No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
The ADMIT series - Issues in Inhalation Therapy. 5) Inhaler selection in children with asthma
Abstract
Many children with asthma do not use their inhalers correctly and consequently gain little or no therapeutic benefit from the treatment. The focus of inhalation therapy should be on those inhalers which are easiest to use correctly by various groups of children and the amount of tuition and training required to obtain a correct technique. It is recommended that clinicians focus on a limited number of inhalers. Most children can be taught effective inhalation therapy by using a pMDI, a pMDI with a spacer ,or a DPI. Most preschool children can be taught effective use of a pMDI and spacer with a valve system and a face mask. Therefore, this is the preferred mode of delivery in these age groups. When the child is capable of using the spacer without a face mask this administration technique should be adopted. In older children pMDIs are more difficult to use correctly than a pMDI with a spacer, a DPI ,or a breath-actuated pMDI. Because DPIs and breath-actuated pMDIs are more convenient to use these devices are normally considered the preferred inhalation devices in these age groups except for administration of beclometasone dipropionate, which for safety reasons should be delivered by a spacer.
... Effective use of MDIs requires co-ordination of actuation and inhalation, which many paediatric patients find difficult. In contrast, the inhalation technique required with a spacer or VHCH is much simpler and hence may lead to more effective respiratory therapy (Pedersen et al., 2010;Ari and Fink, 2011). DPIs were the least frequently supplied, which may be in part due to their suitability for use in older children only. ...
... The age-appropriateness of different respiratory devices is in line with current literature recommendations and reflects the ability of different ages of paediatric patients to use the devices correctly (Pedersen et al., 2010;Ari and Fink, 2011). Nebulizers were listed as being appropriate for the whole paediatric population from birth, and do not require any special co-ordination or breathing technique, whilst all devices were considered to be appropriate for adolescent patients (!12 years). ...
... Caregiver training and counselling on correct oral administration device use reduces dosing errors and improves dosing accuracy (Yin et al., 2008;Hu et al., 2013), especially when used in combination with patient information leaflets (PILs). Training and regular repeated checks on correct inhaler technique and adherence is vital to reduce errors (Crompton et al., 2006;Lavorini et al., 2008;Pedersen et al., 2010;Laube et al., 2011). It is therefore recommended that explanation of and training in correct device use is an integral part of routine patient care and that clear roles and responsibilities for this are defined within the healthcare team. ...
Medical devices are crucial for the proper administration of paediatric medicines to children, but handling and dosing errors commonly appear in daily practice. As both the understanding and the usage of medical devices for oral and respiratory drug administration are heterogeneous among patients and caregivers, the European Paediatric Formulation Initiative (EuPFI) consortium performed a European survey among healthcare professional stakeholders in France, Germany, Hungary, Italy, Spain and UK. The results show country- and age-dependent usage of devices for oral administration of liquid formulations, with a clear preference for oral droppers and syringes in the neonatal phase and in early infancy. In older children, spoons and cups are more frequently used although it is recognised that they may fail in delivering correct doses. The percentage of medicinal products definitely requiring an oral administration device was estimated as 68.8% by the participants. The survey elaborated a similar usage pattern for medical devices for respiratory drug delivery: In young children drug solutions are nebulized, using face-masks and subsequently valved holding chambers or spacers, with increasing age metered-dose inhalers and later dry powder inhalers are preferably used. 56 % of the responding healthcare professionals believed that providing an administration device helps to ensure that the patient receives the correct dose of medicine, and 41 % agreed that patients must be given an administration device with each supply of medicine. Interestingly, 6.7 % thought that patients tend not to use the device provided and remarkably 25.4% stated that patients already have a device. Although there is the highest count of treated children with device supply in Germany and Hungary, there are no observed significant differences in the six investigated European countries (p=0.057). Patient difficulties in correct oral and respiratory device use were identified by respondents and potential solutions discussed.
Copyright © 2015. Published by Elsevier B.V.
... The use of standard concentrations has been advocated to improve patient safety and to take into account paediatric daily fluid allowances. 70 76,77 For example, the use of a pMDI with spacer has been found to be at least as effective as a nebuliser for the delivery of β-agonists to preschool children. 78 Breath actuated and dry powder inhalers may overcome the need for hand-breath coordination although they are not recommended for children aged <5-7 years due to the limited and short inspiratory flow in this patient age group. ...
... 78 Breath actuated and dry powder inhalers may overcome the need for hand-breath coordination although they are not recommended for children aged <5-7 years due to the limited and short inspiratory flow in this patient age group. 76,77 As parents/caregivers are often involved in the administration of medicines to children, appropriate training and support are required. All medicines are supplied with a patient information leaflet. ...
Improved global access to novel age‐appropriate formulations for paediatric subsets, either of new chemical entities or existing drugs, is a priority to ensure that medicines meet the needs of these patients. However, despite regulatory incentives, the introduction to the market of paediatric formulations still lags behind adult products. This is mainly caused by additional complexities associated with the development of acceptable age‐appropriate paediatric medicines. This position paper recommends the use of a paediatric Quality Target Product Profile as an efficient tool to facilitate early planning and decision making across all teams involved in paediatric formulation development during the children‐centric formulation design for new chemical entities, or to repurpose/reformulate off‐patent drugs. Essential key attributes of a paediatric formulation are suggested and described. Moreover, greater collaboration between formulation experts and clinical colleagues, including healthcare professionals, is advocated to lead to safe and effective, age‐appropriate medicinal products. Acceptability testing should be a secondary endpoint in paediatric clinical trials to ensure postmarketing adherence is not compromised by a lack of acceptability. Not knowing the indications and the related age groups and potential dosing regimens early enough is still a major hurdle for efficient paediatric formulation development; however, the proposed paediatric Quality Target Product Profile could be a valuable collaborative tool for planning and decision making to expedite paediatric product development, particularly for those with limited experience in developing a paediatric product.
... Several studies have demonstrated that large numbers of patients do not use their inhalers correctly, thereby gaining little or no therapeutic benefit from the prescribed treatment. [6][7][8] Focussing on which inhalers are the easiest to use correctly by children of varying ages is at least as important as the in vitro output characteristics of any inhaler. Because of patient heterogeneity, no single inhaler will satisfy the needs of all. ...
... 6 Other studies have reported poor inhaler technique in 32-96% of patients. 7,11 Inhalation technique often remains poor after several teaching sessions. 10 Comprehensive training and repeated checks are needed to ensure a reliable inhalation technique. ...
Inhaled medications are the cornerstone of treatment in early childhood wheezing and paediatric asthma. A match between patient and device and a correct inhalation technique are crucial for good asthma control. The aim of this paper is to propose an inhaler strategy that will facilitate an inhaler choice most likely to benefit different groups of children. The main focus will be on pressurised metered dose inhalers and dry powder inhalers. In this paper we will discuss (1) practical difficulties with the devices and with inhaled therapy and (2) the optimal location for deposition of medicines in the lungs, and (3) we will propose a practical and easy way to make the best match between the inhaler device and the individual patient. We hope that this paper will contribute to an increased likelihood of treatment success and improved adherence to therapy.
... Each of these delivery technologies has advantages and disadvantages. MDIs are small and portable, but their effectiveness has been questioned because of problems in patient inhaler technique and the need for frequent re-training [15,16]. This drawback could be amplified in regions where health professionals are already overburdened and unable to provide requisite training to patients. ...
... This drawback could be amplified in regions where health professionals are already overburdened and unable to provide requisite training to patients. Use of valved spacers with MDIs lessens the importance of proper technique and improves lung deposition [16]. Spacers, however, represent an additional cost and require periodic cleaning to remain functional, which lessen their attractiveness for use in resource poor settings. ...
Background:
Respiratory disease accounts for three of the ten leading causes of death worldwide. Many of these diseases can be treated and diagnosed using a nebulizer. Nebulizers can also be used to safely and efficiently deliver vaccines. Unfortunately, commercially available nebulizers are not designed for use in regions of the world where lung disease is most prevalent: they are electricity-dependent, cost-prohibitive, and not built to be reliable in harsh operating conditions or under frequent use.To overcome these limitations, the Human Powered Nebulizer compressor (HPN) was developed. The HPN does not require electricity; instead airflow is generated manually through a hand-crank or bicycle-style pedal system. A health care worker or other trained individual operates the device while the patient receives treatment.This study demonstrates functional specifications of the HPN in comparison with a standard commercially available electric jet nebulizer compressor, the DeVilbiss Pulmo-Aide 5650D (Pulmo-Aide).
Methods:
Pressure and flow characteristics were measured with a rotameter and pressure transducer, respectively. Volume nebulized by each compressor was determined by mass, and particle size distribution was determined via laser diffraction. The Hudson RCI Micro Mist nebulizer mouthpiece was used with both compressors.
Results:
The pressure and flow generated by the HPN and Pulmo-Aide were: 15.17 psi and 10.5 L/min; and 14.65 psi and 11.2 L/min, respectively. The volume of liquid delivered by each was equivalent, 1.097 ± 0.107 mL (mean ± s.e.m., n = 13) for the HPN and 1.092 ± 0.116 mL for the Pulmo-Aide. The average particle size was also equivalent, 5.38 ± 0.040 micrometers (mean ± s.e.m., n = 7) and 5.40 ± 0.025 micrometers, respectively.
Conclusions:
Based on these characteristics, the HPN's performance is equivalent to a popular commercially available electric nebulizer compressor. The findings presented in this paper, combined with the results of two published clinical studies, suggest that the HPN could serve as an important diagnostic and therapeutic tool in the fight against global respiratory health challenges including: tuberculosis, chronic obstructive pulmonary disease, asthma, and lower respiratory infections.
... The ability to perform an inhalation manoeuvre that complies with the requirements for good performance of a particular type of DPI depends on the clinical picture (i.e. disease severity) and age of the patient, due to physical limitations and improper understanding of how to handle the device [3][4][5][6]. Children comprise an important target population for inhalation therapy, but limited fundamental research has been done on their cognitive and inspiratory capacities to operate dry powder inhalers (DPIs). Most studies on dry powder inhalation in children focused either on their ability to operate a specific DPI [7][8][9][10][11][12][13], or on single inspiratory parameters, especially the peak flow rate [14][15][16][17], and how these are affected by the airflow resistance of the inhaler [18][19][20][21]. ...
... Only two 4-year olds finished the study, and both of them did not comprehend the inhalation procedure. Two out of four 5-year olds (50%) were capable of performing a correct inhalation manoeuvre versus 14 out of 15 6-year olds (93%), which is in line with percentages reported before [6]. Furthermore, it should be emphasised that we have not investigated the repeatability and sustainability of the children's inhalation technique. ...
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.
... Although efforts have been made to introduce new asthma delivery devices such as dry powder and soft mist devices, metered dose inhalers are still the most prescribed devices amongst children. [17][18][19] This is also attributed to concerns regarding relatively high inspiratory efforts required for medication release from capsules in dry powder devices. Instead, adjustments could be made to currently prescribed metered dose inhalers and spacers. ...
Purpose
The aim of this paper is to use easily accessible smartphones as a straightforward means for physicians to objectively check Medical Device Inhaler (MDI) technique, without the need for additional devices. Additionally, we seek to assess the frequency of inhaler technique errors and their impact on asthma control.
Patients and Methods
Thirty-two children between the ages of 5 and 18 receiving asthma therapy through MDIs were included. Three surveys were administered to all participants to gauge device history, asthma control, and patient characteristics. Patient technique was scored using inhaler audio signals recorded with a smartphone. For subjects that were able, forced oscillation technique (FOT) was performed during tidal breathing conditions before and after corticosteroid administration.
Results
81% (25/31) of participants used their MDIs incorrectly with the most common errors being rapid shallow breathing, inadequate breath-holding, and excessive actuations. Poor inhaler technique correlated with poorly controlled asthma symptoms.
Conclusion
The use of smartphone recordings can a convenient way to evaluate technique errors and could allow patients to demonstrate and refine their technique and usage without a doctor’s visit, ensuring proper technique and enhancing treatment effectiveness.
... There is evidence that costs increase significantly with the severity of asthma (4), and patients with uncontrolled asthma spend more than twice as much on health care as patients with controlled asthma (5). Many international organizations and academic groups, including the International Primary Care Respiratory Group (IPCRG), Aerosol Drug Management Improvement Team (ADMIT), and American Association of Respiratory Care (AARC), are calling for greater awareness that proper use of devices is the key to successful treatment, and have developed corresponding guidelines for implementing them (2,(6)(7)(8)(9)(10)(11). ...
Objective
Training contributes to the effectiveness of aerosol inhalation therapy. However, qualitative and quantitative evaluation of effective training methods is rarely reported. This study aimed to evaluate the effectiveness of a standardized training model by pharmacists based on verbal instruction and physical demonstration in improving patients' ability to use inhalers using qualitative and quantitative methods. Risk or protective factors affecting correct inhaler use were also explored.
Methods
431 Outpatients with asthma or COPD were recruited and randomly divided into a standardized training group (n = 280) and a usual training group (control group, n = 151). A framework of qualitative (e.g., multi-criteria analysis) and quantitative comparisons [percentage of correct use (CU%), percentage of complete error (CE%), and percentage of partial error (PE%)] was established to evaluate the two training models. In addition, the changes of key factors (age, education level, adherence, device type, etc.) influencing patients' ability to use inhalers of two models were observed.
Results
The multi-criteria analysis showed that the standardized training model had comprehensive advantages in qualitative indicators. The average correct use percentage (CU%) of the standardized training group was significantly higher than that of the usual training group (77.6% vs. 35.5%). A stratified analysis further demonstrated that the ORs (95%CI) in the usual training group of age and educational level was 2.263 (1.165–4.398) and 0.556 (0.379–0.815), while in the standardized training group, age and educational level were not the key factors influencing the ability to use inhaler devices (P > 0.05). Logistic regression analysis demonstrated that standardized training was a protective factor for inhalation ability.
Conclusion
These findings indicate that the framework of qualitative and quantitative comparisons could be used to evaluate training models, and the standardized training model by pharmacists can significantly improve patients' ability to use inhalers correctly and address the influence of older age and lower education because of its methodological advantages. Further studies with more extended follow-up are needed to validate the role of the standardized training model by pharmacists in the correct use of inhalers.
Clinical trial registration
chictr.org.cn, ChiCTR2100043592 (23-02-2021).
... Error rates range from 45% to over 90%, and up to 55% of pediatric asthma patients therefore suffer from uncontrolled asthma. [4][5][6][7] Poor inhaler technique not only leads to inadequate drug efficacy and side effects, but also has a significant impact on treatment adherence. 8,9 Although these complications have existed for years, no significant improvement has been achieved over the past four decades. ...
