Pharmaceutical aerosols provide a number of advantages for treating respiratory diseases that include targeting high doses directly to the lungs and reducing exposure of other organs to the medication, which improve effectiveness and minimize side effects. However, difficulties associated with aerosolized drug delivery to the lungs include drug losses in delivery devices and in the extrathoracic region of human upper airways. Intersubject variability of extrathoracic and thoracic drug deposition is a key issue as well and should be minimized. Improvements to respiratory drug delivery efficiency have been recently proposed by Dr. P. Worth Longest and Dr. Michael Hindle through the use controlled condensational growth methods, which include enhanced condensational growth (ECG) and excipient enhanced growth (EEG). These methods reduce inhaled drug loss through the introduction of an aerosol with an initial submicrometer aerodynamic diameter, which then experiences condensational growth to increase droplet size and enhance thoracic deposition. Tracheobronchial and nasal human airway computational models were developed for this study to assess drug delivery using conventional and EEG methods. Computational versions of these models are used to assess drug delivery and variability with computational fluid dynamics (CFD) simulations, which are validated with experimental data where possible. Using CFD, steady state delivery of albuterol sulfate (AS) during high flow therapy (HFT) through a nasal cannula was characterized with four nasal models developed for this study, with results indicating an increase in average delivered dose from 24.0% with a conventional method to 82.2% with the EEG technique and an initially sized 0.9 µm aerosol, with a corresponding decrease in the coefficient of variation from 15% to 3%. Transient CFD simulations of nebulized AS administration through a mask during noninvasive positive pressure ventilation (NPPV) were performed and validated with experimental data, which resulted in 40.5% delivered dose with the EEG method as compared with 19.5% for a conventional method and a common inhalation profile. Using two newly created face-nose-mouth-throat models, dry powder delivery of ciprofloxacin during NPPV was assessed for the first time with steady state CFD predictions, which showed an increase in average delivered lung dose through a new mask design of 78.2% for the EEG method as compared with 36.2% for conventional delivery, while corresponding differences in delivered dose between the two models were reduced from 45.4% to 12.8% with EEG. In conclusion, results of this study demonstrate (i) the use of highly realistic in silico and in vitro models to predict the lung delivery of inhaled pharmaceutical aerosols, (ii) indicate that the EEG approach can reduce variability in nose-to-lung aerosol delivery through a nasal cannula by a factor of five, and (iii) introduce new high efficiency methods for administering aerosols during NPPV, which represents an area of current clinical need.

ABSTRACT Patients with respiratory failure secondary to acute asthma exacerbation (AAE) frequently present at emergency units. Some patients may develop respiratory muscle fatigue. Current guidelines for the treatment of an AAE center on pharmacological treatment and invasive mechanical ventilation. Noninvasive positive pressure ventilation (NPPV) has an established role in COPD exacerbations. The role it can play in an AAE remains unanswered although it is frequently used in the clinical setting. Aims: The present study proposed to investigate if the early use of NPPV in the forms of continuous positive airway pressure (CPAP) or bilevel positive pressure ventilation (BPPV) together with standard medical therapy in AAE can decrease time of response to therapy compared to standard medical therapy alone. We further tested the effect of BPPV against CPAP. Methods: Asthmatic patients who presented with a severe AAE (PEFR % predicted < 60 %) at the emergency unit were randomized to either standard medical therapy (ST), ST and CPAP or ST and BPPV. Thirty patients fulfilled the inclusion criteria for the study. Groups presented similar baseline characteristics. The mean age for the group was 42.1 ± 12.6 years. Mean baseline PEFR % predicted was 35.2 ± 10.7 % (ST), 30.5 ± 11.7 % (ST + CPAP) and 33.5 ±13.8 % (ST + BPPV). Results: Hourly improvement (Δ) in respiratory rate and sensation of breathlessness was significantly better in the BPPV intervention group. Improvement (Δ) from baseline to end of treatment in respiratory rate and sensation of breathlessness was significant for both CPAP and BPPV (p = 0.0463; p = 0.0132 respectively) compared to ST alone. Lung function was significantly improved in the CPAP intervention group hourly and from baseline to end of treatment (p = 0.0403 for PEFR and p = 0.0293 for PEFR % predicted) compared to ST + BPPV and ST alone. The mean shift (Δ) in PEFR from baseline to 3 hours of treatment was 67.4, 123.5 and 86.8 L/min (p = 0.0445) for ST, ST + CPAP and ST + BPPV respectively. This corresponded to a 38.1, 80.8 and 51.7 % improvement in lung function respectively. Discussion: The effect of BPPV on the reduction of respiratory rate and sensation of breathlessness could be related to the inspiratory assistance provided by BPPV. The significant improvement in lung function in the CPAP group could be related to its intrinsic effect on the airway smooth muscle and / or on the airway smooth muscle load. Conclusion: The present results suggest that adding NPPV to standard treatment for an AAE not only improves clinical signs faster but also improves lung function faster. CPAP seems to have an intrinsic effect on the airway smooth muscle so rendering it more effective in ameliorating lung function.

The use of noninvasive positive pressure ventilation (NPPV) in acute care settings has drastically increased within the past 20 years. Research has indicated that NPPV is equally as effective as traditional mechanical ventilation(MV) in treating acute exacerbations of chronic pulmonary obstructive disease (COPD) and cardiogenic pulmonary edema. Furthermore, the risk of complication from NPPV is much lower than MV, in terms of ventilator-associated pneumonia and sepsis. It is imperative for the nurse to understand the various indications, interfaces, and potential complications associated with NPPV use. In addition to treating acute exacerbations of COPD and cardiogenic pulmonary edema, NPPV has been used for prevention of reintubation, palliative care, and status asthmaticus. Furthermore, NPPV could be delivered through various interfaces, such as nasal, facial, and helmet. Each of these interfaces could eventually cause complications for the patient, such as skin ulceration and sepsis. However, there is limited amount of research available discussing the role of the nurse in caring for the patient with NPPV. There are no standardized guidelines established to assist the nurse in this care, in terms of interface selection, prevention of complications, and staffing patterns. Several recommendations are presented at the end of this thesis to guide future nursing research, education, and clinical practice, such as exploring the role of oral care and education for NPPV patients.

No / Non-invasive positive pressure ventilation (NPPV) provides respiratory support to patients without the need for invasive intubation. Although it has been used for several years in critical care, NPPV has come to prominence as a management option for certain patients with respiratory complications of coronavirus disease 2019 (COVID-19). This has led to increased care provision by nurses with little or no experience and expertise in critical care and NPPV. This article provides an overview of the principles of NPPV and its use in type 1 and type 2 respiratory failure. It explains the pathophysiology of several conditions that often lead to respiratory failure and how NPPV can mitigate respiratory failure and improve gas exchange. An individualised assessment of the patient’s suitability for NPPV and an evaluation of the effectiveness of the therapy are crucial to ensure its safe and effective use. Nurses also have an important role in providing explanations and support to patients.