Article

Optimization of aerosol deposition pressure support in children with cystic fibrosis: An experimental and clinical study

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Abstract

Nebulized aerosols are commonly used to deliver drugs into the lungs of patients with cystic fibrosis (CF). The aim of this study was to assess the effectiveness of pressure-support (PS) ventilation in increasing aerosol deposition within the lungs of children with CF. An in vitro study demonstrated the feasibility of coupling a breath-actuated nebulizer to a PS device. An in vivo study was done with 18 children (ages 6 to 21 yr) with clinically stable CF, each of whom underwent both a standard and a PS-driven ventilation scan (control session and PS session, respectively). In addition, a perfusion scan was used to determine lung outlines and to construct a geometric model for quantifying aerosol deposition by radioactivity counting in MBq. Homogeneity of nebulization was evaluated from the four first-order moments of aerosol distribution in the peripheral and central lung regions. The time-activity nebulization curve was linear in all patients, with higher slopes during the PS than during the control session (0.43 +/- 0.07 [mean +/- SD] MBq/min and 0.32 +/- 0.23 MBq/min, respectively; p < 0.018). Quantitatively, aerosol deposition was about 30% greater after the PS session (4.4 +/- 2.7 MBq) than after the control session (3.4 +/- 2.1 MBq; p < 0.05). Similarly, deposition efficacy (as a percentage of nebulizer output) was significantly better during the PS session than during the control session (15.3 +/- 8.3% versus 11.5 +/- 5.7%, p < 0.05). No differences in the regional deposition pattern or in homogeneity of uptake were observed. In conclusion, our data show that driving the delivery of a nebulized aerosol by noninvasive PS ventilation enhances total lung aerosol deposition without increasing particle impaction in the proximal airways.

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... Moreover, breathing through the nose while using full-face mask reduces the penetration of aerosol to the lungs due to a great loss of the aerosol into nasal cavities. The use of a nose-clip may improve the aerosol delivery with a full-face mask [49]. ...
... There are few observational studies in child-related implications of NIV on aerosol therapy [49]. Fauroux et al. [49] compared the effectiveness of aerosol delivery with NIV in children with stable cystic fibrosis. ...
... There are few observational studies in child-related implications of NIV on aerosol therapy [49]. Fauroux et al. [49] compared the effectiveness of aerosol delivery with NIV in children with stable cystic fibrosis. The deposition of a radiolabeled aerosol from a nebulizer synchronized to deliver aerosol during inspiration was about 30% greater with pressuresupport ventilation compared to use of the nebulizer alone. ...
Chapter
Full-text available
Noninvasive ventilation (NIV) may increase the risk of carbon dioxide (CO2) rebreathing for two reasons: firstly, the single-limb circuit that is preferentially used for NIV causes patients to exhale into the same space from which they inhale, and, secondly, the interfaces used for NIV increase dead space.
... Two options are used for this combination: interrupt NIV and remove the interface for the delivery of the aerosolized drug or continue NIV and combine it with simultaneous aerosol delivery. Even if the feasibility of such combination has been verified [13,14], the optimal settings have not been clearly demonstrated. The different findings reported in adult subjects with acute asthma, COPD and CF are summarized in this document. ...
... Aerosol delivery during NIV offers advantages over aerosol delivery alone. Indeed, application of NIV has been associated with increased tidal volume [13], decreased respiratory rate [13] and reduced aerosol particle size [27,29,36], which should improve aerosol delivery. However, turbulences created by the high flow rate generated during NIV may affect adversely the deposition of drug particles in the lung and outweigh these advantages [29,10]. ...
... Aerosol delivery during NIV offers advantages over aerosol delivery alone. Indeed, application of NIV has been associated with increased tidal volume [13], decreased respiratory rate [13] and reduced aerosol particle size [27,29,36], which should improve aerosol delivery. However, turbulences created by the high flow rate generated during NIV may affect adversely the deposition of drug particles in the lung and outweigh these advantages [29,10]. ...
Article
Introduction: With the gain in popularity of non-invasive ventilation (NIV), particularly in patients requiring drug delivery by aerosol therapy, the feasibility of the combination between NIV and aerosol therapy has regularly been questioned. Areas covered: This review covers the in vitro and in vivo studies which explored the effects of this combination on pulmonary drug delivery (imaging and pharmacological studies) and on physiological measurements. Expert opinion: Even if the feasibility of the combination is evident, the type of nebulizer influences the lung deposition with a greater delivery with vibrating mesh nebulizers. The influence of the interfaces of NIV devices should be further investigated even if vented masks may seem less efficient for nebulization. There is also a need to develop new devices and modalities, or specific components better designed for a more efficient delivery, to offer more optimal particles size to lung delivery. The use of spacer also seems promising to improve the lung delivery even if strong evidences are still missing. Finally, it would be interesting to explore the influence of all spontaneous modes which use different flow-time curves. Further investigations should focus on the synchronization of the delivery with the inspiratory part of the respiratory cycle in patients during NIV, particularly when delivering toxic or expensive drugs.
... A combination in vitro/in vivo study was performed that showed the addition of CPAP while delivering nebulized bronchodilators reduced in vitro mask delivery from 6.9% to 1.3%, but the in vivo spirometric data from 10 asthmatic patients showed no significant difference in symptoms, suggesting that aerosol therapy can be conducted without interrupting CPAP. (15) Fauroux et al. (16) observed that 18 children with cystic fibrosis showed increased total lung deposition when NPPV was used with a mouthpiece interface in combination with bronchodilator or corticosteroid delivery, as opposed to aerosol therapy alone. These results are unexpected considering França et al. (13) found that total lung dose was reduced when NPPV was combined with nebulized aerosol therapy, although the difference may be explained by the use of a mouthpiece for the study conducted by Fauroux et al., (16) which is expected to alter results compared with a mask. ...
... (15) Fauroux et al. (16) observed that 18 children with cystic fibrosis showed increased total lung deposition when NPPV was used with a mouthpiece interface in combination with bronchodilator or corticosteroid delivery, as opposed to aerosol therapy alone. These results are unexpected considering França et al. (13) found that total lung dose was reduced when NPPV was combined with nebulized aerosol therapy, although the difference may be explained by the use of a mouthpiece for the study conducted by Fauroux et al., (16) which is expected to alter results compared with a mask. Very recently, Galindo-Filho et al. (17) compared jet and mesh nebulized aerosol lung delivery efficiency during bilevel positive airway pressure (BiPAP) in healthy adult volunteers. ...
... In addition to the results of Galindo-Filho et al., (17) only a few studies are known to have reported variability estimates from in vitro and in vivo studies for aerosol delivery combined with CPAP, BiPAP, or NPPV. (15,16) Repeatability of bronchodilator delivery during CPAP with a face mask was reported after four in vitro trials, with a mean delivered dose at the interface of 1.3% and an SD of 0.37%. (15) High intersubject variability of radiolabeled aerosol delivery through a mouthpiece to 18 children with cystic fibrosis during NPPV was observed by Fauroux et al., (16) who noted a mean delivered lung dose of 15% with an SD of 8.3%. ...
Article
Full-text available
The number of pediatric and adult patients requiring tracheostomy has increased. Many of them require aerosol therapy as part of their treatment. Practitioners have little guidance on how to optimize drug delivery in this population. The following is a report of a workshop dedicated to review the current status of aerosol delivery to spontaneously breathing tracheostomized patients and to provide practice recommendations.
... A erosol delivery during noninvasive positive pressure ventilation (NIPPV) has been little studied in human clinical trials, other than a few studies focusing specifically on the pulmonary delivery of drugs. (1)(2)(3)(4) Some clinical benefits have been reported in small trials (5)(6)(7)(8) ; however, the evidence is not sufficiently robust to recommend routine use of NIPPV for aerosol therapy. (3) The effectiveness of nebulization is related to the mass of drug deposited in the lungs. ...
... (29) Second, the breathing patterns of healthy volunteers likely differed from NEBULIZATION AND NONINVASIVE VENTILATION 37 the respiratory parameters set in our bench model (e.g., tidal volume, respiratory rate, and inspiratory time) and could have influenced the lung dose delivered with Conti-Neb. (6,14,16,17,24) The increasing of total daily urinary amount of amikacin showed high intersubject variability (Fig. 3). The high increasing for subjects 1 and 4, and low increasing for subjects 2 and 6 may be explained by two factors. ...
... (23,24,53) The use of Inspi-Neb would be more appropriate in clinical situations involving nebulization of expensive or toxic drugs, or when the dose of drug delivered is critical (e.g., antibiotics in ventilated patients with cystic fibrosis (CF)). (6,50) For the administration of quick relief or rescue medications, such as b2-agonists in patients in a phase of exacerbation, the subjects of further research studies should be the development of specific synchronized nebulizers (for use in noninvasive ventilation) with high mass output and short reaction time. ...
Article
Background: A breath-synchronized nebulization option that could potentially improve drug delivery during noninvasive positive pressure ventilation (NIPPV) is currently not available on single-limb circuit bilevel ventilators. The aim of this study was to compare urinary excretion of amikacin following aerosol delivery with a vibrating mesh nebulizer coupled to a single-limb circuit bilevel ventilator, using conventional continuous (Conti-Neb) and experimental inspiratory synchronized (Inspi-Neb) nebulization modes. Materials and methods: A crossover clinical trial involving 6 noninvasive ventilated healthy volunteers (mean age of 32.3 ± 9.5 y) randomly assigned to both vibrating mesh nebulization modes was conducted: Inspi-Neb delivered aerosol during only the whole inspiratory phase, whereas Conti-Neb delivered aerosol continuously. All subjects inhaled amikacin solution (500 mg/4 mL) during NIPPV using a single-limb bilevel ventilator (inspiratory positive airway pressure: 12 cm H2O, and expiratory positive airway pressure: 5 cm H2O). Pulmonary drug delivery of amikacin following both nebulization modes was compared by urinary excretion of drug for 24 hours post-inhalation. Results: The total daily amount of amikacin excreted in the urine was significantly higher with Inspi-Neb (median: 44.72 mg; interquartile range [IQR]: 40.50-65.13) than with Conti-Neb (median: 40.07 mg; IQR: 31.00-43.73), (p = 0.02). The elimination rate constant of amikacin (indirect measure of the depth of drug penetration into the lungs) was significantly higher with Inspi-Neb (median: 0.137; IQR: 0.113-0.146) than with Conti-Neb (median: 0.116; IQR: 0.105-0.130), (p = 0.02). However, the mean pulmonary drug delivery rate, expressed as the ratio between total daily urinary amount of amikacin and nebulization time, was significantly higher with Conti-Neb (2.03 mg/min) than with Inspi-Neb (1.09 mg/min) (p < 0.01). Conclusions: During NIPPV with a single-limb circuit bilevel ventilator, the use of inspiratory synchronized vibrating mesh nebulization may improve pulmonary drug delivery compared with conventional continuous vibrating mesh nebulization.
... A combination in vitro/in vivo study was performed that showed the addition of CPAP while delivering nebulized bronchodilators reduced in vitro mask delivery from 6.9% to 1.3%, but the in vivo spirometric data from 10 asthmatic patients showed no significant difference in symptoms, suggesting that aerosol therapy can be conducted without interrupting CPAP. (15) Fauroux et al. (16) observed that 18 children with cystic fibrosis showed increased total lung deposition when NPPV was used with a mouthpiece interface in combination with bronchodilator or corticosteroid delivery, as opposed to aerosol therapy alone. These results are unexpected considering França et al. (13) found that total lung dose was reduced when NPPV was combined with nebulized aerosol therapy, although the difference may be explained by the use of a mouthpiece for the study conducted by Fauroux et al., (16) which is expected to alter results compared with a mask. ...
... (15) Fauroux et al. (16) observed that 18 children with cystic fibrosis showed increased total lung deposition when NPPV was used with a mouthpiece interface in combination with bronchodilator or corticosteroid delivery, as opposed to aerosol therapy alone. These results are unexpected considering França et al. (13) found that total lung dose was reduced when NPPV was combined with nebulized aerosol therapy, although the difference may be explained by the use of a mouthpiece for the study conducted by Fauroux et al., (16) which is expected to alter results compared with a mask. Very recently, Galindo-Filho et al. (17) compared jet and mesh nebulized aerosol lung delivery efficiency during bilevel positive airway pressure (BiPAP) in healthy adult volunteers. ...
... In addition to the results of Galindo-Filho et al., (17) only a few studies are known to have reported variability estimates from in vitro and in vivo studies for aerosol delivery combined with CPAP, BiPAP, or NPPV. (15,16) Repeatability of bronchodilator delivery during CPAP with a face mask was reported after four in vitro trials, with a mean delivered dose at the interface of 1.3% and an SD of 0.37%. (15) High intersubject variability of radiolabeled aerosol delivery through a mouthpiece to 18 children with cystic fibrosis during NPPV was observed by Fauroux et al., (16) who noted a mean delivered lung dose of 15% with an SD of 8.3%. ...
