malvern Instruments), which is considered to provide greater accuracy and higher acquisition speed.The aim of this study was to compare the use of the two diffractometers to characterize medical liquid aerosols in a wide range of droplet sizes, using four nasal sprays to produce large droplets (10-180 μm) and 10 nebulizers to produce smaller droplets (0.5-20 μm). The influence of the inhalation cell provided with the Spraytec on the measurements was also determined.Correlation between the devices was low for large droplets (R(2)=0.37) and high for smaller droplets (R(2)=0.97). The Spraytec overestimated the median diameter of small droplets by 14%, and Bland-Altman tests showed no equivalence (limits of agreement over 20%). An artifact peak in the large size range was observed with the Spraytec, which could be due to difficulty for the multiple scattering algorithm to process high-density aerosol clouds. The difference was reduced to 5% by using the inhalation cell provided by the Spraytec with a 15 L/min aspiration.The Mastersizer X and the Spraytec cannot be considered as equivalent laser diffraction devices, but the difference can be reduced with the Spraytec inhalation cell.

Aerosol therapy is an expanding technique allowing administration of drugs acting locally in the bronchial tree and lungs or acting systemically after absorption through the respiratory tract. However, the choice of solvents and adjuvants is a critical step in the formulation process of new drugs. Pulmonary tolerance of ethanol, propylene glycol and sorbitan ester was evaluated in a rat model of intratracheal administration using a Microsprayer in a 4-day toxicity study.Four groups of Sprague-Dawley rats (11 rats per group, n = 44) have received, on 4 consecutive days 150 microL of solutions containing the solvents, by intratracheal route using a IA-1B-2 inches-Microsprayer (PennCentury, Philadelphia, PA). Once a day, the rats received deionized water (control) or ethanol 10% or propylene glycol 30% or sorbitan monooleate 10%. All rats were sacrificed 24 h after the fourth administration. Biochemical analysis on bronchoalveolar lavage (BAL) fluid was performed on seven rats per group. The respiratory tract of the remaining four rats/group was examined histologically.Biochemistry and histopathology findings demonstrated that under the conditions tested, deionized water, 10% ethanol, and 30% propylene glycol were tolerated in a qualitatively similar way presenting limited cellular reaction. In contrast, 10% sorbitan monooleate produced an accumulation of foamy macrophages in the lungs and a higher degree of inflammation. In addition, animals in this group showed higher polymorphonuclear neutrophil recruitment and total proteins levels in BAL fluid.The overall results recommended ranking the vehicles according to the degree of inflammation which was induced: deionized water10% ethanolor =30% propylene glycol10% Tween 80.