Background:
Inhalation therapy is the cornerstone of treatment of bronchial asthma. A patient-specific selection of inhalation devices is necessary, as preference for a device plays an important role in terms of error rates in handling and adherence to therapy. However, there is no industry-independent study providing information on children's preferences for common inhaler types. The aim of the present study was to investigate the preference of asthmatic children for inhaler types commonly used in Germany. The effects of age, gender and the type of school visited on device preferences as well as the frequency of patient education and the role of health care providers in the choice for an inhaler were investigated.
Methods:
Eighty children were included in this prospective cross-sectional study (age: 10.87 ± 2.62 years). The analysis was based on a questionnaire and validated checklists. All participants tested the use of nine placebo inhalers (Breezhaler, Diskus, Respimat, Spiromax, Turbohaler, Autohaler, metered-dose inhaler, Easyhaler and Novolizer) in a randomized order. For each device, patients were asked to assess handling, rate different device characteristics and name the device they would prefer most or least.
Results:
The most favored device was the Novolizer. Moreover, the Spiromax scored highest in numerous categories such as suitability in emergencies and "easiest" device to use. Patient preferences with respect to the addressed inhaler features were not significantly related to age, gender or school type.
Conclusion:
The Novolizer and the Spiromax showed higher preference in pediatric patients as compared to other tested devices. Overall, there were significant differences in terms of preference when comparing the tested inhalers in different aspects.
... W tych grupach chorych zachodzi duże ryzyko niewygenerowania optymalnego przepływu wdechowego. Jedynie taki przepływ warunkuje właściwy proces deagregacji i aerozolizacji proszku, optymalną penetrację i depozycję takiego aerozolu w drogach oddechowych, a co za tym idzie, inhalację skuteczną klinicznie [7][8][9][10][11][12][13]. W aktywnych DPI procesy deagregacji i aerozolizacji są niezależne od wdechu chorego, co czyni tego typu inhalatory łatwiejsze w użyciu, z wysoce przewidywalną charakterystyką chmury aerozolowej. ...
W pracy przedstawiono pokrótce aktualnie dostępne inhalatory suchego proszku (DPI). Na podstawie danych z piśmiennictwa omówiono najczęstsze błędy popełniane przez chorych przy stosowaniu DPI oraz ich następstwa kliniczne i ekonomiczne. Szeroko omówiono czynniki wpływające na skuteczność i bezpieczeństwo terapii inhalacyjnej astmy i przewlekłej obturacyjnej choroby płuc (POChP), w tym głównie z DPI. Wskazano możliwości poprawy efektywności terapii inhalacyjnej z perspektywy lekarza oraz chorego na astmę lub POChP. Przedstawiono algorytm wyboru DPI uwzględniający preferencje i kompetencje chorego.
... For children aged 3-6 years, pMDIs with a spacer and a facemask is the most appropriate device for use. After that age (>6 years), children are gradually more capable of using effectively DPIs and breathactivated pMDIs 24 . It is worth mentioning that facemasks can generally reduce the pharmacological efficacy of the inhaled drug, because: 1) they give the option of using the nasal route for drug delivery, which reduces the pulmonary deposition of the drug compared to mouth-breathing 25 ; and 2) if not properly sealed around the nose and mouth (for example in a struggling child), pulmonary deposition of the inhaled aerosol is also reduced 26 . ...
... However, inhalers are not easily interchangeable and the selection of the correct device depends on many factors [54]. The best inhaler for a given patient should be chosen, following the principle of "the right inhaler for a given patient" and not "the same inhaler for all patients" [18,51,55,56]. Each type of inhaler requires specific instructions for use and a new inhaler can be a problem for the patient, even if it would be better for some reason in the opinion of the doctor. ...
The term "carbon footprint" describes the emission of greenhouse gases into the environment as a result of human activities. The healthcare sector is responsible for 5-8% of the value of global greenhouse gas emissions, of which medical aerosols account for only 0.03% of the total emissions. The reduction of greenhouse gases, including those used for the production and use of medicinal products and medical devices, is part of the responsibilities that Poland and the respective countries should undertake in order to implement the assumptions of international law. At the level of medical law, this obligation correlates with the need to exercise due diligence in the process of providing health services, including the selection of low-emission medical products and devices (inhalers) and providing patients with information on how to handle used products and devices, with particular emphasis on those that imply greenhouse gas emissions. Pressurized metered dose inhalers (pMDI) containing the hydrofluoroalkane 134a demonstrate the largest carbon footprint, followed by a metered dose liquid inhaler and dry powder inhalers (DPI). The carbon footprint of DPI with a given drug is 13-32 times lower than it is in the case of the corresponding pMDI. Replacement of pMDI by DPI is one of the effective methods to reduce the carbon footprint of inhalers, and the replacement should be based on current medical knowledge. A recycling system for all types of inhalers must be urgently implemented.
... Aerosol delivery devices are equally effective if they are ageappropriate and used correctly (36,37,52,90). However, the majority of aerosol devices require multiple steps to be used efficiently and many children with pulmonary diseases have problems with the correct delivery technique (91-94) and do not gain therapeutic benefits from therapy that result in poor disease management and increased healthcare costs (95,96). Multiple factors such as the device characteristics, children's psychomotor skills, and the healthcare professionals' knowledge lead to errors with the use of inhalers in children. ...
Although using aerosolized medications is a mainstay of treatment in children with asthma and other respiratory diseases, there are many issues in terms of device and interface selection, delivery technique and dosing, as well as patient and parental education that have not changed for half a century. Also, due to many aerosol devices and interfaces available on the market and the broad range of patient characteristics and requirements, providing effective aerosol therapy to children becomes a challenge. While aerosol delivery devices are equally effective, if they are age-appropriate and used correctly, the majority of aerosol devices require multiple steps to be used efficiently. Unfortunately, many children with pulmonary diseases have problems with the correct delivery technique and do not gain therapeutic benefits from therapy that result in poor disease management and increased healthcare costs. Therefore, the purpose of this paper is to review the current knowledge on aerosol delivery devices used in children and guide clinicians on the optimum device- and interface-selection, delivery technique, and dosing in this patient population. Strategies on how to deliver aerosolized medications in crying and distressed children and how to educate parents on aerosol therapy and promote patient adherence to prescribed medications are also provided. Future directions of aerosol therapy in children should focus on these issues and implement policies and clinical practices that highlight the potential solutions to these problems.
... Studies estimate that more than half of children who use MDIs without devices, such as spacers and valved holding chambers (VHCs) with mouthpieces or masks, gain little to no clinical benefit from their medication because of incorrect inhaler technique (3,4). Previous research has defined correct inhaler technique based on a patient performing a series of steps, ranging from 5 to 14, that are necessary for the inhaled medication to be effectively deposited into the lungs (4). ...
Inhaler misuse is highly prevalent and associated with high morbidity and costs. For metered dose inhalers, proper use can be supported with devices such as spacers/valved holding chambers (VHCs) and masks to effectively deliver inhaled medication to the lungs. However, guidelines are vague about which children with asthma should use spacers/VHCs with masks to deliver medication from metered dose inhalers as well as when they should transition to spacers/VHCs with mouthpieces. In this paper, we provide a focused review of the evidence for mask use, highlighting unclear and conflicting information in guidelines and studies. We synthesize the differences in recommendations and practice. Based on these findings, we call for future research to determine the appropriate age and necessary skills for transitioning children from using metered dose inhalers with spacers/VHCs and masks to using spacers/VHCs and mouthpieces. Guidelines about mask use should be standardized to help ensure optimal medical delivery for patients, provide consistent inhaler prescriptions and education across settings, and support team-based care to help lower pediatric asthma morbidity and costs.
... This means that despite inhaling significantly smaller particles, the therapy efficacy might not be improved. Moreover, one of the available researches indicates that too small particles, i.e., can be exhaled out of the organism leading to unsuccessful treatment [19]. The PE parameter values obtained for the smaller particles are similar for each analyzed density, however, when their size exceeds ca. ...
Purpose:
The effectiveness of inhaled drugs is strictly related to areas reachable by drug particles. Unless particles reach the desired part of the bronchial tree, their influence might not meet the expectations. Consequently, the disease progress might not be stopped or even slowed down. Therefore, the primary objective of this research was to analyze the airflow patterns and particle deposition of a standard inhaled drug using computational fluid dynamics.
Methods:
The study was devoted to the analysis of the particle diameter influence on their deposition areas within the entire respiratory tract. Two patient-specific respiratory tract models, for 6 and 12-year-old patients, were reconstructed based on the computed tomography examinations. Numerical analyses were carried out as stationary ones with the constant inflow of the particles of various diameters (within the range of 1-50 μm). It was proven that depending on the particle size, their deposition within the respiratory tract varies significantly.
Results:
The vast majority of the particles with diameters over 20 μm is gathered on the walls of the throat, whereas particles of diameters 5-15 μm are accumulated mainly on the trachea walls, leaving the alveoli insufficiently supplied with the drug particles.
Conclusions:
The inhaled drug size cannot be treated as negligible factor during the drug spraying. An improper distribution of the particles might not inhibit the symptoms of the asthma. Numerical simulations may improve drugs selection and visualize their distribution along the airways, which might accelerate asthma treatment personalization.
... There are important factors when selecting an inhaler ( Table 2) 49 . For example, the size of the particle, the patient's preference, the ability to use and generate an appropriate level of inspiratory flow for the device 50,51 , and the advantages and disadvantages described for each of them (Table 3). In the pediatric population there are specific problems that must be taken into account when prescribing an inhaler; for example, it is known that crying reduces the aerosol delivery significantly to the peripheral airways, so it should be recommended a calm environment to increase the comfort of this group of patients during the administration of inhaled medications. ...
... Inhaled treatment has many advantages such as direct fast onset of action due to local delivery, high concentration of the drug in the airways with minimal systematic side effects. However, use of these medications with improper technique leads to the inefficacy of treatment [5][6][7][8] . Inefficient inhaler treatment results in poor asthma outcomes, frequent exacerbations, increased hospitalization rates and medication cost 3,5,8,9 . ...
Objective: The percentage of asthma patients that use their inhalers with the correct technique ranges between 10
and 60. Inappropriate use of inhaler leads to disuse of drug, diminished disease control and increased drug use. In this
study, we aimed to determine the effect of proper inhaler therapy on the treatment and control of asthma and the
effect of proper inhaler use on hospitalization due to asthma.
Method: One hundred and sixty five asthma patients over 18 years of age that applied to either in- or out-patient
clinics of a university hospital, that had a diagnosis of asthma according to the criteria of the Global Initiative for
Asthma (GINA) and had been attack-free for at least one month were included. Patients were told to use their inhalers
and any misuse were noted. Patients were put through the Asthma Control Test (ACT). Their forced vital capacity
(FVC), forced expiratory volume in 1 second (FEV1) and peak expiratory flow (PEF) values were also noted. Their
hospitalization status for asthma in the last year was assessed and recorded.
Results: One hundred patients used their asthma inhalers correctly, while 65 did not. Those that used their inhalers
correctly had significantly higher ACT (p=0,0001), FEV1% (p=0,001) and PEF% (p=0,014).
Discussion: Patients must be informed and trained for the correct use of their inhaler drugs. Patients seem to be
under-informed on this subject and there are serious mistakes of use for all inhaler types. Correct use of inhalers leads
to better control of disease, lower rate of asthma-related hospitalization, less drug waste and decreased treatment
cost.
... Each of these processes is dependent from several factors such as the powder formulation, the DPI used and patient' inspiratory effort. Indeed, in DPIs the inhalation maneuver is crucial and reflects the deposition rate of active principle in the respiratory tract; each DPI device has a different inhalation maneuver and the ability to perform a correct process is dependent from patient's characteristics such as age and clinical condition (Brocklebank et al., 2001;Lavorini et al., 2008;Pedersen et al., 2010;Inhaler Error Steering Committee et al., 2013;Lexmond et al., 2014). ...
Chronic obstructive pulmonary disease (COPD) is a common disabling disease characterized by progressive airflow obstruction. Great efforts were spent in the development of drugs able to improve symptoms, quality of life, reduce exacerbations, hospitalizations and the frequency of death of patients with COPD. The cornerstones of treatment are bronchodilator drugs of two different classes: beta agonists and muscarinic antagonists. Currently the Global initiative for COPD suggests the use of long acting beta agonists (LABAs) and long acting muscarinic antagonists (LAMAs) in combination for the majority of COPD patients, thus great interest is associated with the developing of LAMA/LABA fixed combination in the maintenance treatment of stable COPD. Many LAMA/LABA fixed dose combinations have been licensed in different countries and the clinical use of these drugs stimulated the performance of many clinical trials. The purpose of this review is a complete criticism of pharmacological and clinical aspects related to the use of LAMA/LABA single inhalers for the maintenance treatment of stable COPD, with particular mention to the most debated topics and future prospects in the field.
... Choice of inhaler depends on a combination of factors, 49,50 including pulmonary function (ie, inspiratory flow and breathing technique 22,51 ), device handling, 8,52-55 use of a spacer, required inhaler technique, 7,11,56,57 and patient preference. 19,58,59 Correct inhaler technique is important for optimal delivery of the drug to the lungs and peripheral airways, resulting in greater potential for the achievement of disease control. ...
Omar S Usmani National Heart and Lung Institute (NHLI), Imperial College London and Royal Brompton Hospital, Airways Disease Section, London, UK Abstract: Appropriate selection and correct use of inhalation devices is an integral component in the management of asthma and chronic obstructive pulmonary disease (COPD). It is well known that there are many challenges with the use of inhalers, and no one device suits all patients. Challenges can range from difficulties related to lung disease severity and pulmonary function to physical considerations, including manual dexterity and comorbidities such as arthritis. In terms of device selection and adherence, patient engagement and satisfaction are also important factors to consider. Furthermore, problems with inhaler use can be most evident in children and older patients. Here, we discuss aspects for consideration with commonly used devices, including nebulizers, pressurized metered-dose inhalers, dry powder inhalers, and the soft mist inhaler. As each inhaler offers varying technical properties, a tailored and personalized approach to the selection of the most appropriate device for the patient is highly recommended in order to increase the likelihood of achieving improved disease outcomes and enhance persistence with device adherence. Importantly, education and support is crucial, not only to enable patients to recognize the need for optimal disease management, but also to help them develop good inhaler technique. In addition, health care professionals should also aim to increase their knowledge of the devices they prescribe, and develop systems to ensure that they offer comprehensive support to patients in clinical practice. Considering these aspects, this review discusses potential strategies to help address the challenges of inhaler use in asthma and COPD. Keywords: inhaler, asthma, COPD, adherence
... Existen factores importantes cuando se selecciona un inhalador 49 (Tabla 2). Por ejemplo, el tamaño de la partícula, la preferencia del paciente, la habilidad para utilizar y generar un nivel apropiado de flujo inspiratorio para el dispositivo 50,51 , y las ventajas y desventajas descritas para cada uno de ellos (Tabla 3). En población pediátrica existen problemas específicos que hay que tomar en cuenta cuando se prescribe un inhalador; por ejemplo, se sabe que el llanto reduce de manera importante la entrega de aerosol a las vías aéreas periféricas, por lo que se deberá recomendar un ambiente tranquilo que incremente la comodidad de este grupo de pacientes durante la administración de los medicamentos inhalados. ...