Article
Background: Nebulized aerosol drug delivery during the administration of noninvasive positive pressure ventilation (NPPV) is commonly implemented. While studies have shown improved patient outcomes for this therapeutic approach, aerosol delivery efficiency is reported to be low with high variability in lung-deposited dose. Excipient enhanced growth (EEG) aerosol delivery is a newly proposed technique that may improve drug delivery efficiency and reduce intersubject aerosol delivery variability when coupled with NPPV. Materials and methods: A combined approach using in vitro experiments and computational fluid dynamics (CFD) was used to characterize aerosol delivery efficiency during NPPV in two new nasal cavity models that include face mask interfaces. Mesh nebulizer and in-line dry powder inhaler (DPI) sources of conventional and EEG aerosols were both considered. Results: Based on validated steady-state CFD predictions, EEG aerosol delivery improved lung penetration fraction (PF) values by factors ranging from 1.3 to 6.4 compared with conventional-sized aerosols. Furthermore, intersubject variability in lung PF was very high for conventional aerosol sizes (relative differences between subjects in the range of 54.5%-134.3%) and was reduced by an order of magnitude with the EEG approach (relative differences between subjects in the range of 5.5%-17.4%). Realistic in vitro experiments of cyclic NPPV demonstrated similar trends in lung delivery to those observed with the steady-state simulations, but with lower lung delivery efficiencies. Reaching the lung delivery efficiencies reported with the steady-state simulations of 80%-90% will require synchronization of aerosol administration during inspiration and reducing the size of the EEG aerosol delivery unit. Conclusions: The EEG approach enabled high-efficiency lung delivery of aerosols administered during NPPV and reduced intersubject aerosol delivery variability by an order of magnitude. Use of an in-line DPI device that connects to the NPPV mask appears to be a convenient method to rapidly administer an EEG aerosol and synchronize the delivery with inspiration.
... Few studies have evaluated aerosol delivery during CPAP 15,16 or PSV. [17][18][19][20] Some studies found substantial aerosol loss, possibly related to particle impaction in the mask due to the high flow required to generate CPAP. 16 Other studies found that aerosol delivery with CPAP was associated with better lung aerosol deposition 18 or better clinical outcomes. ...
... 16 In children with cystic fibrosis, PSV increased the lung deposition of a radio-labeled aerosol by about 30%, compared to standard nebulization, without increasing particle impaction in the proximal airways. 18 A high flow rate may cause deleterious effects related to low humidity of the inspired gas, 28,29 and optimal humidification may improve comfort and tolerance. 30 Whereas other studies found a significant increase in particle size and reduced lung deposition with heated humidifier, 31,32 we found that heat-and-moisture exchanger did not significantly influence aerosol particle size. ...
... [36][37][38] Of the few studies involving direct lung-deposition measurements in patients, one found decreased lung deposition during NIV, compared to quiet breathing in patients with airway obstruction, 39 but 2 others, in patients with cystic fibrosis, found greater distal lung deposition. 18,40 ...
... S ome clinical studies have investigated the feasibility and effectiveness of coupling aerosol therapy with noninvasive positive pressure ventilation (NIPPV) in patients with respiratory diseases. (1)(2)(3)(4)(5) Inhaled drugs administered during NIPPV enhance lung aerosol deposition (3) and provide greater and faster clinical improvements than when delivered during spontaneous unassisted breathing. (2,(6)(7)(8)(9)(10) The clinical efficiency of inhaled therapy depends on the amount of drug reaching the lungs. ...
... S ome clinical studies have investigated the feasibility and effectiveness of coupling aerosol therapy with noninvasive positive pressure ventilation (NIPPV) in patients with respiratory diseases. (1)(2)(3)(4)(5) Inhaled drugs administered during NIPPV enhance lung aerosol deposition (3) and provide greater and faster clinical improvements than when delivered during spontaneous unassisted breathing. (2,(6)(7)(8)(9)(10) The clinical efficiency of inhaled therapy depends on the amount of drug reaching the lungs. ...
Article
Background: Few studies on performance comparison of nebulizer systems coupled with a single-limb circuit bilevel ventilator are available. Most of these data compared the aerosol drug delivery for only two different systems. Using an adult lung bench model of noninvasive ventilation, we compared inhaled and lost doses of three nebulizer systems coupled with a single-limb circuit bilevel ventilator, as well as the influence of the nebulizer position. Method: Three vibrating mesh nebulizers (Aeroneb(®) Pro, Aeroneb(®) Solo, and NIVO(®)), one jet nebulizer (Sidestream(®)), and one ultrasonic nebulizer (Servo Ultra Nebulizer 145(®)) coupled with a bilevel ventilator were tested. They were charged with amikacin solution (500 mg/4 mL) and operated at two different positions: before and after the exhalation port (starting from the lung). The inhaled dose, the expiratory wasted dose, and the estimated lost dose were assessed by the residual gravimetric method. Results: The doses varied widely among the nebulizer types and position. When the nebulizer was positioned before the exhalation port, the vibrating mesh nebulizer delivered the highest inhaled dose (p<0.001), the jet nebulizer the highest expiratory wasted dose (p<0.001), and the ultrasonic device the highest total lost dose (p<0.001). When the nebulizer was positioned after the exhalation port, the vibrating mesh nebulizers delivered the highest inhaled (p<0.001) and expiratory wasted doses (p<0.001), and the ultrasonic device the highest total lost dose (p<0.001). The most efficient nebulizers were NIVO and Aeroneb Solo when placed before the exhalation port. Conclusions: In a single-limb circuit bilevel ventilator, vibrating mesh nebulizers positioned between the exhalation port and lung model are more efficient for drug delivery compared with jet or ultrasonic nebulizers. In this position, the improved efficiency of vibrating mesh nebulizers was due to an increase in the inhaled dose and a reduction in the exhaled wasted dose compared with placement between the ventilator and the expiratory port. Because of the high total lost dose, the ultrasonic device should not be recommended. Nebulizer placement before the exhalation port increased the inhaled dose and decreased the expiratory wasted dose, except for the jet nebulizer.
... S ome clinical studies have shown the feasibility and the effectiveness of coupling nebulization with noninvasive ventilation (NIV) in patients with respiratory diseases. (1)(2)(3)(4) As the aerosol therapeutic effects depend on the amount of drug reaching the site of action, (5) one of the major challenges during mechanical ventilation is the reduction of drug loss (6,7) especially when expensive and toxic drugs are nebulized. (5,(8)(9)(10) Breath-actuated aerosol systems have long been known to reduce aerosol waste during expiratory phases in intubated and ventilated patients. ...
... In a clinical study, including patients with cystic fibrosis, Fauroux et al. (1) demonstrated the feasibility of coupling an inspiratory synchronized jet nebulizer system to a home ventilator. However, the aim of their study was to evaluate the effectiveness of pressure support ventilation in increasing pulmonary aerosol deposition. ...
Article
Methods: Using an adult lung bench model of NIV, we tested a vibrating mesh device coupled with a bilevel ventilator in both nebulization modes. Inspi-Neb delivered aerosol only during the whole inspiratory phase, whereas Conti-Neb delivered aerosol continuously. The nebulizer was charged with amikacin solution (250 mg/3 mL) and placed at two different positions: between the lung and exhalation port and between the ventilator and exhalation port. Inhaled, expiratory wasted and circuit lost doses were assessed by residual gravimetric method. Particle size distribution of aerosol delivered at the outlet of the ventilator circuit during both nebulization modes was measured by laser diffraction method. Results: Regardless of the nebulizer position, Inspi-Neb produced higher inhaled dose (p < 0.01; +6.3% to +16.8% of the nominal dose), lower expiratory wasted dose (p < 0.05; -2.7% to -42.6% of the nominal dose), and greater respirable dose (p < 0.01; +8.4% to +15.2% of the nominal dose) than Conti-Neb. The highest respirable dose was found with the nebulizer placed between the lung and exhalation port (48.7% ± 0.3% of the nominal dose). Conclusions: During simulated NIV with a single-limb circuit bilevel ventilator, the use of inspiratory synchronized vibrating mesh nebulization improves respirable dose and reduces drug loss of amikacin compared with continuous vibrating mesh nebulization.
... In a study by Fauroux et al., an evaluation of the efficacy of PSV in enhancing pulmonary deposition was conducted. Pulmonary deposition of radiolabeled drug (185 MBq of 99 m Tc phytates in 4 ml of 0.9% NaCl) was evaluated in case of aerosol produced by nebulization coupled with NIV and nebulization alone [44]. It was revealed that total pulmonary deposition was significantly improved by nebulization coupled with NIV, which was reflected in the difference in the total radioactivity count in the lungs after nebulization alone and nebulization coupled with NIV. e radioactivity count increased by ca. ...
... e most efficient devices, in case of positioning between the leak port and the face mask, were the Aeroneb Solo and NIVO [69]. It was also revealed that nebulization during NIV is more efficient than nebulization alone [44]. ...
Article
Full-text available
The administration of aerosolized medication is a basic therapy for patients with numerous respiratory tract diseases, including obstructive airway diseases (OADs), cystic fibrosis (CF), and infectious airway diseases. The management and care for patients requiring mechanical ventilation remains one of the greatest challenges for medical practitioners, both in intensive care units (ICUs) and pulmonology wards. Aerosol therapy is often necessary for patients receiving noninvasive ventilation (NIV), which may be stopped for the time of drug delivery and administered through a metered-dose inhaler or nebulizer in the traditional way. However, in most severe cases, this may result in rapid deterioration of the patient’s clinical condition. Unfortunately, only limited number of original well-planned studies addressed this problem. Due to inconsistent information coming from small studies, there is a need for more precise data coming from large prospective real life studies on inhalation techniques in patients receiving NIV.
... Delivering nebulized bronchodilators via NIV also improves lung aerosol dispersion, and may increase response to bronchodilators, which may improve clinical outcomes (25,26). ...
... Although there are no specific criteria for timing of addition of NIV to chest physiotherapy in children with CF, it may be considered in children with an acceleration of lung function decline requirement admissions. It has been shown that NIV enhances aerosol deposition in cystic fibrosis, but there are no studies investigating the integration of NIV and chest physiotherapy with nebulized treatments (25). ...
Article
Full-text available
Advances in medical care and supportive care options have contributed to the survival of children with complex disorders, including children with chronic lung disease. By delivering a positive pressure or a volume during the patient’s inspiration, NIV is able to reverse nocturnal alveolar hypoventilation in patients who experience hypoventilation during sleep, such as patients with chronic lung disease. Bronchopulmonary dysplasia (BPD) is a common complication of prematurity, and despite significant advances in neonatal care over recent decades its incidence has not diminished. Most affected infants have mild disease and require a short period of oxygen supplementation or respiratory support. However, severely affected infants can become dependent on positive pressure support for a prolonged period. In case of established severe BPD, respiratory support with non-invasive or invasive positive pressure ventilation is required. Patients with cystic fibrosis (CF) and advanced lung disease develop hypoxaemia and hypercapnia during sleep and hypoventilation during sleep usually predates daytime hypercapnia. Hypoxaemia and hypercapnia indicates poor prognosis and prompts referral for lung transplantation. The prevention of respiratory failure during sleep in CF may prolong survival. Long-term oxygen therapy has not been shown to improve survival in people with CF. A Cochrane review on the use NIV in CF concluded that NIV in combination with oxygen therapy improves gas exchange during sleep to a greater extent than oxygen therapy alone in people with moderate to severe CF lung disease. Uncontrolled, non-randomized studies suggest survival benefit with NIV in addition to being an effective bridge to transplantation. Complications of NIV relate mainly to prolonged use of a face or nasal mask which can lead to skin trauma, and neurodevelopmental delay by acting as a physical barrier to social interaction. Another associated risk is pulmonary aspiration caused by vomiting whilst wearing a face mask. Adherence to NIV is one of the major barriers to treatment in children. This article will review the current evidence for indications, adverse effects and long term follow up including adherence to NIV in children with chronic lung disease.
... Also, aerosol therapy during NIV is effective and feasible in patients with bronchospasm. (53)(54)(55)(56)(57)(58)(59) Device selection Aerosolized medications can be administered via pMDIs or nebulizers to patients receiving NIV. (27)(28)(29)60) Previous research reported that aerosol deposition obtained with mesh nebulizer is greater than jet nebulizer during NIV. ...
... (62) Delivery of aerosolized medications with nebulizer during NIV is better than nebulization alone. (57) Interface selection Many interfaces such as the mouthpiece, nasal pillows, nasal mask, oronasal mask, total facemask, and helmet are available to be used during NIV. Whereas the selection of interface is based on patient comfort and the risk for facial skin breakdown, it is important to note that interfaces such as the total facemask and helmet devices are not appropriate for aerosol therapy during NIV due to patient exposure to aerosol medication and flow from the ventilator. ...
Article
Many aerosol delivery devices are available on the market that have different features, characteristics, and operating requirements that need to be considered for the effective treatment of patients with pulmonary diseases. Device selection in aerosol medicine is largely patient dependent. Since there is no aerosol device that suits all patient populations, device selection and successful integration of the prescribed aerosol device to patients is essential. This article explores key issues in differential device selection in spontaneously breathing adults with or without artificial airways, as well as critically ill patients receiving invasive and noninvasive ventilation, with discussion of considerations for integration of aerosol devices to each of these patient populations.
... VNI à deux niveaux de pression et nébulisation. La combinaison d'un nébuliseur et d'un respirateur ne modifie ni les pressions générées, ni le fonctionnement du nébuliseur [72]. Le débit du nébuliseur augmente légèrement lorsqu'une pression est surajoutée, ce qui peut laisser penser que la dose reçue par le patient soit plus importante. ...
