Evaluation of the Target Inhalation Mode (TIM) breathing maneuver in simulated nebulizer therapy in patients with cystic fibrosis.

BACKGROUND: Adaptive Aerosol Delivery (AAD) systems provide efficient drug delivery and improved lung deposition over conventional nebulizers by combining real-time analyses of patient breathing patterns and precisely timed aerosol delivery. Delivery and deposition are further enhanced by breathing techniques involving slow, deep inhalations. METHODS: This exploratory study assessed the acceptability of slow, deep inhalations in 20 patients with cystic fibrosis (CF) during up to eight simulated nebulizer treatments with the I-neb AAD System. The breathing maneuver, Target Inhalation Mode (TIM) breathing, involved the lengthening of the patient's inhalation time over successive breaths with guidance from auditory and tactile (vibratory) feedback from the device. RESULTS: At the end of the first treatment, most patients felt that the instructions were easy to understand (90%) and that the vibratory feedback was pleasant (65%). Half of the patients found the procedure to be comfortable. At the end of the final treatment, most patients felt that the breathing maneuver was easy to understand (90%) and use (80%), but that the duration of the breath was too long (100%). Logged data revealed that 90% of patients were able to comply with the breathing maneuver. The two patients unable to comply had a forced vital capacity of <1.75 L. The average treatment time decreased from 288.4 to 141.6 sec during the first and final treatments, respectively. CONCLUSIONS: This study provides preliminary evidence of the acceptability of the TIM breathing maneuver in patients with CF and their ability to perform repeated TIM breathing during simulated nebulizer therapy with the I-neb AAD System.

Mode of breathing-tidal or slow and deep-through the I-neb Adaptive Aerosol Delivery (AAD) system affects lung deposition of (99m)Tc-DTPA.

BACKGROUND: The I-neb AAD System was designed to deliver aerosol with two different breathing pattern algorithms: the Tidal Breathing Mode (TBM) and the Target Inhalation Mode (TIM). For the purpose of the study, the TBM breathing pattern algorithm was set to guide the subjects to inhalation during tidal breathing with aerosol pulsed during 50-80% of the time spent on inhalation, whereas the TIM breathing pattern was set to guide the subject to a slow and deep inhalation of up to approximately 9 sec with aerosol pulsed for up to 7 sec, leaving 2 sec for particle deposition in the lungs. In TIM, the inspiratory flow was guided to approximately 20 L/min through a built-in resistance in the mouthpiece. METHODS: We have, in a randomized, open-label, crossover study of 12 healthy subjects evaluated lung deposition following administration of a radiolabeled aerosol from the I-neb AAD System with the TBM and TIM breathing patterns. RESULTS: The results showed that mean lung deposition was significantly higher when using the I-neb AAD System with the TIM breathing pattern (73.3%) than with the TBM breathing pattern (62.8%). The mean exhaled fractions were low (<1%) for both breathing patterns. The nebulization time was significantly shorter with the TIM breathing pattern (3.0 min) than with the TBM breathing pattern (4.7 min). CONCLUSIONS: The results of the present study showed that lung deposition with the slow and deep inhalation achieved through the I-neb AAD System in TIM was superior to the lung deposition achieved during tidal breathing in TBM. With the combination of high lung deposition, almost no loss of aerosol during exhalation, and short nebulization time the I-neb AAD System with the TIM breathing pattern should be of special value to patients who require multiple daily dosing of aerosolized medication, are using drugs that should not be wasted into the room air, or would benefit from a more efficient delivery system.

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.

Drug delivery and adherence in young children.

The aim of this pilot study was to compare a the HaloLite Paediatric Nebulizer (HPN) with a pressurized metered dose inhaler and valved holding chamber (pMDI VHC, Aerochamber) in terms of drug delivery, adherence to treatment, compliance with device, true adherence, and acceptability. Fourteen children aged 11-36 months with asthma on regular treatment with inhaled corticosteroids were enrolled into an open, randomized, crossover trial. They received budesonide for 2 weeks with each delivery system. Both devices incorporated a datalogger which recorded information on how the device was used. The HPN was preprogrammed to deliver 25 microg of budesonide to the patient. A single actuation of budesonide 200 microg was used with the pMDI VHC. The median delivered dose of budesonide was 36 microg (range, 31-45 microg; CV, 15%) for the HPN and 53 microg (range, 17-85 microg; CV, 47%) for the pMDI VHC. The median adherence was 68% (range, 11-96%) with the HPN and 71% (range, 11-100%) with the pMDI VHC. The median device compliance was 30% and 51% and the median true adherence was 23% and 36%, respectively. The shape, size, and weight of the HaloLite Paediatric Nebulizer were generally less acceptable than the shape, size, and weight of the pMDI VHC with datalogger. These results indicate that reproducible quantities of drug can be delivered to very young children using AAD technology such as that incorporated into the HPN. Drug delivery with the pMDI VHC was more variable, but parents preferred this device.