Rajiv Dhand

Selecting an accessory device with a metered-dose inhaler: variable influence of accessory devices on fine particle dose, throat deposition, and drug delivery with asynchronous actuation from a metered-dose inhaler.

Accessory devices reduce common problems with metered-dose inhalers (MDIs), namely high oropharyngeal deposition of aerosol and incoordination between actuation and inhalation by the patient. The objective of this study was to systematically compare the performance of various accessory devices in vitro. MDIs were tested alone or in combination with four spacers (Toilet paper roll, Ellipse, Optihaler, Myst Assist) and five holding chambers (Aerochamber, Optichamber, Aerosol Cloud Enhancer, Medispacer, and Inspirease). An Anderson cascade impactor was used to measure aerosol mass median aerodynamic diameter (MMAD) and fine particle dose (MMAD < 4.7 microm). In separate experiments, the influence of asynchronous MDI actuation on drug delivery was determined with a simulated spontaneous breathing model. Compared with the MDI alone, all of the accessory devices reduced aerosol MMAD and increased lung-throat ratio (fine particle dose/throat impaction; p < 0.05 for both parameters). The fine particle dose of albuterol was 40% higher with the Ellipse (p < 0.01), was equivalent with the Toilet Paper Roll, Aerochamber, Optichamber, and Medispacer, and was 33-56% lower with the Optihaler, Myst Assist, Aerosol Cloud Enhancer, and Inspirease (p < 0.03). MDI actuation in synchrony with inspiration produced highest drug delivery; when MDI actuation occurred 1-sec before inspiration or during exhalation, decrease in drug delivery with holding chambers (10-40% reduction) was less than that with spacers (40-90% reduction). Accessory device selection is complicated by variability in performance between devices, and in the performance of each device in different clinical settings. In vitro characterization of a MDI and accessory device could guide appropriate device selection in various clinical settings.

How Should Aerosols Be Delivered During Invasive Mechanical Ventilation

The delivery of aerosols to mechanically ventilated patients presents unique challenges and differs from inhaled drug delivery in spontaneously breathing patients in several respects. Successful aerosol delivery during invasive mechanical ventilation requires careful consideration of a host of factors that influence the amount of drug inhaled by the patient. Pressurized metered-dose inhalers and nebulizers (jet, ultrasonic, and vibrating mesh) are the most commonly used aerosol delivery devices in these patients, although other delivery devices, such as dry powder inhalers, soft mist inhalers, and intratracheal nebulizing catheters, could also be adapted for in-line use. Bronchodilators, inhaled corticosteroids, antibiotics, pulmonary surfactant, mucolytics, biologicals, genes, prostanoids, and other agents are administered by inhalation during mechanical ventilation for a variety of indications. The goals of inhalation therapy during mechanical ventilation could be best achieved by (1) assuring drug delivery; (2) optimizing drug deposition in the lung; (3) providing consistent dosing; (4) avoiding inappropriate therapies; (5) achieving reproducible dosing; (6) employing clinically feasible methods; (7) enhancing the safety of inhaled drugs; and (8) controlling costs of aerosol therapy. The techniques of administration of aerosols with various delivery devices during mechanical ventilation are well known, but there continues to be significant variation in clinical practice and guidelines are needed to provide best practices for a wide range of clinical settings encountered in mechanically ventilated patients.

Inhaled Drug Therapy 2016: The Year in Review

Some recent salient publications related to inhaled drug therapy are discussed. Unexpectedly, a 2.5-μg once-daily dose of tiotropium (Respimat) had greater efficacy than the 5.0-μg daily dose. Occurrence of a reverse dose response serves to caution us that administering more drug is not always beneficial. Small-airway inflammation contributes to pathogenesis of asthma, especially severe asthma. However, there is no conclusive evidence that the use of small-particle aerosols to target small airways improves clinical outcomes in controlled clinical trials. Clinical outcomes of patients with symptomatic asthma have been better in “real-life” studies when fine-particle aerosols were compared with conventional (large-particle) aerosols. In subjects with COPD, the FLAME study indicates that a long-acting antimuscarinic agent/long-acting β-agonist combination was superior to an inhaled corticosteroid/long-acting β-agonist combination in preventing exacerbations. Another study in children with asthma and adults with asthma or COPD showed that peak inhalation flow must be considered in the context of the dry powder inhaler resistance. Investigators from the United Kingdom have shown modest success in replacing the defective cystic fibrosis transmembrane regulator gene in subjects with cystic fibrosis with a plasmid encoding the normal cystic fibrosis transmembrane regulator gene packaged within a non-viral vector. Also, inhaled antibiotics in patients with non-cystic fibrosis bronchiectasis and inhaled interferon-γ in patients with idiopathic pulmonary fibrosis have shown encouraging results but are investigational at this time. Compared to combustion cigarettes, use of e-cigarettes reduces exposure to carcinogens and volatile organic compounds. However, high levels of benzaldehyde in the vapor from cherry-flavored cigarettes raise concerns about the safety of some food flavorings in e-cigarettes.

Nebulized drug delivery in patients breathing spontaneously through an artificial airway

During the past 25 years, incremental gains in knowledge about aerosol delivery to mechanically ventilated patients had a major impact on patient care in this setting. The complex array of factors influencing aerosol delivery during mechanical ventilation made it difficult to elucidate the

Considerations for Optimal Inhaler Device Selection in Chronic Obstructive Pulmonary Disease

Inhalation is the standard route of administration for drugs used to treat chronic obstructive pulmonary disease (COPD) and asthma.[1][1] Inhalation is a quick drug delivery method that offers both efficacy and safety.[2][2],[3][3] Inhaled administration allows targeted delivery of the active drug