Lexmond Anne J, Kruizinga Tonnis J, Hagedoorn Paul, Rottier Bart L, Frijlink Henderik W, de Boer Anne H
Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, The Netherlands.
Division of Paediatric Pulmonology and Paediatric Allergology, Beatrix Children's Hospital, University Medical Centre Groningen, Groningen, The Netherlands.
PLoS One. 2014 Jun 5;9(6):e99304. doi: 10.1371/journal.pone.0099304. eCollection 2014.
Age appropriateness is a major concern of pulmonary delivery devices, in particular of dry powder inhalers (DPIs), since their performance strongly depends on the inspiratory flow manoeuvre of the patient. Previous research on the use of DPIs by children focused mostly on specific DPIs or single inspiratory parameters. In this study, we investigated the requirements for a paediatric DPI more broadly using an instrumented test inhaler. Our primary aim was to assess the impact of airflow resistance on children's inspiratory flow profiles. Additionally, we investigated children's preferences for airflow resistance and mouthpiece design and how these relate to what may be most suitable for them. We tested 98 children (aged 4.7-12.6 years), of whom 91 were able to perform one or more correct inhalations through the test inhaler. We recorded flow profiles at five airflow resistances ranging from 0.025 to 0.055 kPa0.5.min.L-1 and computed various inspiratory flow parameters from these recordings. A sinuscope was used to observe any obstructions in the oral cavity during inhalation. 256 flow profiles were included for analysis. We found that both airflow resistance and the children's characteristics affect the inspiratory parameters. Our data suggest that a medium-high resistance is both suitable for and well appreciated by children aged 5-12 years. High incidences (up to 90%) of obstructions were found, which may restrict the use of DPIs by children. However, an oblong mouthpiece that was preferred the most appeared to positively affect the passageway through the oral cavity. To accommodate children from the age of 5 years onwards, a DPI should deliver a sufficiently high fine particle dose within an inhaled volume of 0.5 L and at a peak inspiratory flow rate of 25-40 L.min-1. We recommend taking these requirements into account for future paediatric inhaler development.
年龄适配性是肺部给药装置尤其是干粉吸入器（DPI）的一个主要关注点，因为其性能很大程度上取决于患者的吸气动作。先前关于儿童使用DPI的研究大多集中在特定的DPI或单一吸气参数上。在本研究中，我们使用一种装有仪器的测试吸入器更广泛地研究了儿科DPI的要求。我们的主要目的是评估气流阻力对儿童吸气流量曲线的影响。此外，我们还调查了儿童对气流阻力和吸嘴设计的偏好，以及这些偏好与最适合他们的因素之间的关系。我们测试了98名儿童（年龄在4.7至12.6岁之间），其中91名能够通过测试吸入器进行一次或多次正确吸入。我们在0.025至0.055 kPa0.5.min.L-1的五个气流阻力下记录了流量曲线，并从这些记录中计算了各种吸气流量参数。使用鼻窦镜观察吸入过程中口腔内的任何阻塞情况。共纳入256条流量曲线进行分析。我们发现气流阻力和儿童的特征都会影响吸气参数。我们的数据表明，中高阻力既适合5至12岁的儿童，也受到他们的好评。发现阻塞的发生率很高（高达90%），这可能会限制儿童使用DPI。然而，最受青睐的长方形吸嘴似乎对口腔通道有积极影响。为了满足5岁及以上儿童的需求，DPI应在0.5 L的吸入体积内，以25至40 L.min-1的吸气峰值流速提供足够高的细颗粒剂量。我们建议在未来儿科吸入器的开发中考虑这些要求。