Inhaled therapy is considered the cornerstone of asthma treatment. However, despite being the ideal form of drug delivery, it is recognized that only 70% of patients have an adequate attachment to their treatment and only 39-67% of physicians can explain the optimal inhaler technique. Inhaled therapy has very specific characteristics. Pulmonary deposit of an inhaled medication through the respiratory tract is more complex than when administered orally and depends on several factors inherent to both the medication and the administration. For successful inhaled therapy, the drug needs to be converted into particles of an appropriate size, which can enter beyond the oropharynx and larynx, and be deposited in the lungs. There are multiple devices for the administration of drugs in the lower respiratory tract, each one with a similar efficacy as long as it is used with the correct technique. The decision of which device should be used is made based on the age of the patient, the ability to coordinate between the inhalation and activation of the device, and the presence of acute symptoms. The choice of the device must be evaluated individually.
Copyright: © 2018 Permanyer.
... In addition, understanding of how to perform the optimal manoeuvre is essential, which includes deep exhalation prior to and a sufficiently long breath hold after inhalation of the powder aerosol [2] to allow for deep penetration in the airways and time for sedimentation respectively. Both aspects are affected by patient characteristics like age and severity of disease [3][4][5][6][7]. It is, therefore, important to study the prerequisites for correct use of DPIs in selected patient populations. ...
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. © 2017 Lexmond et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
... En el mundo, los inhaladores de dosis medida (IDM), son los dispositivos más comúnmente prescritos en el manejo de enfermedades respiratorias (3,4) y en el caso de menores de 6 años, se recomienda su uso con aerocamara y mascara facial (5,6). Se conoce que la principal dificultad en la administración de medicamentos mediante aerosolterapia está en la técnica, y su principal consecuencia es la disminución de medicación que llega a las pequeñas vías aéreas (7,8). ...
INTRODUCCIÓN: Los medicamentos inhalados son la base de la terapia para patologías respiratorias. La técnica inhalatoria es un factor condicionante de su éxito terapéutico. El error más frecuente en aerosolterapia es en la técnica y su principal consecuencia es la disminución de medicación que llega a la vía aérea. OBJETIVO: evaluar el conocimiento y el método de instrucción que tiene el equipo de salud pediátrico sobre la técnica de aerosolterapia con aerocámara para niños menores de 6 años. MATERIAL Y MÉTODO: estudio transversal, analítico. Se realizó una encuesta. Incluyó a profesionales de la salud que ejercen en el área pediátrica. Se realizó estadística descriptiva y comparativa. Se consideró significancia estadística p
... Factors important in patient compliance with therapy include correct use of device, ease and convenience of use of the device and adopting a proper technique while using them [4]. Many children with asthma do not use their inhalational devices correctly and need some kind of education to improve their use [3,[5][6][7]. Though several studies regarding techniques and demonstrations to help patients use inhaler devices in an effective way have been carried out, the role of video aided demonstrations in improving rota haler technique has not yet been studied convincingly. ...
Introduction:
Inhalation therapy is the cornerstone in management of asthma. Failure to use the device properly is one of the factors incriminated in poor control of asthma.
Aim:
To compare the technique of rota haler use in children with persistent asthma immediately after receiving either verbal instruction or a video based demonstration and again at one month following intervention.
Materials and methods:
A total of 28 children, older than six years attending the childhood asthma clinic of our hospital, who were prescribed rota halers for the first time and who were technique naïve were enrolled into the study, after obtaining informed consent from the parents after meeting inclusion and exclusion criteria. They were then randomly assigned to either verbal instructions (group of 14) or video demonstration group (group of 14), for teaching them the rota haler technique. Their technique was then assessed using a modified version of the inhaler device assessment tool immediately after education and one month after the intervention. The proportions of children with good technique in both groups at both time points were compared.
Results:
There was no significant difference in the baseline variables like age, gender, location, socio-economic status and disease duration between both groups. The proportion of children achieving good technique was significantly more in the video group than the oral instruction group at immediate assessment and also at one month post intervention with an odds of 8 and 23.40 respectively (p=0.0262 and 0.0075 respectively).
Conclusion:
Video demonstration is effective in improving the technique of rota haler use at immediate assessment and at one month post intervention. Further studies are needed to validate this study and to assess factors that predict successful device use.
... However, evidence suggests that many children taking an asthma inhaler are either not using it correctly, or regularly miss doses 2,3 . Both incorrect technique and poor adherence to inhaled corticosteroids (ICS) are associated with worse clinical outcomes 3,4 . Suboptimal adherence was thought to contribute to one-third of the asthma deaths in the UK in one year 5 . ...
... Whether a patient is able to perform the inhalation manoeuvre required for a particular type of DPI depends on patient characteristics like age and clinical condition (i.e. type and severity of disease), which may present them with physical limitations or insufficient understanding of how to handle the device (Price et al. 2013;Brocklebank et al. 2001;Lavorini et al. 2008;Pedersen et al. 2010;Lexmond et al. 2014a). ...
Historically, the inhaled route has been used for the delivery of locally-acting drugs for the treatment of respiratory conditions, such as asthma, COPD, and airway infections. Targeted delivery of substances to the lungs has some key advantages over systemic administration, including a more rapid onset of action, an increased therapeutic effect, and, depending on the agent inhaled, reduced systemic side effects since the required local concentration in the lungs can be obtained with a lower dose. Fortunately, when designed properly, inhaled drug delivery devices can be very effective and safe for getting active agents directly to their site of action.
... [2]. kryteria to: nasilenie objawów, dostępność i zasady refundacji sprzętu i leków oraz ograniczenia w zapisach rejestracyjnych leków [1,[49][50][51][52][53]. Zalecaną metodą inhalacji, zarówno w przewlekłej terapii astmy, jak i w terapii jej zaostrzeń u dzieci poniżej 5. r.ż., jest pMDI z odpowiednią KI. ...
Asthma is a chronic, inflammatory, heterogenic disease of the bronchi. It is characterised by bronchial obstruction in the form of wheezing, coughing, shortness of breath and breathing difficulty, showing variable intensity and resolving after medication, or sometimes spontaneously.
Making the diagnosis of asthma in children under 5 years of age is based on clinical criteria – the presence of symptoms of bronchial constriction, confirmation of its reversibility and lack of symptoms suggestive of other clinical diagnosis. The criterion for diagnosis are usually three episodes of bronchial obstruction, or a single episode of severe intensity. A detailed history and physical examination allows in most cases to rule out other diseases with similar clinical course. Frequent recurrence of symptoms is an indication for the initial differential diagnosis in primary health care, including a chest X-ray, blood count, often an ENT and/or allergological consultation. However severe, frequent and not responding to treatment episodes of bronchoconstriction indicate the need for diagnostics in specialist hospital wards.
Chronic treatment of asthma is based on the administration of anti-inflammatory drugs, inhaled therapy is the treatment of choice in most patients. The assessment of the severity of asthma exacerbation determines the range of treatment, on an outpatient basis consisting of bronchodilators, corticosteroids and oxygen therapy. An important element of treatment is appropriate patient education, with particular attention to the exacerbation risk factors and correct inhalation technique. Children suffering from asthma should be vaccinated against pneumococcal disease and against influenza annually.
... For infants and preschool children, in whom active cooperation can be problematic, a pMDI used in conjunction with a spacer is usually preferred for maintenance therapy whereas from approximately 6-year-old children and onward, a dry powder inhaler (DPI) or breath-activated MDI is recommended [3]. Typically, lung deposition from the same pMDI spacer combination could be 1-2% in infants, 4-6% in children aged 2-6 years, and 12% in a 10-year-old child [65]. This finding suggests that children auto-scale dose delivery to the lungs as opposed to delivery at the mouth [66]. ...
Introduction: Long-acting β2-agonists (LABAs) combined with inhaled corticosteroids (ICSs) are still commonly prescribed to asthmatic children. Unfortunately, pediatric LABA use is based primarily on data from adults, despite the fact that children are not simply small adults and the magnitude of changes in dose exposure and/or exposure response may not be solely reflected by differences in body weight.
Areas covered: The differences in pharmacokinetics (PK) and pharmacodynamics (PD) of LABAs are described and discussed with reference children and adults.
Expert opinion: Data on the PK behavior of LABAs is very limited and there is almost no data on once-daily LABAs available in the pediatric population. We do not believe that this is due to a fundamental lack of information because therapeutic response and adverse effects are more useful for the optimization of β2-agonist treatment than measurement of plasma drug concentrations per se. Nevertheless, population PK-PD studies in children are needed according to the European rules in order to define rational, patient-tailored dosing schemes. Population PK-PD modeling and simulation using non-linear mixed effect modeling should be considered as the preferred tool to develop effective and safe dosing regimens for children because they present an opportunity to analyze sparse and unbalanced datasets, thereby minimizing the burden for each child.
... VHCs are widely prescribed for use with pressurized metered dose inhalers (pMDIs) for patients with poor coordination or for the infant, small child or adult who cannot use a mouthpiece to inhale their medication [1][2][3]. In recent years, manufacturers of these add-on devices have introduced materials that do not retain electrostatic charge, as a means both to improve medication delivery efficiency and reliability [4,5]. ...
Background: In recent years 'anti-static' Valved Holding Chambers (VHCs) have become more widely available. They enable use directly out of packet without pre-treatment, as pre-washing with detergent followed by drip-drying in air is time-consuming and not always followed. This laboratory study sought to investigate whether fine particle (<4.7 µm) drug delivery efficiency was similar from four commercially available VHCs, two of which were 'anti-static', the others being non-conducting, when pre-washing was not performed. Materials and Methods: Each VHC (n=3 or 5/group) was evaluated with Seretide® 250 pMDI (fluticasone propionate (FP)/25 salmeterol xinafoate (SX)), sampling the emitted aerosol at 28.3 L/min via an abbreviated Andersen impactor connected to a PhEur/USP induction port. A 5 s delayed inhalation was mimicked using a proprietary apparatus. Recovered FP and SX were assayed by validated HPLC-based methods. Results: The FPM<4.7μm for the non-conducting devices (Compact SpaceChamber Plus® and A2A™ Spacer) were greatly reduced compared with the anti-static devices with as low as 6% of the medication delivered in some cases compared to the best performing Anti-Static VHC. The two Anti-Static VHCs (AeroChamber Plus® Flow-Vu® Anti-Static VHC and OptiChamber® Diamond®) delivered consistently more medication as therapeutically beneficial FPM<4.7μm, however even for these two devices, the performance was not equivalent, with the former device exhibiting significantly higher values (1-way ANOVA, p < 0.001). Conclusions: The results indicate that if pre-conditioning is not performed for non-conducting VHCs then there is likely to be greatly reduced medication delivered to the patient and therefore under-dosing until VHC conditioning occurs. The use of ‘anti-static’ VHCs improves the reliability of medication delivery from pMDI-VHC combinations, although there are still differences in performance, and other factors, such as chamber design can also affect the fine particle delivery. Care should be taken by prescribers in the selection of these devices.
... It has been observed that, in adults, breath-holding only improves lung deposition after an extremely slow inhalation, which may be difficult for children to perform. 5 Information on comparative efficacy of either method is limited. ...
Information on the comparative efficacy of single deep breathing versus tidal breathing for inhaled asthma medications is limited, although such information can be of much use for the treatment of patients suffering from asthma. The objective of the present study was to compare the relative difference in improvement in peak expiratory flow (PEF) with single maximal inhalation with breath-holding versus 5 tidal breaths during inhalation of salbutamol from a pressurized metered dose inhaler (pMDI) with valved holding chamber (VHC) in children 5-15 y of age with asthma.
The randomized controlled trial was carried out on children with asthma between 5 and 15 y of age using a pMDI with a VHC either by a single deep breath with breath-hold or 5 tidal breaths. The experimental group received 200 μg of salbutamol from the pMDI with VHC with a single maximal inhalation and breath-hold technique, whereas the control group received 200 μg of salbutamol from pMDI with VHC using the 5 tidal breaths technique. The outcome variable, PEF, was reassessed 30 min after salbutamol use.
Eighty-two subjects (mean age 8.79 ± 2.5 y, 65 boys and 17 girls) were analyzed. There was significant improvement in the PEF, from baseline (pre-intervention) to post-intervention within the single maximal inhalation with breath-hold group and tidal breathing group independently (P < .001). The mean difference in improvement in PEF between the single maximal inhalation with a breath-hold and 5 tidal breaths group was 30.0 ± 18.16 and 28.29 ± 13.94 L/min, respectively, and was not statistically significant (P = .88).
Single maximal inhalation with a breath-hold technique is not superior to tidal breathing for improvement in PEF following salbutamol inhalation. Either method may be used in children between 5 and 15 y of age.
Copyright © 2015 by Daedalus Enterprises.
DOI: https://doi.org/10.4187/respcare.03213
Dry powder inhalers (DPIs) are now widely prescribed and preferred by the majority of patients. These devices have many advantages over the traditional pressurized metered-dose inhaler (pMDI) but they do have disadvantages. The characteristics of the dose emitted from a DPI are affected by the inhalation manoeuvre used by a patient. Each patient is different and the severity of their lung disease varies from mild to very severe. This affects how they use an inhaler and so determines the type of dose they inhale. An understanding of the pharmaceutical science related to DPIs is important to appreciate the relevance of how patients inhale through these devices. Also, each type of DPI has its unique dose preparation routine, and thus it is essential to follow these recommended steps because errors at this stage may result in no dose being inhaled. All issues related to the inhalation manoeuvre and dose preparation are addressed in this chapter. The importance of the inhalation technique is highlighted with a realization of inhale technique training and checking. During routine patient management, devices should not be switched nor doses increased unless the patient has demonstrated that they can and do use their DPI.
