Annotated Bibliography: Basic Research

Aerosol Deposition

Aerosolized medications play an important role in the management of most respiratory and some systemic conditions; access to peripheral lung regions is vital for effective drug delivery. Therefore, it is important to establish the effect of high frequency chest compression (HFCC) therapy on the pattern and extent of aerosol deposition in the lungs.

1. Chambers C, Klous D, Nantel N, King M, Newhouse M. Does high-frequency chest compression (HFCC) during aerosol therapy affect lung deposition? Am J Respir Crit Care Med 1998; 157(suppl 3):A131.
To assess the effects of high-frequency chest compression (HFCC) on aerosol delivery to the lung, 10 normal subjects inhaled 99m Technetium-labeled Human Serum Albumin (HSA) aerosol alternately with and without HFCC. Study data suggest that, in normal subjects, 1) aerosol delivery is unimpaired by HFCC and 2) deposition to the lower respiratory tract is improved just short of significance.

2. Perry GV, Stites SW, Peddicord T, Cox G, McMillian C. Effect of high frequency chest wall oscillation on the central and peripheral distribution of aerosolized DTPA as compared to standard chest physiotherapy in cystic fibrosis. Am J Respir Care Med 1999; 159(suppl 3):A686.
This crossover study compared deposition of aerosolized technetium 99m diethylene triamine penta-acidic acid (DTPA) administered during high-frequency chest compression (HFCC) therapy versus after standard chest physiotherapy (CPT) in seven cystic fibrosis (CF) patients with moderate to severe lung disease. Aerosol administration combined with HFCC showed greater but non-significant deposition in central lung regions.

3. Stites SW, Perry GV, Peddicord T, Cox G, McMillan C, Becker B. Effect of High-Frequency Chest Wall Oscillation on the Central and Peripheral Distribution of Aerosolized DTPA as Compared to Standard Chest Phyisotherapy in Cystic Fibrosis. Chest 2006; 129:712-717.
This crossover evaluation compared the distribution of aerosolized (99m) Tc diethylene triamine penta-acetic acid (DTPA) administered simultaneously with high frequency chest compression (HFCC) therapy with DTPA after chest physiotherapy (CPT). Subjects included ten cystic fibrosis (CF) patients (ages 22 to 38 years) with moderate-to-severe obstructive disease. The central to peripheral deposition ratio (C/P ratio) of each lung was analyzed in each study group. Use of HFCC in combination with aerosolized DTPA did not result in increased central deposition or reduced peripheral distribution as compared with aerosolized DTPA administered after CPT.

Mechanisms of Action/Effects on Mucus /Physiological Effects

High frequency chest compression (HFCC) technology has been studied extensively using in-vitro and animal models. Studies have elucidated both mechanisms of action and physiological effects.

1. App EM, Lohse P, Matthys H, King M. Physiotherapy and mechanical breakdown of the excessive DNA load in CF sputum-an anti-inflammatory therapeutic strategy. Pediatr Pulmonol 1998; (suppl 17):349, A507.
Results of this study evaluating the effects of high-frequency oscillations on the breakdown of high-molecular-weight DNA in cystic fibrosis (CF) sputum samples suggest that such oscillations can break down DNA as effectively as rhDNAse treatments. Reductions in intact DNA are estimated at approximately 15% after 30 minutes of treatment.

2. Chang HK, Weber ME, King M. E. Mucus transport by high-frequency nonsymmetrical oscillatory airflow. J Appl Physiol 1988; 65:1203-1209.
This in vitro study tested the hypothesis that a mucus mass can be moved by the difference between expiratory and inspiratory airflow velocities induced by high frequency chest compression (HFCC). An experimental model using mucus gel simulants showed that nonsymmetrical airflow and shearing at the air-mucus interface are probable significant factors leading to enhanced mucus clearance during HFCC.

3. Dasgupta B, Tomkiewicz RP, Boyd WP, Brown NE, King M. Effects of combined treatment with rhDNase and airflow oscillations on spinnability of cystic fibrosis sputum in vitro. Pediatr Pulmonol 1995; 20:78-82.
To investigate whether combined treatment with DNase and HFCC results in greater changes in CF sputum than either treatment used alone, an analysis was performed for sputum samples from 8 cystic fibrosis (CF) patients infected with P. aeruginosa and treated with antibiotics, steroids, and bronchodilators but not treated previously with DNase, HFCC, or any mucolytic agent. Data showed optimal spinnability in vitro when rhDNase and simulated HFCC oscillations were administered concomitantly, suggesting that CF patients may experience a greater benefit if treatments include both biochemical (rhDNase) and physical (high-frequency chest wall oscillation).

