PAEDIATRIC RESPIRATORY REVIEWS (2007) 8, 1723

MINI-SYMPOSIUM: AIRWAY CLEARANCE IN CYSTIC FIBROSIS

Airway clearance devices in cystic brosis

John H. Marks*
Associate Professor, Department of Pediatrics and Human Development, Michigan State University College of Human Medicine, East Lansing, and Associate Director, Pediatric Pulmonology and Cystic Fibrosis Center, Michigan State University-Kalamazoo Center for Medical Studies, Kalamazoo, Michigan, USA
KEYWORDS airway clearance; chest physical therapy; cystic brosis; high frequency chest wall oscillation; intrapulmonary percussive ventilation; positive expiratory pressure

Summary Clearance of infected airway secretions is essential to preserve lung function in patients with cystic brosis (CF). Although the value of regular airway clearance treatments has been shown in many studies, adherence to the prescribed treatments is not very good (see Making airway clearance successful, pp. 000000). In the past the only method available was conventional chest physiotherapy (CCPT; also known as manual percussion and postural drainage). CCPT remains the gold standard of airway clearance methods and may be the best choice for some patients, such as infants and young children. However, the many newer methods of airway clearance available now allow CF patients and their families to choose the techniques and devices that best suits them. Most of the newer airway clearance devices have been studied in comparison to standard chest physiotherapy and most studies show no advantage of one method over another. This review will describe newer airway clearance devices available for CF patients and discuss evidence for the effectiveness of these devices compared to standard chest physiotherapy. 2007 Elsevier Ltd. All rights reserved.

Management of the pulmonary complications of cystic brosis (CF) involves airway clearance therapies (ACTs) to remove obstructing secretions from the airways. To aid airway clearance, aerosolized bronchodilators and mucolytics are also often used to dilate respiratory passages and breakdown secretions; other articles in this symposium discuss these. Conventional manual chest physiotherapy with gravity assisted drainage (CCPT) has long been the gold standard method of airway clearance for patients with CF.1 While CCPT has been shown to aid in clearance of pulmonary secretions in CF patients, the time involved and the need for assistance often leads to reduced adherence to this form of therapy. Several independently administered airway clearance devices have been shown to be effective in aiding airway clearance in CF patients, including positive
* Tel.: +1 269 337 6467; Fax: +1 269 337 6474. E-mail address: marks@kcms.msu.edu. 1526-0542/$ see front matter 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.prrv.2007.02.003

expiratory pressure (PEP), the Flutter1 device, the Acapella1, the Cornet1, the intrapulmonary percussive ventilation device (IPV), the PercussiveNeb1, and the high frequency chest wall oscillation devices. This paper will describe each device, the mechanisms (known and proposed) by which the devices aid airway clearance, and the clinical evidence based on short- and long-term clinical trials that supports their use in patients with CF.

POSITIVE EXPIRATORY PRESSURE

The PEP device is the simplest and least expensive of the airway clearance devices. The PEP mask was developed in Denmark in the late 1970s as an alternative to CCPT. The mask has a one-way inhalation valve and an expiratory resistor. Exhalation through the resistor generates positive pressure in the airways which can be measured with a manometer or pressure indicator. Resistance orices of

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different diameters can be chosen so that individual patients can generate pressures of 1020 cm H2O. The patient inhales to mid-lung volumes and then exhales actively with an inspiration to expiration ratio (I:E) of 1:3 or 1:4. After about 10 PEP exhalations the patient does a series of huff coughs, keeping the glottis open. The cycle is repeated several times over about 20 min or until secretions are no longer being expectorated. PEP can also be done with a mouthpiece making sure the cheeks are well supported. A resistor can also be utilized with a nebulizer so aerosolized medications can be delivered during inspiration (Fig. 1). Higher pressure PEP achieving pressures of 6080 cm H2O has also been advocated.2 The proposed mechanism of action of PEP is to stabilize airways and improve aeration to obstructed distal lung units through collateral ventilation via pores of Kohn and canals of Lambert.3 PEP has also been shown to improve the distribution of ventilation and gas mixing in CF patients.4 Most studies assessing the effectiveness of PEP in CF patients have demonstrated equivalence compared to traditional CCPT. One study (16 patients, 8 week crossover design) showed more improvement in forced expiratory volume in 1 s (FEV1) with CCPT.5 Another study (36 patients, 1 year parallel design) showed greater improvement in FEV1 in the PEP group.6 Four evidence-based reviews comparing PEP with CCPT and other airway clearance methods were published in 2006.710 Three Cochrane Database reviews concluded that there was essentially no evidence that PEP was better than CCPT or vice versa. There were trends that showed patients preferred PEP over CCPT. The American College of Chest Physicians Evidence-Based Clinical Practice Guidelines on Nonpharmacologic Airway Clearance Therapies states, In patients with CF, PEP is recommended over conventional chest physiotherapy because it is approximately as effective as chest physiotherapy, and is inexpensive, safe, and can be self-administered.10

