New Nebulizer Technology to Monitor Adherence and Nebulizer Performance in Cystic Fibrosis

Introduction

Topical delivery of aerosolized therapies is an established treatment for chronic airway infection, inflammation, and to improve airway clearance in cystic fibrosis (CF).⁽¹⁾ It is increasingly being recognized that managing and promoting adherence is an essential component of care in chronic disease, where adherence to advice or medical treatment is often less than 50%.⁽²⁾

Recent innovations in nebulizer technology have the potential to greatly impact on the burden of disease experienced by our patients. The development of mesh technology allows the generation of fine particle aerosols and thus more efficient airway deposition. The development of adaptive aerosol delivery (AAD) devices enables much faster delivery times.^(3,4) One such hand-held AAD device (I-neb™ Respironics, Chichester, UK) was introduced into our CF clinic in March 2005 for patients prescribed inhaled antibiotic therapy. The key premise of AAD is that aerosol delivery is timed to certain phases of the respiratory cycle by monitoring flow in and out of the mouthpiece. For the I-neb™, a pulse of aerosol is generated during the early/mid phase of inspiration with a 1-sec pause timed before expiration to avoid large airway deposition.⁽⁴⁾ An additional feature of these new devices is the ability to record and examine the performance of the device by downloading stored data (electronic data capture).⁽⁵⁾ In this way, CF teams can work with patients to optimize performance and support adherence.⁽⁵⁾ The I-neb^™ is available in a limited (but increasing) number of countries at the moment. In the United Kingdom, it is licenced for use with promixin (Colistin), although we also use it to administer other inhaled medications such as DNase and hypertonic saline.

In our center, patients/parents are asked to bring their I-neb devices to each clinic appointment. They know about the data logging facility within the device, and following download, adherence data is shared with them in the clinic and used to inform clinical decision making if appropriate. If the I-neb is forgotten, then this data can be calculated retrospectively as the device has sufficient memory for 5000 treatments. The specialist CF physiotherapist in our clinic predominantly has responsibility for providing teaching and ongoing support regarding inhalation therapy to our patients. Using dedicated I-neb software (Insight System), the data log within the device is accessed via a reading cradle attached to a computer. The software also has a breathing monitor training screen that can be used to optimize breathing technique when using the device.

AAD Adherence Studies in Liverpool Pediatric Clinic

In a series of studies, we have used the I-neb's download facility to examine treatment times and adherence to nebulizer therapy in our pediatric patients.

In our first study, we examined patterns of adherence in children chronically infected with Pseudomonas aeruginosa (PsA) on long-term nebulized colistin therapy.⁽⁵⁾ Treatment times and daily/monthly adherence data were analysed for the first year of inhaled therapy through the I-neb™. In all, 16,102 treatments from 28 children were recorded and analyzed. As a group, overall adherence to nebulized treatments was maintained between 60% and 70% over this 12-month period. However, when adherence was examined from an individual perspective, there was wide variation both between and within individual patients. Interestingly, evening adherence was consistently better than morning adherence.

In a follow-up study, we investigated adherence to treatment in children with “new” or “first” growths of Pseudomonas aeruginosa, prescribed our normal eradication regimen of 3 months of colistin through the I-neb and 3 weeks of oral ciprofloxacin.⁽⁶⁾ Children were designated as “good” or “poor” adherers depending on whether their adherence was greater or less than 80%. Lung function was analyzed at the start and the end of eradication therapy, and then at 6 and 9 months following the growth of Pseudomonas. Eradication was deemed to have occurred if Pseudomonas was not cultured for 6 months following the end of eradication therapy.

In 33 children, 35 “new” or “first” growths of Pseudomonas were isolated, of which 28 of 35 (80%) were successfully eradicated. Eradication rates were similar regardless of adherence to treatment, with Pseudomonas eradicated in 18 of 21 (86%) “good” and 10 of 14 (72%) “poor” adherers. Adherence to treatment through the I-neb was good, 82% for the first month of eradication therapy and then dropped gradually, but was still maintained at 74% over the third month of treatment. Similar to those on chronic anti-Pseudomonal therapy, adherence was significantly better in the evenings than in the mornings (84% vs. 74%; p=0.002).

The TIM Study

We examined whether this novel mode of delivery really did make a difference to treatment times in our cohort of pediatric patients.⁽¹⁰⁾ Twenty patients (median (range) age, 11 (5–17) years), who were already established on Tidal Breathing Mode (TBM) I-neb for long-term nebulized antibiotic therapy, were randomized to either TIM or to continue using TBM for 6 weeks. Each patient undertook a 4-week run-in period on TBM prior to randomization.

For patients allocated TIM, treatment times decreased significantly between the start and the end of the study period by over 3 min from 6.9–3.7 min (p<0.001). In contrast, treatment times for those patients on TBM remained unchanged. Adherence to treatment was also assessed and in the TIM group was maintained, whereas adherence in the TBM group decreased by an average of 5% over the study period. All patients were given the opportunity to switch to TIM following the study, and all preferred TIM to TBM on a short patient preference questionnaire.

Discussion

In these studies we have shown that open routine monitoring of treatment adherence is possible in a busy outpatient setting, and can help to support families maintain long-term aerosol therapy. Adherence tends to be better in the evenings, but it is clear that it varies greatly, both between and within individual patients. Recent advances in nebulizer design have the potential to significantly shorten inhalation treatment times, thus decreasing burden of care still further.

We have found that we can improve adherence by tailoring treatment regimens to the individual. This may involve providing advice on timing and dosing frequency, particularly in adolescent patients. Some patients and families obviously find taking morning treatments a challenge. They may, however, respond well to adapting treatment regimens to one that suits the individual.

Regular monitoring of treatment times and adherence allow us to identify problems at an early stage and technical difficulties can be dealt with quickly. Prolonged treatment times seen on the download may indicate that the mesh is clogged and that cleaning procedures have not been followed. Another cause of prolonged treatment times are difficulties with technique. The breathing monitor can be used to analyze and modify breathing pattern, improving delivery of the drug and thus reducing treatment times.

Good communication between healthcare professionals and patients/families is paramount so that open and honest conversations on which treatments patients are and are not taking can take place. Only with this openness, can we work in partnership with families to achieve realistic and achievable regimes that suit them. On a number of occasions the parent's/patient's perception of adherence has been at odds with that revealed on the download and this can be challenging to provide feedback. We have found that these discussions are best done in a positive and supportive way focusing on what they may have achieved rather than criticize what they have not.

In the future, the ability to monitor adherence will be commonplace and not limited to the I-neb^™. Recently, Akita delivery systems have become available, which are capable of doing this through a smart card. Novel advances in medical devices need to be monitored and assessed rigorously, particularly as new and potentially expensive therapies emerge. Electronic data capture enables CF teams to work in an open partnership with patients to achieve the common goals of improving drug delivery and reducing patient burden.