4. Gross D, Zidulka A, O’Brien C, Wight D, Fraser R, Rosenthal L, King M. Peripheral mucociliary clearance with high frequency chest-wall compression. J Appl Physiol 1985; 58:1157-1163.
To investigate the effect of high frequency chest compression (HFCC) on clearance of secretions from peripheral lung regions, 5 anesthetized, spontaneously breathing dogs received 30 minute treatments of HFCC at 13 Hz & cuff pressures at 50-60 cm H2O. Correlations between peripherial mucus clearance indices (PMCI) and tracheal mucus clearance rates (TMCR) in two outer peripheral regions located under the cuff were statistically significant (13.0 + 2.6; p = < 0.05); lower-middle outer peripheral region (9.1 + 3.0; p = < 0.05). Overall, HFCC enhanced both central and peripheral mucus clearance in normal dogs. Post-mortem, all 5 experimental dogs showed no evidence of pulmonary hemorrhage; Two control dogs had extensive atelectasis and one showed a small pulmonary hemorrhage.

5. Hamel DS, Gentile MA, Craig DM, Quick G, Cheifetz IM. High frequency chest wall oscillation does not adversely affect output in a Swine Model of Pediatric Acute Lung Injury. AARC Abstracts.
In a study to determine whether the external pressure exerted to the chest during HCFF would adversely affect cardiac output (CO), five swine (12.3-19 kg) with acute lung injury induced by saline lavage were ventilated with a Servo 300 ventilator (Siemens, Corp.). CO was measured by the thermodilution technique with a pulmonary artery catheter. HFCC apparatus was placed on the animal and set at a pressure setting of 0.5. For each frequency setting (5, 10, and 15 Hz), CO was measured at baseline without HCFF and during HCFF. The frequencies were re-randomized, and the study was repeated for each animal. Data analysis showed that 1) HCFF at a pressure setting of 0.5, did not alter CO (p=0.53, frequency difference p=0.47) and 2) CO remained stable during HCFF. Investigators speculate that HCFF may be utilized as an adjunct therapy during mechanical ventilation (MV) for improved gas exchange without hemodynamic compromise.

6. Hamel D, Gupta V, Craig D, Kotani T, Quick G, Gentile M, Cheifetz I. High frequency chest wall oscillation improves oxygenation in a pediatric swine model of acute lung injury. Duke Children’s Hospital, Durham, NC (publication pending)
In a study to determine whether high frequency chest compression (HCFF) improves oxygenation in acute lung injury, nine swine (12-20 kg) with a surfactant depletion model were conventionally ventilated at settings maintained constant throughout the data collection. High frequency chest compression (HCFF) was applied to each animal at various combinations of pressure (0.5, 3, and 5) and frequency (5, 10, and 15 Hz) in random order. For each combination of HFCC settings, an arterial blood gas was obtained after a 10-minute stabilization period without HCFF and at the end of a 10-minute period with HCFF. Data showed that HFCC effectively improves oxygenation at a low (0.5) HCFF pressure setting (p<0.04). Investigators speculate HCFF may be a useful technique as an adjunct therapy to conventional ventilation to achieve a more optimal mean lung volume.

7. Hansen LG, Warwick WW, Hansen KL. Mucus transport mechanisms in relation to the effect of high frequency chest compression (HFCC) on mucus clearance. Pediatr Pulmonol 1994; 17:113-118.
This paper reviews in vitro and animal laboratory studies leading to the development of high frequency chest compression (HFCC) technology, describes studies supporting HFCC mechanisms of action and summarizes clinical studies and experience with HFCC. Evidence is cited for mechanisms including mucus-airflow interactions that favorably reduce mucus viscosity, shear forces at the air-mucus interface that dislodge mucus adherent to airway walls, creation of an airflow bias encouraging cephalad mucus flow and resonance enhancement of ciliary beat. More speculative mechanisms are also discussed, such as the possibility that HFCC may stimulate the vagal nerve to augment production of airway surface liquid.