Introduction: Spacers offer a multitude of benefits by reducing the requirement to coordinate inhalation with actuation and improving inhaler technique in patients using a pressurized metered dose inhaler (pMDI). Spacers improve drug targeting by retaining within the spacer large particles normally deposited in the oropharynx, and by creating a prolonged aerosol cloud of fine particles to give the user increased time to inhale after actuation. This is particularly important in young children and the elderly to effectively deliver medication to the airways.
Areas covered: By investigating the history and features of spacers, we demonstrate that the advantages of using spacers far outweigh their limitations. We also discuss the optimal characteristics of spacers in terms of shape, volume, presence of valve and static charge, and present a detailed discussion of the VENTOLIN™ Mini Spacer.
Expert opinion: Generally, the shape and size of spacers makes them inherently inconvenient. Consideration of human factors and modern design may make them more attractive to patients. However, the incentive to use spacers should be their ability to help patients correctly use inhaled medications delivered by pMDIs. Understanding of these principles through education is key to their acceptance by patients.
Experts of four scientific societies and the independent experts described the position paper concerning the role of inhalation chambers in inhalation therapy in children. This document is directed to all paediatricians and family doctors. We have reviewed the most important original and review papers, together with an analysis of the holding chambers market in the country. Recommendations containing indications and principles of the selection as well as methods of inhalation from these devices in children at different age were pointed out.
The circumstances and drivers of the decision to initiate, implement, or persist with a medication differ for individuals at each developmental stage. For school-age children with asthma, the social environment of their family's cultural beliefs and the influence of peer networks and school policies are strong determinants of medication adherence. The stage of adolescence can be a particularly challenging time because there is a reduction in parental supervision of asthma management as the young person strives to become more autonomous. To illustrate the importance of such factors, adherence interventions in children and young adults with asthma have used peer-based supports and social supports, particularly social media platforms. In older patients, it is internal rather than external factors and age-related decline that pose challenges to medication adherence. Seniors face the challenges of polypharmacy, reduced social support, increased isolation, and loss of cognitive function. Strategies to promote adherence must be tailored to the developmental stage and respective behavioral determinants of the target group. This review considers the different attitudes toward medication and the different adherence behaviors in young and elderly patients with chronic respiratory conditions, specifically asthma and chronic obstructive pulmonary disease. Opportunities to intervene to optimize adherence are suggested.
Children cannot be considered as “small adults” as they present different anatomical and physiological characteristics. They present variation in airflow, airway resistance, breathing patterns, and respiratory frequency that impacts on the behavior of aerosol particles in the lungs. Thus, pulmonary deposition of aerosols in the lungs is different and dependent upon the age of the patient. Failure in pulmonary delivery may also be due to the difficulties that some patients may have in using devices properly. The suitability of the delivery system to achieve the appropriate dose of drug for the patient is also to be considered. The different devices and interfaces used in the pediatric population are described and then the selection criteria and the basis of providing recommendations are considered in more detail.
Aerosol therapy is one of the most important administration routes in the treatment of many pulmonary diseases in childhood. The basic advantage of aerosol therapy is that drugs are directly targeted at the diseased site in the lung, which warranties a more rapid therapeutic effect and possibility to lower doses of drug application. Effectiveness of inhalation is dependent on anatomical build and action of child's respiratory system, proper drug application, droplet size, used aerosol delivery devices. Integral part of the aerosol treatment is also patients' good education in childhood. The aerosol administration method should be focus on those inhalers which are easiest to use, correctly matched to the different age groups of children and do not require a large number of training needed to achieve the correct technique. Systems of aerosol therapy differ from each other in terms of construction, way of producing aerosol stream, optimal inhalation technique and difficulties of using. In paediatric pulmonary diseases four different systems to inhale drugs are used: pMDI (pressurized metered-dose inhaler), pMDI with spacer, DPI (dry powder inhaler) and nebulizer apparatus. In young children who breath usually through the nose a difficulty with establishing cooperation may arise, therefore we use a face mask. Regardless of the choice the most important thing is proper and repeated education by demonstration of a breathing technique and of the inhalation process control. Analysis of the needs of the child with pulmonary changes is an important element of the well done inhalation treatment.
Children younger than 15 years old account for 28% of the population worldwide and about one quarter of the US population. As one must undergo the developmental trajectory of childhood to reach adulthood, any discussion of clinical pharmacology would be incomplete without inclusion of how development, the most dynamic period of human life, influences drug disposition and action and creates unique therapeutic scenarios that are not seen in adults. Development, despite being a continuum of physiologic events that culminate in maturity, is often arbitrarily divided into the stages of infancy, childhood, adolescence, and even early adulthood. Across this period of time, organ size and function change, as do body composition, protein expression, and cellular function. Some cellular components are active during early development and subsequently lose function with age, and vice versa . Some tissues may be more sensitive to pharmacologic effects early in life, whereas function may decline later in life. As these developmental changes in function and form occur, their implications must be considered, both with respect to the clinical pharmacology of drugs and to their appropriate place in pediatric pharmacotherapy.
Background: Bronchial asthma is a chronic inflammatory lung disease, which causes recurrent episodes of dyspnoea, wheezing and cough. It is estimated that 10% of children suffer from asthma, and an asthmatic crisis may be a life-threatening event for the young patients. Aim: Literature review of the role of the nurse in the current management of childhood bronchial asthma in the community. Method: A literature search using the Medline, Cinahl and Cochrane databases was made for the period 1.11.2010 to 1.2.2011 using specific key words related to asthma management: Nurse, paediatric bronchial asthma, family, care, parents. Results: Most parents do not have adequate knowledge to enable them to recognize the onset of an asthmatic attack and its trigger factor, and they cannot assess the severity correctly. Many health professionals do not assess properly the severity of an asthmatic crisis, which is often underestimated. The appropriate use of inhalants, nebulizers and other devices, in combination with the removal of environmental allergens, along with education of the family, are the cornerstones of care of the child with asthma. Barriers to effective care of childhood asthma include the persistence of environmental factors, socioeconomic and cultural factors, and fluctuations in the quality of care provided by health professionals. Conclusions: Bronchial asthma is a common and serious health problem of childhood. Community intervention, and in particular family education, constitute a critical focus for the prevention and management of childhood asthma.
Principles of Clinical Pharmacology is a successful survey covering the pharmacologic principles underlying the individualization of patient therapy and contemporary drug development. This essential reference continues to focus on the basics of clinical pharmacology for the development, evaluation, and clinical use of pharmaceutical products while also addressing the most recent advances in the field. Written by leading experts in academia, industry, clinical and regulatory settings, the third edition has been thoroughly updated to provide readers with an ideal reference covering the wide range of important topics impacting clinical pharmacology as the discipline plays an increasingly significant role in drug development and regulatory science. * Includes new chapters on imaging and the pharmacogenetic basis of adverse drug reactions. * Offers an expanded regulatory section that addresses US and international issues and guidelines. * Provides extended coverage of earlier chapters on transporters, pharmacogenetics and biomarkers and also illustrates the impact of gender on drug response. * Presents a broadened discussion of clinical trials from Phase 1 to incorporate Phases II and III.
One of the most frequent causes of poorly controlled asthma is represented - together with poor adherence to the treatment - by faulty inhaler technique. Professional literature including various recommendations pays special attention to frequent mistakes which occur when using different types ofinhalatory systems. Mistakes in inhaler technique are considerably preventable - by the targeted choice of the inhalatory device. The aim of this work is to introduce a simple model of the choice of the inhalatory system- the view of the patient is considered to be a significant clue.
Previous chapters have presented the robust theoretical case for EDA in comparison with current ways of analyzing API mass distribution profiles from OIPs. This chapter is in two distinct parts; the first part examines from the theoretical standpoint, ways in which changes in APSD could potentially go undetected by EDA; the second presents a series of case studies with a variety of OIP types that demonstrate the appropriateness of EDA as a powerful, yet simple-to-use tool for in vitro assessment of CI data. Discussion of theoretical failure modes is presented for general awareness. In a given product/method development, each sponsor would have to conduct their own analysis of potential failure modes based on their situation. Similarly, the case studies are presented as illustrations of EDA and AIM applications for several real OIPs. Each sponsor may develop a different way to implement AIM and EDA, depending on their purpose.
Max was treated with SABA using an MDI and spacer with facemask and responded well to the initial treatment. You explained to the parents that nebulisers are neither required nor recommended in the treatment of wheezing in their child's situation. You advised the parents on the proper technique of MDI use with spacer and facemask, as well as care of the equipment. You also gave them a clearly written action plan regarding the efficient management of the next episode of wheeze with MDI and spacer. You further explained the side effects of oral bronchodilators and nebulisers, and why you refrained from using them. Max was given a follow-up appointment to assess his progress, and his parents were advised on the situations when they should go to a doctor or the emergency department.
Betasympathomimetika stehen für ihre beiden Hauptindikationsgebiete, die Tokolyse und die Therapie obstruktiver Atemwegserkrankungen, in unterschiedlichen Darreichungsformen zur Verfügung. Dabei kommen zur Tokolyse neben parenteralen Arzneiformen auch perorale Darreichungsformen zur Anwendung. Zur Therapie von Atemwegserkrankungen stehen neben parenteralen Zubereitungen perorale und insbesondere pulmonale Arzneiformen zur Verfügung. In der großen Gruppe der pulmonalen Darreichungsformen unterscheidet man prinzipiell Formulierungen, die mithilfe von Verneblern zur Anwendung kommen und solche, die mithilfe von Druckgasdosieraerosolen oder Pulverinhalatoren appliziert werden. Die unterschiedlichen Funktionsprinzipien und auch die Verfügbarkeit unterschiedlicher Wirkstärken der genannten pulmonalen Darreichungsformen gewährleisten eine adäquate Behandlung von Atemwegserkrankungen im Hinblick auf Indikationsstellung, Schwere der Erkrankung und die Bedürfnisse verschiedener Patientengruppen.
Introduction:
The inhaled route has many advantages, but requires the patient to use, and to master the use of, an inhaler device. Poor inhaler technique and non-adherence to therapy lead to a highly variable lung dose in clinical practice, with subsequent loss of clinical efficacy and wastage of economic resources.
Areas covered:
This paper discusses problems of poor inhaler technique, non-adherence to inhaler therapy, other issues relating to the precision of dose delivery, the consequences of these problems and how they can be addressed.
Expert opinion:
The precision of dosing by the pulmonary route can be improved by appropriate choice of inhaler device and by education. It is vital to educate patients about their disease, about the importance of taking prescribed medications and about correct inhaler use. One-on-one sessions with healthcare professionals probably represent the most effective educational method. For some drugs and patient groups, inhalers containing small microprocessors may also be used to control inhalation technique, and hence, to obtain a more reproducible lung dose. As the range of drugs delivered by inhalation increases, the need for correct inhaler technique, adherence to therapy and precise dosing becomes more and more important.
The pressurized metered dose inhalers and dry powder inhalers are the most widely used devices for inhalation therapy in asthma and chronic obstructive pulmonary disease; each of these devices have certain advantages and disadvantages that impact their use. Motivation from the virtues of these devices led to the development of breath-actuated or breath-activated metered dose inhalers. A history of the breath-actuated inhalers, the development and technical aspects, studies about the usability, inhalation technique and patient preference, lung deposition and impact on lung function are presented in this review article. This review presents the use of breath-actuated inhalers in asthma and chronic obstructive pulmonary disease and in children and elderly; and a brief economic evaluation aims to put the clinical efficacy and ease-of-use of the breath-actuated inhaler into perspective by understanding the long-term cost benefits associated with this device.
Three different devices are available for inhaled medications in children: the pressurized metered dose inhalers (pMDIs, breath-actuator synchronized pMDI, and valved holding spacers), the dry powder inhalers, and the nebulizers. To choose the better device for a particular patient, a perfect knowledge of the available devices, of their mode of use, of their advantages and inconvenient is required. The use of a pMDI coupled to a valved holding spacer is the first mode of delivery to propose in children aged less than 6 years. After 6 years old, the DPIs may be proposed depending on the child's competences. At last, the nebulizations are indicated in some particular and severe indications, but new indications are appearing because of recent progresses.
Objective:
Incorrect Metered-Dose Inhaler (MDI)-spacer technique can result in decreased drug delivery to distal airways and poor asthma outcomes. There is lack of research to examine whether the caregivers utilize proper technique when applying an MDI-spacer delivery system for young minority children with persistent asthma in the United States. The objective of this study was to evaluate MDI-spacer utilization and technique among the caregivers of Bronx minority children with persistent asthma and to determine characteristics associated with correct use.
Methods:
We analyzed data from 169 caregivers of urban minority children with persistent asthma (aged 2-9 years). MDI-spacer device technique was assessed using a 10-step checklist derived from the national guidelines, literature and manufacturers' instructions. Based on the median MDI-technique score of six steps demonstrated accurately, caregivers were categorized as correct (seven or more) or incorrect (six or less) users.
Results:
Of the 169 caregivers, 95% were mothers, mean age 32.3 years (SD 7.6), 56% were unemployed; 74% of the children were Hispanic, 87% had either "not well controlled" or "very poorly controlled" asthma, 92% had a spacer at home and 71% used it "all" or "most" of the time. Only one caregiver correctly demonstrated all 10 steps of the MDI-spacer technique. Child's having one or more asthma-related hospitalizations in the past 12 months and higher caregiver educational level were independent predictors of correct MDI-spacer technique.
Conclusions and relevance:
The caregivers of urban, minority children with persistent asthma lack proper MDI-spacer technique, suggesting the potential value of both targeted short- and long-term educational interventions.
Three different devices are available for inhaled medications in children: the pressurized metered dose inhalers (pMDIs, breath-actuator synchronized pMDI, and valved holding spacers), the dry powder inhalers, and the nebulizers. To choose the better device for a particular patient, a perfect knowledge of the available devices, of their mode of use, of their advantages and inconvenient is required. The use of a pMDI coupled to a valved holding spacer is the first mode of delivery to propose in children aged less than 6years. After 6 years old, the DPIs may be proposed depending on the child's competences. At last, the nebulizations are indicated in some particular and severe indications, but new indications are appearing because of recent progresses.
There is an enormous diversity in the number and uses of sprays in the medical community, from disinfectant strategies, drying and coating technologies, as well as target delivery of therapeutic agents to the human body. The number and range of strategies for forming these sprays is almost as varied, but in every application the droplet size distribution, particle velocity, impact dynamics, and hydrodynamic environment contribute immensely to achieving the specific performance parameters. As a result, therapeutic sprays have had difficulty fully achieving the envisioned potential. The following review article will reflect specifically on medical sprays for drug delivery to specific organs (i.e., lung, nasal, ocular, and skin) to review the current state of capabilities, but also comment on specific gaps in ability and knowledge. Our objective is to stimulate a discussion within the spray community that will result in heightened interest directed toward improved performance and efficacy.