Article
Full-text available
Intensive care units are equiped and staffed to provide care and support to patients with critical conditions and multiple organ dysfunctions. Patient-to-physiotherapist ratio has not been well established despite the April 2002 law. Furthermore, the required training program has not been defined and chest physiotherapist speciality has not been recognised yet. Therefore, the physiotherapist role may vary from one unit to another and is mostly dependent on the therapist personnal investment. The physiotherapist is involved in all ventilation aspects, including both non-invasive and mechanical ventilation, patient positioning, aerosoltherapy, weaning process and extubation. Care of the musculoskeletal system is also covered, together with arthropathy prevention and muscular training to facilitate earlier autonomy recovery. The activities of the physiotherapist are to be viewed in the perspective of a shorter length of stay, reduced hospital direct cost but also reduction in the cost related to complications.
... Ces dernières années, les études in vitro et in vivo sur l'intérêt de la nébulisation au cours de la ventilation mécanique se sont multipliées dans les mondes adulte et pédiatrique [1][2][3][4][5]. La déposition pulmonaire reste inférieure à 1 % chez les enfants non intubés ou intubés. ...
Article
Objective The purpose of this study is to determine the impact of nebulizer's position and type on inhaled dose in a model of paediatric non-invasive ventilation with an expiratory leak. Materials and method A ventilator is connected to a modified artificial lung, mimicking a ventilation of a healthy child of about 6 kg. A vibrating mesh nebulizer (Aeroneb Pro™) and a standard jet nebulizer are alternately placed proximally and distally on the inspiratory limb and after the leak. The inhaled dose of mesna (IDmesna) is measured by using the residual gravimetric method. Results The IDmesna of Aeroneb and standard nebulizer placed after the leak are respectively 11.7 ± 3.1% and 1.7 ± 0.5% of the nominal dose (P < 0.01). The IDmesna are lower than 1% for both types of nebulizer in other positions. Conclusion In this paediatric model, only the use of Aeroneb placed after the leak allows for obtaining a significant inhaled dose during non-invasive ventilation with leak. Level of evidence Level III.
... The use of inspiratory pressure support such as aerochamber helps to improve the lung deposition in patients with lower inspiratory flow rate and tidal volume and minimizes inter-occasion and inter-patient variability. A clinical study in CF children used inspiratory pressure support of 10 cm, which led to increased tidal volume and slow inspiratory rate and thus improved 30% deposition in the lungs [72]. Fibrousness of lung or physical obstruction in the respiratory airways found in disease conditions such as CF can also lead to undesirable deposition of lungs and the poorly ventilated site may not receive sufficient drugs [66,67, 70,73] . ...
... NIV Interestingly, about a quarter of aerosols delivered to patients breathing spontaneously concerned patients otherwise undergoing NIV. This may suggest poor knowledge translation given existing data on the efficacy of inhaled bronchodilators delivered within NIV circuits [23][24][25][26]. Conversely, one may hypothesize that clinicians and nursing staff consider aerosol delivery into ventilator circuits too cumbersome, thus calling for progress in equipment simplification. ...
Article
Full-text available
Purpose: Unlike in the outpatient setting, delivery of aerosols to critically ill patients may be considered complex, particularly in ventilated patients, and benefits remain to be proven. Many factors influence aerosol delivery and recommendations exist, but little is known about knowledge translation into clinical practice. Methods: Two-week cross-sectional study to assess the prevalence of aerosol therapy in 81 intensive and intermediate care units in 22 countries. All aerosols delivered to patients breathing spontaneously, ventilated invasively or noninvasively (NIV) were recorded, and drugs, devices, ventilator settings, circuit set-up, humidification and side effects were noted. Results: A total of 9714 aerosols were administered to 678 of the 2808 admitted patients (24 %, CI95 22-26 %), whereas only 271 patients (10 %) were taking inhaled medication before admission. There were large variations among centers, from 0 to 57 %. Among intubated patients 22 % (n = 262) received aerosols, and 50 % (n = 149) of patients undergoing NIV, predominantly (75 %) inbetween NIV sessions. Bronchodilators (n = 7960) and corticosteroids (n = 1233) were the most frequently delivered drugs (88 % overall), predominantly but not exclusively (49 %) administered to patients with chronic airway disease. An anti-infectious drug was aerosolized 509 times (5 % of all aerosols) for nosocomial infections. Jet-nebulizers were the most frequently used device (56 %), followed by metered dose inhalers (23 %). Only 106 (<1 %) mild side effects were observed, despite frequent suboptimal set-ups such as an external gas supply of jet nebulizers for intubated patients. Conclusions: Aerosol therapy concerns every fourth critically ill patient and one-fifth of ventilated patients.
... Ainsi, contrairement aux volontaires sains ou aux patients obstructifs à l'état stable, il semblerait qu'on observe un bénéfice à administrer des bronchodilatateurs au cours de la ventilation non invasive chez les patients au cours d'exacerbations aiguës, l'interaction entre les deux modalités étant additive et possiblement synergique. [59]. La quantification scintigraphique du dépôt pulmonaire montrait un dépôt significativement supérieur en ventilation non invasive, le gain étant de l'ordre de 30 % de masse de médicament placée initialement dans le nébuliseur. ...
Article
Noninvasive ventilation (NIV) and high flow nasal therapy (HFT) are increasingly used in intensive care units. Patients undergoing these respiratory supports often require inhaled therapies, mainly bronchodilators. The principles of aerosol practice in intubated patients in part apply to NIV. Aerosol therapy may nevertheless be challenging because of spontaneous non-controlled breathing and the noninvasive interfaces used. Bench studies evaluating aerosol therapy during NIV show that, with single limb circuits, a greater amount of aerosol is delivered when the aerosol generator is placed between the leak port and the patient. Bench studies of HFT, mainly in pediatric models, show encouraging results, provided that the aerosol generator is positioned closed to the humidification chamber. Clinical studies, only available for NIV, show that significant drug amounts are delivered to the lungs of healthy subject. In patients with obstructive lung disease, significant bronchodilation has been observed after bronchodilator nebulization in the NIV circuit. It is therefore feasible to practice aerosol therapy during NIV in the clinical setting. Some studies even suggested an additive or even synergistic effect of both therapies. If confirmed, those results may trigger specific NIV delivery in order to improve therapeutic efficacy of inhaled drugs. Bench results of aerosol therapy during HFT need to be confirmed in the clinical setting.
... (P=0.01) (14). ...
Article
Pediatric patients are very dependent on inhaled aerosol medications. There are significant differences in how these aerosols deposit in the lungs of children vs. adults that may affect the efficacy of the therapies. Inefficient aerosol delivery to children, caused by factors such as high mouth and throat deposition during oral inhalation, significant losses within adjunct devices such as masks, and high rates of nasal deposition during cannula delivery, can lead to dosing that is difficult to control. Here we discuss the methods, such as deposition scintigraphy, that are used to assess inhaled dose in vivo and review previous studies where these techniques have been applied to measure dosing in children. This includes studies of nebulizers and metered dose inhalers and delivery through adjuncts such as facemasks and nasal cannulas. We discuss the factors that can lead to inefficient inhaled drug delivery and high levels of mouth and throat deposition in children. Finally, we propose areas of innovation to improve inhaled drug delivery to this population. There is a need for child-specific technologies for inhaled drug delivery. This includes the use of smart devices that can guide pediatric breathing patterns and better engage children during treatments, the use of smaller aerosols which are less likely to deposit in the upper airways after inhalation, and the design of better nasal cannula interfaces for aerosol delivery to infants.
... This difference may be attributed to different ways to deliver positive pressure and the population studied, the studies by França et al. 11 and Dolovoch et al. 14 use bi-level ventilation and IPPB and evaluated healthy subjects and patients with stable chronic bronchitis respectively. As with Faraoux et al., 30 the increased deposition found in our study possibly occurred because PEP promotes airway dilation, providing access for greater deposition of the inhaled drug and preventing the collapse of unstable airways during expiration as occurs in asthma and COPD. This improvement may occur by increasing collateral ventilation providing better airflow to lung periphery. ...
Article
While administration of medical aerosols with heliox and positive airway pressure are both used clinically to improve aerosol delivery, few studies have differentiated their separate roles in treatment of asthmatics. The aim of this randomized, double blinded study is to differentiate the effect of heliox and oxygen with and without positive expiratory pressure (PEP), on delivery of radiotagged inhaled bronchodilators on pulmonary function and deposition in asthmatics. 32 patients between 18 and 65 years of age diagnosed with stable moderate to severe asthma were randomly assigned into four groups: (1) Heliox + PEP (n = 6), (2) Oxygen + PEP (n = 6), (3) Heliox (n = 11) and (4) Oxygen without PEP (n = 9). Each group received 1 mg of fenoterol and 2 mg of ipratropium bromide combined with 25 mCi (955 Mbq) of Technetium-99m and 0.9% saline to a total dose volume of 3 mL placed in a Venticis(®) II nebulizer attached to a closed, valved mask with PEP of 0 or 10 cm H2O. Both gas type and PEP level were blinded to the investigators. Images were acquired with a single-head scintillation camera with the longitudinal and transverse division of the right lung as regions of interest (ROIs). While all groups responded to bronchodilators, only group 1 showed increase in FEV1%predicted and IC compared to the other groups (p < 0.04). When evaluating the ROI in the vertical gradient we observed higher deposition in the middle and lower third in groups 1 (p = 0.02) and 2 (p = 0.01) compared to group 3. In the horizontal gradient, a higher deposition in the central region in groups 1 (p = 0.03) and 2 (p = 0.02) compared to group 3 and intermediate region of group 2 compared to group 3. We conclude that aerosol deposition was higher in groups with PEP independent of gas used, while bronchodilator response with Heliox + PEP improved FEV1 % and IC compared to administration with Oxygen, Oxygen with PEP and Heliox alone. Trial registration NCT01268462.
... Respiratory muscle weakness, caused by hyperinflation and malnutrition, can contribute to the impairment of adequate ventilation. Initially, NIMV was used as a "bridge" to transplantation, in patients with end-stage lung disease [11][12][13][14][15]. Subsequently, the indications have evolved and NIMV has been suggested to relieve respiratory failure during acute respiratory exacerbations [16], nocturnal hypoventilation [4,17], exercise [18], chest physiotherapy [19] and even to optimize aerosol deposition in the lungs [20]. ...
Article
Noninvasive mechanical ventilation (NIMV) is increasingly used in children. Three categories of respiratory system dysfunction can justify NIMV: increased respiratory load (due to intrinsic cardiopulmonary disorders or skeletal deformities), ventilatory muscle weakness (due to neuromuscular diseases or spinal cord injury), or failure of neurological control of ventilation (such as the central hypoventilation syndrome). Few studies have evaluated the physiological effects of NIMV in children. The correction of nocturnal hypoventilation and the improvement of gas exchange are well documented. The effects of NIMV on the respiratory muscles, the resetting of hypercapnic central drive and changes in pulmonary mechanics have not been studied. The effect of this therapy on lung growth is an important area requiring investigation. The type of equipment and the specific ventilator settings that should be chosen remain a matter of debate and seem to be driven by commercial developments rather than clear indications from scientific trials. The major advantage of NIMV is that it can be applied at home, combining greater potential for psychosocial development and family function, at lesser cost. The use of home NIMV requires appropriate diagnostic procedures, appropriate titration of the ventilator, cooperative and educated families and careful, well-organized follow-up. The key challenge for NIMV is to improve the well-being of both the family and child with chronic respiratory insufficiency.
... The likely reasons for the poor delivery during those interventions has already been explained; however, NIV benefits from large bore tubing (22 mm inner diameter) and a tight-fitting facemask (no leak). Additionally, with the addition of a fixed minimum positive end expiratory pressure (PEEP), aerosol distribution and deposition is likely to be increased over the lower PEEP levels delivered by LFNT and HFNT [53]. IMV also benefits from larger bore tubing, and depending on the ventilator mode, the bias flow-mediated build-up of an aerosol bolus between inhalations [54]. ...
Article
Full-text available
Lung disease is the main cause of morbidity and mortality in cystic fibrosis (CF). CF patients inhale antibiotics regularly as treatment against persistent bacterial infections. The goal of this study was to investigate the effect of clinical intervention on aerosol therapy during the escalation of care using a bench model of adult CF. Droplet size analysis of selected antibiotics was completed in tandem with the delivered aerosol dose (% of total dose) assessments in simulations of various interventions providing oxygen supplementation or ventilatory support. Results highlight the variability of aerosolised dose delivery. In the homecare setting, the vibrating mesh nebuliser (VMN) delivered significantly more than the jet nebuliser (JN) (16.15 ± 0.86% versus 6.51 ± 2.15%). In the hospital setting, using VMN only, significant variability was seen across clinical interventions. In the emergency department, VMN plus mouthpiece (no supplemental oxygen) was seen to deliver (29.02 ± 1.41%) versus low flow nasal therapy (10 L per minute (LPM) oxygen) (1.81 ± 0.47%) and high flow nasal therapy (50 LPM oxygen) (3.36 ± 0.34%). In the ward/intensive care unit, non-invasive ventilation recorded 19.02 ± 0.28%, versus 22.64 ± 1.88% of the dose delivered during invasive mechanical ventilation. These results will have application in the design of intervention-appropriate aerosol therapy strategies and will be of use to researchers developing new therapeutics for application in cystic fibrosis and beyond.
... Aerosolized medications are administered to patients with respiratory failure receiving noninvasive ventilation. Previous research found that inhalation therapy during NIV is feasible and effective in the treatment of patients with bronchospasm [92][93][94][95] and the effectiveness of inhalation therapy during NIV is better than nebulization alone [96]. Since delivery efficiency of masks with leak port is less than the masks without leak port, clinicians should use ventilator circuits with leak port for inhalation therapy during NIV [97][98][99][100][101]. ...