8. Hansen L, Warwick W. High-frequency chest compression system to aid in clearance of mucus from the lung. Biomed Instrum Technol 1990; 24:289-294.
In a crossover study comparing the volume of mucus cleared using HFCC vs CPT, 5 cystic fibrosis (CF) patients received 30 time and day-matched sessions of each modality administered by a professional therapist. Data showed 1) increased mucus clearance [3.3cc/ HFCC therapy session vs 1.8 cc/ chest physiotherapy (CPT) session.] and; 2) Improved lung function. The paper also includes an outcomes report of a 60-month retrospective/prospective study of HFCC use in a 48 year-old man with CF and Pseudomonas aeruginosa in his sputum and a two-year history of worsening pulmonary function. Results showed: 1) after one year of HFCC, the patient’s pulmonary function returned to the level measured five years before initiation of HFCC therapy; 2) a baseline technetium aerosol scan showed absence of ventilation in the upper lobes, but after 8 months of HFCC, a repeat test showed that ventilation was restored in these regions. For every outcome measure, HFCC therapy was shown to be more effective than standard chest physical therapy.

9. Hamel DS, Gentile MA, Craig DM, Quick G, Cheifetz IM. High frequency chest wall oscillation does not adversely affect output in a Swine Model of Pediatric Acute Lung Injury. AARC Abstracts.
In a study to determine whether the external pressure exerted to the chest during HCFF would adversely affect cardiac output (CO), five swine (12.3-19 kg) with acute lung injury induced by saline lavage were ventilated with a Servo 300 ventilator (Siemens, Corp.). CO was measured by the thermodilution technique with a pulmonary artery catheter. HFCC apparatus was placed on the animal and set at a pressure setting of 0.5. For each frequency setting (5, 10, and 15 Hz), CO was measured at baseline without HCFF and during HCFF. The frequencies were re-randomized, and the study was repeated for each animal. Data analysis showed that 1) HCFF at a pressure setting of 0.5, did not alter CO (p=0.53, frequency difference p=0.47) and 2) CO remained stable during HCFF. Investigators speculate that HCFF may be utilized as an adjunct therapy during mechanical ventilation (MV) for improved gas exchange without hemodynamic compromise.

10. Hamel D, Gupta V, Craig D, Kotani T, Quick G, Gentile M, Cheifetz I. High frequency chest wall oscillation improves oxygenation in a pediatric swine model of acute lung injury. Duke Children’s Hospital, Durham, NC (publication pending)
In a study to determine whether high frequency chest compression (HCFF) improves oxygenation in acute lung injury, nine swine (12-20 kg) with a surfactant depletion model were conventionally ventilated at settings maintained constant throughout the data collection. High frequency chest compression (HCFF) was applied to each animal at various combinations of pressure (0.5, 3, and 5) and frequency (5, 10, and 15 Hz) in random order. For each combination of HFCC settings, an arterial blood gas was obtained after a 10-minute stabilization period without HCFF and at the end of a 10-minute period with HCFF. Data showed that HFCC effectively improves oxygenation at a low (0.5) HCFF pressure setting (p<0.04). Investigators speculate HCFF may be a useful technique as an adjunct therapy to conventional ventilation to achieve a more optimal mean lung volume.

11. Jones RL, Lester RT, Brown NE. Effects of high-frequency chest compression on respiratory system mechanics in normal subjects and cystic fibrosis patients. Can Respir J 1995; 2:40-46.
In this randomized blinded study investigating short-term effects of high frequency chest compression (HFCC) on several indices of respiratory system mechanics, 10 normal and 10 stable cystic fibrosis (CF) volunteers received HFCC at 10 randomized settings (5, 10, 15, 20, 25 Hz; highest and lowest pressures); effects were measured with balloon-tipped esophageal catheters, spirograms and reverse plesmography. Both normal and CF subjects has similar changes in esophageal pressure (Pes) and end-expiratory lung volume (EELV). EELV decreased approximately 30% from the no-HFCC baseline functional residual capacity (FRC). Differences between normals and CF subjects were dependent upon overall airway function. In CF patients with moderate to severe airway obstruction, HFCC at low pressure and 10-15 Hz minimizes decrease in EELV and maximizes oscillatory flow.

