Safety and effectiveness of the high-frequency chest wall oscillation vs intrapulmonary percussive ventilation in patients with severe COPD

Introduction

COPD is a lung disease characterized by chronic airflow limitation associated with an enhanced chronic inflammatory response to noxious particles or gases.¹ Mucus hypersecretion in COPD has many common causes; some of these include cigarette smoke, acute and chronic viral infection, bacterial infection, and/or inflammatory cell activation of mucin gene transcription.² The overproduction of mucus and the hypersecretion from increased degranulation is mediated by neutrophil elastase.³ Moreover, there is a difficulty in clearing secretions because of poor ciliary function, distal airway occlusion, and/or an ineffective cough along with reduced peak expiratory flow. This leads to progressive decline in lung function.^1,4 Respiratory chest physiotherapy and assisted mucus-clearing techniques are critically important in COPD patients.⁵ Postural drainage, assisted cough, active cycle of breathing techniques, autogenic drainage, forced expiratory technique, positive expiratory pressure devices,⁶ oscillatory positive-expiratory pressure devices⁷ and, more recently, high-frequency chest wall oscillation (HFCWO),⁸ intermittent positive pressure breathing (IPPB),⁹ intrapulmonary percussive ventilation (IPV),¹⁰ and temporary positive expiratory pressure^11,12 are the techniques that have been proposed over the years for secretion management. The efficacy of these techniques during acute exacerbation or stable disease remains unclear.¹³ Osadnik et al¹³ reviewed twenty-eight studies including 907 participants in a meta-analysis; however, the quality was considered poor due to inadequate blinding and allocation procedure and the results were limited by heterogeneity of outcome measurement and inadequacy of data. The conclusions were that airway clearance techniques are safe for individuals with COPD, but the benefits are less clear. IPV was designed to promote mobilization of bronchial secretions and improve efficiency and distribution of ventilation, providing intrathoracic percussion and vibration and an alternative system for the delivery of the positive pressure to the lungs. HFCWO involves an inflatable jacket that is attached to a pulse generator by hoses that mechanically enable the equipment to perform at variable frequencies (5–25 Hz).¹⁴ The generator sends air through the hose, which causes the vest to inflate and deflate rapidly. The vibrations not only separate mucus from the airway walls but also help move it up into the large airways.¹⁵ Regarding these two different techniques, we conducted a randomized controlled study aimed at comparing their short-term effects in severe to very severe (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 3–4, assessment C–D) COPD patients.

Methods

The study was carried out at the Pulmonary Rehabilitation Center of the Respiratory Diseases Department of General Hospital of Sestri Levante from April 2013 to December 2013 and was approved by Local Ethics Committee. Written informed consent was obtained from all participants and procedures were conducted according to the Declaration of Helsinki. The study was registered with the Chinese Clinical Trial Registry, with the number ChiCTR-TRC-12002133.

Patients

Seventy nine patients with stable severe to very severe COPD admitted to The Rehabilitation outpatient clinic were recruited. Inclusion criteria were as follows: age at least 35 years, presence of chronic bronchitis and airway obstruction on spirometry (GOLD stage 3–4, C–D assessment), bronchial hypersecretion (daily sputum >20 mL for at least 2 consecutive days), and effective cough (peak expiratory cough flow >360 L/min). Exclusion criteria were the following: exacerbation of COPD or hospitalization for COPD within 8 weeks prior to recruitment, history of bronchial asthma, predominant bronchiectasis, presence of tracheostomy, mechanical ventilation, recent pneumothorax, severe abnormalities of sensory, severe cardiac arrhythmias, hemodynamic instability, and chest radiograph changes. The drop-out criteria were the inability to comply to study procedures or the lack of a written informed consent and the occurrence of any of the exclusion criteria.

Protocol

This was a 4-week parallel randomized controlled study comparing IPV, HFCWO, and the best medical therapy. The aim of the study was to verify the effectiveness and the patients’ preference regarding the two methods. Patients who met inclusion criteria were enrolled and randomized into three groups as depicted in the flowchart in Figure 1. A randomization schedule was generated by an independent statistician using an online random permutation generator from http://www.randomization.com. The randomization assignments were provided to the physicians in sealed envelopes. The investigators who carried out the study data analysis were blinded to patients’ treatment assignment.

