Patients with chronic hypersecretion (CH) of tracheobronchial mucus represent a challenging clinical problem. CH is a socially disabling condition causing a high susceptibility to airway infection and frequent, difficult-to-treat acute exacerbations with a significant impact on prognosis, quality of life, and use of health care resources, particularly in subjects with severely impaired respiratory function and/or chronic respiratory failure (CRF).1–5

Airway clearance techniques (ACTs), commonly performed by respiratory physiotherapists, are intended to aid secretion mobilization and expectoration and to mitigate complications associated with secretion retention.6 There is a lack of evidence on the superiority of any particular ACT or device and the guidelines do not support their routine use in these subjects,6 most of whom have chronic bronchitis (CB), chronic obstructive pulmonary disease (COPD), and/or bronchiectasis, even during an acute exacerbation.7 Nevertheless, ACTs still remain a challenging option of pulmonary rehabilitation (PR) programs.8,9

ACTs consist of a variety of approaches, such as forced exhalation, manual compression, and/or vibration of the thorax, and positive expiratory pressure (PEP) breathing.10,11 Three main clinical indications for PEP are described: to increase lung volumes, i.e., functional residual capacity (FRC) and tidal volume (VT), to reduce hyperinflation, and to improve airway clearance.12 One of the best-known methods to generate increased PEP is to breathe through a resistance device, such as a PEP mask.

More recently, the mechanical generation of low-level PEP during the main part of expiration (temporary positive expiratory pressure, TPEP) has been proposed to enhance airway clearance. A recent randomized clinical trial comparing the addition of TPEP to usual care13 showed an improvement in the level of dyspnea and of some physiological parameters in the TPEP group.

The aim of this retrospective study was to analyze data from our clinical experience over a 4-year period involving ACTs as part of a comprehensive PR program, in order to compare the physiological outcomes (i.e., gas exchanges and lung volumes) of two groups of patients treated with PEP mask and TPEP respectively. We also sought to identify specific indications for different ACTs in different subpopulations of subjects with CH.

By evaluating two groups of subjects with CH in the common clinical scenario, included in a standard PR program and treated with different ACTs, we found improvements in the PaO2/FiO2 ratio and in many important physiological parameters. Furthermore, our data show that TPEP performs as well as is the most commonly used PEP mask. Finally, subgroup analyses indicate that TPEP and PEP could perform differently in different conditions, suggesting that an accurate selection of ACTs, not exclusively tailored to individual preference or comfort, is warranted to obtain a better performance.

A previous report on the experimental use of TPEP showed improvements in symptoms, static and dynamic lung volumes, and a significant and progressive reduction in mucus production and in perceived bronchial encumbrance in chronic respiratory diseases, including COPD, asthma, and cystic fibrosis, and in the preparation of COPD patients for major abdominal surgery.20 Based on those preliminary findings suggesting an effect on the distribution of lung ventilation with significant improvements in ABGs, a multi-center randomized controlled trial was designed.13 The “UNIKO Project” showed that TPEP in combination with manually assisted ACT, namely ELTGOL21–23 (Expiration Lente Totale Glotte Ouverte en Décubitus Latéral) improves lung function and symptoms in subjects with CH and promotes a faster recovery from symptoms during treatment compared to ELTGOL alone. In that study, there were no significant differences in ABG values between the two groups.

Our analysis, performed on subjects admitted to the Pneumology Department of a rehabilitation center and conventionally treated with a comprehensive PR program including ACT techniques, confirms previous experimental results. In particular, it confirms that such an approach can produce significant improvements in respiratory function and ABGs in a mixed population of patients. However, our findings and previous observations18 are in contrast with the “UNIKO Project” report stating that the addition of TPEP did not produce any change in ABGs.

There are a number of differences between our study and the “UNIKO Project” that may explain the differences in the results observed. The study by Venturelli et al.13 had a number of exclusion criteria as it enrolled only subjects in stable conditions, excluding those with acute exacerbation or on MV. In fact, ABG values at the beginning of their treatments were normal, so finding significant changes after treatment would have been very unlikely. Despite this, their TPEP group still showed a better trend in a shorter period of treatment.

In the present study, we evaluated a larger number of subjects in a “real-life” clinical scenario. They were consecutive subjects with CB/COPD or bronchiectasis as primary diagnosis and history of CH who were enrolled in a PR program including ACT. Thus, we included a significant percentage of subjects with acute exacerbations and those on OT and/or MV (39, 47, and 19%, respectively). In addition to our comparison, we differentiated the two types of ACT (TPEP vs. PEP), while Venturelli et al.13 added TPEP to conventional treatment.

