Mechanisms of Action / Effects on Mucus / Physiological Effects

High frequency chest compression (HFCC)/high frequency chest wall oscillation (HFCWO) 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 nonsymmetrical oscillation.  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 high frequency nonsymmetrical oscillation.
  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 high frequency chest compression (HFCC)/high frequency chest  wall oscillation (HFCWO) 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/HFCWO, or any mucolytic agent. Data showed optimal spinnability in vitro when rhDNase and simulated HFCC/HFCWO 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)/high frequency chest wall oscillation (HFCWO) on clearance of secretions from peripheral lung regions, 5 anesthetized, spontaneously breathing dogs received 30 minute treatments of HFCC/HFCWO 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/HFCWO 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 HFCWO 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. HFCWO 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 HFCWO and during HFCWO. The frequencies were re-randomized, and the study was repeated for each animal. Data analysis showed that 1) HFCWO 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 HFCWO. Investigators speculate that HFCWO 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 wall oscillation (HFCWO) 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. HFCWO 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 HFCWO settings, an arterial blood gas was obtained after a 10-minute stabilization period without HFCWO and at the end of a 10-minute period with HFCWO. Data showed that HFCWO effectively improves oxygenation at a low (0.5) HFCWO pressure setting (p<0.04). Investigators speculate HFCWO 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 HFCWO 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. HFCWO 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 HFCWO and during HFCWO. The frequencies were re-randomized, and the study was repeated for each animal. Data analysis showed that 1) HFCWO 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 HFCWO. Investigators speculate that HFCWO 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 wall oscillation (HFCWO) 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 wall oscillation  (HFCWO) 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 HFCWO settings, an arterial blood gas was obtained after a 10-minute stabilization period without HFCWO and at the end of a 10-minute period with HFCWO. Data showed that HFCWO effectively improves oxygenation at a low (0.5) HFCWO pressure setting (p<0.04). Investigators speculate HFCWO 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 wall oscillation (HFCWO) 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  wall oscillation (HFCWO) 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 compression (HFCC)/high frequency chest  wall oscillation (HFCWO) is due, in part, to the expiratory bias in peak flow rate (VE/VI greater than 1) that occurs during HFCC/HFCWO, 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)/high frequency chest wall oscillation (HFCWO) therapy, a pulsating frequency range of 6-19 Hz may not be optimal for mucus drainage. To enhance efficacy of HFCC/HFCWO, 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/HFCWO should be carried out at about 18-34 Hz; they further suggest individual CRF determinations for HFCC/HFCWO 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

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