Article
Aerosolized medications are commonly used for the treatment of patients with pulmonary diseases in acute care. While there are many drug/device combinations available on the market, new devices have been developed in the past few years. Due to differences in their operation, performance and requirements for proper use, it is important to know how to use these aerosol devices effectively during inhalation therapy both in ambulatory and acute settings. This paper reviews aerosol devices used for the treatment of patients with an emphasis on acute and critical care.
... Several clinical studies have shown that in patients with bronchospasm, aerosol therapy during NIV is feasible and effective. (14)(15)(16)(17)(18) Delivery of aerosolized medications into the ventilatory circuit during NIV is affected by ventilator settings, the type of interface used, humidification, the location of the leak port, and the position of the device in the circuit. (19)(20)(21)(22)(23) In addition to this, one of the crucial factors is the type of aerosol device utilized. ...
Article
Background: Advances in aerosol technology have improved drug delivery efficiency during noninvasive ventilation (NIV). Clinical evaluation of the efficacy of aerosol therapy during NIV in the treatment of acute exacerbation of chronic obstructive pulmonary disease (COPD) is very limited. The aim of our study was to compare the efficacy of bronchodilators administered through a vibrating mesh nebulizer (VMN) and jet nebulizer (JN) during NIV in patients with acute exacerbation of COPD. Methods: Prospective randomized cross-over study included 30 patients treated with NIV for acute exacerbation of COPD in an acute care hospital. Patients were consented and enrolled after stabilization of acute exacerbation (3-5 days after admission). Subjects were randomly assigned into two treatment arms receiving salbutamol (2.5 mg): with VMN (Aerogen Solo) and JN (Sidestream) positioned between the leak port and the nonvented oronasal mask during bilevel ventilation with a single-limb circuit. Measurements (clinical data, pulmonary function tests [PFTs], and arterial blood gases) were performed at baseline, 1, and 2 hours after treatment. Results: All measured PFT parameters significantly increased in both groups, but numerically results were better after inhalation with VMN than with JN: for forced expiratory volume in 1 second (FEV1) (mean increase from baseline to 120 minutes-165 ± 64 mL vs. 116 ± 46 mL, p = 0.001) and for forced vital capacity (FVC) (mean increase-394 ± 154 mL vs. 123 ± 57 mL, p < 0.001). There was also a statistically significant reduction in respiratory rate and in Borg dyspnea score after therapy with VMN in comparison with the conventional JN. In both groups, there were improvements in PaCO2, but with VMN these changes were significantly higher. Conclusion: Bronchodilator administration in patients with acute exacerbation of COPD during NIV with VMN resulted in clinically significant improvements in FVC and in Borg dyspnea score. Additional studies required to determine the impact on clinical outcomes.
... Likewise, bronchodilator deposition while applying NIV might be more effective compared with spontaneous breathing without NIV. This would be in accordance with Fauroux et al., 30 who reported that the delivery of a nebulized aerosol by pressure support ventilation enhances total lung aerosol deposition in children with cystic fibrosis. The improvement of tidal volumes when compared with spontaneous breathing during SA might also be beneficial for distal airway aerosol deposition. ...
Article
Objective: Non invasive ventilation (NIV) has been shown to be effective in different causes of respiratory failure in both adult and pediatric patients. However, its role in status asthmaticus (SA) remains unclear. We designed a prospective study to assess the response of children with SA to NIV.
... In contrast to aerosol delivery for pediatric patients receiving mechanical ventilation, there is little research on aerosol delivery during pediatric NIV. 58-63 Fauroux et al 58 performed an in vitro/in vivo study evaluating the effect of pressure support on aerosol delivery/lung deposition of 2 breath-actuated nebulizers. The in vitro study did not show any differences in aerosol delivery. ...
Article
Inhaled medications are the mainstay of therapy for many pediatric pulmonary diseases. Device and delivery technique selection is key to improving lung deposition of inhaled drugs. This paper will review the subject in relationship to several pediatric clinical situations: acute pediatric asthma, transnasal aerosol delivery, delivery through tracheostomies, and delivery during noninvasive and invasive mechanical ventilation. This review will focus on the pediatric age group and will not include neonates.
... With increasing lung disease there is increasing variability in lung deposition of a nebulised drug. This finding is consistent with previous work involving deposition scanning in this patient population [3,4,[21][22][23]. The variability of deposition was not substantially altered by side lying in either group. ...
Article
Full-text available
Background: In people with and without Cystic Fibrosis (CF), does side lying during nebulisation change: the proportion of the dose loaded in the nebuliser that is deposited in the lungs; the uniformity of deposition throughout the lungs; or the apical drug density as a percentage of the drug density in the remaining lung? Do these effects differ depending on the degree of lung disease present? Methods: A randomised crossover trial with concealed allocation, intention-to-treat analysis and blinded assessors, involving 39 adults: 13 healthy, 13 with mild CF lung disease (FEV1 > 80%pred), and 13 with more advanced CF lung disease (FEV1 < 80%pred). In random order, 4 mL of nebulised radioaerosol was inhaled in upright sitting and in alternate right and left side lying at 2-min intervals, for 20 min. Results: Compared to sitting upright, lung deposition and the uniformity of deposition were not significantly altered by side lying in any of the three groups. In sitting, the density of the deposition was significantly less in the apical regions than in the rest of the lung in all participants. Side lying significantly improved apical deposition in healthy adults (MD, 13%; 95% CI, 7 to 19), and in minimal CF lung disease (MD, 4%; 95% CI, 1 to 7) but not in advanced disease (MD, 4%; 95% CI, - 2 to 9). Conclusion: Alternating between right and left side lying during nebulisation significantly improves apical deposition in healthy adults and in adults with mild CF lung disease, without substantial detriment to overall deposition. Trial registration: ACTRN12611000674932 (Healthy), ACTRN12611000672954 (CF) Retrospectively registered 4/7/2011.
... Moreover, NIV itself has shown capable of increasing dosages of aerosol particles deposited in the lungs under specific circumstances. (9)(10)(11)(12) NIV and b2A nebulization could thus offer additive or synergic benefits. To the best of our knowledge, the efficacy of b2A nebulization during NIV in exacerbated COPD patients has not been proven so far. ...
Article
Background: Although nebulizing beta 2-agonists during noninvasive ventilation (NIV) could prove helpful, this administration route has to date never been studied in unstable chronic obstructive pulmonary disease (COPD) patients. We sought to demonstrate that salbutamol could be nebulized through an NIV circuit in COPD exacerbation and improve forced expiratory volume in 1 second (FEV1) as compared with placebo. Patient and Methods: This is a bench study to determine the optimal pattern of nebulization followed by a randomized double-blind parallel-group trial comparing salbutamol and placebo aerosols delivered during NIV to 43 intensive care unit patients. Aerosols were generated by a vibrating mesh nebulizer positioned just after the Y-piece. Spirometry was performed immediately before and at several predetermined time points after nebulization. Clinical and biological safety parameters were recorded. Results: We failed to demonstrate a difference between salbutamol and placebo when changes in FEV1 were assessed immediately after nebulization (-20 vs. -35 mL, p = 0.66). However, FEV1 increased significantly from baseline to 40 minutes after the end of salbutamol nebulization, as compared with placebo (+30 vs. -50 mL, p = 0.04). Nebulization was well tolerated. Conclusion: When assessing FEV1 changes 40 minutes after the end of 5 mg salbutamol nebulization in patients undergoing NIV, we observed a slight improvement that was statistically significant compared with the changes observed with an equivalent saline volume.
... VNI à deux niveaux de pression et nébulisation. La combinaison d'un nébuliseur et d'un respirateur ne modifie ni les pressions générées, ni le fonctionnement du nébuliseur [72]. Le débit du nébuliseur augmente légèrement lorsqu'une pression est surajoutée, ce qui peut laisser penser que la dose reçue par le patient soit plus importante. ...
Article
Chez l’enfant, le recours à la ventilation non invasive (VNI) est de plus en plus fréquent, en première intention, pour la prise en charge des détresses respiratoires. Sous réserve d’une instauration précoce et d’une sélection pertinente du mode de VNI selon le type de détresse, ce support respiratoire peut permettre d’éviter l’épuisement respiratoire et le recours à la ventilation invasive. Des progrès techniques récents sur les interfaces et les respirateurs rendent sa mise en œuvre plus aisée, notamment par une meilleure compensation des fuites et l’amélioration de l’interaction patient–ventilateur. Certaines indications sont étayées par des preuves, notamment les bronchiolites virales, avec un taux d’échec très faible. D’autres restent associées à un taux d’échec important, comme le syndrome de détresse respiratoire aigu (SDRA), incitant à une utilisation très prudente par des équipes expertes. Des indications potentielles, comme l’asthme aigu grave ou le relais de la ventilation invasive, nécessitent des évaluations complémentaires dans le cadre d’essais cliniques. La diffusion de formations théoriques et pratiques, sous l’égide de la société européenne de réanimation du nouveau-né et de l’enfant (ESPNIC), devrait permettre d’uniformiser et de sécuriser cette pratique en plein essor.
Article
A 10-year-old girl with a history of complicated cystic fibrosis was hospitalized for pulmonary exacerbation with allergic bronchopulmonary aspergillosis and severe right upper lobe bronchiectasis diagnosed with chest radiograph and CT. She was started on itraconazole during the hospitalization in attempt to decrease her systemic steroid dose, but she had ongoing coughing and wheezing. The possibility was raised that the right upper lobe bronchiectasis may be a nidus for ongoing aspergillosis. Radioaerosol imaging was performed to determine whether the aerosolized antifungals would reach the area of bronchiectasis.
Article
The use of noninvasive ventilation (NIV) has become increasingly popular in the pediatric intensive care unit (PICU) over the last decade. This review intends to assess our current knowledge on the utilization of noninvasive support in children, especially focusing on its efficacy and safety profile. Recent studies endorse the use of this therapy in the pediatric intensive care setting. NIV appears to be associated with a decrease in the intubation rate in children. Children who are responsive to NIV will usually show improvement in their physiologic parameters shortly after the initiation of this therapy and this improvement is often sustained. NIV is proving to be a well-tolerated alternative to endotracheal intubation, in particular in those patients with primary respiratory failure, postsurgical patients or with postextubation respiratory distress. Most studies represent single-center experience and therefore caution must be exerted when attempting to generalize their results. NIV appears to be a well-tolerated alternative for use in the pediatric population. Its use is associated with decreased intubation rates, which may lead to a decrease in the intubation-related complications. More investigation is needed to fully evaluate the ramifications of increased use of this technology in the PICU.
Article
Background: Early studies have found better clinical efficiency when a nebulizer was used with noninvasive positive pressure ventilation (NPPV), compared with spontaneous breathing without NPPV. However, very limited research addressed factors that might affect aerosol delivery. This study aimed to investigate the influence of exhalation valves and nebulizer positions on aerosol delivery during NPPV. Methods: We determined the efficiency of aerosol delivery in patients receiving NPPV with a lung model that simulates spontaneous breathing. Single-arch exhalation port, plateau exhalation valve, and whisper swivel were chosen as exhalation valves under different levels of inspiratory and expiratory pressures. A nebulizer was filled with 1 mL of 0.5% albuterol solution in 3 mL of normal saline, driven with 8 L/min oxygen, and placed at either a proximal position in the ventilator circuit (near the ventilator outlet, where humidifiers are usually connected) or a distal position in the ventilator circuit (between exhalation valve and lung model connection). Albuterol was collected by filters and then measured by ultraviolet spectrophotometry. The velocities of gas flow were also measured at different nebulizer positions. Results: Significant differences in the gas flow velocity were shown between proximal and distal positions of the breathing circuit under four combinations of inspiratory and expiratory pressure levels (15/5, 15/10, 25/5, and 25/10 cmH2O) (p<0.05). When the nebulizer was positioned distally, the single-arch exhalation port had the highest aerosol delivery, and the whisper swivel had the lowest aerosol delivery (p<0.05). When the nebulizer was placed proximally, the single-arch exhalation port had lower efficiency of aerosol delivery than the whisper swivel and plateau exhalation valve (p<0.05). In addition, higher inspiratory pressure was associated with increased aerosol delivery (p<0.05). The influence of expiratory pressure on aerosol delivery appeared too complex to predict. Conclusions: The type of exhalation valve and the position of the nebulizer in the ventilator circuit have a significant influence on the efficiency of aerosol delivery during NPPV. As a result, with different exhalation valves, an appropriate nebulizer position should be carefully chosen, and the inhaled dose should be adjusted after accurate prediction of aerosol delivery to ensure optimal clinical efficacy.
Article
The method section of this chapter on in vivo regional lung deposition highlights a nonradioactive method to measure regional deposition, which uses a photometer to quantify inhaled and exhaled particles and in that way is able to estimate the lung region from which the particles are exhaled and to what amount. The radioactive methods cover the measurement of clearance of the deposited particles as well as different imaging techniques to determine regional deposition. The result section reviews in vivo trials in human subjects. It also addresses different parameters that influence the regional deposition in the lungs: particle size, inhalation maneuver, carrier gas, disease, and inhalation device. All of these factors can affect regional deposition significantly. By choosing specific values of these parameters, it should be feasible to target different regions of the lungs for the therapy of different diseases.