Purpose of review:
This review analyses published data on the treatment of wheezing in infants and preschoolers with inhaled corticosteroids (ICS), including the effect in subgroups of patients such as 'multiple trigger wheeze' and 'episodic viral wheeze'.
Recent findings:
Therapy with ICS at daily doses of 100-200 μg results in significant clinical improvements in several outcomes in preschoolers and infants suspected of having asthma (multiple trigger wheeze). Such treatment is normally considered well tolerated. Although not well studied, higher daily doses may be associated with measurable effects on growth, which are not cumulative with continued treatment. In children who only wheeze in association with viral infections (episodic viral wheeze), preemptive treatment with high doses of ICS has demonstrated significant clinical effects on several outcomes, whereas lower doses seem to have little effect. Intermittent use of high doses of ICS has been associated with significant reductions in height and weight gain over 1 year.
Summary:
The review illustrates the complexity of treating wheezing in infants and preschoolers and interpreting the study results. It emphasizes the need for more studies in clinical subgroups, more long-term studies and dose-response studies to assess the optimal doses and safety of intermittent as well as regular ICS treatment.
The output and size distribution of aerosols from dry powder inhalers are dependent on the flow rate through the device, Therefore, in an in vivo study, we examined the flow-dependency of the effect of formoterol when delivered from a dry powder inhaler, the Aerolizer(R), in a flow range relevant to schoolchildren. In a preliminary study comprising 126 asthmatic children aged 3-10 yrs, the relationship between age and peak inspiratory flow (PIF) rate through the Aerolizer(R) was determined, Mean PIF was 104 L.min(-1) and all children aged >5 yrs performed a PIF >60 L.min(-1). Sixteen children aged 8-15 yrs with exercise-induced: asthma (EIA) took part in the main trial comparing the protective effect of 12 mu g formoterol inhaled at 60 and 120 L.min(-1). The effect from high and low inspiratory flow was judged from the protective effect against EIA 12 h after drug administration. The decrease in forced expiratory volume in one second (FEV1) after exercise was 34% on the placebo day, but only 15% when formoterol was inhaled at the high flow rate, This difference was statistically significant. The decrease in FEV1 was 23% after treatment with formoterol inhaled at the low flow rate, that was not significantly different from placebo or from high-flow formoterol treatment, These clinical findings correspond with the in vitro findings of flow-dependent fine particle mass from the Aerolizer(R), and corroborate the relationship between fine particle mass of aerosol and clinical effect. The results indicate a flow-dependent effect of formoterol dry powder inhaled from the Aerolizer(R), within the range of inspiratory flow rate obtainable by schoolchildren, This questions its applicability in children with asthma.
The corollary with respect to aerosol drug therapy is that of the aerosols are to be efficiently deposited in peripheral airways in patients with airways obstruction, smaller particles than those commonly used should be produced. Using techniques under controlled conditions, it has been possible to demonstrate that positive pressure breathing of aerosols in patients with airways obstruction failed to produce a more uniform or more peripheral distribution of aerosols than quiet breathing. Thus, despite their low mass of 0.4 μm, such particles might be of potential value in patients with a degree of reversibility of peripheral airways associated with a major fixed obstructive component. This study emphasizes the marked sensitivity of human pulmonary airways to very small topical doses of beta adrenergic agonists. It is important to establish the intrapulmonary dose of a given drug accurately to determine the lowest airway dose necessary to provide maximum bronchodilatation in order to minimize side-effects. Furthermore, for inhalation challenge studies, using histamine or methacholine, to be comparable it is surely useful to have information about the dose of the material actually administered to the airway.
High doses of inhaled corticosteroids are absorbed systemically and may cause long term side effects. As rinsing the mouth out after use and inhaling through a spacing device may reduce systemic absorption this has been further investigated.
Three crossover studies were carried out to assess the effect of budesonide given by dry powder inhaler (Turbuhaler) with and without mouth rinsing and beclomethasone dipropionate given by metered dose inhaler with or without a spacing device (Volumatic) on serum cortisol concentrations and urinary cortisol excretion in patients with asthma taking an inhaled corticosteroid. Each treatment period was two weeks with in a two week washout period. Serum cortisol concentrations at 0800 hours on day 14 and the 24 hour urinary excretion of cortisol were measured. In study 1 24 patients taking beclomethasone dipropionate 500 micrograms twice a day inhaled with (n = 10) or without (n = 14) a Volumatic spacing device were switched to a budesonide dry powder inhaler, 600 micrograms to be taken twice a day without mouth rinsing. In study 2 10 patients took budesonide 800 micrograms twice a day with and without mouth rinsing and without swallowing the rinsing water. In study 3 17 patients took budesonide 800 micrograms twice daily with mouth rinsing and beclomethasone dipropionate 500 micrograms twice daily with the spacing device and mouth rinsing.
In study 1 no difference was seen between budesonide without mouth rinsing and beclomethasone dipropionate without a spacer: beclomethasone with spacer caused less suppression of cortisol (mean (SD) serum cortisol concentration: beclomethasone and spacer 487(148), budesonide 368(145) nmol/l). In study 2 mouth rinsing caused less suppression of morning serum cortisol concentrations (rinsing 440(63), no rinsing 375(56) nmol/1). In study 3 there was no difference in serum or urinary cortisol concentrations between twice daily beclomethasone dipropionate 500 micrograms inhaled by Volumatic spacer or budesonide by Turbuhaler 800 micrograms twice daily, both with mouth rinsing. Individual serum cortisol values were within the normal range in all patients except one in study 1.
Systemic absorption of a corticosteroid inhaled from a metered dose inhaler is reduced by using a spacing device and that from a dry powder inhaler by mouth rinsing.
When used in high doses, inhaled corticosteroids may cause suppression of the hypothalamo-pituitary-adrenal axis. The influence of the mode of drug inhalation on the degree of this suppression is not clear. Hypothalamo-pituitary-adrenal function was assessed by measurement of 0900 h serum cortisol concentrations, a short tetracosactrin test, and 24 hour urine free cortisol excretion in 48 adults with asthma taking 1500-2500 micrograms beclomethasone dipropionate daily via a metered dose aerosol. Twelve patients had hypothalamo-pituitary-adrenal suppression, as judged by subnormal results from at least two of the three tests or (in one patient) by an abnormal insulin stress test response. These patients then changed to inhaling the same dose of beclomethasone dipropionate through a 750 ml spacer device (Volumatic). The endocrine tests were repeated from nine days to eight weeks later in 10 patients. Comparison with initial values showed that adding the spacing device caused an increase in the median 0900 h cortisol concentration from 126 nmol/l to 398 nmol/l, in the post-tetracosactrin cortisol concentration from 402 nmol/l to 613 nmol/l and in 24 hour urine free cortisol excretion from 54 nmol to 84 nmol. The rise in serum cortisol concentration in response to tetracosactrin did not change. Evidence of persisting hypothalamo-pituitary-adrenal axis suppression was present in only four of the 10 patients; the most pronounced improvements in function tended to occur in those who had never required long term oral corticosteroids. The results from this uncontrolled study suggest that asthmatic patients taking high dose beclomethasone dipropionate may minimise adverse effects by using a large volume spacer device.
The lung dose and deposition patterns of drug delivered by dry powder inhaler are not known. The effects of inhaling 400 micrograms salbutamol delivered by dry powder inhaler (two 200 micrograms salbutamol Rotacaps), by pressurised metered dose inhaler, and by Acorn nebuliser were studied in nine subjects with chronic stable asthma. Technetium-99m labelled Teflon particles were mixed with micronised salbutamol in the pressurised metered dose inhaler and in the capsules; technetium-99m labelled human serum albumin was mixed with the salbutamol solution for the nebuliser study. The pressurised metered dose inhaler deposited 11.2% (SEM 0.8%) of the dose within the lungs; this was significantly more than the dose deposited by the dry powder inhaler (9.1% (0.6%], but did not differ significantly from the dose delivered by the nebuliser (9.9% (0.7%]. Distribution within the peripheral third of the lung was significantly greater with the nebuliser than with the other two systems; FEV1 improved to a significantly greater extent after inhalation of 400 micrograms salbutamol from the pressurised metered dose inhaler (35.6% from baseline) than from the nebuliser (25.8%) or dry powder inhaler (25.2%). Thus after inhalation of similar doses of salbutamol a larger proportion of drug was deposited within the lungs when it was inhaled from a metered dose inhaler than from a dry powder system; the nebuliser achieved the greatest peripheral deposition. The bronchodilator response seems to depend on the amount of drug within the lungs rather than its pattern of distribution.
The effect on aerosol deposition from a pressurised metered dose inhaler of a 750 cm3 spacer device with a one way inhalation valve (Nebuhaler, Astra Pharmaceuticals) was assessed by means of an in vivo radiotracer technique. Nine patients with obstructive lung disease took part in the study. The pattern of deposition associated with use of a metered dose inhaler alone was compared with that achieved with the spacer used both for inhalation of single puffs of aerosol and for inhalation of four puffs actuated in rapid succession and then inhaled simultaneously. On each occasion there was a delay of 1 s between aerosol release and inhalation, simulating poor inhaler technique. With the metered dose inhaler alone, a mean (SEM) 8.7 (1.8)% of the dose reached the lungs and 80.9 (1.9)% was deposited in the oropharynx. With single puffs from the spacer 20.9 (1.6)% of the dose (p less than 0.01) reached the lungs, only 16.5 (2.3)% (p less than 0.01) was deposited in the oropharynx, and 55.8 (3.1)% was retained within the spacer itself. With four puffs from the spacer 15.2 (1.5)% reached the lungs (p = 0.02 compared with the metered dose inhaler alone, p less than 0.01 compared with single puffs from the spacer), 11.4 (1.2)% was deposited in the oropharynx, and 67.5 (1.8)% in the device itself. It is concluded that the spacer device gives lung deposition of metered dose aerosols comparable to or greater than a correctly used inhaler and oropharyngeal deposition is greatly reduced. The spacer should be used preferably for the inhalation of single puffs of aerosol but may also be used for the inhalation of up to four puffs actuated in rapid succession and then inhaled simultaneously.
The budesonide dose delivered to the patient from three different spacer devices (Nebuhaler = 750 ml, Aerochamber = 140 ml, and Babyspacer = 260 ml) was assessed by measuring the budesonide dose deposited on a filter inserted between the spacer outlet and the mouth of the patient. Twenty children aged 10-25 months were given a single dose of 200 micrograms budesonide from each spacer device in a randomised crossover study. All spacers had a facemask attached and a one way valve system. The children breathed through the inhalation system for 30 seconds. Furthermore, the minute ventilation of the children through a tightly fitting facemask was measured. The filter dose of budesonide was significantly lower after Aerochamber treatment (39.4 micrograms, range 19-67 micrograms) than after Nebuhaler (53.5 micrograms, range 34-88 micrograms) and Babyspacer (55.5 micrograms, range 39-76 micrograms) treatment. The minute ventilation of the children varied from 1.4 l/min to 7.0 l/min (mean 5.0 l/min). This was sufficient to empty all spacers within the 30 seconds of inhalation. It is concluded that spacer volume does not seem to be so important for children aged 10-25 months as long as spacers with a volume lower than 750 ml are used.
The output and size distribution of aerosols from dry powder inhalers are dependent on the flow rate through the device. Therefore, in an in vivo study, we examined the flow-dependency of the effect of formoterol when delivered from a dry powder inhaler, the Aerolizer, in a flow range relevant to schoolchildren. In a preliminary study comprising 126 asthmatic children aged 3-10 yrs, the relationship between age and peak inspiratory flow (PIF) rate through the Aerolizer was determined. Mean PIF was 104 L.min-1 and all children aged > 5 yrs performed a PIF > 60 L.min-1. Sixteen children aged 8-15 yrs with exercise-induced asthma (EIA) took part in the main trial comparing the protective effect of 12 micrograms formoterol inhaled at 60 and 120 L.min-1. The effect from high and low inspiratory flow was judged from the protective effect against EIA 12 h after drug administration. The decrease in forced expiratory volume in one second (FEV1) after exercise was 34% on the placebo day, but only 15% when formoterol was inhaled at the high flow rate. This difference was statistically significant. The decrease in FEV1 was 23% after treatment with formoterol inhaled at the low flow rate, that was not significantly different from placebo or from high-flow formoterol treatment. These clinical findings correspond with the in vitro findings of flow-dependent fine particle mass from the Aerolizer, and corroborate the relationship between fine particle mass of aerosol and clinical effect. The results indicate a flow-dependent effect of formoterol dry powder inhaled from the Aerolizer, within the range of inspiratory flow rate obtainable by school-children. This questions its applicability in children with asthma.
Drug delivery to patients using dry powder inhalers, such as the Turbuhaler, is believed to be influenced by the inspiratory flow used. Clinical studies have indicated that this delivery system can be used effectively by children. However, it is not known how the total and weight-corrected dose delivered to the airways varies with age. A deposition study using technetium-99m (99mTc)-labelled budesonide was performed in order to determine the effect of age on delivery. Twenty one children with cystic fibrosis, aged 4-16 yrs, were recruited. They were clinically stable with normal lung function. Initially, a gamma camera scan was taken in front of a flood source containing 37 MBq of 99mTc. Subsequently, subjects inhaled through a low resistance inspiratory filter connected to a commercially available Turbuhaler. Immediately afterwards they inhaled from a noncommercial Turbuhaler containing budesonide labelled with 99mTc, and then underwent anterior and posterior gamma camera scans. Both Turbuhaler inhalers were attached to a portable spirometer and the peak inspiratory flow through the Turbuhaler was recorded for each inhalation. The total body dose was calculated from the dose deposited on the inspiratory filter connected to the commercial Turbuhaler. Analysis of the gamma camera images provided information on the proportion of the radiolabel delivered to the lungs compared to that deposited in the upper airway and stomach. As expected, a highly significant positive correlation was noted between the peak inspiratory flow generated by the patient through the Turbuhaler and the dose delivered to the lung. Similarly, there was a highly significant positive correlation between age and "total lung dose". However, when total lung dose was corrected for body weight, there was a nonsignificant negative correlation with age. This study suggests that the "weight-corrected lung dose" achieved when children aged > 6 yrs use the Turbuhaler, is largely independent of age. It would appear that the flow-dependent properties of this device are such that the reduced peak inspiratory flow generated by younger children results in a lower dose to the lungs, but that this is off-set by their lower body weight. This is unlikely to be a property of other devices with different flow/drug delivery characteristics.