Figure 1 Flow chart detailing study methodology. Abbreviations: GOLD, Global Initiative for Chronic Obstructive Lung Diseases; FEV1, forced expiratory volume 1 second; HFCWO, high-frequency chest wall oscillation; IPV, intrapulmonary percussive ventilation.

Treatments protocols

IPV was provided by a respiratory physiotherapist using a percussive ventilator (IPV Impulsator, Percussionaire) (Figure 2A). The impact of calibration (adjustment of inspiratory to expiratory ratio), percussion (frequency of delivered breaths), and source pressure (amplitude/pressure rise of delivered breaths) was adjusted using some suggested setting parameters.¹⁰ Each IPV session lasted fifteen minutes and was performed twice a day (morning and afternoon). HFCWO was delivered by a respiratory physiotherapist using a percussive vest (The Vest Airway Clearance System Model 205, Hill-Rom, Batesville, IN, USA) (Figure 2B) at 13–15 Hz oscillating frequency, based on patient’s tolerance, and at a pressure setting of 2–5 cm H₂O to achieve a tight but comfortable snug fit.^14,15 Each HFCWO session lasted 20 minutes and was performed twice a day (morning and afternoon). Subjects for both procedures were kept in a sitting position. The duration of the treatments for each group was 2 weeks. The patients were evaluated one week before the start of airway clearance treatment and one week after the end of the treatment.

Figure 2 (A) Intrapulmonary percussive ventilator. (B) High-frequency chest wall oscillator.

Measurements and outcomes

The primary outcomes of the study were the assessment of changes in dyspnea and quality of life as well as daily life activity and healthy status assessment. The secondary outcomes were changes in respiratory function testing, hematological tests, and sputum cell count.

Dyspnea was measured with the Modified Medical Research Council (mMRC) Dyspnea Scale;¹⁶ cough and sputum was assessed with the Breathlessness, Cough, and Sputum Scale (BCSS);^17,18 daily life activity and healthy status assessment were measured with COPD Assessment Test (CAT).^19,20 Pulmonary function testing including forced vital capacity (FVC), forced expiratory volume 1 second (FEV₁), FEV₁/FVC%, total lung capacity (TLC), residual volume (RV), diffusing lung capacity monoxide (DLCO), maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), peak cough expiratory flow, and arterial blood gas analysis (Pao₂, Paco₂, pH) were performed with a computerized body plethysmography (VMAX 20 PFT Sensor Medics, Yorba Linda, CA, USA), according to the ATS/ERS Guidelines.^21–23 Inspiratory muscle strength was assessed by measuring the MIP at RV. Expiratory muscle strength was assessed by measuring the MEP at TLC. The value obtained from the best of at least three effort was used. All the measurements were obtained in an upright position.^24,25 Diagnosis and severity of COPD were confirmed using the GOLD Guidelines.²⁶

Sputum collection was made on the day the treatment was started and on the day of the last treatment. The patients were instructed by the physiotherapists or by the nurses to expectorate into the sputum cups during the entire duration of the treatment and to continue expectorating if the patient felt the need to cough. Sputum induction was performed using a previously described method. Briefly, the procedure was started 10 minutes after the administration of 200 μg of inhaled salbutamol using a 3% hypertonic saline solution. Sputum samples were processed within 2 hours after the collection.^27–29 Sputum samples were considered for analysis if they contained expectorated material with cellular viability greater than 50%, had contamination with oropharyngeal squamous cells at a level lower than 20%, and were of sufficient quantity to enable differential counts of 400 cells.^28,29 Finally at the end of treatment, subjects treated with IPV or HFCWO were asked to complete a written questionnaire to rate comfort, effectiveness, ease of use, and convenience of the respective procedures. The answers were given using a 5-point Likert-type scale. The possible responses were extremely =4, very =3, somewhat =2, not very =1, not at all =0.³⁰

Statistical analysis

Clinical data were expressed as counts and mean and SD. We calculated the difference between the two treatments (HFCWO and IPV) and control group using univariate regression analysis. Subsequently, the difference between the two treatments (HFCWO and IPV) was analyzed using univariate regression analysis. In addition, a Wilcoxon test was applied to the patients’ preference rankings. Differences were considered statistically significant when p≤0.05. Data analysis was performed using the statistics software R-Project version 2.13.2.

Results

Sixty-three patients were recruited. Three patients withdrew prior to completing the study. Two patients belonged to the control group and one patient belonged to HFCWO group. Sixty patients completed the study. All patients had similar characteristics. The patient characteristics are given in Table 1. No changes in respiratory therapy or COPD exacerbations were observed during the study period.

