Kurt Nikander

Adaptive Aerosol Delivery (AAD) technology.

Jet nebulisers have, since the 1920s, been used for delivery of inhaled drugs for the treatment of asthma, chronic-obstructive pulmonary disease and pulmonary infections. During the last two decades, recognition of the shortcomings of conventional nebulisers has led to the development of new ‘intelligent’ nebulisers such as the Adaptive Aerosol Delivery (AAD®, Profile Therapeutics, a Respironics company) systems. Diseases of the airways have traditionally been logical candidates for treatment with inhaled drugs. The introduction of the ‘intelligent’ nebulisers has, however, broadened the possibilities for inhaled treatment to include drugs targeted for systemic diseases. These nebulisers offer the possibility to deliver more precise doses of drug, maximise lung deposition, enhance adherence to treatment and compliance with the device through feedback to the patient, and last but not least, offer the possibility to reduce nebulisation times.

Breathing patterns and aerosol delivery: impact of regular human patterns, and sine and square waveforms on rate of delivery

In vitro tests are commonly employed to assess nebulizer performance. Whether the square or sine waveforms employed during in vitro tests could alter the nebulizer performance compared to that observed when a patient breathes through the nebulizer is debatable. Accordingly, the aim of this in vitro study was to compare the rates of delivery from nebulizers with simulated human breathing patterns to those obtained with matching sine and square waveforms. Regular human breathing patterns with tidal volumes (VT) of approximately 40, approximately 200, approximately 500, and approximately 800 mL were selected. Sine and square waveforms that matched the VT, peak inspiratory flow rate (PIF), breathing frequency (f), and inspiratory duty cycle (t(i)/t(tot)) of the human breathing patterns were created with a breathing simulator. The rate of delivery of nebulized technetium-99m-labeled diethylenetriamine pentaacetic acid (99mTC-DTPA) from two different jet nebulizer brands was determined. The rate of delivery was defined as the amount of the 99mTC-DTPA deposited during 30 sec of nebulization on a filter placed between the nebulizer and the breathing simulator. The rate of delivery of 99mTC-DTPA with the human breathing pattern was similar to that measured with the matching sine or square waveforms for either nebulizer. The configuration of the breath (PIF, VT, f, t(i)/t(tot)) did, however, influence the rate of delivery. In conclusion, the shape of the waveform, in other words, one resulting from a human breathing pattern, or a matching sine or square waveform, did not influence the rate of 99mTC-DTPA delivery from a nebulizer in vitro.

Validation of a new breathing simulator generating and measuring inhaled aerosol with adult breathing patterns

The use of breathing simulators for the in vitro determination of the inhaled mass of drug from nebulizers has become widely accepted. Their use is, however, based on the assumption that there is a correlation between the in vitro and in vivo inhaled mass of drug. The aim of the study was therefore to investigate whether a new breathing simulator--the MIMIC Breathing Emulator (Medic-Aid Limited, Bognor Regis, UK)--could accurately emulate the in vivo inhaled mass of budesonide suspension for nebulization. Eight adult healthy subjects were included. Each subject inhaled for 2 min from a Spira Module 1 jet nebulizer (Respiratory Care Center, Hämeenlinna, Finland), charged with 1.0 mg of budesonide suspension for nebulization (0.5 mg mL-1, 2 mL suspension, AstraZeneca, Sweden) and supplied with an inhaled mass filter between the nebulizer and the subject. The breathing patterns were recorded during the nebulization and simulated in vitro at two different experimental sites (simulations A and B) with the breathing simulator. With the patients breathing through the filters (in vivo test), inhaled mass of budesonide averaged 103.6 micrograms. The two in vitro experiments using the simulator revealed similar results with in vitro simulation A equal to 101.0 micrograms and simulation B 99.1 micrograms. There were no statistically significant differences between the in vivo results and those of in vitro simulation A. Results were significantly different for simulation B (p = 0.032) although the difference was less than 4.5%. These data indicate that the breathing simulator can be used to accurately simulate sine waveforms, human breathing patterns, and the in vitro and in vivo inhaled mass of budesonide suspension for nebulization.

Domiciliary Experience of the Target Inhalation Mode (TIM) Breathing Maneuver in Patients with Cystic Fibrosis

BACKGROUND The time requirements for multiple daily nebulizer treatments are important impediments to the quality of life for most patients with cystic fibrosis (CF). The I-neb Adaptive Aerosol Delivery (AAD) System can be used with a new mode of breathing during inhalation of aerosol, the Target Inhalation Mode (TIM). As a function of the TIM algorithm, the patient is guided to a slow and deep inhalation, which can result in shorter treatment times. METHODS This study was conducted as a 3-month patient handling study of the I-neb AAD System in 42 patients with CF aged 12-57 years. The I-neb AAD System was supplied in both the standard Tidal Breathing Mode (TBM), and in TIM. Patients were trained to use the I-neb AAD System in TIM for the delivery of all their inhaled medications, but if they were not comfortable with the TIM maneuver they could change to the TBM maneuver. The primary variables were compliance with the correct use of the I-neb AAD System, and treatment times. The secondary variables were based on study questionnaires at the end of the study and covered ease of use, patient confidence, and patient satisfaction with the I-neb AAD System. RESULTS There were a total of 10,240 complete treatments and of these, 8979 (88%) were in TIM. Compliance with the correct use of the I-neb AAD System was 97.6%. The mean treatment time for complete treatments in TIM was 4.20 min, compared with 6.83 min when using the I-neb AAD System in TBM. The responses to the questionnaires indicated that over 77% of the patients found the I-neb AAD System in TIM to be either: very easy, easy, or acceptable to use. CONCLUSIONS The results demonstrated that by using the I-neb AAD System in TIM, a 40-50% reduction of nebulizer treatment times, and a high level of compliance could be achieved. The results also showed that the patients found the I-neb AAD System easy to use.

Challenges and opportunities in respiratory drug delivery devices

Recent reviews conclude that there is a need to improve the management of respiratory diseases treated with inhaled drugs, mainly asthma and chronic obstructive pulmonary disease (COPD). Healthcare professionals – mainly in primary care – seem to lack to some degree the evidence-based information required for the selection of the most appropriate respiratory drug delivery devices (inhalers) for the patients, whereas some of the patients often tend to have poor inhaler technique. This could have an impact on the ability to control the respiratory diseases in question. There are probably several reasons for these apparent challenges in the primary care arena. Owing to the abundance of inhalers available at present, especially for the treatment of asthma and COPD, it is quite a challenge to pick the ‘right’ inhaler for each patient. For an inhaler to be optimal, the patient has to be able to master the inhaler technique required for the specific inhaler. The patient–inhaler interfaces – mouthpieces or facemasks – can add important challenges that further diminish the efficacy of the treatment.