OSCILLATORY DEVICES
Flutter1
The Flutter1 (Axcan Scandipharm, Birmingham, Alabama, USA) is a small, handheld, mucus clearance device that provides PEP therapy with oral airway oscillations. It is shaped like a pipe with a hardened plastic mouthpiece at one end, a plastic, protective, perforated cover at the other end, and a high-density stainless steel ball resting in a plastic circular cone on the inside (Fig. 2). The patient sits comfortably and inhales to about 75% of inspiratory capacity, then exhales through the Flutter keeping the stem parallel to the oor. During exhalation, pressure from the airways is transmitted to the Flutter causing the steel ball to bounce and roll up and down, creating several opening and closing cycles with each breath (Fig. 3). PEP develops in the range of 1025 cm H2O at an oscillatory frequency of about 15 Hz. Tilting the device adjusts the frequency to achieve the greatest amount of airway vibration (the individuals pulmonary resonance frequency). Several series of ve to ten exhalations each followed by one or two forceful exhalations and huff coughs are done over 1020 min. The proposed mechanisms of action of the Flutter include shearing of mucus from airway walls by oscillatory action, stabilization of airways preventing airway collapse, accelerating expiratory airow to move mucus upward to the trachea, and possibly by altering mucus quality, although data for direct effects of thinning of airway secretions by any AC device is scant.11 Evidence for effectiveness of the Flutter has been shown in short- and long-term studies. Expectorated sputum volume was greater after a 15 min session with the Flutter compared to sessions of CCPT or directed vigorous cough (18 patients, three-way crossover over 2 weeks).12 Two studies demonstrated no difference in effectiveness of Flutter and CCPT during hospital treatment of an acute

Figure 1 Pari PEP device (Pari Respiratory Equipment, Midlothian, Virginia, USA) used with a Pari LC nebulizer. Resistance is set by choosing one of the various orices over the exhalation port (inset). A pressure monitor is at right.

Figure 2 Top: Flutter device components showing the pipe stem, cone with steel ball and perforated top. Bottom: the Acapella device.

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Figure 4 Figure 3 Oscillating up and down action of the steel ball in the Flutter. (From Flutter1 mucus clearance device, Instructions for use, Axcan Scandipharm, Birmingham, Alabama, USA.)

The RC-Cornet device.

term effectiveness of the Cornet in CF patients are available yet. The Cornet is available in Europe but not in the USA.

pulmonary exacerbation.13,14 One study showed the Flutter was less effective than PEP (40 patients over 1 year) in maintaining pulmonary function and clinical scores.15 These conicting studies point out the difculty of drawing conclusions as to the efcacy of an AC device when a study is small and often statistically underpowered.

Intrapulmonary Percussive Ventilation IPV-11

The IPV-11 (Percussionaire, Sand Point, Idaho, USA) is a positive pressure ventilator device (Fig. 5) that delivers small bursts of air through a mouthpiece at a rate of 200300 cycles/min (25 Hz) using a sliding venturi to cause rapid ow interruptions. It entrains an aerosol of up to 20 ml of saline with or without a bronchodilator over about 20 min. It delivers a positive pressure at the mouth of 1030 cm H2O. The optimal effect achieved by pressure and frequency is determined by direct observation of chest movement and patient comfort. Oscillations occur mainly during inhalation, but may occur throughout the respiratory cycle. The pressure source can be either an oxygen cylinder or an air compressor. The presumed mechanisms of action of the IPV include bronchodilation from increased airway pressure and delivery of nebulized bronchodilator, prevention of airway collapse, improved distribution of ventilation and stimulation of cough. Evidence to support the effectiveness of IPV treatment in CF patients is limited. Three short-term studies and one long-term study have been published. Two single intervention studies established safety and demonstrated no difference in effects on pulmonary function and sputum production with IPV compared to CCPT and Flutter.17,18 A short-term study in hospitalized CF patients (24 subjects, crossover design) demonstrated an increased sputum wet weight after IPV compared to high frequency chest wall oscillation.19 A 6-month study (16 CF patients, parallel design) that compared daily IPV with standard bronchodilator aerosol and CCPT showed no signicant differences in pulmonary function, number of hospitalizations, use of oral or intravenous antibiotics and anthropometrics.20

