Mesh nebulizers have become the first choice for new nebulized pharmaceutical drug developments.

In the 24 years since first being marketed, the mesh nebulizer has been developed by five main manufacturers into a viable solution for the delivery of high-value nebulized drugs. Mesh nebulizers provide increased portability, convenience and energy efficiency along with similar lung deposition and increased ease of use compared with jet nebulizers. An analysis of EU and US clinical trial databases has shown that mesh nebulizers are now preferred over jet nebulizers for clinical trials sponsored by pharmaceutical companies. The results show a strong preference for the use of mesh nebulizers in trials involving high cost and niche therapy areas. Built-in capability to optimize the way patients use their mesh nebulizer and manage their disease will further increase uptake. [Formula: see text].

Development of an Intelligent Spacer Data Logger System.

BACKGROUND: Although delivery of drugs from pressurized metered dose inhalers (pMDIs) via spacer devices is widespread it cannot be assumed that patients take their medication as prescribed or use their spacer appropriately. We developed a Spacer Data Logger device to record patient adherence and whether patients had shaken the pMDI, actuated it soon after shaking, and inhaled a sufficient volume from it. METHODS: We report an assessment of the Spacer Data Logger to measure and record that the pMDI was adequately shaken, the time to actuation, and the volume "inhaled" from the spacer up to 26 seconds after actuation. The effect of a delay in actuation following shaking on the dose available for inhalation from the spacer and the effect of a delay in extraction of aerosol from the spacer were assessed using different strengths of beclomethasone dipropionate (50 and 100 µg) and fluticasone propionate (50, 125 and 250 µg). RESULTS: The volumes measured by the Spacer Data Logger were in close agreement with the reference volumes of four simulated breathing patterns. A delay between shaking and actuating the pMDI resulted in a significant increase in the dose available for inhalation after only 4 seconds for the 50 and 250 µg strengths of fluticasone propionate pMDIs (p = 0.004 and p < 0.001, respectively). A delay between actuation of the drug into the spacer and "inhalation" of aerosol from the spacer also resulted in a steady decline in the dose available from the spacer (p < 0.0001). CONCLUSIONS: These results confirmed the importance of using the pMDI spacer correctly by actuating directly after shaking and inhaling the aerosol from the spacer as soon after actuation as possible to optimize the dose available for inhalation. The Spacer Data Logger should be a useful tool to determine adherence to and "optimum" use of pMDI spacers in patients with asthma and chronic obstructive pulmonary disease (COPD).

The evolution of spacers and valved holding chambers.

Spacers and valved holding chambers (VHCs) are pressurized metered dose inhaler (pMDI) accessory devices, designed to overcome problems that patients commonly experience when administering aerosol via a pMDI. Spacers were developed in direct response to patient-related issues with pMDI technique, particularly, poor coordination between actuation and inhalation, and local side-effects arising from oropharyngeal deposition. Current clinical guidelines indicate the need for widespread prescription and use of spacers, but, despite their apparent ubiquity, the devices themselves are, unfortunately, all too commonly "disused" by patients. An understanding of the background from which spacers developed, and the key factors influencing the optimization of the spacer and the later VHC, is crucial to developing an appreciation of the potential of these devices, both contemporary and future, for improving the delivery of pressurized aerosols to patients. This review, informed by a full patent search and an extensive scientific literature review, takes into account the clinical and laboratory evidence, commercial developments, and the sometimes serendipitous details of scientific anecdotes to form a comprehensive perspective on the evolution of spacers, from their origins, in the early days of the pMDI, up to the present day.

Adherence monitoring in drug delivery.

Adherence monitoring is an important issue in inhaled drug delivery. Adherence is commonly found to be low and poor adherence is associated with increased mortality and morbidity and increased use of health services. Improving adherence is essential to maintaining disease and symptom control for patients and decreasing health costs. Feedback on actual adherence has been shown to increase subsequent adherence. In addition, education programs, reminder systems and increased patient-clinician interaction can also improve adherence. However, improved adherence is not sufficient if inhalation devices are being used incorrectly; the emphasis must be on devices being used in accordance with both the prescribed regimen and the instructions for use. As a result of technological advancements, drug delivery devices that both monitor adherence and address poor inhaler technique are now available. These devices combine monitoring systems with various feedback mechanisms in order to 'coach' the patient to use the device correctly. Some devices also incorporate connectivity to communicate accurate adherence and inhaler technique data to the clinician. This editorial considers current and future adherence monitoring devices and the impact that such technology could have on improving the patient's adherence and inhaler technique.