12. King M, Phillips D, Gross D, Vartian V, Chang HK, Zidulka A. Enhanced tracheal mucus clearance with high frequency chest wall compression. Am Rev Respir Dis 1983; 128:511-515.
In this study of the effects of high frequency chest compression (HFCC) on mucus clearance in the trachea, HFCC was administered to 9 anesthetized dogs by oscillating the pressure in a thoracic cuff such that it produced oscillatory tidal volumes of 25 to 100 cc at frequencies of 3 to 17 Hz. The tracheal mucus clearance rate (TMCR) was determined by direct observation of the rate of displacement of a charcoal particle spot by means of a fiberoptic bronchoscope. Baseline TMCR during spontaneous breathing averaged 8.2 +/- 5.6 mm/min in the 9 dogs. The TMCR during 2 min of HFCC was increased at 5, 8, 11, 13, 15, and 17 Hz but not at 3 Hz. The enhancement of clearance was most pronounced in the range of 11 to 15 Hz, reaching a peak value of 340% of control at 13 Hz. This early study suggested that HFCC might be of considerable potential benefit

13. King M, Phillips D, Zidulka A, Chang HK. Tracheal mucus clearance in high-frequency oscillation: chest wall versus mouth oscillation. Am Rev Respir Dis 1984; 130:703-706.
A comparison of the tracheal mucus clearance rate (TMCR) in anesthetized dogs during spontaneous breathing (SB) showed that high frequency chest compression (HFCC enhances tracheal mucus clearance when compared with spontaneous breathing, whereas high-frequency oscillation at the mouth does not. Seven dogs received ventilation by high-frequency oscillation at the airway opening (HFO/AO), and ventilation by high-frequency chest compression (HFCC) and the rate of displacement of a charcoal marker in the lower trachea was observed by fiberoptic bronchoscope. Mean TMCR with HFCC was 240% of control (p = < 0.001) and 76% of control with HFO/AO (NS).

14. King M, Zidulka A, Phillips D, Wight D, Gross D, Chang HK. Tracheal mucus clearance in high-frequency oscillation: effect of peak flow rate bias. Eur Respir J 1990; 3:6-13.
To investigate whether previously shown increases in tracheal mucus clearance rate (TMCR) in dogs during high frequency chest wall compression (HFCC) is due, in part, to the expiratory bias in peak flow rate (VE/VI greater than 1) that occurs during HFCC, TMCR in 8 anaesthetized, spontaneously breathing dogs was studied by comparing several randomized maneuvers designed to assess that effect. TMCR was determined by direct bronchoscopic visualization of charcoal particle transport. Results showed that TMCR during HFCC was 2.4x control (p = < 0.001), in line with previous results, was influenced by expiratory flow-rate bias.

15. Majaesic CM, Montgomery M, Jones R, King M. Reduction in sputum viscosity using high frequency chest compression compared to conventional chest physiotherapy. Pediatr Pulmonol 1996; (suppl 13):A358.
This randomized, crossover controlled comparison of the viscosity of mucus cleared by HFCC and by CPT included 14 stable CF children (6-18 yrs) randomized to receive either normal saline (N.S.) or DNase nebulization, followed by either HFCC or CPT. A statistician blinded to treatment allocations analyzed expectorated sputum viscosity (rigidity index, log G*) finding an average reduction in log G* = 0.55 (p = < 0.1), where a change in log G* of 0.3 represents an approximate twofold reduction in sputum viscosity. Data suggest that HFCC reduces sputum viscosity significantly when compared to CPT.

16. Ong JH, Ghista DN. Applied chest-wall vibration therapy for patients with obstructive lung disease. Chapter 8: 158-169. In: Human Respiration: Anatomy and Physiology, Mathematical Modeling, Numerical Simulation and Applications. V. Kulish, Ed., WIT Press Southampton, Boston (2006).
Investigators suggest that, with high frequency chest compression (HFCC) therapy, a pulsating frequency range of 6-19 Hz may not be optimal for mucus drainage. To enhance efficacy of HFCC, chest resonance frequencies (CRF) were measured in 23 healthy volunteers. Average CRFs for males and females were 26.7 Hz and 27.8 Hz respectively. Based on their findings, authors conclude that HFCC should be carried out at about 18-34 Hz; they further suggest individual CRF determinations for HFCC candidates with respiratory muscle and chest wall abnormalities in order to select frequencies best for them.