Article
Full-text available
There have been few reports of factors affecting aerosol delivery during noninvasive ventilation (NIV). Nebulization is a standard practice and our objective was to determine the effect of spontaneous breathing and NIV mode on 99m-Technetium (Tc) lung deposition in subjects with normal lung. Thirteen healthcare volunteers were submitted to a randomized radioaerosol nebulization with 99m-Tc during spontaneous breathing (SB), continuous positive airway pressure - CPAP (10 cmH2O) and bilevel positive pressure ventilation - Bilevel (Inspiratory/Expiratory pressures of 15/5 cmH2O). NIV was performed by a ResMed VPAP II ST-A. The radioaerosol deposition was evaluated by pulmonary scintigraphy after 10 minutes of inhalation. Regions of interest (ROI) were outlined on left lung (LL) and right lung (RL) and trachea (TRQ). The average number of counts per pixel in each ROI was determined and the ratio of lung and trachea was calculated. The three techniques showed comparable lung deposition. Analysis of radioaerosol deposition in the lungs showed a mean count at RL of 108.7±40 with CPAP, 111.5±15 with Bilevel, and 196.6±167 with SB. At LL, the finding values were 92.7±15 with CPAP, 98.4±14 with Bilevel and 225.0±293 with SB. There was no difference between the means of radioaerosol deposition in the RL, LL or TRQ, as well as the lung calculated ratio [LCR = (RL + LL) / TRQ], which was similar comparing ventilatory strategies. Based on our data, there is an equivalent deposition of inhaled substances in individuals with healthy lungs, when spontaneous breathing, CPAP and Bilevel are compared.
Article
La ventilation mécanique (VM) était historiquement considérée comme une barrière à l’administration de médicaments sous forme d’aérosols inhalés. En détaillant les différents éléments de l’interaction complexe entre l’aérosol et la VM, nous verrons que l’administration d’aérosols médicamenteux au travers du circuit de VM est tout à fait pertinente à l’heure actuelle. La disponibilité de bêta-2-mimétiques et de corticoïdes sous forme d’aérosolsdoseurs rend leur administration simple, moyennant l’utilisation de chambres d’inhalation dédiées à la VM. L’administration d’autres molécules, comme les antibiotiques, nécessite le recours à des nébuliseurs: le choix entre nébuliseurs pneumatiques, ultrasoniques et à grille perforée sera discuté. Un certain nombre de moyens permettent d’optimiser le rendement de nébulisation: placement des nébuliseurs continus 15 à 40 cm en amont de la pièce en Y, réduction du débit inspiratoire et utilisation de nébuliseurs synchronisés sur l’inspiration. L’ensemble de ces moyens d’optimisation de l’aérosolthérapie au cours de la VM a permis d’obtenir des résultats cliniques significatifs. Nous ferons le point sur les données expérimentales et cliniques concernant l’efficacité des bêta-2-mimétiques, corticoïdes et antibiotiques inhalés au cours de la VM. En particulier, le traitement par voie inhalée des pneumonies acquises sous VM offre des perspectives cliniques intéressantes. Enfin, nous terminerons avec des recommandations concrètes pour la mise en oeuvre pratique de l’aérosolthérapie au cours de la VM.
Article
La Ventilación Mecánica No Invasiva (VMNI) es una estrategia utilizada en la atención de pacientes que requieren soporte ventilatorio, que ha venido ganando aceptación. El sistema de salud nacional presenta una demanda creciente de niños que requieren este soporte. Objetivo: Normarla aplicación y vigilancia de la VMNI en un establecimiento de salud de nivel terciario. Materiales y Métodos: Se evaluaron los estudios y documentos consultados según la escala de valoración de la evidencia y gradación de las recomendaciones recomendada por la Scottish Intercollegiate Guidelines Network (SIGN)y se plasmaron en el protocolo propuesto. Se plantearon las siguientes interrogantes: 1)¿Cuáles son las modalidades de VMNI empleadas en pediatría?; 2) ¿Cuáles son las indicaciones clínicas y/o de laboratorio para iniciar la VMNI?; 3) ¿Cuáles son las indicaciones clínicas y/o de laboratorio para iniciar la VMNI en los Servicios de Emergencia, Hospitalización y la Unidad de Cuidados Intensivos Pediátricos?; 4) ¿Durante qué tiempo y cuál es el intervalo para monitorizar si la VMNI está resultando como alternativa terapéutica?; 5) ¿Cuáles son las complicaciones de la VMNI?; 6) ¿Cuáles son los mejores predictores de éxito y de fracaso de la aplicación de la VMNI?; 7) ¿Cuáles son los mejores indicadores para monitorizar el empleo de VMNI?; 8) ¿Cuál es la conducta a seguir frente al fracaso de la VMNI?; 9) ¿Qué personal está calificado para la aplicación de la VMNI?; 10) ¿Qué personal y material es requerido para la aplicación de la VMNI?; 11) ¿Cuál es la secuencia recomendada para la aplicación de la VMNI de inicio? Resultados: Se desarrolla el protocolo y se presentan las recomendaciones graduadas según nivel de evidencia incluyendo el algoritmo y definiciones. Conclusión: Se presenta un protocolo de manejo de la ventilación mecánica no invasiva en niños, basado en la mejor evidencia disponible. Palabras Clave: Ventilación mecánica no invasiva, protocolo, niños.
Article
Full-text available
Nowadays, the effectiveness of inhalation drug therapy during non-invasive ventilation (NIV) has been proved. The delivery of aerosol drugs during non-invasive ventilation depends on numerous factors, such as the choice of inhalation equipment and a mask, position of the leak port and position of the device in the respirator settings. Innovations in the field of inhalation therapy resulted in the development new devices able to optimize pulmonary deposition and reduce the time of inhalation therapy. Compared to standard jet nebulizers, mesh nebulizers can deliver the 4 fold higher dose of the drug to the patient's airways. Further research is needed in order to investigate the opportunities of aerosol therapy during high-flow oxygen therapy by means of nasal cannulae.
Chapter
Children requiring noninvasive and invasive chronic ventilator support are frequently prescribed therapeutic aerosols. Little guidance is available regarding the optimal ways of delivering aerosol to these children. In addition to the frequently reported factors that affect drug delivery, this population poses several challenges. The presence of humid/heated air and the passage through artificial and ventilator circuits are some of the factors that can hinder aerosol delivery. Most of the pediatric data are based on in vitro experiments and few animal studies. We will discuss the currently available data and provide suggested best practice.
Article
Noninvasive ventilation (NIV) and high-flow nasal cannula (HFNC) are increasingly used for patients with acute respiratory failure. Some patients receiving these therapies might also benefit from inhaled drug delivery. Thus, it is attractive to combine aerosol therapy with NIV or HFNC. The purpose of this paper is to review the available evidence related to the use of inhaled aerosols with NIV or HFNC. Available evidence supports the delivery of aerosols during NIV. Inhaled bronchodilator response might be improved with the use of NIV in acute asthma, but the evidence is not sufficiently mature to recommend this as standard therapy. Evidence does support aerosol delivery without discontinuation of NIV. Clinical studies on aerosol delivery during HFNC are needed, and based on the available in vitro evidence, it is not possible to make a recommendation for or against aerosol delivery during HFNC. Copyright © 2015 by Daedalus Enterprises.
Article
The context of this thesis is the modelling of particle deposition in the human lung in order to optimise the administration of inhaled drugs. As the alveolar region plays a crucial role both physiologically and functionally, especially for systemic delivery, the objective of this work is to set-up a particle deposition model specific to the acinar region which could be integrated in whole lung deposition model. The first two chapters concentrate on the anatomical and functional aspects of the lung and on the physical principles involved in the flow and particle transport mechanisms in the lung. Then a computational fluid dynamics model was setup in a simplified alveolar geometry. Aerosol bolus transport was studied through an Eulerian approach, for one or several breathing cycles. The impact of flow irreversibilities on bolus dispersion was quantified. The last chapter deals with the integration of the previous results in an analytical model of particle deposition in the whole lung. The results generated by this model are then compared to experimental data from the literature or obtained from an ongoing clinical trial. The results of the new theoretical model show an increase of particle deposition in the acinar region which improves correlation of theory with experimental data. This model could favourably help designing therapies targeting the alveolar region of the lung
Article
Full-text available
Congenital pulmonary airway malformations constitute, together, a wide spectrum of development abnormalities, some of which may be asymptomatic and be accidently discovered in the imaging studies. They may form a part of more complex syndromes and often be associated to other congenital abnormalities, mainly of the cardiovascular system. Although they are not rare, it is difficult to state their precise frequency, with published percentages ranging from 7.5 to 18.7%. Their classification continues to be difficult and controversial. Currently, the extended use of the ultrasonography and fetal magnetic resonance have made it possible to make an earlier diagnosis and increase the detection of silent cases, given rise to changes in the therapeutic orientation.
Article
Noninvasive ventilation (NIV) for pediatric acute respiratory illness reduces work of breathing, improves ventilation, and potentially avoids complications associated with endotracheal intubation and mechanical ventilation. Modalities of NIV include continuous positive airway pressure and bilevel positive airway pressure, which have been used in a range of pediatric diseases. In addition, high-flow nasal cannula is a newer modality that is increasingly used in pediatric patients. This article describes the properties of different modalities of NIV and reviews the medical literature regarding use of NIV in pediatric patients with acute respiratory illness.
Article
Background and objective: Pseudomonas aeruginosa is a multi-drug resistant bacterium, with its biofilm-growing mucoid (alginate-producing) strains being particularly resistant. As atomized drug administration is a common practice in pediatric patients, we compared the effect of inhalational therapy with erythromycin plus ciprofloxacin, with that of ambroxol plus ciprofloxacin, against biofilm producing strains of P. aeruginosa. Results: Both combined treatment regimens were associated with a significant reduction in bacterial counts in endotracheal (ET) tubes and lungs, as compared to that observed with ambroxol and erythromycin monotherapies (P<0.05). Ciprofloxacin plus ambroxol appeared to have a higher efficacy than ciprofloxacin plus erythromycin, both in lowering bacterial counts (P<0.05) and in disrupting the structural integrity of biofilm. Histopathological changes in the lungs were milder in the two combined treatment groups, as compared to that in groups treated with single drugs. Conclusion: Erythromycin or ambroxol in combination with ciprofloxacin could eliminate P. aeruginosa biofilms. When combined with ciprofloxacin, ambroxol outperformed erythromycin in eradicating P. aeruginosa biofilm.
Article
Non-invasive ventilation (NIV) is an option of ventilatory support without airway invasion. While the invasive ventilation is a very efficient technique, it entails a considerable comorbidity and is not free of potentially severe complications. Due to the NIV systems development and the increasing knowledge of this treatment's benefits, NIV use has spread progressively, in adults and also in children. This article aims at describing the bases of this therapeutic option, bringing a current review of the indications of home-based NIV in chronic pediatric patients, explaining contraindications and its most frequent complications, and addressing some practical concepts for its management in children.
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Background: Non-invasive ventilation may be a means to temporarily reverse or slow the progression of respiratory failure in cystic fibrosis by providing ventilatory support and avoiding tracheal intubation. Using non-invasive ventilation, in the appropriate situation or individuals, can improve lung mechanics through increasing airflow and gas exchange and decreasing the work of breathing. Non-invasive ventilation thus acts as an external respiratory muscle. This is an update of a previously published review. Objectives: To compare the effect of non-invasive ventilation versus no non-invasive ventilation in people with cystic fibrosis for airway clearance, during sleep and during exercise. Search methods: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearching relevant journals and abstract books of conference proceedings. We searched the reference lists of each trial for additional publications possibly containing other trials.Most recent search: 08 August 2016. Selection criteria: Randomised controlled trials comparing a form of pressure preset or volume preset non-invasive ventilation to no non-invasive ventilation used for airway clearance or during sleep or exercise in people with acute or chronic respiratory failure in cystic fibrosis. Data collection and analysis: Three reviewers independently assessed trials for inclusion criteria and methodological quality, and extracted data. Main results: Ten trials met the inclusion criteria with a total of 191 participants. Seven trials evaluated single treatment sessions, one evaluated a two-week intervention, one evaluated a six-week intervention and one a three-month intervention. It is only possible to blind trials of airway clearance and overnight ventilatory support to the outcome assessors. In most of the trials we judged there was an unclear risk of bias with regards to blinding due to inadequate descriptions. The six-week trial was the only one judged to have a low risk of bias for all other domains. One single intervention trial had a low risk of bias for the randomisation procedure with the remaining trials judged to have an unclear risk of bias. Most trials had a low risk of bias with regard to incomplete outcome data and selective reporting.Six trials (151 participants) evaluated non-invasive ventilation for airway clearance compared with an alternative chest physiotherapy method such as the active cycle of breathing techniques or positive expiratory pressure. Three trials used nasal masks, one used a nasal mask or mouthpiece and one trial used a face mask and in one trial it is unclear. Three of the trials reported on one of the review's primary outcome measures (quality of life). Results for the reviews secondary outcomes showed that airway clearance may be easier with non-invasive ventilation and people with cystic fibrosis may prefer it. We were unable to find any evidence that non-invasive ventilation increases sputum expectoration, but it did improve some lung function parameters.Three trials (27 participants) evaluated non-invasive ventilation for overnight ventilatory support compared to oxygen or room air using nasal masks (two trials) and nasal masks or full face masks (one trial). Trials reported on two of the review's primary outcomes (quality of life and symptoms of sleep-disordered breathing). Results for the reviews secondary outcome measures showed that they measured lung function, gas exchange, adherence to treatment and preference, and nocturnal transcutaneous carbon dioxide. Due to the small numbers of participants and statistical issues, there were discrepancies in the results between the RevMan and the original trial analyses. No clear differences were found between non-invasive ventilation compared with oxygen or room air except for exercise performance, which significantly improved with non-invasive ventilation compared to room air over six weeks.One trial (13 participants) evaluated non-invasive ventilation on exercise capacity (interface used was unclear) and did not reported on any of the review's primary outcomes. The trial found no clear differences between non-invasive ventilation compared to no non-invasive ventilation for any of our outcomes.Three trials reported on adverse effects. One trial, evaluating non-invasive ventilation for airway clearance, reported that a participant withdrew at the start of the trial due to pain on respiratory muscle testing. One trial evaluating non-invasive ventilation for overnight support reported that one participant could not tolerate an increase in inspiratory positive airway pressure. A second trial evaluating non-invasive ventilation in this setting reported that one participant did not tolerate the non-invasive ventilation mask, one participant developed a pneumothorax when breathing room air and two participants experienced aerophagia which resolved when inspiratory positive airway pressure was decreased. Authors' conclusions: Non-invasive ventilation may be a useful adjunct to other airway clearance techniques, particularly in people with cystic fibrosis who have difficulty expectorating sputum. Non-invasive ventilation, used in addition to oxygen, may improve gas exchange during sleep to a greater extent than oxygen therapy alone in moderate to severe disease. The effect of NIV on exercise is unclear. These benefits of non-invasive ventilation have largely been demonstrated in single treatment sessions with small numbers of participants. The impact of this therapy on pulmonary exacerbations and disease progression remain unclear. There is a need for long-term randomised controlled trials which are adequately powered to determine the clinical effects of non-invasive ventilation in cystic fibrosis airway clearance and exercise.
