Range Of Inspiratory Flow Rates Research Articles

Estimation of inhalation flow profile using audio-based methods to assess inhaler medication adherence.

Asthma and chronic obstructive pulmonary disease (COPD) patients are required to inhale forcefully and deeply to receive medication when using a dry powder inhaler (DPI). There is a clinical need to objectively monitor the inhalation flow profile of DPIs in order to remotely monitor patient inhalation technique. Audio-based methods have been previously employed to accurately estimate flow parameters such as the peak inspiratory flow rate of inhalations, however, these methods required multiple calibration inhalation audio recordings. In this study, an audio-based method is presented that accurately estimates inhalation flow profile using only one calibration inhalation audio recording. Twenty healthy participants were asked to perform 15 inhalations through a placebo Ellipta™ DPI at a range of inspiratory flow rates. Inhalation flow signals were recorded using a pneumotachograph spirometer while inhalation audio signals were recorded simultaneously using the Inhaler Compliance Assessment device attached to the inhaler. The acoustic (amplitude) envelope was estimated from each inhalation audio signal. Using only one recording, linear and power law regression models were employed to determine which model best described the relationship between the inhalation acoustic envelope and flow signal. Each model was then employed to estimate the flow signals of the remaining 14 inhalation audio recordings. This process repeated until each of the 15 recordings were employed to calibrate single models while testing on the remaining 14 recordings. It was observed that power law models generated the highest average flow estimation accuracy across all participants (90.89±0.9% for power law models and 76.63±2.38% for linear models). The method also generated sufficient accuracy in estimating inhalation parameters such as peak inspiratory flow rate and inspiratory capacity within the presence of noise. Estimating inhaler inhalation flow profiles using audio based methods may be clinically beneficial for inhaler technique training and the remote monitoring of patient adherence.

The Particle Size of Mometasone Furoate 100 μg and 200 μg Dry Powder Formulations

RATIONALE: Regional lung deposition of inhaled particles depends on particle size as well as inspiratory flow rate and other factors. Inhaled particles of aerodynamic size around 2 μm have been found to deposit most efficiently in the alveolar region across a broad range of inspiratory flow rates. In vivo studies of mometasone furoate (MF) delivered by the Twisthaler® showed mean peak inspiratory flow rates (PIFR) at satisfactory levels in adult/adolescent patients aged ≥12 years (69 L/min), children aged 9-12 years (>60 L/min), and children aged 5-8 years (>50 L/min). We report particle size findings from an in vitro study analyzing the mass median aerodynamic diameter (MMAD) of MF.METHODS: Twelve inhalers each of the 110 and 220 μg/inhalation strengths were tested in vitro at the beginning and end of unit lives at a 60 L/min flow rate. Aerosolized MF was collected by cascade impaction for 2 inhalations from the 110 μg/inhalation strength and 1 inhalation from the 220 μg/inhalation strength, thereby providing similar particle masses.RESULTS: The average MMAD of the 110 μg strength for beginning and ending inhalations (n=24) was 2.0 μm (range, 1.9-2.1 μm), while the 220 μg strength for beginning and ending inhalations (n=24) was 2.2 μm (range, 2.0-2.4 μm).CONCLUSION: Average MMAD values of MF for both strengths measured in vitro at a clinically relevant flow rate, together with in vivo particle-size efficiency deposition models, suggest that the particle size of MF is optimal (∼2 μm) for efficient alveolar deposition when administered via the Twisthaler®. RATIONALE: Regional lung deposition of inhaled particles depends on particle size as well as inspiratory flow rate and other factors. Inhaled particles of aerodynamic size around 2 μm have been found to deposit most efficiently in the alveolar region across a broad range of inspiratory flow rates. In vivo studies of mometasone furoate (MF) delivered by the Twisthaler® showed mean peak inspiratory flow rates (PIFR) at satisfactory levels in adult/adolescent patients aged ≥12 years (69 L/min), children aged 9-12 years (>60 L/min), and children aged 5-8 years (>50 L/min). We report particle size findings from an in vitro study analyzing the mass median aerodynamic diameter (MMAD) of MF. METHODS: Twelve inhalers each of the 110 and 220 μg/inhalation strengths were tested in vitro at the beginning and end of unit lives at a 60 L/min flow rate. Aerosolized MF was collected by cascade impaction for 2 inhalations from the 110 μg/inhalation strength and 1 inhalation from the 220 μg/inhalation strength, thereby providing similar particle masses. RESULTS: The average MMAD of the 110 μg strength for beginning and ending inhalations (n=24) was 2.0 μm (range, 1.9-2.1 μm), while the 220 μg strength for beginning and ending inhalations (n=24) was 2.2 μm (range, 2.0-2.4 μm). CONCLUSION: Average MMAD values of MF for both strengths measured in vitro at a clinically relevant flow rate, together with in vivo particle-size efficiency deposition models, suggest that the particle size of MF is optimal (∼2 μm) for efficient alveolar deposition when administered via the Twisthaler®.