17. Perry RJ, Man GCW, Jones RL. Effects of positive end-expiratory pressure on oscillated flow rate during high-frequency chest compression. Chest 1998; 113:1028-1033.
A comparative study of six normal subjects and six with stable COPD showed that, in the COPD group, the addition of a small amount of positive end expiratory pressure (PEEP) during HFCC therapy prevents decreased end-expiratory lung volume and increased mean oscillated flow rate during both phases of spontaneous breathing. The higher oscillated flow rates achieved during HFCC+PEEP may improve the effectiveness of HFCC in clearing mucus from the lungs of patients with airway disease.

18. Rubin E, Scantlen G, Chapman A, Eldridge M, Menendez R, Wanner A. Effect of chest wall oscillation on mucus clearance: comparison of two vibrators. Pediatr Pulmonol 1989; 6:122-126.
A comparison of the effect of an experimental low-energy chest wall oscillator and a commercial chest percussor on central airway mucociliary clearance was made using 5 normal anesthetized, intubated, supine dogs placed in a trough to which the oscillator or percussor was mounted. Tracheal mucus velocity (TMV) was measured by radiopaque particle or charcoal spot movement. The commercial percussor (a fixed sinusoidal device) used at its minimum frequency of 40 Hz, produced a mean (+/- SE) maximum expiratory flow rate of 0.25 +/- 0.04 L/sec at the airway opening, and had no measurable effect on TMV. The experimental oscillator, when operated at a level sufficient to generate flows of 2-3 L/sec, and with an unbiased 13-Hz sine wave (estimated energy, 150 W), increased mean TMV to 204 +/- 13% of control (P = < 0.003); the percent increase was independent of baseline TMV. Results suggest that moderate oscillatory power applied to the chest wall enhances mucus clearance in central airways, but currently available commercial percussors do not.

19. Sohn K, Warwick WJ, Lee YW, Lee J, Holte JE. Investigation of non-uniform airflow signal oscillation during high frequency chest compression. Biomed Eng Online. 2005; 4:34.
This observational study of respiratory airflow during use of high frequency chest compression (HFCC) showed the airflow oscillation by HFCC was strongly influenced by the nonlinearity of the respiratory system. A computational model-based approach, using an electrical circuit analogue, was used to analyze respiratory airflow during use of HFCC. Although imperfect, the circuit analogue model permits effective simulation of the nonlinear characteristics of the respiratory system. Data showed that the amplitudes of HFCC airflow signals behave as a function of spontaneous airflow signals and that this is due to the nonlinearity of the respiratory system, particularly variations in airway resistance.

20. Tomkiewicz RP, Biviji AA, King M. Effects of oscillating air flow on the rheological properties and clearability of mucous gel simulants. Biorheology 1994; 31:511-20.
Mucus clearance-related changes in the physical properties of mucus gel simulants occurring during high frequency chest compression (HFCC) were studied in vitro to investigate possible mechanisms of action. Rheological variables including spinnability and viscoelasticity were measured. Two derivative parameters, mucociliary clearability index (MCI) and cough clearability index (CCI), were computed from the rheological variables, based on relationships established from model studies of clearance. Data show that oscillating air flow may act as a physical "mucolytic", thus enhancing cough clearability.

21. Warwick W. High-frequency chest compression moves mucus by means of sustained staccato coughs. Pediatr Pulmonol 1991; (suppl 6):283, A219.
To investigate mechanism/s by which high frequency chest compression (HFCC) moves mucus from the bronchial airways, a Fleish pneumotach was used to measure inspiratory and expiratory airflows while subjects received HFCC at integral frequencies from 5-25 Hz. Coughs were analyzed from total lung capacity (TLC) to residual volume (RV) for all integral frequencies. Comparisons were made using conventional spirometry. Data showing that the passive staccato coughs produced using HFCC result in the expulsion of much greater volumes of air from the lungs than with forced expiration support the hypothesis that the ability of HFCC to clear mucus relies, in part, on the 300-1500 staccato coughs produced per minute with HFCC. The amplitude of HFCC coughs equals or exceeds voluntary coughs at tidal lung volume and can continue at lung volumes below the RV of the forced expiration with substantial power to clear mucus both small and large airways

Sputum Induction

Sputum cytology is an established, low-cost test for lung cancer and an important method for detecting a variety of other diseases and pathological markers. For a sputum sample to be diagnostically useful, it must contain exfoliated or circulating cells from target areas of the lung, including both peripheral and central airways. Numerous studies demonstrate that high frequency chest compression (HFCC) used with nebulized saline solution or water yields larger, better quality sputum samples than other methods.