Acapella1
The Acapella1 (Smiths Medical Inc, Carlsbad, California, USA) is a handheld airway clearance device (Fig. 2) that operates on the same principle as the Flutter, i.e. a valve interrupting expiratory ow generating oscillating PEP. Utilizing a counterweighted plug and magnet to achieve valve closure, the Acapella is not gravity dependent like the Flutter. The Acapella comes in three models, a low ow (<15 L/min), high ow (>15 L/min) and the Acapella Choice. The high and low ow models have a dial to set expiratory resistance while the Choice model has a numeric dial to adjust frequency. All models can be used with a mask or mouthpiece and can be used in line with a nebulizer. While these attributes may offer the Acapella some advantage over the Flutter, no long-term studies have been done in CF patients. A bench study of the performance characteristics of the two devices showed a slight advantage for the Acapella, with more stable wave form and a wider range of PEP at low air ow.16

RC-Cornet1
The RC Cornet1 (R. Cegla, Montabaur, Germany) consists of a semi-circular tube containing a exible latex-free hose (Fig. 4). Expiration through the Cornet causes the hose to ex, buckle and unbuckle, causing oscillating positive pressure in the airways which uctuates many times per second. The mouthpiece can be adjusted to produce the optimal effect. Operating principle and use are similar to the Flutter valve, although the Cornet is not gravity dependent and can be used in any position. Like the Flutter the Cornet cannot be used in line with a nebulizer. No studies showing the long-

PercussiveNeb1
The PercussiveNeb1 (P-Neb; Vortran Medical Technology 1, Sacramento, California, USA) is an oral intrapulmonary

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Figure 5

The IPV-1 device.

percussive treatment device that incorporates a large volume nebulizer (20 ml) for delivery of aerosolized medication with oscillating positive pressure (Fig. 6). Oscillatory frequency ranges from 6 to 30 Hz with airway pressures of 615 cm H2O. The P-Neb oscillates during both inhalation and exhalation, enhancing aerosol delivery and maintaining airway patency (Fig. 7). The pressure source is a highoutput compressor capable of delivering a gas ow >60 L/ min. Most of the ow is utilized to operate the modulator piston that causes the oscillatory effect. The patient lls the nebulizer reservoir with bronchodilator medication, starts

Figure 7 Mouth pressure and amplitude recording with PTHF in two CF patients. Top: Pressure recorded shows oscillations at approximately 10 Hz with an amplitude of 06 cm H2O during inhalation and 814 cm H2O during exhalation. Bottom: There are no oscillations during inhalation and lower amplitude and frequency during exhalation. (Adapted with permission from Marks et al.21)

the compressor and occludes the mouthpiece until the device begins to cycle. After placing the mouthpiece in the mouth, the ow is adjusted to accommodate the patients comfort and breathing pattern. Oscillating amplitude can be adjusted from soft to hard. Presumed mechanisms of action are similar to the IPV and include bronchodilation, prevention of airway collapse and shearing of mucus from airway walls, and possible thinning of secretions by high expiratory percussive ow (Fig. 8). There are no published long-term studies of the P-Neb in CF patients. A single intervention study of the precursor device, the PercussiveTech HF, in CF patients showed it to be safe and probably as effective as CCPT.21 A 6-month study (16 CF patients, parallel design) comparing daily use of the PercussiveTech HF with the Flutter showed no differences in pulmonary function or days of hospital or home intravenous antibiotic use.22 It should be noted that for all the oral positive expiratory pressure devices, especially when used with a mouthpiece, the cheeks should be kept at and rigid and a nose clip should be considered so that the pressure and oscillations are primarily delivered to the lower airways.

High frequency chest wall oscillation

Figure 6 The PercussiveNeb device.