Dose Delivery Characteristics of the AIR® Pulmonary Delivery System Over a Range of Inspiratory Flow Rates

The purpose of this study was to evaluate the in vitro and in vivo dose delivery characteristics of the AIR pulmonary delivery system over a range of flow rates. A 5-mg placebo powder of engineered particles with low densities (<0.4 g/cc) and large geometric diameters (>5 microm) was delivered via a simple, capsule based, passive dry powder inhaler. The emitted dose, geometric and aerodynamic particle size distributions (aPSDs) were obtained over a range of flow rates (15-60 LPM). The in vitro results demonstrated improved powder dispersion with increasing flow rate through the inhaler. The in vivo dose delivery characteristics were obtained by gamma scintigraphy. Twelve healthy subjects performed the following three inhalation maneuvers: (i) a targeted peak inspiratory flow rate (PIFR) of 20 +/- 10 LPM, (ii) a deep comfortable inhalation, and (iii) a deep forced inhalation. PIFR and inhaled volume were obtained during the inhalation of the dose using a spirometer. In vivo dose delivery was characterized by high and reproducible emitted doses (mean = 87%; inter and intra-subject CV = 5%) and high lung deposition (mean = 51% of the total dose), with low inter and intra-subject CVs (18% and 13%, respectively) across a range of PIFRs (12-86 LPM). Lung deposition of the total dose was shown not to be dependent on PIFR by analysis of variance across the range of inspiratory flow rates (p = 0.29). This was due to the competing effects of smaller aPSDs, increased extrathoracic deposition and higher emitted doses with increasing PIFR. Fully characterizing the effect of inspiratory flow rate requires analysis of the therapeutic response, as well as in vitro dose delivery and lung deposition.

An improved pocket rescue mask incorporating a novel visual breathing indicator

The difficulties inherent in the ‘Look, Listen and Feel’ method of identifying respiratory arrest prompted the authors to develop a simple mechanical breathing indicator that can show clearly, at a glance, whether or not a patient is breathing. The novel indicator was designed to be highly visible so that its interpretation should be obvious to medical personnel and the lay public, and yet sufficiently simple so that it could be easily and inexpensively incorporated into the type of pocket rescue masks currently in use. The indicator needs no power source, works indoors and outdoors and does not interfere with the delivery of rescue breaths during resuscitation. A prototype of the improved pocket mask incorporating the new indicator was made and was tested for its ability to detect breaths over a range of inspiratory flow rates and inspiratory pressures. The authors found that the indicator responded to peak inspiratory flow rates of between 15 and 120 l/min, inspiratory pressures as low as 0.18 cm H 2O with no supplemental oxygen flowing to the mask and 0.22 cm H 2O with supplemental oxygen flowing at 9 l/min, minute ventilation volumes between 7.1 and 21.8 l/min, tidal volumes between 0.36 and 2.92 l and a respiratory rate range of 7–24 breaths per min. The authors conclude that the new indicator, when attached to a pocket rescue mask, is sensitive enough to identify clearly and reliably those patients at the scene of collapse who have stopped breathing. Additionally it may assist rescuers in timing the delivery of assisted rescue breaths in those patients with poor respiratory effort.