1. Agostinis R, Man SFP, Mourad WA, Nguyen A, Thurber DL, Lien DC, Jones RL. High-frequency chest compression in combination with hypertonic saline improves induced sputum cytologic yield. Am J Crit Care Med 1995; 151:A844.
In this assessment of the sputum-induction efficacy of a thirty-minute treatment with high-frequency chest compression (HFCC) combined with hypertonic saline (HS) solution, specimens from 9 subjects yielded significantly greater sputum volumes ( 4.9 vs 3.7 ml than with HS alone [p = < 0.05] and 0.76 ml with HFCC alone [ p = < 0.001]). Cell counts were higher (2.6x 109 vs. 2.1x 109 and 2.2X 109) respectively. A higher percentage of cells were derived from peripheral lung regions with a greater percentage of alveolar macrophages with combined HS/HFCC than when subjects were treated for an equal time with either saline solution or HFCC alone.

2. Jones RL, Man SFP, Lien DC. Use of high-frequency chest compression plus hypertonic saline aerosol to provide sputum samples for diagnosis of lung cancer. Abstract presented at the Alberta Respiratory Diseases Symposium, Jasper, Alberta, 1995.
Investigators used high frequency chest compression (HFCC) plus inhaled hypertonic saline (HS) as a sputum induction technique to determine the usefulness of the specimen for lung cancer diagnosis in patients with radiological abnormalities. Samples obtained by HFCC-HS and by "gold standard" bronchoscopy methods were sent to cytopathology for diagnosis and interpretation. HFCC – HS induced sputum was found to have a cytological sensitivity of 71%, specificity of 80%, positive predictive value of 63%, negative predictive value of 86% and an accuracy of 77%. Two of 22 patients yielded cells diagnostic of lung cancer with HFCC-HC but had negative bronchoscopies, suggesting the value the technique for the investigation of lung cancer.

3. Lam S. Key issues in lung cancer chemoprevention trials of new agents. Cancer Res 2003; 163:182-195.
This discussion of key issues in phase II trials of promising lung cancer chemopreventive agents includes the potential usefulness of sputum biomarkers. The author describes his success with high-frequency chest compression (HFCC) plus hypertonic aerosolized saline as a method to obtain specimens with both high specificity and sensitivity.

4. McKinnon M, Payne P, MacAulay C, LeRiche JC, Lee A, Palcic B, Lam S. Optimal sputum cytology collection method. Chest 1996; 110:S1.
To identify an optimal sputum cytology collection method, 52 heavy smokers were randomly assigned to produce sputum after 20 minutes of inhalation of nebulized water (NW) or induction with nebulized water +high frequency chest compresion (NW+ HFCC). Specimen adequacy was determined by presence of alveolar macrophages. Analysis showed that 90% of NW + HFCC specimens were adequate vs 74% NW; the fraction of normal, atypical and malignant bronchial epithelial cells (BEC) were 1.3 + 1.5% with NV + HFCC vs 0.97 + 1.0% with NW only; all NW+ HFCC samples contained BEC vs 93 % of those obtained with NW alone. NW + HFCC produced significantly more adequate specimens with higher yields of diagnostically important cells.

5. Rhame F, Armstrong J, Beneke J, McComb C, Klous D, Sandowski P. Comparison of high frequency chest compression (HFCC) with hypertonic saline for the induction of sputum. Int Conf AIDS 1992; Jul 19-24; 8:51 (Abstract no. PuB 7017.
In a study comparing the efficacy of sputum induction using high frequency chest compression (HFCC) with nebulized hypertonic saline (NHS), patients with HIV infection were randomized to either HFCC or NHS. Using recovery of alveolar macrophages as the outcome measure, both methods were judged adequate and similarly effective.