There are two devices utilizing an inatable vest connected to an air-pulse generating compressor to deliver

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Figure 8 Diagram of exhalation without PEP or oscillations (upper gure) and with oscillatory PEP (lower gure). (Adapted from PercussiveNeb1 Users Guide, Vortran Medical Technology 1, Sacramento, California, USA.)

high-frequency chest wall oscillation (HFCWO), The Vest1 (Hill-Rom, St Paul, Minnesota) and the SmartVest1 (Electromed, New Prague, Minnesota) (Fig. 9). The airpulse generator rapidly inates and deates the vest, gently compressing and releasing the chest wall several times per second. Oscillation frequency can be adjusted from 5 to 25 Hz with pressure to the vest ranging from 3 to 25 cm H2O. The chest wall oscillations are transmitted to the airways creating mini-coughs. Treatment sessions generally last 20 to 30 min and consist of short segments at different frequencies separated by huff coughs. An example would be 5 min sessions at 8, 10, 12, 15, 17 and 20 Hz. Keeping the frequency set at 12 Hz for the entire treatment is a simpler option. Nebulized bronchodilator can be taken before or during a vest treatment session. Vests

come in different sizes to accommodate children and adults. The proposed mechanism of action of HFCWO is enhancement of mucus transport in three essential ways: by altering the rheologic properties of mucus, by creating a cough-like expiratory airow bias that shears mucus from the airway walls, and by enhancing ciliary beat frequency, all of which help move mucus toward central airways.23 HFCWO has also been shown to improve distribution of ventilation.24 One study found that patients with moderate or severe airway obstruction may benet from lower vest pressures at frequencies of 1015 Hz to minimize decrease in end-expiratory lung volume and maximize oscillatory ow.25 There is evidence to support the use of HFCWO in CF patients based on several studies looking at acute and longterm effects. When comparing HFCWO to oscillating PEP and CCPT, the acute effect, as assessed by sputum production, showed no difference or superiority of HFCWO using a vest device compared to CCPT and IPV.26 HFCWO using the Hayek Oscillator (Breasy Medical Equipment Ltd, London, UK), a rigid cuirass ventilator, and oscillating PEP using two similar oral airway oscillating devices (Sensormedics, Yorba Linda, California, USA) demonstrated, comparable augmenting effects on expectorated sputum weight with no effect on pulmonary function.27 Therapy during hospitalization for a pulmonary exacerbation showed no differences in outcomes with HFCWO compared to CCPT or PEP as assessed by sputum production and pulmonary function.28,29 A short-term crossover trial comparing HFCWO to CCPT and oscillating PEP found no differences in pulmonary function or clinical score between therapies. Patients tended to prefer HFCWO.30 A long-term study (16 patients, 22 months with historical controls) showed a signicant decrease in the rate of decline in pulmonary function during the HFCWO treatment period compared to standard CPT.31 The Hayek Oscillator was compared to active cycle of breathing technique (ACBT) in a 2-day crossover study; HFCWO was found to be less effective than ACBT.32 No long-term studies using this device have been published.

CONCLUSION
Several devices have been developed to enhance airway clearance in CF patients. With the exception of the PEP valve, these devices all involve airway oscillation, either orally or via chest wall vibration. The advantage of these devices is that they can be used by patients independently without the need for an assistant or caregiver. Most of these devices have been studied in either short- or longterm comparisons with CCPT. The studies are generally underpowered and it is not clear which outcome measurements are most useful for comparing various clear-

Figure 9 The SmartVest1 showing the compressor unit and vest. (Adapted from SmartVest1 product information, Electromed, New Prague, Minnesota, USA.)

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ance techniques. Short-term studies, especially those measuring sputum production, are not helpful in demonstrating equivalence of any airway clearance methods. In spite of a lack of adequately powered, long-term trials, two Cochrane evidence-based reviews conclude that there is evidence that CCPT is generally at least as effective as these airway clearance devices.8,9 The ACCP Evidence-Based Clinical Practice Guidelines states, In patients with CF, devices designed to oscillate gas in the airway, either directly or by compressing the chest wall, can be considered as an alternative to chest physiotherapy.10 Evidence in these reviews also suggests that these self-administered therapy devices may be preferred by CF patients, which may lead to increased adherence to treatment.

PRACTICE POINTS
 Airway clearance devices as alternatives to CCPT allow CF patients to choose the therapy that best fits their lifestyle and allows greatest independence  Airway clearance devices are preferred by many patients compared to CCPT and may result in better adherence.  PEP may be more effective for airway clearance than CCPT.  Oscillating positive expiratory pressure devices and HFCWO appear to be at least as effective as CCPT.

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