To evaluate the systemic availability and basic pharmacokinetic parameters of budesonide after nebulisation and intravenous administration in preschool children with chronic asthma.
Plasma concentrations of budesonide were measured for three hours after an intravenous infusion of 125 micrograms budesonide. The children then inhaled a nominal dose of 1 mg budesonide through the mouthpiece of a Pari LC Jet Plus nebuliser connected to a Pari Master compressor, and the plasma concentrations of budesonide were measured for another six hours. The amount of budesonide inhaled by the patient ("dose to subject") was determined by subtracting from the amount of budesonide put into the nebuliser, the amount remaining in the nebuliser after nebulisation, the amount emitted to the ambient air (filter), and the amount found in the mouth rinsing water.
Ten patients aged 3 to 6 years completed both the intravenous and the inhaled treatment. The mean dose to subject was 23% of the nominal dose. The systemic availability of budesonide was estimated to be 6.1% of the nominal dose (95% confidence intervals (CI), 4.6% to 8.1%) or 26.3% of the dose to subject (95% CI, 20.3% to 34.1%). Budesonide clearance was 0.54 l/min (95% CI, 0.46 to 0.62), steady state volume of distribution 55 litres (95% CI, 45 to 68), and the terminal half life was 2.3 hours (95% CI, 2.0 to 2.6).
Approximately 6% of the nominal dose (26% of the dose to subject) reached the systemic circulation of young children after inhalation of nebulised budesonide. This is about half the systemic availability found in healthy adults using the same nebuliser.
Pressurized metered dose inhalers (pMDI) are widely used together with spacers for the treatment of asthma in children. However, the variability of daily medication dose for pMDI/spacer combinations is not known. Electrostatic charge is a potential source of dose variability. Metal spacers have no static charge. This study assessed and compared within-subject variability of aerosol delivery of metal and plastic spacers. This was a randomized, crossover study in children with stable asthma aged 1-4 (group I, n=17) and 5-8 (group II, n=16) yrs. In both groups the amount of drug delivered to the mouth by a metal spacer (Nebuchamber) and one of two plastic (polycarbonate) spacers, i.e. Babyhaler in group I and Volumatic in group II was measured. The metal and plastic spacers were tested at home in a randomized order for 7 days each, using budesonide (200 microg b.i.d.). Aerosol was collected on a filter positioned between spacer and facemask or mouth. Budesonide on the filter was assessed by high performance liquid chromatography. The mean filter dose for each child (mean+/-SD) during the 7 days was expressed as a percentage of the nominal dose. Within-subject variability was expressed as coefficient of variation (CV). Mean filter dose in group I was 41.7+/-10.1% for Nebuchamber and 26.0+/-4.0% for Babyhaler (p<0.001). Mean filter dose in group II was 50.2+/-9.2% for Nebuchamber and 19.4+/-7.2% for Volumatic (p<0.001). Mean CV in group I was 34% for Nebuchamber and 37% for Babyhaler (p=0.44). Mean CV in group II was 23% for Nebuchamber and 34% for Volumatic (p=0.003). There was substantial within-subject dose variability in aerosol delivery in children using a pMDI/spacer at home. This variability was lower for the metal than for the plastic spacer in children 5-8 yrs of age. The dose delivered to the mouth was about two-fold higher for the metal than the plastic spacer independent of age.
Asthma patients can be treated safely and effectively with the compounds and inhalation devices currently available. However, the choice of devices is so wide that the healthcare professional may be easily confused, and the effectiveness of treatment reduced. Clear guidelines are needed to help resolve this difficulty; however, those currently available do not contain enough useful information on the different delivery systems to assist the selection process. The function of the anti-asthma drug (i.e., preventer or reliever) should determine the choice of device. For inhaled corticosteroids, the device should provide effective and reliable delivery, while simplicity in use will aid good inhalation technique. A device that minimizes systemic absorption of these drugs will improve drug safety. The devices of choice are pressurized metered dose-inhalers (pMDIs) with spacers and some dry powder inhalers (DPIs). The main selection criteria for short-acting beta2-agonists are portability and patient acceptability. DPIs and pMDIs are the most suitable systems for these drugs. Cost is an important consideration for both drug types.
Pharmacokinetic studies can be used to measure lung dose of inhaled drugs. The aim of this study was to compare the lung deposition of budesonide (BUD) inhaled from Turbuhaler (AstraZeneca, Lund, Sweden) and fluticasone propionate (FP) inhaled from Diskus (GlaxoSmithKline, London, UK) and to assess if the study design used for pharmacokinetic studies can be simplified. Plasma levels of BUD and FP were measured for 21 hours on five separate days in 15 patients aged 8 to 14 years: (1) Intravenous infusion of 200 microg BUD, (2) intravenous infusion of 200 microg fluticasone dipropionate, (3) inhalation of 800 microg BUD via Turbuhaler, (4) inhalation of 750 microg FP via Diskus, and (5) inhalation of BUD and FP on the same day. Charcoal was ingested to eliminate drug uptake from the gastrointestinal tract. The mean lung deposition of drug after Turbuhaler and Diskus inhalation was 30.8 and 8.0% when BUD and fluticasone were administered on separate days and 29.5% (BUD) and 7.6% (fluticasone) when the two drugs were inhaled on the same day. Lung deposition is four times higher in children after inhalation from Turbuhaler than after inhalation from Diskus. Pharmacokinetic studies with BUD and FP can be simplified because the two treatments can be administered on the same day.
Until now, care provided by asthma nurses has been additional to care provided by paediatricians. A study was undertaken to compare nurse led outpatient management of childhood asthma with follow up by a paediatrician.
Seventy four children referred because of insufficient control of persistent asthma were randomly allocated to 1 year follow up by a paediatrician or asthma nurse. The main outcome measure was the percentage of symptom-free days. Additional outcome measures were airway hyperresponsiveness, lung function, daily dose of inhaled corticosteroids (ICS), number of exacerbations, number of additional visits to the general practitioner, absence from school, functional health status, and disease specific quality of life.
There were no significant differences at the end of the 1 year study period between the two treatment groups in percentage of symptom-free days (mean difference 2.5%; 95% CI -8.8 to 13.8), airway hyperresponsiveness (log10 PD20 0.06; -0.19 to 0.32), functional health status (10.1; -0.3 to 19.8), disease specific quality of life of patients (0.08; -0.9 to 0.7), and disease specific quality of life of caregivers (0.09; -0.2 to 0.3), nor in any other outcome parameters. Most outcome parameters improved considerably over the 1 year study period. These improvements were achieved although the daily dose of ICS was reduced by a mean of 26% compared with the dose received by children at referral. All parents were satisfied with the asthma care received.
After initial assessment in a multidisciplinary clinic, childhood asthma can be successfully managed by an asthma nurse in close cooperation with a paediatrician. During close follow up by paediatrician or asthma nurse, asthma control improved despite a reduction in ICS dose.
The proliferation of inhaler devices has resulted in a confusing number of choices for clinicians who are selecting a delivery device for aerosol therapy. There are advantages and disadvantages associated with each device category. Evidence-based guidelines for the selection of the appropriate aerosol delivery device in specific clinical settings are needed.
(1) To compare the efficacy and adverse effects of treatment using nebulizers vs pressurized metered-dose inhalers (MDIs) with or without a spacer/holding chamber vs dry powder inhalers (DPIs) as delivery systems for beta-agonists, anticholinergic agents, and corticosteroids for several commonly encountered clinical settings and patient populations, and (2) to provide recommendations to clinicians to aid them in selecting a particular aerosol delivery device for their patients.
A systematic review of pertinent randomized, controlled clinical trials (RCTs) was undertaken using MEDLINE, EmBase, and the Cochrane Library databases. A broad search strategy was chosen, combining terms related to aerosol devices or drugs with the diseases of interest in various patient groups and clinical settings. Only RCTs in which the same drug was administered with different devices were included. RCTs (394 trials) assessing inhaled corticosteroid, beta2-agonist, and anticholinergic agents delivered by an MDI, an MDI with a spacer/holding chamber, a nebulizer, or a DPI were identified for the years 1982 to 2001. A total of 254 outcomes were tabulated. Of the 131 studies that met the eligibility criteria, only 59 (primarily those that tested beta2-agonists) proved to have useable data.
None of the pooled metaanalyses showed a significant difference between devices in any efficacy outcome in any patient group for each of the clinical settings that was investigated. The adverse effects that were reported were minimal and were related to the increased drug dose that was delivered. Each of the delivery devices provided similar outcomes in patients using the correct technique for inhalation.
Devices used for the delivery of bronchodilators and steroids can be equally efficacious. When selecting an aerosol delivery device for patients with asthma and COPD, the following should be considered: device/drug availability; clinical setting; patient age and the ability to use the selected device correctly; device use with multiple medications; cost and reimbursement; drug administration time; convenience in both outpatient and inpatient settings; and physician and patient preference.
Pressurized metered-dose inhalers attached to spacers are now the most common form of delivery of anti-asthma medication in children. However, no reliable data are available of how much drug reaches the lungs in children of different ages. This information is crucial, as it determines the efficacy of therapy. In this study, we present information on the amount of drug reaching the lungs in children from a pressurized metered-dose inhaler attached to a detergent-coated spacer. We studied 18 asthmatic children inhaling radiolabeled salbutamol through detergent treated spacers to minimize electrostatic charge on the spacer wall. Lung deposition was much higher than expected when using detergent-coated spacers. Mean (SD) lung deposition, expressed as a percentage of the total actuated dose (five actuations), was 16.4% (5.5) in younger children inhaling through a small volume spacer, and 28.2% (6.7) and 41.8% (3.8) in older children inhaling with different breathing patterns through a large volume spacer. These findings have major implications for dosage regimens for inhaled anti-asthma medication in children. Lower doses may be sufficient for adequate drugs delivered through spacers treated for static to achieve a desired clinical response. Pediatr Pulmonol, 2000; 29:389-393, (C) 2000 Wiley-Liss, Inc.
The correct use of inhaler devices is important for the efficacy of the treatment of childhood asthma. Few studies have compared the use of inhaler devices in real life, in particular in children.
In order to evaluate whether children can be taught the efficient use of a pressurized terbutaline aerosol with a tube spacer 71 children were given careful instruction in aerosol inhalation technique according to the manufacturer's instructions. Inhalation technique, was assessed as being efficient when a child achieved an increase of more than 19% in FEV1 10 min after taking two puffs of terbutaline (each puff = 0.25 mg). After instruction about 37% of children aged 5–7 years and about 80% of children over 7 year were efficient in inhalation technique. Inhalation through the nose after actuation into the mouth accounted for about 50% of treatment failures, with the problem being more frequent in the younger age group. When this error was corrected about 83% of the children were efficient in the technique. Coordination problems and too rapid inspiration after actuation were also common errors. The findings stress the importance of checking all children's inhalation technique before prescribing inhalation therapy. Careful instruction was not enough. The possibility of nasal inhaling should be borne in mind when looking for causes of treatment failure.
Pressurized metered dose inhalers (pMDI) are widely used together with spacers for the treatment of asthma in children. However, the variability of daily medication dose for pMDI/spacer combinations is not known. Electrostatic charge is a potential source of dose variability. Metal spacers have no static charge. This study assessed and compared within-subject variability of aerosol delivery of metal and plastic spacers. This was a randomized, crossover study in children with stable asthma aged 1–4 (group I, n=17) and 5–8 (group II, n=16) yrs. In both groups the amount of drug delivered to the mouth by a metal spacer (Nebuchamber®) and one of two plastic (polycarbonate) spacers, i.e. Babyhaler® in group I and Volumatic® in group II was measured. The metal and plastic spacers were tested at home in a randomized order for 7 days each, using budesonide (200 µg b.i.d.). Aerosol was collected on a filter positioned between spacer and facemask or mouth. Budesonide on the filter was assessed by high performance liquid chromatography. The mean filter dose for each child (mean±sd) during the 7 days was expressed as a percentage of the nominal dose. Within-subject variability was expressed as coefficient of variation (CV).Mean filter dose in group I was 41.7±10.1% for Nebuchamber and 26.0±4.0% for Babyhaler (p<0.001). Mean filter dose in group II was 50.2±9.2% for Nebuchamber and 19.4±7.2% for Volumatic (p<0.001). Mean CV in group I was 34% for Nebuchamber and 37% for Babyhaler (p=0.44). Mean CV in group II was 23% for Nebuchamber and 34% for Volumatic (p=0.003).There was substantial within-subject dose variability in aerosol delivery in children using a pMDI/spacer at home. This variability was lower for the metal than for the plastic spacer in children 5–8 yrs of age. The dose delivered to the mouth was about two-fold higher for the metal than the plastic spacer independent of age.
The Montreal Protocol requires limitation of the use of devices powered by chlorofluorocarbons (CFCs), which reduce stratospheric ozone levels. Albuterol, a medication commonly used for the treatment of asthma that is delivered by metered-dose inhalers with CFCs as propellants, will be withdrawn from the U.S. market by December 2008. This review article summarizes useful information about albuterol in metered-dose inhalers with non-CFC propellants and discusses associated economic issues.
The aim of this study was to evaluate the effect of instructions to children with asthma (given by general practitioners or by pharmacy assistants) on how to inhale from metered dose inhalers with spacers (MDI/s) or dry powder inhalers (DPI). We scored inhalation technique of asthmatic children according to criteria defined by the Netherlands Asthma Foundation, and related the performance to the inhalation instructions given. For each inhaler, a number of steps were considered essential for reliable drug delivery. Patients newly referred for asthma were asked to demonstrate their inhalation technique and to fill out a questionnaire on the inhalation instruction received prior to referral. Children participating in a clinical trial, who had received repeated comprehensive inhalation instructions, served as a control group. Sixty-six newly referred patients (1-14 years of age, median age 5 years; 37 boys) and 29 control patients (5-10 years of age, median age 7 years; 21 boys) completed the study. Sixty patients (91%) had received inhalation instruction prior to referral. Only 29% of these patients, using a dry powder inhaler, performed all essential steps correctly, compared to 67% of children using a metered dose inhaler/spacer combination (P < 0.01). Children who had received comprehensive inhalation instructions with repeated checks of proper inhalation technique at the pharmacy or in the clinical trial setting were more likely to perform all essential steps correctly (79% and 93%, respectively) than children who had received a single instruction by a general practitioner (39%, P < 0.01). Many asthmatic children use their inhalers devices too poorly to result in reliable drug delivery, even after inhalation instruction. Comprehensive inhalation instruction and repeated check-ups are needed to assure reliable inhalation technique.
