Positive expiratory pressure physiotherapy for airway clearance in people with cystic fibrosis
Abstract
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:
The purpose of this review is to determine the effect of PEP compared to other scientifically evaluated forms of chest physiotherapy in improving mucus clearance in people with CF.
The following hypotheses will be tested:
1. PEP is more effective for people with CF than other forms of chest physiotherapy.
2. PEP is more acceptable to people with CF than other forms of chest physiotherapy.
Background
Cystic Fibrosis (CF) is a relatively common, inherited, life limiting disorder. The basic genetic defect causes abnormal mucus secretion in the airways, potentially leading to airway obstruction and mucus plugging (Zach 1990). This predisposes the airways to infection and inflammation, which in turn promote further mucus secretion. Persistent infection and inflammation within the lungs are the major contributory factors to airway damage and the progressive loss of respiratory function (Cantin 1995; Konstan 1997). Treatment methods which improve mucus clearance are considered essential in optimising respiratory status and reducing the progression of lung disease, although a Cochrane Systematic Review comparing any form of chest physiotherapy with no chest physiotherapy found insufficient evidence to demonstrate this (van der Schans 2001). A variety of methods are used, some physical, e.g. chest physiotherapy, and some chemical, e.g. inhaled medications.
Chest physiotherapy is widely prescribed to assist the clearance of airway secretions and is usually commenced as soon as the diagnosis of CF is made. Traditionally, chest physiotherapy relied on postural drainage (gravity assisted drainage positions) combined with percussion and vibration (performed by an assistant such as a physiotherapist or relative), forced expirations (huffing) and coughing. Some included deep breathing exercises. This form of chest physiotherapy is time consuming, sometimes uncomfortable, and as it requires assistance, may have an adverse effect on adherence. Recently, several self administered alternatives, able to be used in upright sitting positions, have been developed. Among these are a range of positive expiratory pressure (PEP) devices, which provide a constant back pressure to the airways during expiration. It has been theorised that PEP devices are able to improve clearance by building up air behind secretions via collateral ventilation, thus making expiratory manoeuvres more effective (Groth 1985). Despite the increase in popularity of these PEP devices, the conclusions of different studies using different methods are contradictory (Williams 1994). This review will compare the effect and acceptability of PEP devices to those of any other scientifically evaluated techniques used for secretion clearance.
The most effective technique for secretion clearance during an infective exacerbation of CF may differ from that which is most effective for maintenance therapy. Studies will therefore also be analysed in subgroups based on disease state. PEP is also used in combination with various other interventions (e.g. pharmacological therapies, other physical therapy techniques, or the modifications to the technique known as high pressure PEP). The results of PEP with and without these co‐interventions will be analysed separately.
Objectives
The purpose of this review is to determine the effect of PEP compared to other scientifically evaluated forms of chest physiotherapy in improving mucus clearance in people with CF.
The following hypotheses will be tested:
1. PEP is more effective for people with CF than other forms of chest physiotherapy.
2. PEP is more acceptable to people with CF than other forms of chest physiotherapy.
Methods
Criteria for considering studies for this review
Types of studies
This review will include randomised clinical trials in which PEP is evaluated in people with CF and compared with any other form of chest physiotherapy.
Types of participants
People with CF, of any age, diagnosed on the basis of clinical criteria and sweat testing or genotype analysis, with any degree of disease severity.
Types of interventions
For the purposes of this review, the intervention used in the studies will be required to meet one of the following descriptions:
Positive expiratory pressure (PEP) mask, mouthpiece or bottle therapy as described by the authors is to be the primary intervention, with or without additional techniques. PEP is defined as breathing with a positive expiratory pressure of 5‐25 cm H2O.
High pressure PEP (hPEP) mask therapy as described by the authors is to be the primary intervention, with or without additional techniques. High pressure PEP is a modification of the above technique which includes a full forced expiration against a fixed mechanical resistance.
Two reviewers will independently categorise the intervention into PEP, hPEP (with level of pressure) or neither. An estimate of agreement will be made between the two reviewers.
Types of outcome measures
Primary Outcome Measures
1. Forced Expiratory Volume at one second (FEV1).
Change in FEV1 between baseline and post‐intervention. Litre and percent (%) predicted values will both be provided wherever possible.
2. Number of respiratory exacerbations per year.
Respiratory exacerbations must have been defined either by symptoms or by changes in treatment after medical assessment.
