Journal of Aerosol Medicine and Pulmonary Drug Delivery

Inhaled antibiotics for treating bronchiectasis have been investigated in the cystic fibrosis population since 1981 and long-term clinical benefits have been reported. However, studies on noncystic fibrosis bronchiectasis (NCFB) have only been performed more recently. Owing to limited evidence, inhaled antibiotics are not currently approved for treating NCFB by the U.S. Food and Drug Administration and the European Medicines Agency. The aim of this study was to evaluate the efficacy and safety of tobramycin inhalation therapy in patients with bronchiectasis with Pseudomonas aeruginosa (PA) colonization.

In this retrospective cross-sectional study, NCFB patients who were Pseudomonas positive on three consecutive cultures 1 month apart and receiving tobramycin inhalation therapy were evaluated. Evaluation of the following parameters was done in this study: age, gender, smoking history, symptoms, pulmonary function test results, sputum culture results, tobramycin treatment duration, side effects of tobramycin and response evaluation, and hospital admissions before and after treatment. Treatment with 300 mg tobramycin through nebulizer twice daily for 28 days on-off cycles for a total of 6 months was considered to be one treatment period. The approvals for the study were received by the local ethics committee and institutional review board.

Of the 27 patients, 21 patients completed the first period, 7 patients completed the second period, 4 patients completed the third period, and 1 patient completed the fourth period. Sputum culture was negative in 10 (47.6%) of the 21 patients who completed the first period. Decreased sputum purulence and quantity, dyspnea, and cough were observed during treatment. The frequency of hospitalizations before treatment was 1.24 ± 1.36, whereas after treatment, it decreased to 0.52 ± 0.91, this difference was statistically significant (p = 0.019). The most common side effect was increased dyspnea after nebulization in five patients.

Tobramycin inhalation appears to be a well-tolerated treatment in patients with PA colonization with bronchiectasis. This treatment may decrease the hospitalization rates and improve the symptoms.

Peripheral deposition of inhaled medication is important as small airway disease has a key role in asthma. In this study, we compared the lung deposition at different mean flow rates of three inhaled corticosteroid (ICS)/long-acting beta₂-agonist (LABA) combinations delivered by dry powder inhaler (DPI), that is, Foster NEXThaler^® (extrafine formulation of beclomethasone/formoterol), Relvar Ellipta^® (fluticasone furoate/vilanterol trifenatate), and Symbicort Turbohaler^® (budesonide/formoterol).

In vitro drug delivery parameters were applied to lung computerized tomography (CT) scans of 20 asthma patients by functional respiratory imaging (FRI). Aerosol airway deposition patterns were calculated as percentage (standard deviation) intrathoracic versus extrathoracic deposition, percentage peripheral deposition, and central-to-peripheral (C/P) ratio at different inspiratory mean flow rates.

At 60 and 40 L/min, intrathoracic deposition of ICS/LABA was significantly higher with NEXThaler versus Ellipta. Peripheral deposition (60 L/min) with NEXThaler was higher than Ellipta for ICS (24.7% [3.5%] vs. 5.0% [2.0%]; p < 0.001) and LABA (25.3% [3.5%] vs. 13.0% [3.0%]; p < 0.001). C/P ratio with NEXThaler was lower (indicating higher peripheral deposition) than Ellipta (ICS: 0.63 vs. 1.63; LABA: 0.63 vs. 0.99). Inspiratory flow rate did not impact lung deposition with NEXThaler or Ellipta. In contrast, Turbohaler performance was negatively impacted by decreasing inspiratory flow rate. In fact, although lung deposition with Turbohaler was similar to that of NEXThaler at 60 L/min, lung deposition with Turbohaler was significantly lower than NEXThaler at both 40 L/min (∼30%) and 30 L/min (∼50%).

Using FRI, we demonstrated better peripheral deposition and C/P ratios of ICS/LABA with NEXThaler versus Ellipta. NEXThaler demonstrated inspiratory flow rate independency of lung deposition versus Turbohaler. These findings suggest that the extrafine formulation is superior to large particle formulations in delivering ICS/LABA consistently both to the large and small airways.

The precaution of airborne transmission of viruses, such as influenza, SARS, MERS, and COVID-19, is essential for reducing infection. In this study, we applied a zero-valent nanosilver/titania-chitosan (nano-Ag⁰/TiO₂-CS) filter bed, whose broad-spectrum antimicrobial efficacy has been proven previously, for the removal of viral aerosols to minimize the risk of airborne transmission.