Many patients benefit from using metered-dose inhalers (MDIs) with spacer or reservoir devices. Concomitant therapy with separate MDI doses of cromolyn sodium and a beta-agonist is common practice. If two puffs from each drug could be placed into a chamber, the patient could administer both medications at once, enhancing compliance. A multistage liquid impinger (a four-stage inertial impaction device incorporating an inlet bend and an absolute filter, which separates an aerosol cloud into six fractions) was used to investigate such a possibility. Cromolyn sodium and albuterol MDIs were used with an Aerochamber (Monaghan Medical Corp., Plattsburgh, N.Y.) and an Inspirease (Schering Corp., Kenilworth, N.J.). Results are reported by analyzing milligrams of cromolyn sodium per actuation retrieved. With the Aerochamber, two puffs of cromolyn sodium followed by two puffs of albuterol resulted in the total "dose to patient" being reduced by 75% (0.19 versus 0.05 mg) and the effective dose of fine particles (less than 6.5 microns) being reduced by 80% (0.13 versus 0.03 mg) compared to two puffs of cromolyn sodium alone. With the Inspirease, total dose was decreased by 80% (0.32 versus 0.06 mg), whereas the effective dose of fine particles was reduced by 60% (0.19 versus 0.05 mg) compared to one puff of cromolyn sodium alone. The use of cromolyn sodium and albuterol MDIs in a multipuff combination with the Aerochamber or the Inspirease is not recommended because this leads to a loss of the dose delivered compared to a single administration.
Many studies in which patient's inhaler use technique has been studied have shown that one of the major problems patients have, in using an inhaler correctly, is that of poor coordination of inhaler actuation with inspiration. We have studied a new breath-actuated inhaler ("Autohaler" 3M Riker) which is designed to ensure correct coordination automatically. This study involves 100 children (aged 3-10 years) and includes both normal children and asthmatic patients. None of these children have previous experience using any type of inhaler. Each child is taught to use the "Autohaler" containing a placebo only. A video film is employed in order to standardize the teaching technique. Once the child is able to operate the new inhaler correctly, he or she inspires through an "Autohaler" unit specially modified so that the inspiratory flow rate and the volume of air inhaled is measured by a pneumotachograph in series with the inhaler. The time point, within the inspiratory cycle, at which the inhaler is triggered is also recorded. The majority of children older than 7 years were able to use the "Autohaler" after a few minutes instruction. Therefore, this is a valuable alternative in this age group.
Plasma concentrations of cromolyn sodium (SCG) have been measured in 13 normal subjects on three occasions after inhalation from a Spinhaler (20 mg) delivery system under conditions of controlled inspiratory flow rate. High inspiratory flow rates were associated with high peak plasma concentrations and areas under the plasma concentration-time curve. A 10-sec breath hold at the end of inspiration did not alter significantly the plasma concentration-time curve. Instillation of SCG (1 mg) directly into a second-order bronchus of 14 patients undergoing diagnostic examination gave plasma concentration-time curves similar to those seen in normal volunteers at high inspiratory flow rates. Additional studies in normal volunteers showed that SCG was poorly absorbed from the gastrointestinal tract. The shorter terminal half-life seen after i.v. infusion compared with inhalation indicates that the drug shows absorption rate limited disposition kinetics after inhalation. These studies in large numbers of subjects support the conclusions of limited earlier investigations that SCG is absorbed slowly but almost completely from the airways, that there is little gastrointestinal absorption of SCG, that only a small proportion of the Spinhaler dose (about 10%) reaches the airways and that the amount reaching the airways is related directly to inspiratory flow rate.
Two Nebuhaler techniques were compared by measuring the response to terbutaline 0.25 mg in 13 asthmatic children. Five breaths each sufficient to operate the Nebuhaler valve resulted in greater bronchodilatation after 10 minutes (P less than 0.05) than two deep inspirations from residual volume each held for 5 seconds. The peak responses were similar and both methods produced significant bronchodilatation compared with placebo. Either method is satisfactory in children but the former is easier to perform.
1. Coordination difficulties, stop of inhalation at actuation and fast inhalations are the most important problems children experience when using a PA while difficulties with correct loading and splitting of the capsule are the most prevalent problems with the RO. 2. Most children older than 5 years can be taught effective use of an inhaler and once the correct technique has been learned is it rarely forgotten if the inhaler is used regularly. 3. Insufficient instruction at the time of prescription is the major cause of inefficient inhaler use in children who use their inhalers regularly. 4. Use of a TS makes it easier for children to inhale slowly. Furthermore, compared with a PA and TS reduces the occurrence of coordination problems and stop of inhalation when the aerosol is fired; otherwise there seems to be little clinical difference between a PA and a TS. 5. Problems with correct inhaler use are accentuated during episodes of acute wheeze when supervision or help from an adult may be needed. 6. Pauses between doses of inhaled bronchodilators are likely to improve bronchodilation during episodes of acute wheeze, whereas there is no need to recommend pauses between the puffs of bronchodilators or between puffs of bronchodilators and corticosteroids in the routine day to day management of patients. 7. Children using a TS should be taught to inhale as slowly as possible. Tilting the head back during inhalation, breath-holding after the inhalation and exhalation through the nose do not enhance response. Furthermore, the lung volume at which the aerosol is actuated is relatively unimportant as long as the child inhales as deeply as possible after actuating the aerosol. 8. The effect of powder inhalers is dependent upon a certain inspiratory flow rate and therefore there is a risk of reduced effect during episodes of acute wheeze or in children with low pulmonary function. This risk may be greater with a RO than with a FPI. 9. Children using a Rotahaler or a Fenoterol powder inhaler should be taught to inhale as fast as possible. They need not tilt the head backwards during inhalation or hold their breath afterwards. 10. Conclusions from one inhaler should be applied with caution to other inhalers. 11. The long list of instructions currently considered to represent the essentials of correct inhalation technique can be markedly simplified without any significant loss of effect in children receiving inhaled therapy with bronchodilators and corticosteroids.(ABSTRACT TRUNCATED AT 400 WORDS)
The influence on the adrenocortical function of high-dose topical glucocorticoids inhaled via conventional devices and via a Nebuhaler, was studied in ten children with asthma. In patients treated with dosages of beclomethasone dipropionate or budesonide, in excess of 2100 micrograms/1.73 m2 body surface, the 24-h urinary excretion of free cortisol increased when the inhaler device was changed from a conventional one to a Nebuhaler. This suggests a decreased systemic influence of the inhaled glucocorticoids when these were administered via a Nebuhaler.
256 asthmatic children receiving regular inhalation therapy demonstrated how they used their inhalers. Pulmonary function measurements (PFM) were made before and after the demonstrations, and errors in technique were recorded. 242 children had reversible airway obstruction on the day of study. In only 109 (45%) did the inhalation result in an increase in FEV1 greater than or equal to 15% (efficient technique). An efficient inhalation technique was found in 46% of children who demonstrated a pressurized aerosol, 59% who demonstrated a tube spacer aerosol and 46% who demonstrated a rotahaler, and the frequency of efficient technique varied from 17% to 84% between six different groups of instructors. 87% of children controlled and 25% not controlled with PFM at the time of prescription had an efficient technique. Children under 6 years had a more inefficient and a more faulty technique than older children, but otherwise age did not influence the result. Neither was time since instruction of any importance for efficiency or number of errors. The errors recorded that seem to influence efficiency most were: coordination problems, rapid inspirations, ceasing to inspire when the aerosol was fired, and inhalation through the nose. The results emphasize the paramount importance of clear instructions and control of inhalation technique at the time the treatment is prescribed.
Although the manufacturers of pressurized aerosol bronchodilators issue instructions for using the inhalers, little or no experimental verification exists. Furthermore, the instructions often fail to take into account known facts about aerosol deposition. We have reviewed the evidence for the most effective mode or modes of inhalation of pressurized aerosol bronchodilators, some of which has arisen from experiments performed in our laboratory. In order to achieve a maximal effect following inhalation of terbutaline sulphate bronchodilator aerosol (Bricanyl, Astra Pharmaceuticals), the canister should be actuated during a slow (25 l min-1), deep inhalation and breath held subsequently for 10 s. Bronchodilatation may be reduced if aerosol is inhaled rapidly (80 l min-1) or if breath is held for 4 s. We have considered the applicability of these simple rules to other types of bronchodilator and to all patients, irrespective of their diagnosis or degree of airway obstruction. The lung volume at which aerosol is released into the airstream, the importance of coordinating inhalation with aerosol actuation, and the relative merits of "open" and "closed" mouth inhalation techniques are also discussed.
In order to evaluate whether children can be taught the efficient use of a pressurized terbutaline aerosol with a tube spacer 71 children were given careful instruction in aerosol inhalation technique according to the manufacturer's instructions. Inhalation technique was assessed as being efficient when a child achieved an increase of more than 19% in FEV1 10 min after taking two puffs of terbutaline (each puff = 0.25 mg). After instruction about 37% of children aged 5-7 years and about 80% of children over 7 years were efficient in inhalation technique. Inhalation through the nose after actuation into the mouth accounted for about 50% of treatment failures, with the problem being more frequent in the younger age group. When this error was corrected about 83% of the children were efficient in the technique. Coordination problems and too rapid inspiration after actuation were also common errors. The findings stress the importance of checking all children's inhalation technique before prescribing inhalation therapy. Careful instruction was not enough. The possibility of nasal inhaling should be borne in mind when looking for causes of treatment failure.
Although the use of pressurised aerosol inhalers is widespread, little is known about the actual deposition of the aerosol in the respiratory tract, since this has previously been difficult to measure. We have incorporated Teflon particles (mean diameter 2 micrometer) with aerodynamic properties similar to those of bronchodilator drug crystals into pressurised aerosol canisters. Controlled inhalations by eight patients with obstructive airways disease showed that on average 8.8% of the dose was deposited in the lungs (3.0% in the alveoli and 5.8% on the conducting airways) and 80% in the mouth. These figures are in good agreement with previous indirect estimates of deposition based on metabolic studies. The remainder of the dose was either expired (1.0%) or deposited in the aerosol actuator (9.8%). This method should have wide application for measurement of deposition patterns under various conditions and for assessment of therapeutic effects.
Using radiolabelled metered-dose inhaler (MDI) generated aerosols the factors determining optimum bronchopulmonary delivery were determined. Maximum dose to the thoracic airways was achieved by activating the MDI 4 cm from the wide-open mouth, inhaling the released dose over 5 or 6 sec (<1 L/sec) from FRC, and breath-holding for 10 sec at TLC.
We wanted to assess the protective effects on exercise-induced asthma as well as the clinical efficacy and safety of increasing doses of a new sustained-release formulation of terbutaline sulphate, in 17 asthmatic children aged 6-12 yrs (mean 9 yrs). Placebo, 2, 4 and 6 mg terbutaline were given b.i.d. for 14 days, in a randomized, double-blind, cross-over design. At the end of each two week period, an exercise test was performed and plasma terbutaline was measured. Compared with placebo, no significant effect was seen on asthma symptoms monitored at home, or on exercise-induced asthma. The percentage falls in FEV1 after the exercise test were 36, 35, 27 and 28%, after placebo, 4, 8 and 12 mg terbutaline.day-1, respectively. There was no correlation between plasma terbutaline and dose of terbutaline. A small but statistically significant dose-related increase in morning and evening peak expiratory flow (PEF) recordings occurred, but the incidence of side-effects also increased with the dose given. There was a trend towards more side-effects when the high doses were used, and two patients withdrew from the study because of side-effects at this dose. It is concluded that continuous treatment, even with high doses of oral terbutaline, does not offer clinically useful protection against exercise-induced asthma.
A randomised double blind, two period cross over study was designed to compare the ability of 51 hospitalised asthmatics with acute exacerbations to use each of two inhalers. The inhalers compared were a new breath actuated metered dose inhaler, the Autohaler inhalation device, and a dry powder device, the Rotahaler. Preassessment data included the measurement of peak inspiratory flow rate (PIFR), peak expiratory flow rate (PEFR), pulse rate, and oxygen saturation. Therapeutic response to each inhaler was compared by measurement of PEFR, oxygen saturation, and pulse rate. PIFR was sufficient in all children to fire the Autohaler, including the youngest. No significant difference was found between the two inhalers as assessed by PEFR. However the Autohaler inhalation device could be actuated 99/100 times successfully compared with 74 for the Rotahaler. There was a consistent, but clinically insignificant, increase in pulse rate after use of the Rotahaler compared with the Autohaler. All 11 patients under 6 years of age failed to empty the Rotahaler but five of these patients received a significant benefit from using the Autohaler compared with after the Rotahaler. A significant drop in oxygen saturation was observed 15 minutes after use of either inhaler. This may at times reach levels of clinical importance.
To study the impact of both audiovisual information and nurse-training on the use of budesonide Turbuhaler in preschool children who had never used a dry powder inhaler.
A single-blind, randomized, parallel-group trial studied 72 children aged 3-5 y. All children and their parents were shown an instructional video and given written instruction. After this, peak inspiratory flow (PIF1) through Turbuhaler was measured. Children in group A (n = 36) then received individual training by a nurse while those in Group B (n = 36) did not and PIF2 was measured. Afterwards, Group B received similar individual training while Group A received no additional training, and PIF3 was measured. Group A was given a placebo Turbuhaler and encouraged to practice at home. Two weeks later, both groups returned to the clinic where PIF4 was measured.
The number of children who were able to correctly perform PIF1, PIF2 and PIF4 in Group A was 27, 34 and 36, respectively. The corresponding numbers for Group B were 30, 29, and 29. No effect of training was seen in 3-y-old children. Individual training by a nurse was associated with a statistically significant increase in PIF2 (10 l/min; p = 0.014). Moreover, 2 weeks of home training was associated with an additional increase in PIF of 8 l/min compared with Group B (p < 0.015). After individual instruction and home training, mean PIF in children aged 4 and 5 was 56 (42-72) and 55 (41-66) l/min, respectively.
After individual instruction and training at home, the vast majority of children aged 4 and 5 y can use Turbuhaler correctly. Audiovisual information and individual instruction is not sufficient in the majority of these children. Few 3-y-old children can learn the correct use of Turbuhaler.
Unlabelled:
The aim of our study was to evaluate the effect of age on lung deposition of radiolabelled budesonide, delivered as a dry powder via Turbuhaler to asthmatic children. A group of 23 asthmatic children, aged 6 to 16 years, with relatively stable asthma inhaled 99mTc-labelled budesonide from a dry powder inhaler (Turbuhaler). Body and lung deposition was assessed using a gamma camera. The mean (range) median peak inspiratory flow during inhalation was 65 1 x min(-1) (45 to 76 1 x min(-1)). Mean (range) total lung deposition of 99mTc-labelled budesonide, expressed as a percentage of the metered dose, was 29.1% (15.6-47.2%) and was positively and significantly correlated with age, height and peak inspiratory flow.