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Although many different drugs are administered to patients undergoing mechanical ventilation, inhaler bronchodilators and steroids are the most commonly used drugs. Both in vitro and in vivo studies have contributed toward improving our understanding of the complex factors governing aerosol delivery. If the optimal technique can be employed, inhaler bronchodilator delivery during noninvasive mechanical ventilation is feasible and effective.
Article
Nebuliser systems are used to deliver medications to control the symptoms and the progression of lung disease in people with cystic fibrosis. Many types of nebuliser systems are available for use with various medications; however, there has been no previous systematic review which has evaluated these systems. To evaluate effectiveness, safety, burden of treatment and adherence to nebulised therapy using different nebuliser systems for people with cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearching of relevant journals and abstract books of conference proceedings. We searched the reference lists of each study for additional publications and approached the manufacturers of both nebuliser systems and nebulised medications for published and unpublished data. Date of the most recent search: 15 Oct 2012. Randomised controlled trials or quasi-randomised controlled trials comparing nebuliser systems including conventional nebulisers, vibrating mesh technology systems, adaptive aerosol delivery systems and ultrasonic nebuliser systems. Two authors independently assessed studies for inclusion. They also independently extracted data and assessed the risk of bias. A third author assessed studies where agreement could not be reached. The search identified 40 studies with 20 of these (1936 participants) included in the review. These studies compared the delivery of tobramycin, colistin, dornase alfa, hypertonic sodium chloride and other solutions through the different nebuliser systems. This review demonstrates variability in the delivery of medication depending on the nebuliser system used. Conventional nebuliser systems providing higher flows, higher respirable fractions and smaller particles decrease treatment time, increase deposition and may be preferred by people with CF, as compared to conventional nebuliser systems providing lower flows, lower respirable fractions and larger particles. Nebulisers using adaptive aerosol delivery or vibrating mesh technology reduce treatment time to a far greater extent. Deposition (as a percentage of priming dose) is greater than conventional with adaptive aerosol delivery. Vibrating mesh technology systems may give greater deposition than conventional when measuring sputum levels, but lower deposition when measuring serum levels or using gamma scintigraphy. The available data indicate that these newer systems are safe when used with an appropriate priming dose, which may be different to the priming dose used for conventional systems. There is an indication that adherence is maintained or improved with systems which use these newer technologies, but also that some nebuliser systems using vibrating mesh technology may be subject to increased failures. Clinicians should be aware of the variability in the performance of different nebuliser systems. Technologies such as adaptive aerosol delivery and vibrating mesh technology have advantages over conventional systems in terms of treatment time, deposition as a percentage of priming dose, patient preference and adherence. There is a need for long-term randomised controlled trials of these technologies to determine patient-focused outcomes (such as quality of life and burden of care), safe and effective dosing levels of medications and clinical outcomes (such as hospitalisations and need for antibiotics) and an economic evaluation of their use.
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Quiet breathing by mouth of a 3-mum aerosol was compared with intermittent positive pressure delivery of the same aerosol to the lung in a group of bronchitics. The pattern of lung deposition and the total dose delivered to the lung were measured. The differences between quiet breathing and intermittent positive pressure breathing were found not to be significant (P greater than 0.5). In addition, during similar or greater total ventilation, intermittent positive pressure breathing delivered a mean of 32% less aerosol to the lung than did quiet breathing. These findings suggest that intermittent positive pressure breathing as currently used for aerosol delivery cannot be expected to enhance peripheral deposition of inhaled aerosols in patients with airway obstruction.
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Nebulized aerosols are commonly used to deliver drugs for the treatment of respiratory disease in children, but there are inadequate data on the dose of drug depositing in the lungs in this age group, and the effect of age on this dose. We therefore aimed to quantify total and regional deposition of nebulized aerosol in children of widely differing age. Twelve infants (median age 0.8 yrs, range 0.3-1.4 yrs) who were asleep, and eight older children (median age 10.8 yrs, range 6.3-18.0 yrs) with cystic fibrosis were studied. Radiolabelled normal saline aerosol was generated by a Turret nebulizer, with a driving flow of 9 l.min-1. All subjects inhaled aerosol via the nasal route, whilst the older children undertook a second study with inhalation via the oral route. Following aerosol inhalation, planar and single-photon emission computed tomography (SPECT) scans were obtained. For the nasal route, total lung deposition was lower in infants (median 1.3%, range 0.3-1.6%) than in older children (median 2.7%, range 1.6-4.4%). For the older children inhaling via the nasal or oral route, there was no influence of age on lung, upper respiratory tract, or the sum of upper respiratory tract and lung deposition. We conclude that the dose of a nasally inspired aerosol reaching the lungs of infants who are asleep is approximately half that for older children, when the nebulizer is operating at 9 l.min-1. Age does not affect deposition of nasally or orally inspired aerosols in older children.
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This study evaluated the effectiveness of aerosolized cyclosporine as rescue therapy for refractory acute rejection in lung-transplant patients that is unresponsive to conventional therapy. Over 2 yr, nine allograft recipients with histologic evidence of persistent acute rejection and worsening pulmonary function were enrolled. Twenty-two patients with similar degrees of unremitting rejection served as historical controls. Aerosolization of cyclosporin A (300 mg in 4.8 ml propylene glycol) using an AeroTech II jet nebulizer was instituted daily for 12 consecutive days followed by a maintenance regimen of 3 d/wk. Cyclosporine and tacrolimus blood and plasma levels were maintained within therapeutic ranges throughout this trial. Efficacy was assessed by histologic grade of rejection, interleukin-6 (IL-6) mRNA expression by graft bronchoalveolar lavage cells, and pulmonary function testing before and during cyclosporine therapy. In seven patients, results were correlated to deposition of cyclosporine aerosol in the allograft(s) as measured by radioisotopic techniques. At a mean of 37 d after initiation of aerosolized cyclosporine, graft histology improved in eight of the nine patients. Cellular IL-6 mRNA expression decreased significantly in seven patients (mean IL-6/actin +/- SD, 40.96 +/- 118 versus 0.33 +/- 0.57 [p = 0.038]). Pulmonary function (FEV1), which had decreased posttransplant (over a mean of 347 d of observation) from a best value of 1.98 +/- 0.8 L to 1.59 +/- 0.6 L (p = 0.0077), improved over time (152 d) to a posttransplant value of 1.90 +/- 0.8 (p = 0.025). In the control subjects, FEV1 inexorably declined over a comparable period of observation (best posttransplant value 2.36 +/- 0.86 to 1.32 +/- 0.53, p < 0.0001). There was a strong correlation between cyclosporine deposition in the allograft and improvement in FEV1 (r = 0.900, p < 0.01). Fewer cycles of pulsed corticosteroids (1.4 +/- 0.9 versus 0.2 +/- 0.4, p = 0.011) and anti-thymocyte globulin 0.8 +/- 0.4 versus 0, p = 0.018) and reduced doses of oral prednisone (10.8 +/- 3.1 versus 6.1 +/- 4.2 mg/d, p = 0.026) were observed during treatment with aerosolized cyclosporine. Episodes of pneumonia also were reduced significantly during aerosol therapy (2.6 versus 0.95 episodes/100 d, p = 0.029). Nephrotoxicity and hepatotoxicity did not occur, and no patients withdrew from the study. Aerosolized cyclosporine appears to be safe and effective therapy for refractory acute rejection, but confirmation by a larger, randomized trial is necessary. The correlation observed between deposition of cyclosporine aerosol and physiologic improvement of lung function suggests that there is a dose-response relationship between the concentration of cyclosporine in the allograft and immunologic tolerance.
Article
The survival beyond childhood of patients with cystic fibrosis is being noted with increasing frequency. This is explained by improved diagnostic methods, with the early recognition of mild cases, and by the application of effective therapeutic measures. The largest number of survivors beyond the age of 10 included in one report is in that of McIntosh.1 However, there have been no reports dealing with the results of long-term care provided to a large group of patients with cystic fibrosis. It is obvious that the end-results of such a study would reflect diagnostic acumen, for the earlier the case is recognized and the milder the disease the better should be the end-result. It is for this reason that we have introduced a system of clinical evaluation which can be used as a measuring device to compare one patient with the next. It is well, also, to point out some of
Article
Study objective: To determine whether beta-adrenergic agonist aerosols are more effective in treating acute bronchospasm if delivered by nasal bilevel positive airway pressure (BiPAP) than by a small-volume nebulizer (SVN). We hypothesized that BiPAP would reduce the work of breathing in asthmatic patients and thereby hasten improvement of bronchospasm from beta-agonist therapy. Previous trials with aerosols given by intermittent positive-pressure breathing were unrewarding, but BiPAP is unique in that inspiratory (IPAP) and expiratory (EPAP) support pressures may be set separately. Design: Convenience-randomized prospective clinical study. Setting: Emergency department of an urban tertiary care teaching hospital. Participants: Afebrile, wheezing patients between 18 and 40 years of age. Interventions: Patients were randomly assigned to receive two doses of aerosolized albuterol (2.5 mg in 3 mi normal saline solution), 20 minutes apart, delivered by either SVN (n=40) or BiPAP (n=60) by nosemask or facemask (IPAP, 10 cm H2O; EPAP, 5 cm H2O). Results: Peak expiratory flow rate (PEEP), arterial blood oxygen saturation (by pulse oximetry), and pulse and respiratory rates were measured at baseline and after each treatment. The two treatment groups had similar values for pulse oximetry, pulse rate, respiratory rate, and percent of predicted peak expiratory flow rate (%PPEFR) at entry, and all patients experienced similar changes in the first three of these variables through the course of treatment. BiPAP patients had a significantly greater increase in %PPEFR after each treatment (P=.0011) and from baseline to completion (P=.0013). Increase in absolute PEEP was greater in the BiPAP group (from 211+/-89 [mean+/-SD] to 357+/-108 L/minute for BiPAP, from 183+/-60 to 280+/-87 L/minute for SVN; P=.0001).
Article
BACKGROUND Preliminary evidence suggests that regular inhalation of nebulised amiloride reduces sputum viscoelasticity, increases the clearance of sputum by mucociliary mechanisms and by coughing and reduces the rate of deterioration in lung function in patients with cystic fibrosis. These effects depend on adequate delivery of amiloride to the airways. This study was performed to quantify and compare pulmonary deposition of amiloride produced by two different nebuliser systems. METHODS The pulmonary deposition of nebulised amiloride (1 mg in 3 ml saline) was measured in eight patients with cystic fibrosis when given via a jet (System 22 with CR 60 compressor) and an ultrasonic (Fisoneb) nebuliser. Human serum albumin labelled with technectium-99m was used as an indirect marker for amiloride and its deposition in the lung was detected with a gamma camera. RESULTS Amiloride inhalation caused no side effects or changes in spirometric indices. The mean (SD) total pulmonary amiloride deposition was 57 (24) micrograms with the System 22 and 103 (53) micrograms with the Fisoneb nebuliser. Pulmonary deposition was completed more rapidly with the Fisoneb (4-5 minutes) than with the System 22 nebuliser (7-8 minutes) and the Fisoneb was preferred by the patients. CONCLUSIONS Both nebulisers appeared to deliver adequate amounts of amiloride to the lungs, but treatment with the Fisoneb nebuliser was quicker, more efficient, and more acceptable to the patients. Of the two nebulisers assessed, the Fisoneb would be preferred for clinical trials.