The photochemical deposition method was used to synthesize the nano-Ag⁰/TiO₂-CS antiviral material. The surface morphology, elemental composition, and microstructure of the nano-Ag⁰/TiO₂-CS were analyzed by a scanning electron microscopy/energy dispersive X-ray spectroscopy and a transmission electron microscopy, respectively. The MS2 bacteriophages were used as surrogate viral aerosols. The antiviral efficacy of nano-Ag⁰/TiO₂-CS was evaluated by the MS2 plaque reduction assay (PRA) and filtration experiments. In the filtration experiments, the MS2 aerosols passed through the nano-Ag⁰/TiO₂-CS filter, and the MS2 aerosol removal efficiency was evaluated by an optical particle counter and culture method.

In the MS2 PRA, 3 g of nano-Ag⁰/TiO₂-CS inactivated 97% of MS2 bacteriophages in 20 mL liquid culture (2 ± 0.5 × 10¹⁶ PFU/mL) within 2 hours. The removal efficiency of nano-Ag⁰/TiO₂-CS filter (thickness: 6 cm) for MS2 aerosols reached up to 93%. Over 95% of MS2 bacteriophages on the surface of the nano-Ag⁰/TiO₂-CS filter were inactivated within 20 minutes. The Wells–Riley model predicted that when the nano-Ag⁰/TiO₂-CS filter was used in the ventilation system, airborne infection probability would reduce from 99% to 34.6%. The nano-Ag⁰/TiO₂-CS filter could remain at 50% of its original antiviral efficiency after continuous operation for 1 week, indicating its feasibility for the control of the airborne transmission.

Obstructive patients may benefit from nasal high-flow (NHF) therapy, but the use of pressurized metered-dose inhalers (pMDIs) has not been evaluated in this situation.

Using an adult circuit and medium-sized cannula, we have tested different NHF rates, pMDI positions, breathing patterns, spacers, and spacer orientation. First, we evaluated albuterol delivery at the nasal cannula outlet. The second set of experiments made use of a nasopharyngeal cast to estimate the mass of albuterol potentially reaching the lungs. Albuterol was caught on filters placed at the cannula outlet and downstream of the nasal cast, and albuterol was quantified by spectrophotometry.

The highest amounts of albuterol delivered at the cannula outlet were observed with a 30 L/min flow rate (vs. 45 and 60 L/min) and placing the device close to the nasal cannula (in comparison with a position on the dry side of the humidification chamber). The use of a spacer was associated with higher delivery. The highest albuterol delivery was observed placing the spacer close to the nasal cannula, oriented for aerosol delivery following the gas flow and a 30 L/min NHF rate. Using this optimal setting, activating the pMDI at the beginning of inspiration (compared to expiration) increased albuterol delivery downstream of the nasopharyngeal cast. Whether in a quiet- or distress-breathing pattern, our measurements showed an amount of albuterol potentially delivered to the lungs exceeding 10% of the actuated dose in optimal conditions.

Albuterol delivery with pMDIs is feasible within NHF circuits. Drug delivery sufficient to induce bronchodilation can be achieved using a spacer placed just upstream of the nasal cannula, a low NHF rate, and activation of the pMDI at the beginning of inspiration. Further testing in a clinical setting is required, however.

Chronic rhinosinusitis (CRS) is a disease that can significantly reduce patients' quality of life (QoL). Intranasal steroid therapy is the most commonly used treatment for CRS. There are many evaluation tools dedicated to assessing CRS patients' QoL, but none of them evaluates QoL during local steroid therapy. Mucosal atomization devices (MADs) and nasal saline irrigation (NSI) are effective and safe methods of applying intranasal steroids for CRS patients.

The sample population for this prospective study comprised 43 CRS patients. Following endoscopic sinus surgery, all participants received intranasal steroids administered via an MAD, followed by NSI for 1.5 months. Each participant completed the SNOT-22 (22-item Sino-Nasal Outcomes Test) score and a new questionnaire, the Complementary Topical Nasal Drug Delivery Questionnaire (the Complementary Questionnaire), at the end of 3 months of intranasal steroid therapy.

The patients' responses in both the SNOT-22 score and the Complementary Questionnaire revealed significant differences in their adverse experiences. The patients who received intranasal steroid treatment using NSI experienced more frequently delayed nasal drainage, higher frequency of ear symptoms, and facial pain/pressure, while those whose therapy was administered using an MAD reported complaints such as nasal irritation, nasal dryness, and postnasal drip with unpleasant taste/smell.

We used the Complementary Questionnaire as an effective tool for assessment of the QoL of CRS patients. The SNOT-22 score and the Complementary Questionnaire make it possible to select an intranasal applicator tailored to a CRS patient's specific complaints.