Conclusion:
Total lung deposition of radiolabelled budesonide from a dry powder inhaler (Turbuhaler), is age dependent in children with moderate asthma. However, lung deposition is still satisfactory, even in younger children with lower peak inspiratory flows.
Powder inhalers rely on the patient's inspiratory flow for delivery and aerosolization of the medicament. Different inhalers offer different resistances to inspiration through the device. The flow rate attained by a patient depends on the effort expended and on the air flow resistance of the device; flow rate is thus a device-dependent variable. A comparison between powder inhalers should therefore take their air flow resistances into account. An empirical relation between the peak inspiratory flow rate through a device and the flow resistance of the device has been developed using results from healthy subjects and verified to a limited extent using data from asthmatic patients. The flow resistance was measured as the pressure drop at a fixed flow rate. The empirical relation can be used to predict the change in peak inspiratory flow rate resulting from a change in flow resistance. Matching flow rates, representing equal inspiratory efforts, may thus be calculated for different inhalation devices.
In comparison with pressurized metered dose inhalers (pMDIs), dry powder inhalers (DPIs) emit a semi-stable aerosol cloud and are inspiratory flow actuated and inspiratory flow driven. In vitro studies show that different DPIs vary in their efficiency as delivery systems of fine drug particles (aerodynamic diameter < 5 microns). The efficiency of DPIs may vary according to the inspiratory force used to generate the aerosol. In comparison with other DPIs, Turbuhaler has been shown to be an efficient fine particle generator at weak, moderate and strong inspiratory forces. Deposition studies using human throat casts have shown that the throat has a minor influence on the deposition of drugs delivered from DPIs, whereas the throat has a major influence on the deposition of drug delivered from pMDIs. The fine particle dose able to penetrate the human throat casts was considerably higher for budesonide Turbuhaler than for budesonide pMDI, whereas for fluticasone propionate the fine particle dose was considerably higher from the pMDI than from Diskhaler. Thus, whether the fine particle dose and the deposition pattern of a drug generated from DPIs can equal that generated from pMDIs depends on the drug, the formulation and the patient.
The metered-dose inhalers are the most commonly used devices in the treatment of asthma, but dry powder inhalers (eg, Turbohaler) are being increasingly used. Studies evaluating how well children can use a Turbohaler are lacking.
We assessed whether the correct use of a Turbohaler could be easily taught to unselected stable asthmatic children.
One hundred sixty-one asthmatic children aged 5 to 17 years (mean, 9.8 years) consecutively attending the outpatient clinic were included in study. After a demonstration and 10 minutes of training, the inhalation technique was checked in a standardized way (yes/no response). Keeping the device upright, proper preparation of the drug dose and inspiratory flow on inhalation were measured by the Turbohaler trainer.
One hundred thirty-three children (83%) performed every step correctly (ie, 96% of children older than 8 years but only 55% of children between 5 and 8 years; P <.001). Of 28 children incorrectly using the Turbuhaler-trainer, 20 generated insufficient inspiratory flow through the device. There was no significant difference in airway obstruction (expressed as percent of predicted forced vital capacity, FEV1, and Tiffeneau index) between correct and incorrect users, but when measured through the pneumotachograph, mean peak inspiratory flow (expressed as percent predicted) was significantly lower in those children incorrectly using the device. Turbohaler use was reevaluated after 4.7 +/- 2.0 months in a subset of 64 patients. Fifty-three of 64 (83%) children again used the device correctly. Only 3 of 13 who used the device incorrectly at the first evaluation used it correctly at the second evaluation.
We conclude that the correct use of the Turbohaler can be easily taught to asthmatic children older than 8 years. Those who use the device correctly after initial instructions continue to do so afterwards.
Salbutamol is a short-acting beta 2 agonist which is effective as a rescue therapy in the treatment of asthma. This study uses in vitro test methods to compare the capability of four alternative devices to deliver an accurate and precise dose of salbutamol. It is demonstrated that the conventional metered dose inhaler (MDI) achieves excellent accuracy and precision in dose delivery. Additionally, it is the most efficient inhaler in terms of generating in-vitro a fine particle fraction from the dose. A spacer device has been shown to further enhance the dosing characteristics. When tested over a wide range of inspiratory air flow rates, the Diskus (GlaxoWellcome, Hertfordshire, UK) has comparable accuracy and precision to the MDI tested at 60 L/min, and it offers an advantage over two alternative dry powder inhalers (DPIs), delivering a more consistent dose across the range of flow rates tested and being more efficient at generating a fine particle fraction than either Turbuhaler (Astra, Lund, Sweden) or Diskhaler (GlaxoWellcome) at both 28 and 60 L/min inspiratory flow rates. Diskus, Diskhaler, Ventolin, Volumatic, and Rotadisk are trademarks of the GlaxoWellcome Group of companies. The Accuhaler is the alternative to the Diskus in those countries where the Diskus trademark is not available. Inspiryl and Turbuhaler are trademarks of the Astra Group of companies.
most patients use their inhalers incorrectly and recent asthma management clinical guidelines recommend demonstrating skills and correcting performance at each asthma follow-up visit. However, this statement is poorly evidence-based and few intervention studies have assessed quantitatively the effectiveness of this recommendation.
from a total of 3,076 children and adolescents with asthma attending an outpatient clinic, a random, representative sample of 255 was obtained and assessed at baseline with a standardised questionnaire regarding their skills when using one of three inhaler devices: pressurised direct aerosol (PDA), dry powder (DP) and aerosol pressurised in expanded camera (APEC). Structured sessions of correct use and handling of inhalers were offered and a new assessment was undertaken after an average of 10.5 months (SD 4.5).
only 142 asthmatics maintained the same inhaler device during the study period. An increase of correct manoeuvres was observed for all three devices, and the relative risk and 95% confidence interval (RR and 95% CI) of incorrect post-intervention use was 0.23 (95% CI 0.10-0.56) for PDA, 0.59 (95% CI 0.38-0.92) for DP, and 0.54 (95% CI 0.32-0.90) for APEC. A multivariate analysis indicates that this improvement was observed irrespective of gender and age interval, and that it was even better when parents cooperated with medical and nursing staff.
a dramatic improvement in correct manoeuvres with any of three inhaler devices after active performance training was observed. This easy, highly effective, low cost (in terms of time and personnel) intervention should be routinely implemented in any control visit of asthmatics, leading to a better management of asthma.
Pressurized metered-dose inhalers attached to spacers are now the most common form of delivery of anti-asthma medication in children. However, no reliable data are available of how much drug reaches the lungs in children of different ages. This information is crucial, as it determines the efficacy of therapy. In this study, we present information on the amount of drug reaching the lungs in children from a pressurized metered-dose inhaler attached to a detergent-coated spacer. We studied 18 asthmatic children inhaling radiolabeled salbutamol through detergent treated spacers to minimize electrostatic charge on the spacer wall. Lung deposition was much higher than expected when using detergent-coated spacers. Mean (SD) lung deposition, expressed as a percentage of the total actuated dose (five actuations), was 16.4% (5.5) in younger children inhaling through a small volume spacer, and 28.2% (6.7) and 41.8% (3. 8) in older children inhaling with different breathing patterns through a large volume spacer. These findings have major implications for dosage regimens for inhaled anti-asthma medication in children. Lower doses may be sufficient for adequate drugs delivered through spacers treated for static to achieve a desired clinical response.
Many children with asthma use their inhaler device incorrectly even after comprehensive inhalation instruction. The aim of this study was to identify factors associated with correct inhalation technique. Two hundred children with asthma demonstrated their inhalation technique. Patient characteristics and the components of inhalation instructions they had received were compared for children demonstrating a correct or incorrect inhalation technique. In addition, the inhalation technique of 47 newly referred patients was followed-up prospectively after repeated comprehensive instruction sessions. Seventy-eight percent of all patients demonstrated a correct inhalation technique. Patients who had received repeated instruction sessions and patients who had previously been asked to demonstrate the use of their inhaler during an instruction session were more likely than other children to demonstrate a correct inhalation technique (p < 0.001 and p= 0.03, respectively). Multiple logistic regression analysis showed that repetition of instructions was significantly associated with a correct inhalation technique (odds ratio (OR) 8.2, 95% CI 3.2–21.5; p < 0.0001) irrespective of type of inhaler used. Demonstration of the inhaler use by the patient was significantly associated with a correct inhalation technique for patients using a metered dose inhaler plus spacer device (OR 3.5,95% CI 1.0–12.6; p= 0.05), but not for patients using a dry powder inhaler (OR 1.6,95% CI 0.4-6.4; p= 0.54). The number of newly referred patients demonstrating a correct inhalation technique improved from 57.4% to 97.9% after three comprehensive instruction sessions.
Conclusion: Inhalation instruction should be given repeatedly to achieve and maintain correct inhalation technique in asthmatic children.
The goal of this study was to establish a reliable method to evaluate systemic bioavailability and to determine equisystemic effects (microgram dose producing equal systemic cortisol suppression) of inhaled corticosteroids (ICS). Steroid naive asthma subjects (n = 156) were enrolled at six centers. A 1-week doubling dose design was used for each of six ICS and matched placebos for a total of four doses. Systemic effect was evaluated by hourly plasma cortisol concentrations (8 P.M. to 8 A.M.), 12- and 24-hour urine cortisol concentrations, and a morning blood osteocalcin. The area under the concentration-time curve for hourly cortisol concentrations was the best outcome variable to assess systemic effect. For the six ICS and matching placebos (beclomethasone-chlorofluorocarbon [CFC], budesonide dry powder inhaler [DPI], fluticasone DPI, fluticasone-CFC metered dose inhaler [MDI], flunisolide-CFC, and triamcinolone-CFC), only the placebo group and fluticasone DPI did not demonstrate a significant dose-response effect. Thus microgram comparison of all ICS could only be performed at a 10% cortisol suppression: flunisolide-CFC - 936; triamcinolone-CFC - 787; beclomethasone-CFC - 548; fluticasone DPI - 445; budesonide DPI - 268; fluticasone-CFC MDI - 111. This study represents the first step in evaluation of ICS efficacy based on equisystemic (cortisol suppression) effects of a given ICS, rather than doses judged arbitrarily to be comparable on a microgram basis.
An atomic force microscope (AFM) colloid probe technique has been used to investigate the effect of relative humidity (RH) on the adhesion properties of pharmaceutical powder surfaces. The adhesion between a model substrate, alpha-lactose monohydrate, and model particulate drugs, salbutamol sulphate and budesonide, was investigated between RHs of 15 and 75%. The surface topography of the model alpha-lactose monohydrate was produced by controlling the supersaturation conditions during crystal growth to produce sub-nanometre scale roughness. The adhesion interactions between lactose and drug probes of salbutamol sulphate and budesonide were shown to be significantly increased with each incremental rise in humidity. Capillary forces were significantly more dominant for the adhesion in the budesonide-lactose system up to 60% RH but were more dominant for salbutamol sulphate-lactose above 60% RH. These studies suggested that non-surface-specific capillary forces play a dominant role in the adhesion between drug and carrier, which may significantly reduce the deaggregation and dispersion properties of a dry powder formulation.
The atomic force microscope (AFM) has been used to characterize the cohesive nature of a micronized pharmaceutical powder used for inhalation therapy. Salbutamol sulfate (also referred to as albuterol sulfate), a therapeutic drug commonly delivered from dry powder inhalers (DPI), was chosen as a model system because the cohesion and subsequent de-agglomeration during inhalation are critical aspects to the efficacy of such a delivery system. Salbutamol sulfate drug particulates were mounted on V-shaped AFM cantilevers using a novel micromanipulation technique. Force-distance curves obtained from the measurements between cantilever drug probes and model compacts of salbutamol sulfate were integrated to determine separation energies. The effect of humidity (15-75% RH) on the energy required to separate a drug particle from model drug surface was determined using a custom-built perfusion apparatus attached to the AFM. Separation energy measurements over 10 x 10-microm areas of the compact surface (n = 4096) exhibited log normal distributions (apparent linear regression, R(2) >or= 0.97). Significant increases in the median separation energies (p < 0.05) between the salbutamol sulfate drug probes and salbutamol sulfate model surfaces were observed as humidity was increased. This result is most likely attributed to capillary interactions becoming more dominant at higher humidities. This investigation has shown the AFM to be a powerful technique for quantification of the separation energies between micronized drug particulates, highlighting the potential of the AFM as a rapid preformulation tool.
To compare the efficacy of beta-agonists given by metered-dose inhaler with a valved holding chamber (MDI+VHC) or nebulizer in children under 5 years of age with acute exacerbations of wheezing or asthma in the emergency department setting.
Published (1966 to 2003) randomized, prospective, controlled trials were retrieved through several different databases. The primary outcome measure was hospital admission.
Six trials (n=491) met criteria for inclusion. Patients who received beta-agonists by MDI+VHC showed a significant decrease in the admission rate compared with those by nebulizer (OR, 0.42; 95% CI, 0.24-0.72; P=.002); this decrease was even more significant among children with moderate to severe exacerbations (OR, 0.27; 95% CI, 0.13-0.54; P=.0003). Finally, measure of severity (eg, clinical score) significantly improved in the group who received beta-agonists by MDI+VHC in comparison to those who received nebulizer treatment (standardized mean difference, -0.44; 95% CI, -0.68 to -0.20; P=.0003).
The use of an MDI+VHC was more effective in terms of decreasing hospitalization and improving clinical score than the use of a nebulizer in the delivery of beta-agonists to children under 5 years of age with moderate to severe acute exacerbations of wheezing or asthma.
The modern era of aerosol therapy began with the introduction of the Medihaler Epi in 1956, after a 13-year-old asthmatic told her father, an officer in the Riker company, that asthma medications should be as convenient to use as hair spray and she complained that the bulb atomizer leaked in her school bag. Since then, advances in technology have made aerosol delivery much more efficient, so that it is now the most widely used mode of medication delivery for chronic airways diseases. Today the pressurized metered-dose inhaler (pMDI) is a metal canister containing a mixture of propellants, surfactants, preservatives, and drug. However, pMDIs are underused in the United States. One barrier to use is the misconception related to pMDI effectiveness relative to small-volume nebulizers, especially among pediatricians. This is despite the strongest evidence of pMDI superiority, from well-controlled pediatric studies. In this manuscript we discuss ways to optimize the use of medications given via pMDI and examine recent changes in pMDI technology that will make drug delivery more efficient and consistent.