3. Number of days of intravenous antibiotics per year.
Intravenous antibiotics must have been prescribed in response to a respiratory exacerbation.
4. Well being.
Quality of life or well‐being, or ability to participate in activities of daily living.
5. Adverse effects.
Deaths or other adverse changes in condition from baseline (pre‐treatment), such as pneumothorax, bronchospasm or haemoptysis.
6. Survival.
7. Exercise tolerance.
Subjective exercise tolerance, or objective measures such as six minute walk test.
8. Patient preference.
Patient preference may be determined either as the nominated technique of choice by the subject at the conclusion of the study, or by a comparison of technique acceptability (e.g. visual analogue scale).
Secondary Outcome Measures
1. Direct measures of mucus clearance.
Mucus transport rate or mucociliary clearance rate as assessed by radioactive tracer.
2. Expectorated secretions, dry or wet weight, or volume.
An increase in the amount of expectorated secretions as a short term (less than seven days) effect of the intervention is considered as beneficial. In long term studies this outcome variable will not be included.
3. Other pulmonary parameters.
Forced Vital Capacity (FVC), Forced Expiratory Flow 25‐75% (FEF25‐75), Total Lung Capacity (TLC), Residual Volume (RV) and Functional Residual capacity (FRC) post‐intervention change from baseline.
4. Blood oxygen levels.
This may be measured by arterial blood gas, pulse oximetry or transcutaneous oximetry.
5. Ventilation scanning.
Radiological or nuclear medicine imaging.
6. Nutritional status.
Difference in growth (cm / year), weight (kg / year), or body composition (BMI).
7. Cost of intervention (equipment and duration).
8. Adherence to treatment.
Search methods for identification of studies
Relevant trials will be identified in the Cochrane Cystic Fibrosis and Genetic Disorders Group Specialised Register of Controlled Trials. This register was compiled by conducting computerised searches of Medline from 1966 to the present and from Embase from 1974 to the present. The register of RCTs is updated every three months. Unpublished work will be identified by searching through the abstract books of the three major CF conferences; the International CF conference, the European CF conference, and the North American CF conference.
The electronic database CINAHL, which is not covered by the CRG search strategy, will be searched using the following search terms:
a. Positive expiratory pressure OR PEP OR High pressure PEP
b. Cystic fibrosis OR CF OR Mucoviscidosis
c. #a AND #b
The first reviewer will conduct this search for the years 1982 ‐ 2001, and any additional trials identified from this search will be included on the Cochrane Cystic Fibrosis and Genetic Disorders Group Specialised Register of Controlled Trials.
The authors will contact other centres where trials on PEP are being undertaken. The authors will also contact manufacturers of PEP devices regarding any additional trials.
Data collection and analysis
All studies identified by the search will be reviewed by two independent reviewers from different centres to determine which trials should be included. The quality of the studies will be assessed as described by Jadad (Jadad 1996). This assessment will also be done independently by two reviewers. If there is disagreement about either whether a trial should be included, or the quality score it should receive, an independent reviewer from a third centre will be asked to review the paper(s) in question. Only the first arm of the data from cross‐over trials will be included. Data will be extracted by each reviewer on the outcome measures listed above. First authors of the included trials will be contacted to verify their data. Cochrane Review Manager 4.1 will be used to compile and analyse the data.
For all studies included, the following details will be given: definition of the base population, methods of subject selection, and baseline characteristics of the active and placebo groups including age, sex, genotype and lung function.
For continuous outcomes, either the mean change from baseline for each group or mean post treatment/intervention values and the standard deviation or standard error for each group will be recorded. In the case of binary outcomes, data will be collected on the number of subjects with each outcome event by allocated treated group irrespective of compliance and whether or not the patient was later thought to be ineligible or otherwise excluded for treatment or followup to allow an intention to treat analysis.
Studies in which the intervention consists of a single treatment will be analysed separately from those studies in which a course of treatments is used. Within the latter group, studies of less than seven days treatment will be analysed separately from studies of longer duration.
Outcome data from longer term studies (more than seven days) will be grouped into those measured at one, three, six, twelve months, and annually thereafter. If outcome data is recorded at other time periods, then consideration will be given to examining these as well.
Subgroup analysis will be performed on the following factors: level of PEP, use of hPEP, disease state (exacerbation vs stable), use of co‐interventions, age (paediatric, adolescent, adult), gender, and disease severity.