Table 1 Demographic, clinical, and functional parameters at baseline in the three groups Notes: Data are expressed as mean ± SD, unless otherwise stated. p-value <0.05; F-test for continuous variables and χ2 for categorical variables. Abbreviations: 6MWT, 6-minute walk test; ϒGL, gammaglobulin; BCSS, Breathlessness, Cough and Sputum Scale; BMI, body mass index; CAT, COPD Assessment Test; CRP, C-reactive protein; DLCO, diffusing lung capacity monoxide; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; HFCWO, high-frequency chest wall oscillation; IPV, intrapulmonary percussive ventilation; MEP, maximal expiratory pressure; MIP, maximal inspiratory pressure; mMRC, modified Medical Research Council; RV, residual volume; TLC, total lung capacity.

Primary outcomes

Patients in both the IPV group and the HFCWO group showed a significant improvement in the tests of dyspnea and daily life and health status assessment (mMRC, BCSS, and CAT) compared to those in the control group. Moreover, IPV patients showed an improvement in BCSS (p<0.001) and CAT (p<0.02) scores in comparison with HFCWO. The results are reported in Table 2. The box-plots of BCSS and CAT scores are shown in Figure 3.

Table 2 Results of primary outcomes Note: Data are expressed as mean ± SD. Abbreviations: BCSS, Breathlessness, Cough and Sputum Scale; CAT, COPD Assessment Test; HFCWO, high-frequency chest wall oscillation; IPV, intrapulmonary percussive ventilation; mMRC, modified Medical Research Council.

Figure 3 Median changes in BCSS and CAT before and after treatment in the three groups. Abbreviations: BCSS, Breath, Cough and Sputum Scale; CAT, COPD Assessment Test; HFCWO, high-frequency chest wall oscillation; IPV, intrapulmonary percussive ventilation.

Secondary outcomes

Both the techniques improved several parameters in the patient groups compared to control group (white blood cells, neutrophils, and lymphocytes; C-reactive protein; FVC; FEV₁; FEV₁/FVC%; TLC; RV; RV/TLC%; DLCO; MIP; MEP; PaO₂; PaCO₂; and pH). However, in the group comparison analysis for the same variables between IPV group and HFCWO group, we observed a significant improvement in the IPV group in TLC and TLC% (p<0.03), RV and RV% (p<0.04), and DLCO, MIP, and MEP (p<0.01). These results are summarized in Table 3.

Table 3 Results of secondary outcomes (hematological, biochemical, and respiratory function parameters) Abbreviations: CRP, C-reactive protein; DLCO, diffusing lung capacity monoxide; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; HFCWO, high-frequency chest wall oscillation; IPV, intrapulmonary percussive ventilation; MEP, maximal expiratory pressure; MIP, maximal inspiratory pressure; RV, residual volume; TLC, total lung capacity.

Sputum changes

A significant change in total cell count and neutrophil, lymphocyte, and macrophage counts in sputum samples were observed in the patients receiving either of the two treatments (IPV and HFCWO) compared to control group. Only a slight significant change in neutrophil count was observed in the IPV group compared to HFCWO group (p<0.05). All the results of the sputum cells count measurements are reported in Table 4.

Table 4 Changes in sputum cell count Notes: Total cells count 106/g. Neutrophils, lymphocytes, eosynophils, and macrophages are expressed as percentage ± SD. Abbreviations: HFCWO, high-frequency chest wall oscillation; IPV, intrapulmonary percussive ventilation.

Measurement of patient acceptability

The 40 patients who finished the study (20 in each group) completed the questionnaire and rated the comfort, efficacy, ease of use, and convenience. A similar ranking was expressed by the patients for both the techniques. Table 5 shows the mean ± SD rating and the ranking.

Table 5 Ratings and ranking of patient preferences for airway clearance techniques Note: Values are expressed as mean ± SD. Abbreviations: HFCWO, high-frequency chest wall oscillation; IPV, intrapulmonary percussive ventilation.