Ventilatory Effects

The FDA has approved high frequency chest compression (HFCC) to promote secretion clearance and currently it is marketed solely for that purpose. Several research studies suggest that HFCC may provide clinically beneficial ventilatory effects. Although this potential has not been fully evaluated, encouraging data suggest that further evaluation is merited.

1. al-Saady NM, Fernando SS, Petros AJ, Cummin AR, Sidhu VS, Bennett ED. External high-frequency oscillation in normal subjects and in patients with acute respiratory failure. Anaesthesia 1995; 50:1031-1035.
Twenty healthy volunteers treated with an external chest wall oscillation (ECWO) device (the Hayek Oscillator) demonstrated significant improvement in lung ventilation. Effective ventilation was measured in terms of the fall in alveolar PCO2 immediately after oscillation. In the same study, ECWO was compared with intrapulmonary positive pressure ventilation (IPPV) in five patients with respiratory failure. After a 30 minute treatment with IPPV, therapy was replaced with 30 minutes of ECWO. Oxygenation improved by 16% and PCO2 decreased by 6%, indicating that ECWO can maintain adequate ventilation is this group of patients.

2. Calverley PMA, Chang HK, Vartian V, Zidulka A. High-frequency chest wall oscillation: assistance to ventilation in spontaneously breathing subjects. Chest 1986; 89:218-223.
Five normal spontaneously breathing supine-positioned subjects received high-frequency chest wall compression (HFCC) at frequencies of 3, 5 and 8 Hz for fifteen minute sessions at both maximal and half-maximal peak tolerable cuff pressures. Each session was separated by 15 minutes of control spontaneous ventilation. A significant decrease with HFCC in spontaneous minute ventilation at maximal and half-maximal pressures by 35 and 40 per cent respectively; at 3 Hz and by 25 and 35 percent respectively at 5 Hz and with little change at 8 Hz suggests a potential role as an aid to ventilation in spontaneously breathing patients without requiring an endotracheal tube.

3. Dolmage TE, Eisenberg HA, Davis LL, Goldstein RS. Chest wall oscillation at 1 Hz reduces spontaneous ventilation in healthy subjects during sleep. Chest 1996; 110:128-135.
To determine whether external chest wall oscillation (ECWO) during sleep 1) reduces spontaneous ventilation while maintaining adequate gas exchange over several hours; 2) influences the quality and distribution of sleep and; 3) increases the number of respiratory events, 7 healthy volunteers received one night of ECWO at 1 Hz and a night during which the cuirass was applied without ECWO. ECWO resulted in 1) a significant decrease in spontaneous minute ventilation (VE) in all stages of sleep; 2) was associated with a reduction in the total sleep time and; 3) a reduction in rapid eye movement (REM) sleep. Mean PCO2 was similar between the control and cuirass nights (44 to 46 mm Hg) and mean arterial oxygen saturation (SaO2) was maintained at 96 to 97% throughout sleep during the control, cuirass, and ECWO nights. Results suggest that ECWO can be tolerated for several hours and will assist ventilation while maintaining normal mean PCO2 and mean SaO2 during sleep.

4. George RJ, Winter RJ, Flockton SJ, Geddes DM. Ventilatory saving by external chest wall compression or oral high-frequency oscillation in normal subjects and those with chronic airflow obstruction. Clin Sci (Lond). 1985; 69:349-359.
Oscillation of the air within the lungs at high frequency is associated with an increased clearance of CO2. In this study, high-frequency oscillations were superimposed upon tidal breathing by using a loudspeaker attached to a mouthpiece to produce oral high-frequency oscillation (OHFO) or by external chest wall compression (ECWC). Changes in ventilation and breathlessness using OHFO and ECWC in normal subjects were compared with those in patients with chronic airflow obstruction (CAO). The pattern of breath conservation was then related to the resonant frequencies of the respiratory system as a whole (5-10 Hz in normal subjects, 16-26 Hz in CAO) and those of the ribcage (70 Hz). OHFO reduced minute ventilation (VE) by up to 46% in normal subjects (P = < 0.01) and 29% in CAO (P = < 0.01) without any rise in CO2. ECWC reduced VE by 27% in normal subjects (p = < 0.01) and 16% in CAO (p = < 0.01) without a rise in CO2. High-frequency oscillation by either method relieved breathlessness in those with CAO, was comfortable and well tolerated and may have value as a supplement to ventilation.