Efficacy of salbutamol via Easyhaler®unaffected by low inspiratory flow

The fine particle dose delivered via dry powder inhalers (DPIs) is often affected by the inspiratory flow rate generated during inhalation. This has clinical implications, since the fine particle dose determines the amount of drug reaching the lungs. With Easyhaler®DPI the fine particle dose remains relatively constant over the range of inspiratory flow rates from 30–60 l min−1. The aim of this study was to confirm that clinical efficacy is maintained even at low flow rates by comparing the bronchodilating effect of salbutamol (100 μ g) delivered via Easyhaler®at a target inspiratory flow of 30 l min−1with the same dose of salbutamol via pressurised metered-dose inhaler (pMDI) plus spacer.This was a double-blind, randomized, cross-over study with double-dummy technique. Twenty-one paediatric and adult asthmatic patients completed the study, which was conducted over 2 study days. The main outcome parameter was forced expiratory volume in 1 sec (FEV1). The patients were trained to generate a low peak inspiratory flow rate (PIFR) of 30 l min−1, and the actual PIFR through Easyhaler®was recorded.The average PIFR through Easyhaler®was 28·7 l min−1. The difference in the maximum value of FEV1(FEV1max) between the treatments after drug inhalation was 0·01 l. The mean of FEV1maxwas 2·67 l after pMDI plus spacer compared to 2·69 l after Easyhaler®. Improvements in FEV1were clinically significant. No significant differences between treatments were found.A reasonably low inspiratory flow rate through Easyhaler®produces an equivalent improvement in lung function to a correctly used pMDI plus spacer. Hence, Easyhaler®can be used with confidence in patients who may have difficulty in generating a high inspiratory flow rate, such as children and the elderly.

An easy-to-use dry-powder inhaler.

The mometasone furoate dry-powder inhaler is a novel device designed to support compliance by delivering a topical corticosteroid in a simple three-step operation. This breath-actuated inhaler uses a stabilized agglomerate formulation to measure and deliver accurate, uniform, and precise doses of drug over a range of inspiratory flow rates. Laboratory and clinical data have shown that the design produced a simple, clinically effective inhaler for the treatment of adults and children 12 years of age and older with mild, moderate, or severe persistent asthma.

Dry powder inhalation as a potential delivery method for vaccines

Measles vaccine is administered to millions of children annually via a percutaneous injection. There are, however, compelling reasons to search for alternative routes of administration, especially in mass vaccination campaigns. Two key factors are (1) decreased stability of the vaccine upon reconstitution and, (2) the potential risks of contamination associated with needles. Dura has developed a unique inhaler that can deliver a powder dose via the pulmonary route for local or systemic action. The breath-actuated Spiros® inhaler uses electromechanical energy to aerosolize and deliver a consistent dose over a wide range of inspiratory flow rates. To achieve alveolar (deep lung) deposition for subsequent systemic absorption, dry-powder vaccine is size reduced to a mass median diameter between 1 and 5 μm. Small vaccine particles are blended with an inert carrier to improve dispersion. Measles vaccine formulated as a powder blend may be more thermostable than existing reconstituted formulations. The Spiros® technology is available in three powder storage platforms. Two of these formats are designed specifically for moisture and/or light sensitive compounds and may be particularly suitable for delivery of measles vaccines in mass campaigns because their design (1) eliminates the need for powder reconstitution, and (2) reduces the risk of contamination.

Apparatus and method for measuring regional distribution of therapeutic aerosols and comparing delivery systems

An apparatus has been designed to estimate the respiratory tract distribution of therapeutic aerosols. It consists of an accurate life size model of the human oral passage extending from lips to mid-trachea, a Y branch for flow adjustment and a cascade impactor. Aerosol delivery devices are positioned to introduce the generated aerosol into the oral entrance, simulating their in vivo delivery. The aerosol which penetrates the oral airway model cast passes to the cascade impactor for aerodynamic size classification to estimate regional delivery to the bronchial and pulmonary zones. The apparatus has been tested using a metered dose inhaler (MDI) at a range of inspiratory flow rates.