Discussion

Techniques for increasing the normal airway clearance are a vital component of therapy. Mechanisms which can be performed without an assistant or without being dependent on a caregiver provide greater control as well as patient satisfaction and are considered important in many areas of medicine (eg, diabetes). Techniques which can be used in a majority of adolescents and adults with pulmonary disease that lead to an increase in adherence with daily therapy have been developed in the recent years.³¹ Thus, methods such as the application of positive expiratory pressure and use of flutter valves or high-frequency chest compression vests have been evaluated with good results in cystic fibrosis patients; these techniques have not been well studied in the COPD patient population. There are a few trials that have studied chest physiotherapy or directed coughing techniques in COPD patients. These trials have shown some improvements in mucus clearance, but no changes in lung function.^2,32,33 Several studies have been published regarding the two instruments, both in bronchiectasis and cystic fibrosis patients,^{8,9,30,34–49} or in COPD patients,^49–60 but only two studies compared IPV and HFCWO.^30,61 In the previously published studies, IPV reduced the incidence of exacerbations,^49,53 improved arterial blood gas values,^51,53,54,57 reduced diaphragmatic workload,⁵⁰ and improved dyspnea,^34,51 some respiratory functional parameters,^34,52,57 and sputum volume.³⁰ HFCWO showed the following findings: improvement of wet weight sputum or greater sputum expectoration,^8,40,43 reduction of dyspnea (Borg score),^44,59 improvement of healthy scores (CAT and BCSS) and quality of life (St Georges Respiratory Questionnaire),^14,60 improvement in ventilation distribution and gas mixing,⁴¹ improvement of respiratory function parameters (FVC, and FEV₁),^8,14,15,41 and changes in sputum cell counts.¹⁴ The study by Varekojis et al³⁰ has compared the therapeutic effectiveness and preference of postural drainage and percussion with IPV and HFCWO. Effectiveness was evaluated by measuring the weight of the wet and dry sputum obtained with each method as well as based on the results of preference obtained by using a Likert-type scale. The wet sputum weight differed significantly and was greater in the IPV group. The second study compared IPV and HFCWO in pediatric tracheostomized patients. IPV was more effective than HFCWO in reducing lower respiratory tract infections, steroid and bronchodilator use, as well as the number of hospitalizations.⁶¹ Our study has evaluated short-term effects of the two techniques on patients with severe to very severe COPD. We have found a significant improvement in the dyspnea, scores on health status assessment scales, as well as in pulmonary function tests and gas exchange.

Besides, in the group comparison analysis for the same variables between the IPV group and the HFCWO group, a significant improvement in the IPV group in TLC, RV, DLCO, MIP, MEP, BCSS, and CAT was observed. The latter data may suggest that IPV can also act on small bronchial airway obstruction and improve alveolar ventilation. Moreover, the reduction of lung hyperinflation decreases respiratory workload as shown by the reduction of maximal inspiratory and expiratory pressure. Finally, changes in sputum cellularity showed a reduction in the number of inflammatory cells (neutrophils and macrophages) and an increase in the number of lymphocytes as a result of utilization of the two techniques (previously observed for HFCWO)¹⁴ and suggests a modulation of inflammatory cells (greater for IPV). This is the first study that has investigated sputum cellularity for COPD patients; further studies need to confirm our findings, particularly concerning its impact on exacerbations.

Limitations

This study has some limitations. It was done in a single center with a relatively modest sample size. We have evaluated only the short-term effects of these techniques; this does not allow us to establish the duration of the effects of the treatment and how many cycles of therapy every patient needs per year.

Moreover, we have not considered the exacerbations; we should have expected a reduction in the number of exacerbations related with the changes in sputum cellularity. Finally, the absence of a sham ventilation therapy group makes our conclusion somewhat less powerful, especially with regard to subjective factors such as dyspnea.

Conclusion

This study shows that both IPV and HFCWO can improve lung function, muscular strength, dyspnea, and scores on health status assessment scales. IPV demonstrated a greater effectiveness in improving test results linked to small bronchial airways and alveolar ventilation (RV and DLCO) and muscular strength (MIP and MEP) as well as scores on daily life and health status assessment scales (BCSS and CAT) compared with HFCWO. These techniques should be considered as additional therapy in patients with severe to very severe COPD.

Acknowledgments

The authors thank Mr Giles Wilson, Sales Manager Percussionaire Corporation for his valuable help in reviewing the manuscript and Dr Sergio Lanata, Histopathology Unit, Hospital of Sestri Levante, for his valuable help in data analysis and collection. The abstract of this manuscript was presented at the Poster session of Chest Annual Meeting, Austin, October 25–30, 2014. The publication was financially supported by a grant from Medigas Italia srl.

Disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. The authors report no conflicts of interest in this work.

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