Although aerosolized pentamidine (AP) has recently been approved for prophylaxis and is undergoing clinical trials for treatment of pneumocystis, pneumonia (PCP), factors important in the deposition of AP have not been described. Using radioaerosol techniques, deposition was measured in 22 patients receiving AP for prophylaxis or treatment of PCP. In all patients total and regional deposition of pentamidine, breathing pattern, pulmonary function (PFT), regional ventilation, and type of nebulizer were analyzed. Bronchoalveolar lavage (BAL) was performed 24 h after inhalation to assess the relationship between pentamidine levels in BAL fluid and measured aerosol deposition. The nebulizers tested were the Marquest Respirgard II and the Cadema AeroTech II, both previously characterized in our laboratory. The aerosol particles consist of water droplets containing dissolved pentamidine and technetium 99m bound to albumin. Analysis of particles sampled during inhalation via cascade impaction confirmed a close relationship between radioactivity in the droplets and the concentration of pentamidine as measured by HPLC (r = 0.971, p less than 0.0001; n = 18). Deposition was measured by capturing inhaled and exhaled particles on absolute filters and measuring radioactivity. This technique allows the determination of the deposition fraction (DF, the fraction of the amount inhaled that is deposited), which provides information on factors strictly related to the patient. To confirm the filter measurements, pentamidine deposition was also measured by gamma camera. The camera measurement was possible because each patient's thoracic attenuation of radioactivity was determined by a quantitative perfusion scan (mg pentamidine deposited via both techniques, r = 0.949, p less than 0.0001; n = 26). Regional lung volume and ventilation were determined by xenon 133 equilibrium scan and washout. Pentamidine deposition varied markedly between patients, but BAL levels of pentamidine significantly correlated with measured deposition (r = 0.819, p less than 0.01; n = 9). DF averaged 0.621 +/- 0.027 (SEM) and did not correlate with any measured lung parameter, including breathing pattern and PFT. Regional deposition did not correlate with regional ventilation. The major factor influencing pentamidine deposition was aerosol delivery (mg deposited versus mg inhaled; r = 0.963, p less than 0.0001; n = 26). The nebulizer was an important determinant of aerosol delivery, with the AeroTech delivering between 2.5 and 5 times more drug than the Respirgard. These observations are important in assessing treatment failure and cost of therapy.
Persistent inability to tolerate discontinuation from mechanical ventilation is frequently encountered in patients recovering from acute respiratory failure. We studied the ability of inspiratory pressure support, a new mode of ventilatory assistance, to promote a nonfatiguing respiratory muscle activity in eight patients unsuccessful at weaning from mechanical ventilation. During spontaneous breathing, seven of the eight patients demonstrated electromyographic signs of incipient diaphragmatic fatigue. During ventilation with pressure support at increasing levels, the work of breathing gradually decreased (p less than 0.02) as well as the oxygen consumption of the respiratory muscles (p less than 0.01), and electrical signs suggestive of diaphragmatic fatigue were no longer present. In addition, intrinsic positive end-expiratory pressure was progressively reduced. For each patient an optimal level of pressure support was found (as much as 20 cm H2O), identified as the lowest level maintaining diaphragmatic activity without fatigue. Above this level, diaphragmatic activity was further reduced and untoward effects such as hyperinflation and apnea occurred. When electrical diaphragmatic fatigue occurred, the activity of the sternocleidomastoid muscle was markedly increased, whereas it was minimal when the optimal level was reached. We conclude that in patients demonstrating difficulties in weaning from the ventilator: (1) pressure support ventilation can assist spontaneous breathing and avoid diaphragmatic fatigue (pressure support allows adjustment of the work of each breath to provide an optimal muscle load); (2) clinical monitoring of sternocleidomastoid muscle activity allows the required level of pressure support to be determined to prevent fatigue.
Article
We characterized the bronchopulmonary distribution of a 0.9 percent saline aerosol (1.12 microM) labelled with 99mTc sulfur colloid in nine normal subjects and five patients with CF. Homogeneity of distribution was quantified using indices derived from computerized analysis of Anger camera pulmonary images including skew (a measure of distribution asymmetry) and kurtosis (a measure of distribution range). Aerosol clearance in 97 minutes (a measure of large, central airway deposition) was also assessed. Values of skew and kurtosis were reproducible for the patients with CF and were significantly elevated compared to the normal subjects. Reproducibility of skew and kurtosis were not studied in the normal subjects. Clearance was not significantly different in the two groups. We conclude that the bronchopulmonary distribution of this radioaerosol is nonuniform in patients with CF, compared to normal subjects, and clearance may be impaired in patients with CF who are severely ill.
Article
1. Oral high-frequency oscillation (OHFO) may have important effects on aerosol deposition in the lungs. In order to investigate these, a technique was devised to measure regional deposition rates of a nebulized radio-labelled aerosol in the lungs during normal tidal breathing. 2. The effect of three frequencies of OHFO on pulmonary aerosol deposition rate (PADR) in four normal subjects and five patients with chronic airways obstruction (CAO) were assessed using the technique. 3. In separate experiments employing three normal subjects, the effect of OHFO was studied on the deposition rate of aerosol on the oropharynx and delivery apparatus, and on the amount and characteristics of aerosol inhaled by the subjects. 4. Total PADR was significantly reduced by OHFO at 8 Hz and 16 Hz in the normal subjects, and by all three frequencies of OHFO in the CAO patients. In the normal subjects, the regional distribution of aerosol deposition was unchanged, but in the CAO patients a larger proportion of total aerosol deposition occurred in peripheral lung. 5. OHFO reduced the oropharyngeal aerosol deposition rate, increased the loss of aerosol to the atmosphere before inhalation, and increased the deposition of aerosol on the delivery apparatus. The end result was a reduction in the amount of aerosol inhaled, and in the particle sizes measured at the mouthpiece. 6. We conclude that OHFO reduces the amount of aerosol inhaled, but may improve peripheral deposition of inhaled aerosol in patients with CAO. This effect may be of value in the clinical administration of nebulized drugs.
Article
Antibiotic aerosol treatment is successful in treating Pseudomonas infection in some patients with cystic fibrosis, but the amount of drug reaching the lungs is unknown. The deposition patterns of carbenicillin aerosols delivered from two commercially available nebuliser systems (the Turret nebuliser plus Maxi compressor and the Inspiron nebuliser plus Traveller compressor) have been compared in six patients with cystic fibrosis during tidal breathing. The aerosol mass median diameters were 3.2 and 7.3 microns. In addition, the aerosol from the Turret-Maxi nebuliser system was inhaled by a combination of tidal and deep breathing. After two minutes' breathing via a mouthpiece the mean (SEM) deposition in the lungs was 15.60 (1.5) mg carbenicillin with the Turret nebuliser plus Maxi compressor, but only 6.54 (1.09) mg with the Inspiron nebuliser plus Traveller compressor; the distribution pattern within the lung was significantly more peripheral with the former nebuliser system. These differences may be ascribed partly to the smaller droplet size from the Turret system and partly to the higher nebulisation rate from the more powerful Maxi compressor. Tidal plus deep breathing produced a further small but non-significant increase in lung aerosol deposition. A seventh patient, who failed to complete the trial, had little aerosol deposited in his lungs because he inhaled through his nose. These results emphasise the importance of correct selection of nebuliser equipment for antibiotic aerosol treatment.
In cystic fibrosis (CF), the clinical effectiveness of aerosolized antibiotics is controversial. Previous investigators have not considered the type of nebulizer, droplet size, and dose to the lung in assessing the results of aerosol therapy. The present study tests the importance of these factors by standardizing an aerosol system for delivery of antibiotics and other agents to patients with CF. Particle size, distribution, and output from a commercially available nebulizer were measured. Thirteen patients with CF inhaled aerosol (MMAD = 1.1 micron) containing gentamicin (160 mg in nebulizer) and 99mTc-labeled human serum albumin. Patients' sputum and serum were analyzed for gentamicin levels by immunoenzymatic assay (Emit; Syva Corp., Palo Alto, CA). Using a gamma camera and suitable filters, central versus peripheral deposition (C/P ratio) and whole lung deposition were measured and related to sputum gentamicin levels. Gentamicin deposit averaged 12.3 mg +/- 5.9 (SD) or 7.69% of the original amount placed in the nebulizer. Peak sputum levels averaged 376.6 micrograms/ml +/- 275, whereas serum levels were undetectable in all patients. When peak sputum levels were normalized for the amount deposited, a close correlation with C/P ratio was obtained (r = 0.88, p less than 0.05). Furthermore, an inverse relationship was found between the C/P ratio and the %FEV1 (r = 0.76, p less than 0.05). Finally, a bell-shaped relationship between deposited dose and minute ventilation was seen in the patients (r = 0.88, p less than 0.05), i.e., an optimal minute ventilation was shown. These relationships may be important when designing future clinical studies.
Article
The efficiency of delivery of an aerosol to 22 children with cystic fibrosis, aged 8 months to 17 years, was investigated with the use of a standard ultrasonic nebulizer. The study was designed to simulate clinical conditions as closely as possible. Retention of the aerosol was monitored with a scintillation camera interfaced to a small digital computer. The children also had ventilation studies with xenon-133, which allowed comparison of the distribution of aerosol with regional ventilation. The aerosol was visualized within the lungs of all 22 patients. Between 0.8 and 6.5 per cent of the initial activity was deposited in the lungs, representing an average of 0.27 ml. per therapy session or 0.013 ml. per kilogram of body weight. There was a positive correlation (r=0.89; p<0.01) between increasing age and greater pulmonary deposition of the aerosol. There was decreased aerosol entry to regions which were poorly ventilated. The efficiency of aerosol deposition is variable in children with cystic fibrosis, depending primarily on the age of the patient, whereas its distribution within their lungs is related to regional variations in the severity of the pulmonary diseases.
Article
The deposition of aerosol consisting of Teflon particles (mass median aerodynamic diameter 3.2 micrometers) labelled with 99Tcm has been measured in patients with obstructive airways disease. Aerosol was inhaled at 30 l min-1 with 4 s breath holding (patient group A) and at 30 l min-1 with 10 s breath holding (patient group B). A further group of patients (group C) inhaled at 90 l min-1 with 10 s breath holding. Each subject was given the aerosol during inhalation at three different lung volumes (20% VC, 50% VC and 80% VC) on three different days. The greatest whole lung, tracheobronchial and alveolar depositions occurred in group B patients, irrespective of the lung volume of aerosol actuation. By comparison, deposition was similar in groups A and C only when the aerosol was actuated at 20% VC. Whole lung deposition in groups A and B was significantly correlated both with the bronchodilator response to terbutaline sulphate aerosol administered under the same inhalation conditions and with the residence time of airborne particles in the respiratory tract. The optimum inhalation technique for a beta-adrenergic aerosol indicated by these data (slow inhalation with 10 s breath holding) confirms the results of previous studies.
Article
Quantitative indices are described for assessing the distribution of ventilation imaging agents (radioaerosols, in particular) within the lung. They have been applied to images obtained with 99Tcm aerosol particles (0.5-2.0 micrometer diameter) and with 81Krm gas in 12 patients with a wide range of lung function. In patients with normal lung function aerosol distribution was similar to that of 81Krm. In patients with airways obstruction, the aerosol tended to penetrate less well than 81Krm to the lung periphery and to show a less homogeneous distribution there. Quantitative analysis confirms that the aerosol technique is an effective substitute for 81Krm in patients with normal lung function. When lung function is impaired aerosol images may still be valuable particularly in confirming a diagnosis of pulmonary embolism though they must be interpreted with caution in attempting to exclude that diagnosis. We conclude that small particle radioactive aerosols provide a readily available ventilation technique for clinical ventilation-perfusion imaging.
Article
Wide variation in the pattern of deposition of inhaled aerosols has previously been described in both healthy and diseased humans. To investigate the factors responsible for such variation, the authors studied a group of 13 healthy nonsmoking subjects. One two occasions each subject inhaled a monodisperse 8.1 mm (mass median aerodynamic diameter) Fe2O3 aerosol labelled with 99mTc using a standardized breathing pattern. Pulmonary function was defined by tests of forced expiratory airflow. Total activity in the right lung at 0 hr and at 24 hr (24-hr percent retention) was measured using a gamma camera. Numerical indices of deposition pattern were derived in several ways from the initial gamma camera image of the right lung by comparing the ratio of activity within a mid- and peripheral lung region of interest, by analyzing the profile of radioactivity within a horizontal band across the right lung from the midline to the lung edge, and by analysis of a distribution histogram of activity within the whole lung (skew and kurtosis). The 24-hr percent retention of aerosol showed considerable intrasubject variability unlike the deposition indices. The various deposition indices were found to correlate with the 24-hr percent retention, FEV1.0, FEV1.0/FVC%, and MMFR at varying levels of significance. Results indicate that the pattern of aerosol deposition in healthy humans is influenced by mild degrees of obstruction to airflow, as reflected by tests of forced expiratory airflow, increasing airways obstruction being associated with more central deposition of the inhaled aerosol. Deposition indices derived from the initial pattern of aerosol distribution within the lung may prove to be more reliable and sensitive than measurements of 24-hr percent retention in defining aerosol deposition pattern.