5. Hamel D, Gupta V, Craig D, Kotani T, Quick G, Gentile M, Cheifetz I. High frequency chest wall oscillation improves oxygenation in a pediatric swine model of acute lung injury. Duke Children’s Hospital, Durham, NC (publication pending)
In a study to determine whether high frequency chest compression (HCFF) improves oxygenation in acute lung injury, nine swine (12-20 kg) with a surfactant depletion model were conventionally ventilated at settings maintained constant throughout the data collection. High frequency chest compression (HCFF) was applied to each animal at various combinations of pressure (0.5, 3, and 5) and frequency (5, 10, and 15 Hz) in random order. For each combination of HFCC settings, an arterial blood gas was obtained after a 10-minute stabilization period without HCFF and at the end of a 10-minute period with HCFF. Results showed that HFCC effectively improves oxygenation at a low (0.5) HCFF pressure setting (p<0.04). Investigators speculate HCFF may be a useful technique as an adjunct therapy to conventional ventilation to achieve a more optimal mean lung volume.

6. Harf A, Zidulka A, Chang HK. Nitrogen washout during tidal breathing with superimposed high-frequency chest-wall oscillation. Am Rev Respir Dis 1985; 132:350-353.
To assess the efficacy of high-frequency chest compression (HFCC) superimposed on tidal ventilation, multiple-breath nitrogen washout curves were obtained in 7 normal seated subjects. HFCC at 5 Hz was superimposed on the regulated tidal breathing; the magnitude of the oscillatory tidal volume measured at the airway opening was 20 ml in one phase of the trial and 40 ml for a second phase. Results of analysis of the washout curve suggested that during inspiration HFCC enhances gas mixing in the lung periphery and that during expiration HFCC improves gas mixing in the airways.

7. Isabey D, Piquet J. The ventilatory effect of external oscillation. Acta Anaesthesiol Scand 1989; 33 (Suppl 90):87-92.
External oscillation applied around the chest wall [EOCW] may provide non-invasive high frequency ventilation in large animals and humans. Results obtained with EOCW in both normal and bronchoconstricted subjects showed beneficial effects in bronchoconstricted rabbits in terms of a slight improvement in gas exchange and a potentially positive effect on inspiratory muscle fatigue. Data support the concept that HFCC may assist ventilation in bronchoconstricted subjects with high lung compliance, such as babies, neonates and normal adults.

8. Khoo M, Gelmont D, Howell S, Johnson R, Yang F, Chang HK. Effects of high-frequency chest-wall oscillation on respiratory control in humans. Am Rev Respir Dis 1989; 139:1223-1230.
An investigation of spontaneous breathing patterns of 10 normal adults during high-frequency chest compression (HFCC) showed that HFCC increased the breath-to-breath variability of spontaneous respiration in all subjects; some subjects experienced short apneas. PACO2 decreased significantly (p = <0.05). The effects on minute ventilation, tidal volume, and inspiratory and expiratory durations remained variable across subjects although average expiratory duration increased by a non-significant 29%. Ventilatory responses to CO2 with and without HFCC showed normocapnic (PACO2 = 40 mm Hg) ventilatory drive increased significantly (p = < 0.05) in six subjects and decreased substantially in the others. With hypercapnia, the changes in drive were attenuated in all subjects.

9. Piquet J, Isabey D, Chang HK, Harf A. High-frequency transthoracic ventilation improves gas exchange during experimental bronchoconstriction in rabbits. Am Rev Respir Dis 1986; 133:605-608.
To evaluate the efficacy of ventilation by high frequency transthoracic oscillation (HFTO) in obstructive lung disease, 10 anesthetized and paralyzed rabbits with experimentally induced bronchoconstriction were placed in a body-box connected to a piston pump and in random order administered frequencies of 1 Hz ( representing "conventional" ventilation), and 5 Hz (for high frequency ventilation). Several oscillation rates were used. Data showed improved gas exchange at 5 Hz and only a minor increase in lung volume. No significant hemodynamic changes occurred.

Research and Evidence

Clinical Trials

• Safety and Efficacy
• Secretion Clearance
• Pulmonary Function

Research Studies

• Mechanisms of Action

Annotated Bibliography

• Clinical Research
• Basic Research
• Miscellaneous
• Review Articles

Articles

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