Lexmond Anne J, Hagedoorn Paul, Frijlink Henderik W, Rottier Bart L, de Boer Anne H
Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, The Netherlands.
Division of Pediatric Pulmonology and Pediatric Allergology, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
PLoS One. 2017 Aug 11;12(8):e0183130. doi: 10.1371/journal.pone.0183130. eCollection 2017.
Correct inhalation technique is essential for effective use of dry powder inhalers (DPIs), as their effectiveness largely depends on the patient's inhalation manoeuvre. Children are an especially challenging target population for DPI development due to the large variability in understanding and inspiratory capacities. We previously performed a study in which we determined the prerequisites for a paediatric DPI in a mostly healthy paediatric population, for which we used an empty test inhaler with variable internal airflow resistance and mouthpiece. In the current study we investigated what specifications are required for a DPI for children with cystic fibrosis (CF), for which we expanded on our previous findings. We recorded flow profiles of 35 children with CF (aged 4.7-14.7 years) at three airflow resistances (0.031-0.045 kPa0.5.min.L-1) from which various inspiratory parameters were computed. Obstructions in the mouth during inhalation were recorded with a sinuscope. All children were able to perform a correct inhalation manoeuvre, although video analysis showed that children did not place the inhaler correctly in the mouth in 17% of the cases. No effect was found of medium to high airflow resistance on total inhaled volume, which implies that the whole resistance range tested is suitable for children with CF aged 4-14 years. No effect could be established of either mouthpiece design or airflow resistance on the occurrence of obstructions in the mouth cavity. This study confirms our previous conclusion that the development of DPIs specifically for children is highly desired. Such a paediatric DPI should function well at 0.5 L inhaled volume and a peak inspiratory flow rate of 20 to 30 L/min, depending on the internal airflow resistance. This resistance can be increased up to 0.045 kPa0.5.min.L-1 (medium-high) to reduce oropharyngeal deposition. A higher resistance may be less favourable due to its compromising effect on PIF and thereby on the energy available for powder dispersion.
正确的吸入技术对于有效使用干粉吸入器（DPI）至关重要，因为其有效性很大程度上取决于患者的吸入动作。由于理解能力和吸气能力差异很大，儿童是DPI开发中特别具有挑战性的目标人群。我们之前进行了一项研究，在主要为健康儿童的人群中确定了儿科DPI的先决条件，为此我们使用了具有可变内部气流阻力和吸嘴的空测试吸入器。在当前研究中，我们调查了囊性纤维化（CF）儿童使用的DPI需要哪些规格，为此我们扩展了之前的研究结果。我们记录了35名CF儿童（年龄4.7 - 14.7岁）在三种气流阻力（0.031 - 0.045 kPa0.5.min.L-1）下的流量曲线，并据此计算了各种吸气参数。使用鼻窦镜记录吸入过程中口腔内的阻塞情况。所有儿童都能够进行正确的吸入动作，尽管视频分析显示17%的情况下儿童未将吸入器正确放入口中。未发现中到高气流阻力对总吸入量有影响，这意味着所测试的整个阻力范围适用于4 - 14岁的CF儿童。未发现吸嘴设计或气流阻力对口腔内阻塞的发生有影响。本研究证实了我们之前的结论，即非常需要专门为儿童开发的DPI。这种儿科DPI应在吸入量为0.5 L且吸气峰值流速为20至30 L/min时良好运行，具体取决于内部气流阻力。该阻力可增加至0.045 kPa0.5.min.L-1（中高）以减少口咽部沉积。由于其对吸气峰值流速（PIF）以及进而对粉末分散可用能量的不利影响，更高的阻力可能不太有利。