The Adaptive Aerosol Delivery (AAD) technology: Past, present, and future.

Conventional aerosol delivery systems and the availability of new technologies have led to the development of "intelligent" nebulizers such as the I-neb Adaptive Aerosol Delivery (AAD) System. Based on the AAD technology, the I-neb AAD System has been designed to continuously adapt to changes in the patient's breathing pattern, and to pulse aerosol only during the inspiratory part of the breathing cycle. This eliminates waste of aerosol during exhalation, and creates a foundation for precise aerosol (dose) delivery. To facilitate the delivery of precise metered doses of aerosol to the patient, a unique metering chamber design has been developed. Through the vibrating mesh technology, the metering chamber design, and the AAD Disc function, the aerosol output rate and metered (delivered) dose can be tailored to the demands of the specific drug to be delivered. In the I-neb AAD System, aerosol delivery is guided through two algorithms, one for the Tidal Breathing Mode (TBM), and one for slow and deep inhalations, the Target Inhalation Mode (TIM). The aim of TIM is to reduce the treatment time by increasing the total inhalation time per minute, and to increase lung deposition by reducing impaction in the upper airways through slow and deep inhalations. A key feature of the AAD technology is the patient feedback mechanisms that are provided to guide the patient on delivery performance. These feedback signals, which include visual, audible, and tactile forms, are configured in a feedback cascade that leads to a high level of compliance with the use of the I-neb AAD System. The I-neb Insight and the Patient Logging System facilitate a further degree of sophistication to the feedback mechanisms, by providing information on long term adherence and compliance data. These can be assessed by patients and clinicians via a Web-based delivery of information in the form of customized graphical analyses.

The Adaptive Aerosol Delivery system in a telehealth setting: patient acceptance, performance and feasibility.

BACKGROUND: The telehealth service is one of the fastest growing healthcare segments. It is increasingly utilizing computer technology and telecommunication equipment to either provide continuous vital sign monitoring or facilitate patient care at home, rather than relying solely on in-person care. METHODS: We conducted a 6-week open study in nineteen patients with cystic fibrosis enrolled from three centers, to investigate patient perception of a telehealth enabled nebulizer system (Prodose Adaptive Aerosol Delivery [AAD] System), which enabled the doorstep delivery of repeat medication. RESULTS: The results showed that patient confidence in the device and perception of ease of use was high with no significant change between the start and end of the trial. Views on the home delivery of medication were split between 'great' and 'inconvenient.' However, if the delivery system had been more flexible and delivered all the patients' drugs, the majority of patients would have had their medication delivered in this way. CONCLUSIONS: The trial showed that it was possible to build telehealth technology into an advanced nebulizer system, and that patient acceptance of the technology was unlikely to be a barrier to the adoption of such a telehealth system.

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.

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.

Parents' adherence with nebulizer treatment of their children when using an adaptive aerosol delivery (AAD) system.

The objective of this study was to analyze data on parents' adherence to their child's prescribed nebulizer treatment regimen and compliance with the demands of the nebulizer and the face mask. Data on adherence and compliance were recorded in a 24-week double-blind, randomized, parallel-group study with budesonide inhalation suspension in 125 young children with mild to moderate asthma. Budesonide was administered with an Adaptive Aerosol Delivery (AAD) system, which recorded adherence to treatment and compliance with the AAD system. A total of 35,481 treatments were recorded and analyzed. A study questionnaire regarding the parents' and children's acceptance of the AAD system has also been analyzed. The adherence to the treatment regimen was 91.3%, and the compliance with the AAD system was 90.4%. True adherence, the product of adherence and compliance, was 82.5%. Approximately 90% of the parents found the face mask easy to seal and the AAD equipment easy to use, and over 90% of the children accepted it within 1 week. In conclusion, the results indicate that the AAD system could be of real clinical advantage for treatment of asthma in young children.