Our results show that on average both groups had equally improved physiological parameters such as lung volumes, flows, and ABG values. Both PEP-mask and TPEP are classified as PEP methods aimed to favor the mobilization of secretions in the lung by “stenting” the airways. The mechanism and effects of PEP are widely described in the literature. PEP increases intrathoracic pressure and FRC, with improvement in collateral ventilation.24 The application of a 15cmH2O PEP temporarily increases VT, reducing respiratory frequency,25 and both inspiratory and expiratory muscle activity.26 In addition, a temporary increase in FRC, related with increasing PEP has been shown.27 This leads to changes in breathing pattern, with decreased expiratory flows, increased expiratory time, and a smaller exhaled volume.28 PEP pressures higher than 10cmH2O are required to open the airways.12

With this in mind, it seems difficult to understand how a pressure as little as 1cmH2O, such as that generated by TPEP when measured at the mouth, could be as effective as the PEP mask. Other factors probably play a role. In fact, in the TPEP device, there is a pressure sensor that detects exhalation, activating a compressor that blows air against the expiratory flow. The resistance delivery time depends on the ability of the subject to sustain a certain flow as long as possible. A forced exhalation will generate a peak of expiratory flow causing a sudden drop in pressure (that leads to a collapse of the peripheral airways). The best performance is obtained when the expiratory flow is a little higher than during quiet breathing, almost reaching residual volume and achieving the same goal as that of other classical ACTs such as autogenic drainage and ELTGOL.22,29 Another difference between the two ACTs is that, with the PEP mask, the flow is variable and effort-dependent,24,30,31 while the TPEP device gives feedback and guides the subject to adapt inspiration and expiration to reach the goal. Furthermore, while blowing into the mouthpiece, an oscillation is clearly perceived while resistance is active, due to the reciprocating compressor. High-frequency oscillations are thought to have a mucolytic effect on bronchial secretions,32 and this feature could play some role in explaining the mechanism of this technique.

Operational differences between PEP mask and TPEP may also account for the differences found between the effects obtained by the two ACT techniques in our study. Subgroup analysis gave some preliminary indications. Subjects with emphysema showed a reduced need for oxygen (O2) supply, FiO2, and PaCO2. The above data, combined with the general reduction in the need for O2 in OT subjects and with the increase in PaO2 in those without CRF, seems to indicate that TPEP may facilitate gas exchange. During TPEP, very low pressures are applied to the airways, making unlikely any direct recruitment effect or changes in surfactant activities and/or production as seen with PEP systems.30

We speculate that breathing pattern and the effective mucus clearance achieved by the increase in gas–liquid interaction33 during sustained expiratory flow could explain gas-exchange improvements. It would also be interesting to investigate if any post-treatment change is present in respiratory pattern and mechanics or in airway resistance. In fact, TPEP forces patients to breathe in a regular way, with open glottis, for the entire treatment time, and this “training” could have contributed to improve the ability to control breathing in subjects with emphysema.26,34

We observed a statistically significant difference between groups when evaluating subjects on MV only for the forced expiratory flows (FEF50%). The interpretation of this finding is difficult particularly because volumes or gas exchange parameters did not differ between subjects on MV. We might speculate that MV, providing positive pressure inside the airways, can overcome the TPEP effects on FEF. On the contrary, the administration of a higher PEP with FET maneuvers could have enhanced mid-expiratory flows. Clearly, further analyses are needed to confirm this hypothesis.

Comfort is another important factor we take into account when allocating patients to different treatments. Notably, many of the subjects treated with TPEP were already PEP-mask users at home and found the new device more comfortable and simple to use, since less effort is required compared to the PEP mask with the same subjective perception of efficacy. This feedback was important, prompting us to continue investigations and, as underlined by many authors,10,11,35–38 it might improve adherence to the treatment.

The major limitation of the study is the retrospective design and other sources of bias such as the consequent lack of randomization and intention-to-treat analysis. Thus, caution should be applied when interpreting the results of this study. Moreover, future randomized controlled trials are warranted to confirm the results of this study.

Other limitations include the lack of data on the volume and characteristics of sputum, symptoms and health-related quality of life, not systematically available in the clinical documentation for all patients included. Furthermore, allocation to one or other treatment group may have been affected by the patient's perception and compliance during the first assessment. TPEP requires less effort than PEP to be activated: this might explain in part why a greater proportion of subjects with an acute exacerbation were in the TPEP group, though no significant differences were found between the effects of treatment in relation to the presence of an acute condition.

Nevertheless, no other differences in baseline parameters were found between groups. Furthermore, the PEP mask is a well-established technique that physiotherapists and patients are familiar with, while at that time, TPEP had just been introduced into clinical practice, a fact that probably was the cause of the smaller number of subjects treated with this newer technique.

In conclusion, our data showed that, in most subjects with CH in current clinical practice, TPEP yields similar results to the PEP mask. Both groups significantly and similarly improved physiological parameters, but subgroup analysis suggests that TPEP could provide some advantages to subjects with emphysema or those on OT, while PEP would be more advantageous in patients on MV. TPEP added to a standard PR program applied in subjects with CH appears to be a safe and well-accepted ACT and a valid alternative to PEP. We need further prospective, high quality randomized controlled trials to confirm preliminary results indicating that different subgroups/phenotypes can benefit more from one or the other type of treatment.

The authors declare no conflict of interest.