Article
To determine whether beta-adrenergic agonist aerosols are more effective in treating acute bronchospasm if delivered by nasal bilevel positive airway pressure (BiPAP) than by a small-volume nebulizer (SVN). We hypothesized that BiPAP would reduce the work of breathing in asthmatic patients and thereby hasten improvement of bronchospasm from beta-agonist therapy. Previous trials with aerosols given by intermittent positive-pressure breathing were unrewarding, but BiPAP is unique in that inspiratory (IPAP) and expiratory (EPAP) support pressures may be set separately. Convenience-randomized prospective clinical study. Emergency department of an urban tertiary care teaching hospital. Afebrile, wheezing patients between 18 and 40 years of age. Patients were randomly assigned to receive two doses of aerosolized albuterol (2.5 mg in 3 mL normal saline solution), 20 minutes apart, delivered by either SVN (n = 40) or BiPAP (n = 60) by nosemask or facemask (IPAP, 10 cm H2O; EPAP, 5 cm H2O). Peak expiratory flow rate (PEFR), arterial blood oxygen saturation (by pulse oximetry), and pulse and respiratory rates were measured at baseline and after each treatment. The two treatment groups had similar values for pulse oximetry, pulse rate, respiratory rate, and percent of predicted peak expiratory flow rate (%PPEFR) at entry, and all patients experienced similar changes in the first three of these variables through the course of treatment. BiPAP patients had a significantly greater increase in %PPEFR after each treatment (P = .0011) and from baseline to completion (P = .0013). Increase in absolute PEFR was greater in the BiPAP group (from 211 +/- 89 [mean +/- SD] to 357 +/- 108 L/minute for BiPAP, from 183 +/- 60 to 280 +/- 87 L/minute for SVN; P = .0001). In this population, response to initial ED management of bronchospasm, as measured by PEFR, was better with aerosols delivered by BiPAP than with those delivered by SVN.
Article
Nebulised pentamidine is effective for preventing Pneumocystis carinii pneumonia in adults with acquired immunodeficiency syndrome. The nebuliser dose required to produce equivalent lung concentrations of pentamidine in children is unknown. This study was performed to measure pulmonary pentamidine deposition in children and to relate this to age, ventilation pattern, and body size. Nebulised pentamidine (50 mg in 6 ml saline) was administered to 12 children (including one with lymphocytic interstitial pneumonitis) and to six adults with human immunodeficiency virus infection using a Respirgard II nebuliser. Technetium-99m labeled colloidal human serum albumin was used as an indirect marker for pentamidine and deposition in the lungs was detected by a gamma camera. Absolute deposition of pentamidine was not related to age, height, weight, spirometry, or ventilation characteristics. Deposition, as a mean (SD) percentage of nebuliser output, was similar in children aged 8-11 years (5.5(2.4)%), teenagers aged 12-15 years (7.2(2.2)%) and adults (7.1(2.6)%). Aerosol concentration within the lungs (% nebuliser output deposited/predicted total lung capacity) was therefore higher in children (1.9(1.5)%/1) and teenagers (1.9(0.7)%/1) than in adults (1.0(0.7%)/1), and was negatively correlated with height (r = -0.69) and weight (r = -0.50). Deposition of aerosol in the region of the large central airways was particularly marked in children. Small reductions in forced expiratory volume in one second and forced vital capacity after treatment did not differ significantly between adults and children and visual analogue scores of subjective adverse effects did not vary with age. These results suggest that children probably require lower nebuliser pentamidine doses to produce lung pentamidine concentrations equivalent to those found to be effective for preventing P carinii pneumonia in adults using the Respirgard II nebuliser.
Article
A bench study using an artificial lung model and a clinical study in patients were performed to evaluate six commercially available home pressure support devices. Six devices were tested in the in vitro study, including five designed for home use and one designed for use in intensive care units. Minimal positive end-expiratory pressure (PEEP) varied across home devices, from 0.5 cm H2O to 4.3 cm H2O. Work imposed during exhalation varied up to six-fold across devices. A substantial rebreathing volume has present for the three home devices with a common inspiratory and expiratory line. This rebreathing volume decreased with increasing PEEP level, as expected, but remained substantial at the widely used PEEP level of 5 cm H2O. Use of a non-rebreathing valve increased both the work imposed by the circuit during the exhalation phase and the time required to attain the relaxation equilibrium. Except for two home devices and a bilevel positive airway pressure (BiPAP) device equipped with a non-rebreathing valve, differences in inspiratory trigger sensitivities were small between home and intensive care devices. During pressure support, the total work performed by the machines did not differ by more than 15% between devices, whereas differences of more than 300% were observed in flow acceleration. Only one home device gave a flow acceleration similar to or better than that obtained with the intensive care device. In a randomized, crossover clinical study, we compared a home device to a device specially designed for intensive care use in seven intubated patients during weaning from mechanical ventilation. The main differences between the two devices were trigger sensitivity and initial flow acceleration. For the same level of pressure support, there were no significant differences in arterial PCO2, tidal volume, respiratory rate, or minute ventilation between these two devices. However, the esophageal pressure-time product was 30% higher with the home device (165 +/- 93 versus 119 +/- 80 cm H2O/min, p < 0.05). In conclusion, differences exist between devices in terms of occurrence of rebreathing, speed of attainment of stable pressure support level, and expiratory resistance. These differences characterizing the delivery of pressure support may have clinical impact on the inspiratory effort of patients.
Article
Medication nebulizers are commonly used to delivery aerosolized medications to patients with respiratory disease. We evaluated output and respirable aerosol available to the patient (inhaled mass) for 17 medication nebulizers using a spontaneous breathing lung model. Three nebulizer fill volumes (3, 4, and 5 mL containing 2.5 mg of albuterol) and 3 oxygen flows (6, 8, and 10 L/min) were evaluated using the 17 nebulizers. A cotton plug at the nebulizer mouthpiece was used to trap aerosol during simulated spontaneous breathing. Following each trial, the amount of albuterol remaining in the nebulizer and the amount deposited in the cotton plug were determined spectrophotometrically. Aerosol particle size was determined using an 11-stage cascade impactor. Increasing fill volume decreased the amount of albuterol trapped in the dead volume (p < 0.001) and increased the amount delivered to the patient (p < 0.001). Increasing flow increased the mass output of particles in the respirable range of 1 to 5 microns (p = 0.004), but the respirable mass delivered to the patient was affected to a greater extent by nebulizer brand (p < 0.001) than flow. Although 2.5 mg of albuterol was placed into the nebulizers, less than 0.5 mg in the respirable range of 1 to 5 microns was delivered to the mouthpiece. The performance of medication nebulizers is affected by fill volume, flow, and nebulizer brand. When they are used for research applications, the nebulizer characteristics must be evaluated and reported for the conditions used in the investigation.
Article
Twenty asymptomatic infants with cystic fibrosis (CF) were studied to determine the amount of radiolabeled aerosol [99m technetium diethylenetriamine penta acetic acid (Tc99m DTPA)] deposited in the respiratory system and its distribution. Aerosols were generated by jet nebulization systems that were used in the wards and the laboratory. Subjects were studied in three groups: group A (n = 10) was sedated with chloral hydrate; children inhaled an aerosol of 7.7 μm mass median diameter (MMD); group B (n = 5) was not sedated, using the same nebulization system (same aerosol particle size as group A); and group C (n = 5) was not sedated; these children inhaled an aerosol with an MMD of 3.6 μm. Normal saline plus 4 mCi of Tc99m bound to DTPA was added to each nebulizer. A closed system was used to collect the expired aerosol. Radioactivity in each infant and in the equipment was measured with a gamma camera on completion of nebulization. In groups A and B, the percentages of the total dose deposited in the lung were 0.97 ± 0.35% and 0.76 ± 0.36%, respectively. In group C, 2.0 ± 0.71% was deposited in the lung (P < 0.01). Deposition in the nose, mouth, and pharynx was least in group C (P < 0.01). In groups A and B, the intrathoracic deposition occurred predominantly in the trachea and main bronchi, whereas in group C, significantly more aerosol was deposited in the lung region. There was marked inter-subject variability in the percentage of aerosol deposition within the three groups. There was no correlation between percentage of aerosol deposited in the respiratory system and age, height, or weight. Sedation did not have a significant effect on deposition of aerosol in infants. This study indicates that only a small proportion of nebulized solution is deposited in the lungs of infants and that this proportion is influenced by the particle size of the aerosol. The smaller particle size (3.6 μm MMD) was deposited in the lung better than large particles.
Article
Rates of fresh gas flow (FGF) commonly used when continuous positive airway pressure (CPAP) is delivered by face mask theoretically reduce the delivery and availability of therapeutic aerosols. As it may be hazardous for patients with acute respiratory failure to interrupt mask CPAP, the effects of CPAP on aerosol kinetics and bronchodilator efficacy were investigated. The effect of CPAP at 10 cm H2O at a FGF rate of 50 l/min on the delivery of technetium labelled aerosol generated from a readily available jet nebuliser was measured using a bench model of spontaneous respiration. In a separate clinical study the bronchodilator responses to incremental doses of nebulised salbutamol were measured in nine stable asthmatic subjects in a random sequence of conventional nebulisation (control) or nebulisation whilst receiving CPAP via a tight fitting face mask. Each patient acted as his or her own control. CPAP significantly reduced total aerosol delivery to the face mask from 6.85 (1.52)% to 1.3 (0.37)% of the initial nebuliser charge. In the clinical study a significant bronchodilator response to nebulised salbutamol was seen during both conventional nebulisation and nebulisation whilst receiving CPAP by face mask. The shape of the dose-response curves and the magnitude of the total increase in the forced expiratory volume in one second (FEV1) was identical for CPAP and control conditions. Despite a reduction in aerosol presented to the proximal airway, the bronchodilator response to inhaled beta 2 agonists in stable asthmatic subjects was not affected when CPAP was delivered by face mask. Despite a high rate of FGF, nebulised beta 2 agonists are effective when administered in conjunction with CPAP delivered by face mask.
Article
Chest physiotherapy (CPT) is an integral part of the treatment of patients with cystic fibrosis (CF). CPT imposes additional respiratory work that may carry a risk of respiratory muscle fatigue. Inspiratory pressure support ventilation (PSV) is a new mode of ventilatory assistance designed to maintain a constant preset positive airway pressure during spontaneous inspiration with the goal of decreasing the patient's inspiratory work. The aim of our study was 1) to evaluate respiratory muscle fatigue and oxygen desaturation during CPT and 2) to determine whether noninvasive PSV can relieve these potential adverse effects of CPT. Sixteen CF patients in stable condition with a mean age of 13 +/- 4 years participated to the study. For CPT, we used the forced expiratory technique (FET), which consisted of one or more slow active expirations starting near the total lung capacity (TLC) and ending near the residual volume. After each expiration, the child was asked to perform a slow, nonmaximal, diaphragmatic inspiration. After one to four forced breathing cycles, the child was asked to cough and to expectorate. A typical 20-minute CPT session consisted of 10 to 15 FET maneuvers separated by rest periods of 10 to 20 breathing cycles each. During the study, each patient received two CPT sessions in random order on two different days, at the same time of day, with the same physiotherapist. During one of these two sessions, PSV was provided throughout the session (PSV session) via a nasal mask using the pressure support generator ARM25 designed for acute patients (TAEMA, Antony, France). The control session was performed with no nasal mask or PSV. Both CPT sessions were performed without supplemental oxygen. Lung function and maximal inspiratory pressures (PImax) and expiratory pressures (PEmax) were recorded before and after each CPT session. Mean lung function parameters were comparable before the PSV and the control sessions. Baseline pulse oximetry (SpO2) was significantly correlated with the baseline vital capacity (% predicted) and forced expiratory volume in 1 second (FEV1) (% predicted). PSV was associated with an increase in tidal volume (Vt) from 0.42 +/- 0.01 liters to 1.0 +/- 0.02 liters. Respiratory rate was significantly lower during PSV. SpO2 between the FET maneuvers was significantly higher during PSV as compared with the control session. SpO2 decreases after FET were significantly larger during the control session (nadir: 91.8 +/- 0. 7%) than during the PSV session (93.8 +/- 0.6%). Maximal pressures decreased during the control session (from 71.9 +/- 6.1 to 60.9 +/- 5.3 cmH2O, and from 85.3 +/- 7.9 to 77.5 +/- 4.8 cmH2O, for PImax and PEmax, respectively) and increased during the PSV session (from 71.6 +/- 8.6 to 83.9 +/- 8.7 cmH2O, and from 80.4 +/- 7.8 to 88.0 +/- 7.4 cmH2O, for PImax and PEmax, respectively). The decrease in PEmax was significantly correlated with the severity of bronchial obstruction as evaluated based on baseline FEV1 (% predicted). Forced expiratory flows did not change after either CPT session. The amount of sputum expectorated was similar for the two CPT sessions (5.3 +/- 5.3 g vs 4.6 +/- 4.8 g after the control and PSV session, respectively; NS). Fifteen patients felt less tired after the PSV session. Ten patients reported that expectoration was easier with PSV, whereas 4 did not note any difference; 2 patients did not expectorate. Nine patients expressed a marked and 5 a small preference for PSV, and 2 patients had no preference. The physiotherapists found it easier to perform CPT with PSV in 14 patients and did not perceive any difference in 2 patients. Our study in CF children shows that respiratory muscle performance, as evaluated based on various parameters, decreased after CPT and that significant falls in oxygen saturation occurred after the FET maneuvers despite the quiet breathing periods between each FET cycle. These unwanted effects of CPT were
Variability in the measurement of nebulized aerosol deposition in man
  • Shl Thomas
  • J A Langford
  • Rjd George
  • D M Geddes
Thomas SHL, Langford JA, George RJD, Geddes DM. Variability in the measurement of nebulized aerosol deposition in man. Clin Sci 1988; 75:535-542.
Respiratory self-monitoring of inhalation increases the deep deposition of aerolized amikacin in cystic fibrosis patients
  • F Faurisson
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  • A Grimfeld
Faurisson F, Prévot B, Just J, Fauroux B, Chevret S, Grimfeld A. Respiratory self-monitoring of inhalation increases the deep deposition of aerolized amikacin in cystic fibrosis patients [abstract]. Am Rev Respir Dis 1994;149:A666.